Activation of Ras-ERK pathway by Fgf8 and its downregulation by Sprouty2 for the isthmus organizing activity

In the previous studies, we showed that strong Fgf8 signaling activates the Ras-ERK pathway to induce cerebellum. Here, we show importance of negative regulation of this pathway. 'Prolonged' activation of ERK by misexpression of _Fgf8b_ and dominant-negative _Sprouty2_ (_dnSprouty2_) did not change the fate of the mesencephalic alar plate. Downregulation of ERK activity using a MEK inhibitor, U0126, or by tetracycline dependent Tet-off system after co-expression of _Fgf8b_ and _dnSprouty2_, forced the mesencephalic alar plate to differentiate into cerebellum. We then paid attention to Mkp3. After misexpression of _dnMkp3_ and _Fgf8b_, slight downregulation of ERK activity occurred, which may be due to Sprouty2, and the mesencephalon transformed to the isthmus-like structure. The results indicate that ERK must be once upregulated and then be downregulated for cerebellar differentiation, and that differential ERK activity level established by negative regulators receiving Fgf8 signal may determine regional specificity of mesencephalon and metencephalon

CRYSTAL GROWTH OF A HECTORITE-LIKE LAYERED SILICATE ON MONODISPERSE SPHERICAL SILICA PARTICLES WITH DIFFERENT DIAMETERS

Fine crystals of hectorite-like layered silicate formed using hydrothermal reactions on monodisperse spherical silica particles with diameters of 0.2, 0.6 and 1.0 μm. The reactions were performed in a colloidal spherical silica suspension with lithium and magnesium ions under alkaline conditions at 373 K in a rotating Teflon-lined autoclave at the LiF:MgCl_2:SiO_2 molar ratio of 0.21:0.8:8.0. The grain size distributions were quite uniform irrespective of the silica size in the initial mixtures, as a result of the high rate of heterogeneous nucleation reaction than that of the homogeneous nucleation. The amount of a cationic surfactant that was intercalated tended to be large when the grain size of the silica spheres was small, while the negative layer charge of the hectorite-like silicate was same extent.ArticleClay Science. 19(2): 45-51 (2015)journal articl

Reaction of 3′,5′-di-O-acetyl-2′-deoxyguansoine with hypobromous acid

AbstractHypobromous acid (HOBr) is formed by eosinophil peroxidase and myeloperoxidase in the presence of H2O2, Cl−, and Br− in the host defense system of humans, protecting against invading bacteria. However, the formed HOBr may cause damage to DNA and its components in the host. When a guanine nucleoside (3′,5′-di-O-acetyl-2′-deoxyguansoine) was treated with HOBr at pH 7.4, spiroiminodihydantoin, guanidinohydantoin/iminoallantoin, dehydro-iminoallantoin, diimino-imidazole, amino-imidazolone, and diamino-oxazolone nucleosides were generated in addition to an 8-bromoguanine nucleoside. The major products were spiroiminodihydantoin under neutral conditions and guanidinohydantoin/iminoallantoin under mildly acidic conditions. All the products were formed in the reaction with HOCl in the presence of Br−. These products were also produced by eosinophil peroxidase or myeloperoxidase in the presence of H2O2, Cl−, and Br−. The results suggest that the products other than 8-bromoguanine may also have importance for mutagenesis by the reaction of HOBr with guanine residues in nucleotides and DNA

Precocious activation of APC/C-Cdh1 at pre-anaphase causes genome instability

Faithful chromosome segregation and thereby accurate gene transmission are crucial for all organisms. Until proper attachment of the mitotic spindle to the kinetochore is established, the ubiquitin ligase (E3) Cdc20-activated APC/C (anaphase promoting complex/cyclosome) is repressed by the spindle assembly checkpoint (SAC) and sister chromatin cohesion is protected. Mutants defective in SAC fail to arrest at metaphase even in the presence of damaged microtubules. Interestingly, a similar phenomenon occurs in yeast cells defective in Bub2, a negative factor of the mitotic exit network (MEN), which is required for telophase onset, although its precise molecular mechanism is unknown. Here, we show that chromosome missegregation occurs frequently in bub2∆ cells in the presence of damaged microtubules. The loss of Bub2 caused precocious activation of APC/C-Cdh1/Hct1 at pre-anaphase, leading to securin degradation and then separase-mediated cohesin cleavage. Overexpression of CDH1 and CDC14, encoding Cdc14 phosphatase, at pre-anaphase similarly caused chromosome missegregation. Thus, sequential activation of APC/C-Cdc20 and then APC/C-Cdh1 is critical for precise chromosome segregation and precocious activation of APC/C-Cdh1 at pre-anaphase causes genomic instability. Since degradation of human securin is also mediated by APC/C-Cdc20 and APC/C-Cdh1, this study predicts that precocious activation APC/C-Cdh1 in human cells similarly causes genomic instability, and thereby cell death or tumorigenesis

A Qualitative Study on The Function of Information and Communication Technology Utilization in Teaching Students with Intellectual Disabilities: Implications for Techniques of Teaching/Job Coaching

Background: Recently, the use of Information and Communication Technology (ICT) in education has been promoted in Japan. However, teachers do not yet fully understand using ICT for persons with intellectual disabilities. Objective: This study clarifies the support functions of ICT as perceived by teachers involved in special needs education (support for students with intellectual disabilities). Methods: We conducted in-depth interviews with five teachers involved in special-needs education. We qualitatively analyzed the interview data obtained using content analysis. Results: From the interviews, 53 ICT-utilization episodes were obtained. These episodes were categorized into 13 categories of utilization and seven aspects of support: understanding, communication, behavior, meta-cognition, environment, memory, and opportunities. Conclusion: ICT is a beneficial tool to compensate for intellectual disabilities and help students with intellectual disabilities learn better. We believe that teachers can better assist students with intellectual disabilities by successfully matching individual needs with the ICT features. The results obtained in this study will be helpful while considering support for persons with intellectual disabilities, not only in education but also in vocational training, employment support, and telework support for persons with intellectual disabilities

Preliminary study of discrimination of human vocal commands in walrus (Odobenus rosmarus divergens)

Walruses seem to use various acoustic signals in social context. So, the auditory faculty is seems to be important for walruses. Can walruses understand another animals' vocal information using auditory sense? This study tested whether a male walrus could discriminate human vocal words and perform different actions corresponding to each one under various conditions. The subject, a male walrus (Odobenus rosmarus) named Pou, was set on the ground, and the experimenter spoke one of the ten words to the subject under the following conditions; (1) The experimenter stood close to the subject and spoke each vocal stimulus wearing a black cloak and goggles so that the experimenter's eye and body movements would not influence the subject's behavior, (2) A wooden board was placed between the experimenter and the subject so that the subject could not see the experimenter, (3) A wooden board was placed between the experimenter and the subject so that the subject could not to see the experimenter, and the experimenter uttered each vocal stimulus through an audio speaker. Under each condition, when the subject performed the correct action corresponding to the vocal stimulus, he was rewarded with a piece of fish. As a result, the subject responded correctly to almost all the human vocal stimuli in every condition, including when the speaker was not visible. This means that he was indeed responding to the vocal words and not the experimenter's cues. This study demonstrated that walruses can hear and identify human vocal words using their auditory sense and can form correspondence between vocal words and their meanings

Crystal architectures of a layered silicate on monodisperse spherical silica particles cause the topochemical expansion of the core-shell particles

Anisotropic structural changes in an expandable layered silicate (directed towards the c-axis) occurring on isotropic and monodisperse microspheres were detected by measurable increases in the grain size. The hierarchical changes were observed through pursing the sophisticated growth of expandable layered silicate crystals on monodisperse spherical silica particles with diameters of 1.0 mu m; the core-shell hybrids with a quite uniform grain size were successfully produced using a rotating Teflon-lined autoclave by reacting spherical silica particles in a colloidal suspension with lithium and magnesium ions under alkaline conditions at 373 K. The size distribution of the core-shell particles tended to be uniform when the amount of lithium ions in the initial mixture decreased. The intercalation of dioctadecyldimethylammonium ions into the small crystals through cation-exchange reactions expanded the interlayer space, topochemically increasing the grain size without any change occurring in the shapes of the core-shell particles. (C) 2015 Elsevier Inc. All rights reserved.ArticleMICROPOROUS AND MESOPOROUS MATERIALS. 215:168-174 (2015)journal articl

Assessing the Sustainability of Ski Fields in Southern Japan under Global Warming

This is the first study in assessing the impact of climate change on Japanese ski fields with ensemble dynamical downscaling simulations. We target three ski fields in Ehime Prefecture, a southern border area for skiing in Japan. Our field survey revealed that a field located above 1200 m altitudes currently operates on natural snow supply, but those located at lower altitudes depend solely or partially on artificial snow supply. Fields are currently open for 82∼105 days. We analyzed ensemble high-resolution (5 km) dynamical downscaling simulations for future ski season durations with natural and artificial snow supplies. The future projection results for the end of the twenty-first century suggested that there would be virtually no natural snow accumulation in the study area for skiing. With artificial snow supply, a field located above 1200 m would be able to retain more than two months of ski season duration. Fields located at lower altitudes would only be able to open for 37∼43 days even with artificial snow supply. While the above projections suggest a severe outlook for the targeted ski fields, it is important to note that there is a strong demand from local skiers at beginner/intermediate levels for these ski fields. Thus, as long as these demands remain in the future, and if a business model to maximize profit during short opening periods is established, it may be possible to offset profit loss due to climate change

Vibrational spectroscopy analysis of ligand efficacy in human M₂ muscarinic acetylcholine receptor (M₂R)

振動分光法を駆使した薬剤効能測定法の開発 --アセチルコリン受容体を標的とした神経疾患の治療薬開発への期待--. 京都大学プレスリリース. 2021-12-01.The intrinsic efficacy of ligand binding to G protein-coupled receptors (GPCRs) reflects the ability of the ligand to differentially activate its receptor to cause a physiological effect. Here we use attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy to examine the ligand-dependent conformational changes in the human M₂ muscarinic acetylcholine receptor (M₂R)). We show that different ligands affect conformational alteration appearing at the C=O stretch of amide-I band in M2R. Notably, ATR-FTIR signals strongly correlated with G-protein activation levels in cells. Together, we propose that amide-I band serves as an infrared probe to distinguish the ligand efficacy in M₂R) and paves the path to rationally design ligands with varied efficacy towards the target GPCR

Atomic structure and magnetism of the Au-Ga-Ce 1/1 approximant crystal

We report a new Au-Ga-Ce 1/1 approximant crystal (AC) which possesses a significantly wide single-phase region of 53 - 70 at% Au and 13.6 - 15.1 at% Ce. Single crystal X-ray structural analyses reveal the existence of two types of structural degrees of freedom, i.e., the Au/Ga mixing sites and the fractional Ce occupancy site: the former enables a large variation in the electron concentration and the latter allows a variation in the occupancy of a magnetic impurity atom at the center of the Tsai-type cluster. Following these findings, the influences of two types of structural modifications on the magnetism are thoroughly investigated by means of magnetic susceptibility and specific heat measurements on the Au-Ga-Ce 1/1 AC. The spin-glass (SG) state is found to be the ground state over the entire single-phase region, showing a robust nature of the SG state against both structural modifications. In addition, a gigantic specific heat (C/T) is commonly observed at low temperatures for all the compositions, which is consistently explained as a consequence of the spin-freezing phenomenon, not of a heavy Fermion behavior as reported elsewhere. Moreover, the origin of the SG state in the 1/1 Au-Ga-Ce AC is attributed to the existence of non-magnetic atom disorder in the Au/Ga mixing sites. Furthermore, a Kondo behavior is observed in the electrical resistivity at low temperatures, which is enhanced by increasing the Ce concentration, verifying that a Ce atom introduced at the cluster center behaves as a Kondo impurity for the first time.Comment: 8 pages, 4 figure