Kanazawa University is a national university of Japan located in the city of Kanazawa, the capital of Ishikawa Prefecture.Kanazawa University is divided into two main campuses: Kakuma and Takaramachi. Student enrollment is about 11,000 including 350 international students. Wikipedia.
Kanazawa University | Date: 2015-02-25
A power generation element of inverse magnetostrictive type has: a first power generation part including a first magnetostrictive rod made of magnetostrictive material, a first coil wound around the first magnetostrictive rod, and a first magnetic rod having appropriate rigidity and a shape to apply a uniform compressive force or tensile force to the first magnetostrictive rod and being placed in parallel with the first magnetostrictive rod; a frame made of magnetic material bent in a substantially U shape, whose one end and other end across the bent location constitute a fixed end and free end, respectively; and a magnet. The power generation element can suppress the loss of kinetic energy while vibrating so that vibration will last long. The power generation element can be used in an actuator.
News Article | May 13, 2017
Sleep is of absolute necessity for us humans, although if one falls asleep all of a sudden while being awoken, it would cause a big trouble. The brain is equipped with sleep mechanism and wakefulness mechanism, which are regulated to be on or off in an adequate manner. It is orexin*1 that is important in regulating this switch. If orexin neurons are lost, one suffers from narcolepsy*2, a sleep disorder, where sleep and wakefulness are inadequately switched on and off. The typical symptoms are excessive daytime sleepiness and cataplexy*3. Cataplexy takes place when one is very excited in terms of one's emotion and if severe, one may lose the muscle tone of the whole body and fall down. Sleep is categorized into two, REM sleep and non-REM sleep. Dreams are dreamt usually during REM sleep, where most of the muscles are controlled to be relaxed (called atonia) in order to prevent the dreamer to make real actions. Cataplexy attack is thought that atonia, a characteristics of REM sleep, takes place while one is awoken. The research team previously found two types of neurons preventing narcolepsy by receiving orexin from orexin neurons. The one is noradrenaline neurons in the locus coeruleus of the brain, suppressing strong sleepiness, and the other is serotonin*4 neurons in the dorsal raphe nucleus of the brain, inhibiting cataplexy. In this study, the international research team led by the researchers of Kanazawa University has discovered that serotonin neurons in the dorsal raphe nucleus inhibits catalepsy by reducing activities of the amygdala*5 that controls emotion. Serotonin neurons in the dorsal raphe nucleus extend projections throughout the brain and send information. In this study, with an optogenetic*6 tool, the team has discovered that catalepsy was almost completely inhibited by artificial augmentation of serotonin release induced by selectively stimulating serotonin nerve terminals in the amygdala in the narcolepsy model mice*7. The same experimental operation in the other brain region that controls REM sleep did not inhibit cataplexy. In addition, the team found that serotonin release reduced the amygdala activity. When the amygdala activity was artificially reduced in a direct manner, cataplexy was inhibited, while artificially augmented, frequency of cataplexy attack increased. Furthermore, the effect of orexin neurons inhibiting cataplexy was found to be abolished when serotonin release was inhibited selectively in the amygdala. Cataplexy takes place, triggered by a sudden emotional excitement of positive valence such as a big laughter. This study has revealed that serotonin neurons do not directly suppress muscle tone weakening but inhibit cataplexy by reducing and controlling activities of the amygdala, which is involved in communicating emotional excitement. In fact, it is known that the amygdala of narcolepsy patients without orexin neurons responds excessively when the patients see, for example, interesting photos. By identifying neuronal pathway, orexin neuron - serotonin neuron in the dorsal raphe nucleus - the amygdala, the team believes that the current study has made a big step forward to understanding of the whole picture of the narcolepsy mechanism. It is also highly expected that new therapy would be developed for cataplexy. Orexin A and orexin B are neuropeptides produced from a single gene in certain neurons of the hypothalamus. They consist of about 30 amino acid residues and function as neurotransmitters to convey information between neurons. Orexin producing neurons (orexin neurons) extend nerve projections throughout the brain. Orexin released from the orexin nerve terminal exerts different functions in various regions of the brain. It is known to prevent narcolepsy by stably maintaining wakefulness as well as to function for promotion of eating and metabolism and of response for reward. A sleep disorder characterized with excessive daytime sleepiness and with cataplexy. Caused by degeneration and loss of orexin neurons. Most patients experience their first narcolepsy symptoms in adolescence, and it is said that one patient is found out of 500 to 2000 persons. Cataplexy is triggered by strong emotion and marked by sudden weakening of muscle tone of the whole body, the knee, the low back, the jaw, or the eyelid, but without consciousness impairment in many cases. One of the major characteristics of narcolepsy. Serotonin is one of the physiologically active amines and functions as a neurotransmitter to convey information between neurons in the brain. Serotonin producing neurons are found in specific regions of the brain and the dorsal raphe nucleus is one such region. Serotonin neurons extend projections throughout the brain. Serotonin released from the nerve terminals is involved in a wide variety of brain functions. Since the activities of serotonin neurons are high during wakefulness but low during sleep, serotonin is thought to be involved in regulating wakefulness and sleep. There is a hypothesis that low level of serotonin in the brain is one of the causes of depression. A brain region playing essential roles in processing emotional responses as well as in emotional memory. Emotion is defined as a temporal and big change of feelings induced rather in an acute manner, such as anger, terror, delight and sorrow. Emotion is accompanied with physical, physiological, and behavioral changes, and is distinguished from mood, that signifies weak feelings prevailing for a mid- and long-term in a mild manner. Technique to manipulate the functions of cells by exogenously expressing light-activatable proteins and illuminating light. Genetically modified mouse, which lacks signal transduction by orexins, such as orexin-gene knockout mouse and orexin-receptor-gene knockout mouse. Narcolepsy model mouse exhibits symptoms similar to those of a narcolepsy patient. In this study, genetically modified mice with their orexin neurons being degenerated are used as narcolepsy model mice.
News Article | May 15, 2017
A new study shows cells in the initial stage of cancer change their metabolism before getting eliminated by the surrounding normal cells, providing a novel target for developing cancer prevention drugs. Most cancers begin when one or more genes in a cell mutate. These newly "transformed" cells get extruded and eliminated after losing a competition against the surrounding normal cells in the epithelium, or the outer layer of the body. However, the mechanism by which normal cells recognize and attack the transformed cells remains elusive. A research team led by Professor Yasuyuki Fujita of Hokkaido University's Institute for Genetic Medicine explored this natural defense mechanism using cultured mammalian cells and a mouse model. The study uncovered two metabolic changes occurring in the newly transformed cells: mitochondrial dysfunction and an elevated glucose uptake. The changes were significant only when the transformed cells were surrounded by normal epithelial cells, indicating that the changes are induced by the normal cells. Furthermore, according to the study, the metabolic changes play an important role in eliminating the transformed cells. Interestingly, these metabolic changes are similar to the Warburg effect, which is observed in cancerous cells in the middle and latter stages of cancer. The Warburg effect is generally thought to play tumor promoting roles whereas the newly discovered metabolic changes could suppress cancer in its initial stage. "Although these two processes have similar metabolic alterations, mitochondrial downregulation and increased glycolysis, they are governed by distinct regulators and have opposing effects on the development of cancer," says Fujita. Their findings shed new light on the inherent ability of normal cells to eliminate cancerous cells and opens up potential avenues for cancer prevention. "Considering that the metabolic changes could either suppress or promote cancer cells depending on the stage, further elucidation of the mechanism is essential to help develop cancer prevention drugs while avoiding adverse effects," Fujita commented. This research was conducted by scientists from Hokkaido University, Kyoto University, Kanazawa University, Keio University, Osaka University and University College London, and published in the May issue of Nature Cell Biology. The paper is also featured in the "News and Views" section of the issue.
Yamashima T.,Kanazawa University
Progress in Lipid Research | Year: 2012
Despite the well-known effects of polyunsaturated fatty acids (PUFA) on synaptic plasticity, PUFA-modulated signaling mechanism is unknown especially in humans. In 2003, three groups reported that G protein-coupled receptor 40 (GPR40) induces Ca2+ mobilization in response to PUFA. Although GPR40 gene is abundantly expressed in the primate brain, it is negligible in the rodent brain. Diverse PUFA including docosahexaenoic acid (DHA) are in vitro ligands for GPR40, but nobody knows its downstream pathway. cAMP-response element binding protein (CREB) is a transcription factor transmitting extracellular signals to change gene expression. Although PUFA, transported by fatty acid binding proteins (FABP), directly phosphorylate CREB in rodents, hydrophobic PUFA cannot access to the nuclei in the primate neurons because of lack of a cargo protein. Ischemia-enhanced adult neurogenesis in monkeys showed concomitant upregulation of GPR40 and phosphorylated CREB, and localization of both in the neurogenic niche. Here, 'PUFA-GPR40-CREB signaling' hypothesis was highlighted as a regulator of adult neurogenesis specific for primates. © 2012 Elsevier Ltd. All rights reserved.
Hayashi Y.,Kanazawa University
Coordination Chemistry Reviews | Year: 2011
Many synthetic methods for heteropolyoxovanadates and lacunary polyoxovanadates have been developed in recent years. We outline various approaches used to produce new polyoxovanadate species, including heterometal-incorporated complexes of tetravanadates, hexavanadates, decavanadates and dodecavanadates. In particular, three types of synthetic routes are explored; based on (i) coordination of metavanadate species to transition metal cations, (ii) oxidation of reduced polyoxovanadates, and (iii) template synthesis. Metavanadate species can coordinate to metal cations as inorganic macrocyclic ligands to form heteropolyoxovanadates. The incorporation of a heterometal cation into decavanadates has also been reported. The oxidation reaction of reduced polyoxovanadates provides a new route to the formation of the lacunary polyoxovanadates, which can serve as inorganic host molecules. Dodecavanadates are bowl-type molecules of particular structural interest; a chloride anion can be incorporated into the bowl through a template synthesis. Structural transformations between these dodecavanadate species and alkoxopolyoxovanadates are also described. © 2011 Elsevier B.V.
Tamai I.,Kanazawa University
Advanced Drug Delivery Reviews | Year: 2012
Transporters play important roles in tissue distribution and urinary- and biliary-excretion of drugs and transporter molecules involved in those processes have been elucidated well. Furthermore, an involvement of efflux transporters such as P-glycoproteins, multidrug resistance associated protein 2, and breast cancer resistance protein as the intestinal absorption barrier and/or intestinal luminal secretion mechanisms has been demonstrated. However, although there are many suggestions for the contribution of uptake/influx transporters in intestinal absorption of drugs, information on the transporter molecules responsible for the intestinal absorptive process is limited. Among them, most studied absorptive drug transporter is peptide transporter PEPT1. However, utilization of PEPT1 for oral delivery of drugs may not be high due to the chemical structural requirement of PEPT1 limited to peptide-mimetics. Recently, organic anion transporting polypeptide (OATP) family such as OATP1A2 and OATP2B1 has been suggested to mediate intestinal absorption of several drugs. Since OATPs exhibit species difference in expressed tissues and functional properties between human and animals, human studies are essential to clarify the intestinal absorption mechanisms of drugs via OATPs. Recent pharmacogenomic studies demonstrated that OATP2B1 is involved in the drug absorption in human. In addition, information of drug-juice interaction in the intestine also uncovered the contribution of OATP1A2 and OATP2B1 in drug absorption. Since OATP1A2 and OATP2B1 exhibit broader substrate selectivity compared with PEPT1, their potential to be applied for oral delivery should be high. In this review, current understanding of characteristics and contribution as the absorptive transporters of OATPs in small intestine in human is described. Now, it is getting clearer that OATPs have significant roles in intestinal absorption of drugs, therefore, there are higher possibility to utilize OATPs as the tools for oral delivery. © 2011 Elsevier B.V.
Sakurai T.,Kanazawa University
Nature Reviews Neuroscience | Year: 2014
Wakefulness and vigilance levels are required for maintaining purposeful activities and motivated behaviours, which are often triggered by sensory information conveying external cues. An increasing body of work has suggested that orexins (also known as hypocretins)-a pair of neuropeptides that are crucial for maintaining wakefulness-are also involved in the regulation of motivated behaviours, including feeding, emotional behaviour and reward seeking, and that these functions are mediated by two subtypes of orexin receptors. Autonomic and endocrine responses, which accompany these motivated behaviours, are also influenced by the orexin system. Orexin-producing neurons act as a hub that links information about the internal and external environments of an animal to vigilance levels and internal bodily functions to support various motivated behaviours. © 2014 Macmillan Publishers Limited. All rights reserved.
Uchihashi T.,Kanazawa University
Nature protocols | Year: 2012
High-speed atomic force microscopy (HS-AFM) allows direct visualization of dynamic structural changes and processes of functioning biological molecules in physiological solutions, at subsecond to sub-100-ms temporal and submolecular spatial resolution. Unlike fluorescence microscopy, wherein the subset of molecular events that you see is dependent on the site where the probe is placed, dynamic molecular events unselectively appear in detail in an AFM movie, facilitating our understanding of how biological molecules function. Here we present protocols for HS-AFM imaging of proteins in action, including preparation of cantilever tips, step-by-step procedures for HS-AFM imaging, and recycling of cantilevers and sample stages, together with precautions and troubleshooting advice for successful imaging. The protocols are adaptable in general for imaging many proteins and protein-nucleic acid complexes, and examples are described for looking at walking myosin, ATP-hydrolyzing rotorless F(1)-ATPase and cellulose-hydrolyzing cellulase. The entire protocol takes 10-15 h, depending mainly on the substrate surface to be used.
Le Huu D.,Kanazawa University
Blood | Year: 2013
Chronic graft-versus-host disease (cGVHD) is an increasingly frequent cause of morbidity and mortality of allogeneic hematopoietic stem-cell transplantation. Sclerodermatous cGVHD (Scl-cGVHD) is characterized by fibrosis and autoimmune features resembling those of systemic sclerosis (SSc). Transplantation of B10.D2 bone marrow and splenocytes into irradiated BALB/c mice is an established model of human Scl-cGVHD. To examine the role of B cells in Scl-cGVHD, CD19-deficient (CD19(-/-)) mice were used as donors or recipients. CD19(-/-) donors induced more severe Scl-cGVHD than wild-type donors, but use of CD19(-/-) recipients resulted in no significant differences compared with wild-type recipients. Moreover, CD19 deficiency on donor B cells resulted in the expansion of splenic interleukin (IL) -6-producing monocytes/macrophages, cytotoxic CD8(+) T cells, and Th1 cells during the early stage of disease and increased the infiltration of T cells, TGF-β-producing monocytes/macrophages, and Th2 cells into the skin in the later stage of Scl-cGVHD. IL-10-producing regulatory B cells (B10 cells) were not reconstituted by CD19(-/-) donor cells, and early adoptive transfer of B10 cells attenuated the augmented manifestations of CD19(-/-) donor-induced Scl-cGVHD. Therefore, donor-derived B10 cells have a suppressive role in Scl-cGVHD development, warranting future investigation of regulatory B-cell-based therapy for treatment of Scl-cGVHD and SSc.
Miyasaka H.,Kanazawa University
Accounts of Chemical Research | Year: 2013
Charge transfer (CT) of D0A0 D δ+Aδ- not only involves an electron transfer from D to A, but also generates a new spin set of S = 1/2 spins with an exchange interaction. Therefore, the control of CT in multidimensional frameworks could be an efficient way to design electronically/magnetically functional materials. The use of redox-active metal complexes as D and/or A building blocks expands the variety of such D/A frameworks with the formulation of DmA n (m, n ≥ 1), permitting the design of donor/acceptor metal-organic frameworks (D/A-MOFs). This Account summarizes our ongoing research on the design of D/A-MOFs and on the systematic control of CT in such D/A-MOFs toward the discovery of unique electronic/magnetic materials exhibiting nontrivial phenomena. For this purpose, the D/A combinations of carboxylate-bridged paddlewheel-type diruthenium(II,II) complexes ([Ru 2II,II]) that act as one-electron (1e-) donors and polycyanoorganic acceptors such as 7,7,8,8-tetracyano-p-quinodimethane (TCNQ) and N,N′-dicyanoquinodiimine (DCNQI) have been chosen.Even in the covalently bonded motif, the CT in this system is systematically dependent on the intrinsic ionization potential (ID) and electron affinity (E A) of the D and A units, respectively, which is controllable by chemical modification of the D/A units. As we consider the energy difference between the HOMO of D and the LUMO of A (ΔEH-L(DA)) instead of hνCT ID - EA|, the neutral (N) and ionic (I) states can be defined as follows: (i) the D/A materials with ΔE H-L(DA) > 0 (i.e., the LUMO level of A is higher than the HOMO level of D) should be neutral, and (ii) complexes adopted when ΔE H-L(DA) < 0 are, meanwhile, ionic. Materials located near ΔEH-L(DA) ≈ 0, that is, at the boundary between the N and I phases, are candidates for the N-I transition driven by external stimuli such as temperature, pressure, and photoirradiation. Even in the ionic state, two distinct states could be isolated for the D2A type: (ii-1) the 1e- transferred D2A-MOFs provide mixed-valence systems of D+D0A- possibly involving intervalence CT, which produce magnetic correlations via radical A- units, and (ii-2) when the 2e- reduced form of A (e.g., TCNQ2-) is energetically favored beyond the on-site Coulomb repulsion on A, the oxidation state of D+2A2- is produced, for which magnetic measurements reveal a paramagnetic state attributed to the isolated D + units.The interspatial Coulombic interaction is another factor in determining the charge distribution in materials, which is related to the spatial Coulombic stability of D/A packing and possibly yields a mixture of N and I domains when it is more advantageous to get Coulombic gain than in the uniform N or I phase. Such a phase could be observed at the boundary between N and I phases involving the N-I transition.These charge-distributed states/phases are systematically demonstrated in a D/A-MOF system made by the combination of [Ru2II,II] and TCNQ/DCNQI; however, we immediately recognize the charge distribution of D/A-MOF only by understanding the nature of the starting D/A units. The present D/A-MOF system should be an intriguing platform to look for new functionalities with synergistic correlations among charge, spin, and lattice. © 2012 American Chemical Society.