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Search Results: 1 - 10 of 845 matches for " Tsuyoshi Inoshita "
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PINK1-Mediated Phosphorylation of Parkin Boosts Parkin Activity in Drosophila
Kahori Shiba-Fukushima,Tsuyoshi Inoshita,Nobutaka Hattori ,Yuzuru Imai
PLOS Genetics , 2014, DOI: doi/10.1371/journal.pgen.1004391
Abstract: Two genes linked to early onset Parkinson's disease, PINK1 and Parkin, encode a protein kinase and a ubiquitin-ligase, respectively. Both enzymes have been suggested to support mitochondrial quality control. We have reported that Parkin is phosphorylated at Ser65 within the ubiquitin-like domain by PINK1 in mammalian cultured cells. However, it remains unclear whether Parkin phosphorylation is involved in mitochondrial maintenance and activity of dopaminergic neurons in vivo. Here, we examined the effects of Parkin phosphorylation in Drosophila, in which the phosphorylation residue is conserved at Ser94. Morphological changes of mitochondria caused by the ectopic expression of wild-type Parkin in muscle tissue and brain dopaminergic neurons disappeared in the absence of PINK1. In contrast, phosphomimetic Parkin accelerated mitochondrial fragmentation or aggregation and the degradation of mitochondrial proteins regardless of PINK1 activity, suggesting that the phosphorylation of Parkin boosts its ubiquitin-ligase activity. A non-phosphorylated form of Parkin fully rescued the muscular mitochondrial degeneration due to the loss of PINK1 activity, whereas the introduction of the non-phosphorylated Parkin mutant in Parkin-null flies led to the emergence of abnormally fused mitochondria in the muscle tissue. Manipulating the Parkin phosphorylation status affected spontaneous dopamine release in the nerve terminals of dopaminergic neurons, the survivability of dopaminergic neurons and flight activity. Our data reveal that Parkin phosphorylation regulates not only mitochondrial function but also the neuronal activity of dopaminergic neurons in vivo, suggesting that the appropriate regulation of Parkin phosphorylation is important for muscular and dopaminergic functions.
Peripheral, Central and Behavioral Responses to the Cuticular Pheromone Bouquet in Drosophila melanogaster Males
Tsuyoshi Inoshita,Jean-René Martin,Frédéric Marion-Poll,Jean-Fran?ois Ferveur
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0019770
Abstract: Pheromonal communication is crucial with regard to mate choice in many animals including insects. Drosophila melanogaster flies produce a pheromonal bouquet with many cuticular hydrocarbons some of which diverge between the sexes and differently affect male courtship behavior. Cuticular pheromones have a relatively high weight and are thought to be — mostly but not only — detected by gustatory contact. However, the response of the peripheral and central gustatory systems to these substances remains poorly explored. We measured the effect induced by pheromonal cuticular mixtures on (i) the electrophysiological response of peripheral gustatory receptor neurons, (ii) the calcium variation in brain centers receiving these gustatory inputs and (iii) the behavioral reaction induced in control males and in mutant desat1 males, which show abnormal pheromone production and perception. While male and female pheromones induced inhibitory-like effects on taste receptor neurons, the contact of male pheromones on male fore-tarsi elicits a long-lasting response of higher intensity in the dedicated gustatory brain center. We found that the behavior of control males was more strongly inhibited by male pheromones than by female pheromones, but this difference disappeared in anosmic males. Mutant desat1 males showed an increased sensitivity of their peripheral gustatory neurons to contact pheromones and a behavioral incapacity to discriminate sex pheromones. Together our data indicate that cuticular hydrocarbons induce long-lasting inhibitory effects on the relevant taste pathway which may interact with the olfactory pathway to modulate pheromonal perception.
Phosphorylation of Mitochondrial Polyubiquitin by PINK1 Promotes Parkin Mitochondrial Tethering
Kahori Shiba-Fukushima,Taku Arano,Gen Matsumoto,Tsuyoshi Inoshita,Shigeharu Yoshida,Yasushi Ishihama,Kwon-Yul Ryu,Nobuyuki Nukina,Nobutaka Hattori ,Yuzuru Imai
PLOS Genetics , 2014, DOI: doi/10.1371/journal.pgen.1004861
Abstract: The kinase PINK1 and the E3 ubiquitin (Ub) ligase Parkin participate in mitochondrial quality control. The phosphorylation of Ser65 in Parkin's ubiquitin-like (UBl) domain by PINK1 stimulates Parkin activation and translocation to damaged mitochondria, which induces mitophagy generating polyUb chain. However, Parkin Ser65 phosphorylation is insufficient for Parkin mitochondrial translocation. Here we report that Ser65 in polyUb chain is also phosphorylated by PINK1, and that phosphorylated polyUb chain on mitochondria tethers Parkin at mitochondria. The expression of Tom70MTS-4xUb SE, which mimics phospho-Ser65 polyUb chains on the mitochondria, activated Parkin E3 activity and its mitochondrial translocation. An E3-dead form of Parkin translocated to mitochondria with reduced membrane potential in the presence of Tom70MTS-4xUb SE, whereas non-phospho-polyUb mutant Tom70MTS-4xUb SA abrogated Parkin translocation. Parkin binds to the phospho-polyUb chain through its RING1-In-Between-RING (IBR) domains, but its RING0-linker is also required for mitochondrial translocation. Moreover, the expression of Tom70MTS-4xUb SE improved mitochondrial degeneration in PINK1-deficient, but not Parkin-deficient, Drosophila. Our study suggests that the phosphorylation of mitochondrial polyUb by PINK1 is implicated in both Parkin activation and mitochondrial translocation, predicting a chain reaction mechanism of mitochondrial phospho-polyUb production by which rapid translocation of Parkin is achieved.
The Parkinson’s Disease-Associated Protein Kinase LRRK2 Modulates Notch Signaling through the Endosomal Pathway
Yuzuru Imai?,Yoshito Kobayashi?,Tsuyoshi Inoshita,Hongrui Meng?,Taku Arano?,Kengo Uemura?,Takeshi Asano?,Kenji Yoshimi?,Chang-Liang Zhang?,Gen Matsumoto
PLOS Genetics , 2015, DOI: 10.1371/journal.pgen.1005503
Abstract: Leucine-rich repeat kinase 2 (LRRK2) is a key molecule in the pathogenesis of familial and idiopathic Parkinson’s disease (PD). We have identified two novel LRRK2-associated proteins, a HECT-type ubiquitin ligase, HERC2, and an adaptor-like protein with six repeated Neuralized domains, NEURL4. LRRK2 binds to NEURL4 and HERC2 via the LRRK2 Ras of complex proteins (ROC) domain and NEURL4, respectively. HERC2 and NEURL4 link LRRK2 to the cellular vesicle transport pathway and Notch signaling, through which the LRRK2 complex promotes the recycling of the Notch ligand Delta-like 1 (Dll1)/Delta (Dl) through the modulation of endosomal trafficking. This process negatively regulates Notch signaling through cis-inhibition by stabilizing Dll1/Dl, which accelerates neural stem cell differentiation and modulates the function and survival of differentiated dopaminergic neurons. These effects are strengthened by the R1441G ROC domain-mutant of LRRK2. These findings suggest that the alteration of Notch signaling in mature neurons is a component of PD etiology linked to LRRK2.
An Inhibitory Sex Pheromone Tastes Bitter for Drosophila Males
Fabien Lacaille, Makoto Hiroi, Robert Twele, Tsuyoshi Inoshita, Daisuke Umemoto, Gérard Manière, Frédéric Marion-Poll, Mamiko Ozaki, Wittko Francke, Matthew Cobb, Claude Everaerts, Teiichi Tanimura, Jean-Fran?ois Ferveur
PLOS ONE , 2007, DOI: 10.1371/journal.pone.0000661
Abstract: Sexual behavior requires animals to distinguish between the sexes and to respond appropriately to each of them. In Drosophila melanogaster, as in many insects, cuticular hydrocarbons are thought to be involved in sex recognition and in mating behavior, but there is no direct neuronal evidence of their pheromonal effect. Using behavioral and electrophysiological measures of responses to natural and synthetic compounds, we show that Z-7-tricosene, a Drosophila male cuticular hydrocarbon, acts as a sex pheromone and inhibits male-male courtship. These data provide the first direct demonstration that an insect cuticular hydrocarbon is detected as a sex pheromone. Intriguingly, we show that a particular type of gustatory neurons of the labial palps respond both to Z-7-tricosene and to bitter stimuli. Cross-adaptation between Z-7-tricosene and bitter stimuli further indicates that these two very different substances are processed by the same neural pathways. Furthermore, the two substances induced similar behavioral responses both in courtship and feeding tests. We conclude that the inhibitory pheromone tastes bitter to the fly.
Minocycline for Schizophrenia: A critical review  [PDF]
Tsuyoshi Miyaoka
Open Journal of Psychiatry (OJPsych) , 2012, DOI: 10.4236/ojpsych.2012.224056
Abstract: Minocycline, an antibiotic of the tetracycline family, has been shown to display neurorestoractive or neuroprotective properties in various models of neurodegenerative diseases. In particular, it has been shown to delay motor alterations, inflammation and apoptosis in models of Huntington’s disease, amyotrophic lateral sclerosis and Parkinson’s disease. Despite controversies about its efficacy, the relative safety and tolerability of minocycline have led to the launching of various clinical trials. Previously, we reported the antipsychotic effects of minocycline in patients with schizophrenia. In a pilot investigation, we administered minocycline as an open-label adjunct to antipsychotic medication to patients with schizophrenia. The results of this trial suggested that minocycline might be a safe and effective adjunct to antipsychotic medications, and that augmentation with minocycline may prove to be a viable strategy for “boosting” antipsychotic efficacy and for treating schizophrenia. Recently, in randomized double-blind placebo-controlled clinical trials, the addition of minocycline to treatment as usual early in the course of schizophrenia predominantly improves negative symptoms. The present review summarizes the available data supporting the clinical testing of minocycline for patients with schizophrenia. In addition, we extend our discussion to the potential applications of minocycline for combining this treatment with cellular and molecular therapy.
Ferromagnetic instability of interlayer floating electrons in quasi-two-dimensional electride Y$_2$C
Takeshi Inoshita,Noriaki Hamada,Hideo Hosono
Physics , 2015, DOI: 10.1103/PhysRevB.92.201109
Abstract: Ab initio electronic structure calculations show that the recently identified quasi-two-dimensional electride Y$_2$C is a weak itinerant ferromagnet or at least close to a ferromagnetic instability. The ferromagnetism is induced by the electride electrons, which are loosely bound around interstitial sites and overlap with each other to form two-dimensional interlayer conduction bands. The semimetallicity and two-dimensionality of the band structure are the key to understanding this ferromagnetic instability.
Electrodeposition of Bi-Sb alloy using Cu electrodes  [PDF]
Masato Ohmukai, Akira Tsuyoshi
Materials Sciences and Applications (MSA) , 2012, DOI: 10.4236/msa.2012.37069
Abstract: Bi-Sb alloys were grown by means of an electrodeposition method using Cu electrodes. The alloys were studied with the help of an x-ray diffractometer and an electron probe microanalysis. The both investigations have shown no trace of Cu in the obtained alloys. It can be concluded that Cu electrodes can be used for the deposition of Bi-Sb alloys; which results in an advantage of availability of the electrode.
Scoping the Possibilities: Student Preferences towards Open Textbooks Adoption for E-Learning  [PDF]
Deepak Prasad, Tsuyoshi Usagawa
Creative Education (CE) , 2014, DOI: 10.4236/ce.2014.524227
Abstract: Many universities have begun implementing e-Learning systems due to their low cost. However, publishers of expensive textbooks stand in the way of e-Learning’s ability to provide a cost-effective educational delivery model. While many universities aim to overcome this opposition and replace traditional publishers’ textbooks with free open textbooks, such plans cannot be executed successfully unless students are open to their use. As such, a study into students’ preferences towards open textbook adoption is vital to provide clear indication as to their opinions regarding open textbook use. Thus, this study conducted a study of University of the South Pacific (USP) students’ preferences towards open textbook adoption for e-Learning using a survey administered during Semester 2, 2013 which generated 1077 responses. Areas examined include: Impacts of textbook costs on students’ academic careers; preferences towards open textbook adoption; perceived barriers to and motivations for adoption of open textbooks; and preferred digital features and reading devices. Results show that textbook prices adversely impact students. Furthermore, a high level of acceptance towards the adoption of open textbooks was found. The study revealed that the preference for reading printed material was the highest rated barrier to open textbook adoption, while the free availability of open textbooks was rated the greatest motivator. Study findings are being used to inform efforts to develop open textbooks at the USP and may assist other universities seeking to start similar projects.
Comparison between Amorphous and Tandem Silicon Solar Cells in Practical Use  [PDF]
Masato Ohmukai, Akira Tsuyoshi
Journal of Power and Energy Engineering (JPEE) , 2017, DOI: 10.4236/jpee.2017.54002
Abstract: Solar cells are now widely used as a clean method for electric energy generation. Among various type of solar cells, we compared the ability between amorphous and tandem (amorphous and polycrystalline) silicon solar cells by means of simultaneous running test. This kind of comparison is of importance practically, because the comparison of only inherent characteristics cannot include environmental parameters such as temperature totally. It was concluded that both types of solar cells provided almost the same energy for one year. The amorphous silicon solar cell provided more energy in summer while the tandem solar cell was advantageous in winter. It is due to the fact that the decrease in energy conversion at the higher cell temperature is more noticeable in tandem solar cells.
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