22 research outputs found
Diarylethene Self-Assembled Monolayers: Cocrystallization and Mixing-Induced Cooperativity Highlighted by Scanning Tunneling Microscopy at the Liquid/Solid Interface
International audienceThe control over 2-D multi-component molecular orderings on surfaces is a key technology to realize advanced materials with stimuli-responsive properties. The fractional coverage (θ) at a given concentration can be determined from two parameters: the equilibrium constant (Ke) and the degree of cooperativity (σ). The parameters for the formation of self-assembled monolayer of pure diarylethene isomers were obtained by STM measurements on HOPG. These mono-component parameters were used as references to highlight a cocrystallization process between the open-and closed-ring isomers. Moreover it was observed that the presence of the closed-ring isomer induces cooperativity in the formation of the molecular ordering of the open-ring isomer. The quantitative analysis of the ordering formation process by using a model simulation presented in this work provides a better understanding of mixing of components in a molecular ordering and photoinduced interchanges at the liquid/solid interface. (1) Sakano, T.; Imaizumi, Y.; Hirose, T.; Matsuda, K. Chem. Lett. 2013, 42, 1537. (2) Yokoyama, S.; Hirose, T.; Matsuda, K. Chem. Commun. 2014, 50, 5964. (3) Frath, D.; Sakano, T.; Imaizumi, Y.; Yokoyama, S.; Hirose, T.; Matsuda, K. Chem. Eur. J. 2015, 21, 11350
Diarylethene Self-Assembled Monolayers: Cocrystallization and Mixing-Induced Cooperativity Highlighted by Scanning Tunneling Microscopy at the Liquid/Solid Interface
International audienceThe control over 2-D multi-component molecular orderings on surfaces is a key technology to realize advanced materials with stimuli-responsive properties. The fractional coverage (θ) at a given concentration can be determined from two parameters: the equilibrium constant (Ke) and the degree of cooperativity (σ). The parameters for the formation of self-assembled monolayer of pure diarylethene isomers were obtained by STM measurements on HOPG. These mono-component parameters were used as references to highlight a cocrystallization process between the open-and closed-ring isomers. Moreover it was observed that the presence of the closed-ring isomer induces cooperativity in the formation of the molecular ordering of the open-ring isomer. The quantitative analysis of the ordering formation process by using a model simulation presented in this work provides a better understanding of mixing of components in a molecular ordering and photoinduced interchanges at the liquid/solid interface
Cooperativity Analysis of the Open-, Closed-and Annulated-Isomers of Diarylethene that form 2-D Ordering at the Liquid/Solid Interface and their Photochemical Interchanges
International audienc
Plasma Free Amino Acid Profiling of Five Types of Cancer Patients and Its Application for Early Detection
BACKGROUND: Recently, rapid advances have been made in metabolomics-based, easy-to-use early cancer detection methods using blood samples. Among metabolites, profiling of plasma free amino acids (PFAAs) is a promising approach because PFAAs link all organ systems and have important roles in metabolism. Furthermore, PFAA profiles are known to be influenced by specific diseases, including cancers. Therefore, the purpose of the present study was to determine the characteristics of the PFAA profiles in cancer patients and the possibility of using this information for early detection. METHODS AND FINDINGS: Plasma samples were collected from approximately 200 patients from multiple institutes, each diagnosed with one of the following five types of cancer: lung, gastric, colorectal, breast, or prostate cancer. Patients were compared to gender- and age- matched controls also used in this study. The PFAA levels were measured using high-performance liquid chromatography (HPLC)-electrospray ionization (ESI)-mass spectrometry (MS). Univariate analysis revealed significant differences in the PFAA profiles between the controls and the patients with any of the five types of cancer listed above, even those with asymptomatic early-stage disease. Furthermore, multivariate analysis clearly discriminated the cancer patients from the controls in terms of the area under the receiver-operator characteristics curve (AUC of ROC >0.75 for each cancer), regardless of cancer stage. Because this study was designed as case-control study, further investigations, including model construction and validation using cohorts with larger sample sizes, are necessary to determine the usefulness of PFAA profiling. CONCLUSIONS: These findings suggest that PFAA profiling has great potential for improving cancer screening and diagnosis and understanding disease pathogenesis. PFAA profiles can also be used to determine various disease diagnoses from a single blood sample, which involves a relatively simple plasma assay and imposes a lower physical burden on subjects when compared to existing screening methods
Mechanistic insights into intramembrane proteolysis by E. coli site-2 protease homolog RseP
細胞膜の中ではたらく特殊なタンパク質分解酵素の構造を解明 --細菌感染症の新たな治療法の開発へ期待--. 京都大学プレスリリース. 2022-08-25.Site-2 proteases are a conserved family of intramembrane proteases that cleave transmembrane substrates to regulate signal transduction and maintain proteostasis. Here, we elucidated crystal structures of inhibitor-bound forms of bacterial site-2 proteases including Escherichia coli RseP. Structure-based chemical modification and cross-linking experiments indicated that the RseP domains surrounding the active center undergo conformational changes to expose the substrate-binding site, suggesting that RseP has a gating mechanism to regulate substrate entry. Furthermore, mutational analysis suggests that a conserved electrostatic linkage between the transmembrane and peripheral membrane-associated domains mediates the conformational changes. In vivo cleavage assays also support that the substrate transmembrane helix is unwound by strand addition to the intramembrane β sheet of RseP and is clamped by a conserved asparagine residue at the active center for efficient cleavage. This mechanism underlying the substrate binding, i.e., unwinding and clamping, appears common across distinct families of intramembrane proteases that cleave transmembrane segments
Deficiency of MicroRNA-23-27-24 Clusters Exhibits the Impairment of Myelination in the Central Nervous System
Several microRNAs (miRNAs), including miR-23 and miR-27a have been reportedly involved in regulating myelination in the central nervous system. Although miR-23 and miR-27a form clusters in vivo and the clustered miRNAs are known to perform complementary functions, the role of these miRNA clusters in myelination has not been studied. To investigate the role of miR-23-27-24 clusters in myelination, we generated miR-23-27-24 cluster knockout mice and evaluated myelination in the brain and spinal cord. Our results showed that 10-week-old knockout mice had reduced motor function in the hanging wire test compared to the wild-type mice. At 4 weeks, 10 weeks, and 12 months of age, knockout mice showed reduced myelination compared to wild-type mice. The expression levels of myelin basic protein and myelin proteolipid protein were also significantly lower in the knockout mice compared to the wild-type mice. Although differentiation of oligodendrocyte progenitor cells to oligodendrocytes was not inhibited in the knockout mice, the percentage of oligodendrocytes expressing myelin basic protein was significantly lower in 4-week-old knockout mice than that in wild-type mice. Proteome analysis and western blotting showed increased expression of leucine-zipper-like transcription regulator 1 (LZTR1) and decreased expression of R-RAS and phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) in the knockout mice. In summary, loss of miR-23-27-24 clusters reduces myelination and compromises motor functions in mice. Further, LZTR1, which regulates R-RAS upstream of the ERK1/2 pathway, a signal that promotes myelination, has been identified as a novel target of the miR-23-27-24 cluster in this study
Development of a human neuromuscular tissue-on-a-chip model on a 24-well-plate-format compartmentalized microfluidic device
Post-discharge clinical, laboratory and radiographic features of coronavirus disease 2019 (COVID-19) patients at university hospitals in Japan
Generation of human melanocytes from induced pluripotent stem cells.
Epidermal melanocytes play an important role in protecting the skin from UV rays, and their functional impairment results in pigment disorders. Additionally, melanomas are considered to arise from mutations that accumulate in melanocyte stem cells. The mechanisms underlying melanocyte differentiation and the defining characteristics of melanocyte stem cells in humans are, however, largely unknown. In the present study, we set out to generate melanocytes from human iPS cells in vitro, leading to a preliminary investigation of the mechanisms of human melanocyte differentiation. We generated iPS cell lines from human dermal fibroblasts using the Yamanaka factors (SOX2, OCT3/4, and KLF4, with or without c-MYC). These iPS cell lines were subsequently used to form embryoid bodies (EBs) and then differentiated into melanocytes via culture supplementation with Wnt3a, SCF, and ET-3. Seven weeks after inducing differentiation, pigmented cells expressing melanocyte markers such as MITF, tyrosinase, SILV, and TYRP1, were detected. Melanosomes were identified in these pigmented cells by electron microscopy, and global gene expression profiling of the pigmented cells showed a high similarity to that of human primary foreskin-derived melanocytes, suggesting the successful generation of melanocytes from iPS cells. This in vitro differentiation system should prove useful for understanding human melanocyte biology and revealing the mechanism of various pigment cell disorders, including melanoma