Increase in α-tubulin modifications in the neuronal processes of hippocampal neurons in both kainic acid-induced epileptic seizure and Alzheimer's disease

Neurodegeneration includes acute changes and slow-developing alterations, both of which partly involve common cellular machinery. During neurodegeneration, neuronal processes are impaired along with dysregulated post-translational modifications (PTMs) of cytoskeletal proteins. In neuronal processes, tubulin undergoes unique PTMs including a branched form of modification called glutamylation and loss of the C-terminal tyrosine residue and the penultimate glutamic acid residue forming Δ2-tubulin. Here, we investigated the state of two PTMs, glutamylation and Δ2 form, in both acute and slow-developing neurodegenerations, using a newly generated monoclonal antibody, DTE41, which had 2-fold higher affinity to glutamylated Δ2-tubulin, than to unmodified Δ2-tubulin. DTE41 recognised glutamylated Δ2-tubulin preferentially in immunostaining than in enzyme-linked immunosorbent assay and immunoblotting. In normal mouse brain, DTE41 stained molecular layer of the cerebellum as well as synapse-rich regions in pyramidal neurons of the cerebral cortex. In kainic acid-induced epileptic seizure, DTE41-labelled signals were increased in the hippocampal CA3 region, especially in the stratum lucidum. In the hippocampi of post-mortem patients with Alzheimer’s disease, intensities of DTE41 staining were increased in mossy fibres in the CA3 region as well as in apical dendrites of the pyramidal neurons. Our findings indicate that glutamylation on Δ2-tubulin is increased in both acute and slow-developing neurodegeneration.This work was supported in part by grants-in-aid for Challenging Exploratory Research (26670091) and for Scientific Research on Innovative Areas (23117517) to K.I., and by grants-in-aid for Scientific Research on Innovative Areas (Comprehensive Brain Science Network, 221S0003) and for Platform of Supporting Cohort Study and Biospecimen Analysis (JSPS KAKENHI JP 16H06277). H.T.V. is receiving a scholarship from MEXT and formerly from Shizuoka Bank

CORPORATE WORKERS’ IMAGES OF FARMING AND STRESS ALLEVIATION THROUGH GARDENING ACTIVITIES: A CASE STUDY OF ONE-DAY GARDENING TOUR IN A SUBURB OF TOKYO

This study explores the potential of one-off gardening experience tours for the reduction of mental stress of urban corporate workers. By using both medical and sociological data, it examines how the participants’ preconceived images of farming and other factors may influence the stress-reducing effects of gardening activities. The examination of several salivary substances and a medical questionnaire (POMS2®) suggest that the gardening activity had a clear stress-reducing effect for most participants. It was also revealed that the stress-reducing effect was greater for those who have positive images of farming than those with negative images. This suggests that gardening activities may not necessarily be beneficial for all walks of life, depending on one’s preconceived image of farming. At the same time, in order to evaluate the stress-reducing effect of the entire tour, there is a need to pay attention to aspects other than the gardening activity itself, in particular communication with the other participants as well as travel distances

Separated pulsed laser deposition for nanostructured thin films

Abstract We have developed an alternative laser deposition technique for preparation of droplet-free thin films and fine particles. This separated pulsed laser deposition (SPLD) consists of an ablation chamber and a deposition chamber which are independently evacuated under different ambient gases. High quality ZnO films exhibiting both particle-free and uniform deposition were obtained such as at an ablation pressure of 5 mTorr (Ar) and a deposition pressure of 10 mTorr (O 2 ). It is shown that, when the bias voltage and magnetic field are simultaneously applied in the deposition chamber, the E × B drift motion of about 70 km/s over the substrates contributes to deposit the smooth and high quality films. XRD and optical transmittance for the deposited films were investigated to clarify the operating properties of the SPLD assisted by the electric field and magnetic field. This SPLD is a promising technique for preparation of films and nanostructured particles

Consideration of some features of the English curriculum at Doshisha Women\u27s College from the viewpoint of needs analysis and several suggestions form improvements of the present curriculum

This paper mainly reports the results and its analysis of the questionnaire research of needs analysis conducted at Doshisha Women\u27s College in 2011. The number of participants of this research is 205 with different majors. One of the main findings of this research is that frequency of reading ability in the class is very high whereas the importance of speaking English is the highest in the field after their graduation. We also find that most students have more or less difficulty in reading English, writing English, speaking English and listening to English. It is a surprising finding that 80% of the students want to read novels as reading materials. Knowledge of vocabulary, general listening comprehension and reading quickly are the top three items they consider very important to improve their English abilities. Based on the findings of the research, we make six suggestions which we hope are of some help for making a revision of the present English curriculum

Submolecular-scale imaging of α-helices and C-terminal domains of tubulins by frequency modulation atomic force microscopy in liquid

In this study, we directly imaged subnanometer-scale structures of tubulins by performing frequency modulation atomic force microscopy (FM-AFM) in liquid. Individual α-helices at the surface of a tubulin protofilament were imaged as periodic corrugations with a spacing of 0.53 nm, which corresponds to the common pitch of an α-helix backbone (0.54 nm). The identification of individual α-helices allowed us to determine the orientation of the deposited tubulin protofilament. As a result, C-terminal domains of tubulins were identified as protrusions with a height of 0.4 nm from the surface of the tubulin. The imaging mechanism for the observed subnanometer-scale contrasts is discussed in relation to the possible structures of the C-terminal domains. Because the C-terminal domains are chemically modified to regulate the interactions between tubulins and other biomolecules (e.g., motor proteins and microtubule-associated proteins), detailed structural information on individual C-terminal domains is valuable for understanding such regulation mechanisms. The results obtained in this study demonstrate that FM-AFM is capable of visualizing the structural variation of tubulins with subnanometer resolution. This is an important first step toward using FM-AFM to analyze the functions of tubulins. © 2011 Biophysical Society

Transmembrane and Ubiquitin-Like Domain-Containing Protein 1 (Tmub1/HOPS) Facilitates Surface Expression of GluR2-Containing AMPA Receptors

Some ubiquitin-like (UBL) domain-containing proteins are known to play roles in receptor trafficking. Alpha-amino-3- hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) undergo constitutive cycling between the intracellular compartment and the cell surface in the central nervous system. However, the function of UBL domain-containing proteins in the recycling of the AMPARs to the synaptic surface has not yet been reported. Here, we report that the Transmembrane and ubiquitin-like domain-containing 1 (Tmub1) protein, formerly known as the Hepatocyte Odd Protein Shuttling (HOPS) protein, which is abundantly expressed in the brain and which exists in a synaptosomal membrane fraction, facilitates the recycling of the AMPAR subunit GluR2 to the cell surface. Neurons transfected with Tmub1/HOPSRNAi plasmids showed a significant reduction in the AMPAR current as compared to their control neurons. Consistently, the synaptic surface expression of GluR2, but not of GluR1, was significantly decreased in the neurons transfected with the Tmub1/HOPS-RNAi and increased in the neurons overexpressing EGFP-Tmub1/HOPS. The altered surface expression of GluR2 was speculated to be due to the altered surface-recycling of the internalized GluR2 in our recycling assay. Eventually, we found that GluR2 and glutamate receptor interacting protein (GRIP) were coimmunoprecipitated by the anti-Tmub1/ HOPS antibody from the mouse brain. Taken together, these observations show that the Tmub1/HOPS plays a role in regulating basal synaptic transmission; it contributes to maintain the synaptic surface number of the GluR2-containing AMPARs by facilitating the recycling of GluR2 to the plasma membrane

Liver Parenchyma Perforation following Endoscopic Retrograde Cholangiopancreatography

Although endoscopic retrograde cholangiopancreatography (ERCP) is an effective modality for the diagnosis and treatment of biliary and pancreatic diseases, it is still related with several severe complications. We report on the case of a female patient who developed liver parenchyma perforation following ERCP. She underwent ERCP with sphincterotomy and extraction of a common bile duct stone. Shortly after ERCP, abdominal distension was identified. Abdominal computed tomography revealed intraabdominal air leakage and leakage of contrast dye penetrating the liver parenchyma into the space around the spleen. Since periampullary perforation related to sphincterotomy could not be denied, she was referred for immediate surgery. Obvious perforation could not be found at surgery. Cholecystectomy, insertion of a T tube into the common bile duct, placement of a duodenostomy tube and drainage of the retroperitoneum were performed. She did well postoperatively and was discharged home on postoperative day 28. In conclusion, as it is well recognized that perforation is one of the most serious complication related to ERCP, liver parenchyma perforation should be suspected as a cause

The Japanese space gravitational wave antenna; DECIGO

DECi-hertz Interferometer Gravitational wave Observatory (DECIGO) is the future Japanese space gravitational wave antenna. DECIGO is expected to open a new window of observation for gravitational wave astronomy especially between 0.1 Hz and 10 Hz, revealing various mysteries of the universe such as dark energy, formation mechanism of supermassive black holes, and inflation of the universe. The pre-conceptual design of DECIGO consists of three drag-free spacecraft, whose relative displacements are measured by a differential Fabry– Perot Michelson interferometer. We plan to launch two missions, DECIGO pathfinder and pre- DECIGO first and finally DECIGO in 2024

DECIGO pathfinder

DECIGO pathfinder (DPF) is a milestone satellite mission for DECIGO (DECi-hertz Interferometer Gravitational wave Observatory) which is a future space gravitational wave antenna. DECIGO is expected to provide us fruitful insights into the universe, in particular about dark energy, a formation mechanism of supermassive black holes, and the inflation of the universe. Since DECIGO will be an extremely large mission which will formed by three drag-free spacecraft with 1000m separation, it is significant to gain the technical feasibility of DECIGO before its planned launch in 2024. Thus, we are planning to launch two milestone missions: DPF and pre-DECIGO. The conceptual design and current status of the first milestone mission, DPF, are reviewed in this article

Genetic association between the interleukin-2 receptor-alpha gene and mode of onset of type 1 diabetes in the Japanese population.

CONTEXT/OBJECTIVE: The IL-2 receptor-alpha (IL2RA), also known as CD25, is expressed on the regulatory T cells, which play an important role in the control of immune responses and the maintenance of immune homeostasis. Our objective was to determine whether variants in the IL2RA gene are associated with type 1 diabetes in the Japanese population. DESIGN/PATIENTS: We genotyped the four single-nucleotide polymorphisms (rs706778, rs3118470, ss52580101, and rs11594656) of the IL2RA in 885 patients with type 1 diabetes and 606 control subjects of Japanese origin. The allele and genotype frequencies were examined in the patient groups stratified by their mode of onset in a case-control study. RESULTS: We found evidence of association with acute-onset, but not slow-onset and fulminant, type 1 diabetes for two of the four single-nucleotide polymorphisms genotyped (rs706778 and rs3118470). The rs706778 A allele and the rs3118470 G allele were associated with an increased disease risk [odds ratio (OR) for rs706778 AA genotype 1.54, P = 4.2 x 10(-4) and OR for rs3118470 GG genotype 1.50, P = 0.0019, respectively]. Furthermore, the A-G haplotype was associated with increased type 1 diabetes risk in the acute-onset form (OR 1.30, P = 0.002). CONCLUSIONS: The present data confirm the type 1 diabetes association with IL2RA and provide evidence that the different contributions of the IL2RA in the susceptibility to acute-onset and other forms of type 1 diabetes in the Japanese population