KIF3A is a classical member of the kinesin superfamily proteins (KIFs), ubiquitously expressed although predominantly in neural tissues, and which forms a heterotrimeric KIF3 complex with KIF3B or KIF3C and an associated protein, KAP3. To elucidate the function of the kif3A gene in vivo, we made kif3A knockout mice. kif3A −/− embryos displayed severe developmental abnormalities characterized by neural tube degeneration and mesodermal and caudal dysgenesis and died during the midgestational period at ∼10.5 dpc (days post coitum), possibly resulting from cardiovascular insufficiency. Whole mount in situ hybridization of Pax6 revealed a normal pattern while staining by sonic hedgehog (shh) and Brachyury (T) exhibited abnormal patterns in the anterior-posterior (A-P) direction at both mesencephalic and thoracic levels. These results suggest that KIF3A might be involved in mesodermal patterning and in turn neurogenesis.
The nerve axon is a good model system for studying the molecular mechanism of organelle transport in cells. Recently, the new kinesin superfamily proteins (KIFs) have been identified as candidate motor proteins involved in organelle transport. Among them KIF1A, a murine homologue of unc-104 gene of Caenorhabditis elegans, is a unique monomeric neuron– specific microtubule plus end–directed motor and has been proposed as a transporter of synaptic vesicle precursors (Okada, Y., H. Yamazaki, Y. Sekine-Aizawa, and N. Hirokawa. 1995. Cell. 81:769–780). To elucidate the function of KIF1A in vivo, we disrupted the KIF1A gene in mice. KIF1A mutants died mostly within a day after birth showing motor and sensory disturbances. In the nervous systems of these mutants, the transport of synaptic vesicle precursors showed a specific and significant decrease. Consequently, synaptic vesicle density decreased dramatically, and clusters of clear small vesicles accumulated in the cell bodies. Furthermore, marked neuronal degeneration and death occurred both in KIF1A mutant mice and in cultures of mutant neurons. The neuronal death in cultures was blocked by coculture with wild-type neurons or exposure to a low concentration of glutamate. These results in cultures suggested that the mutant neurons might not sufficiently receive afferent stimulation, such as neuronal contacts or neurotransmission, resulting in cell death. Thus, our results demonstrate that KIF1A transports a synaptic vesicle precursor and that KIF1A-mediated axonal transport plays a critical role in viability, maintenance, and function of neurons, particularly mature neurons.
Oxetanocin-G (OXT-G), a potent antiviral agent, is a novel nucleoside isolated from the culture filtrate of Bacillus megaterium. We investigated the antiviral effect of oral administration of OXT-G for five days on woodchuck hepatitis virus (WHV), in vivo, using 12 woodchucks. Woodchucks were randomized into each of four treatment groups according to the dose of OXT-G. Two out of six woodchucks treated with 1.0 or 2.0 mg/kg/day of OXT-G died. After treatment with OXT-G, serum levels of WHV-DNA significantly decreased in all woodchucks. However, the antiviral effect was only partial and levels of serum WHV-DNA returned after the cessation of treatment. The amount of viral replicative intermediates was decreased in livers of woodchucks treated with OXT-G. Although further study of the toxicity of this compound would be essential before studies in man can be carried out, OXT-G has potent antiviral activity against WHV and may deserve evaluation as an antiviral agent in the treatment of chronic hepatitis B infections in humans.
Inelastic deformation of gold (Au) atomic cluster is investigated by using molecular dynamics (MD) simulations. We performed compression and unloading tests in which silicon (Si) plates approach each other and push single Au cluster of 4 nm diameter in between. Possibility of super-elastic (hyper-elastic) behavior is first discussed in the present study. The potential function of embedded atom method is adopted inside Au cluster, whereas other interactions are formulated by simplified Lennard-Jones interaction. The cluster in MD simulation shows large recovery strain which is reversible in unloading process after compression. The recovery strain is estimated on average from 5 to 10%. It is found that there are deformation mechanisms depending on temperature of the cluster. Mechanism for low temperature is based on slip motion and that for high temperature is dominated by surface reconstruction. The strength of interaction energy between Si plate and the Au cluster which may cause pulling force and produce tensile state is investigated, referring to our AFM experiment.
We are interested in the users' level of understanding of an innovative Japanese portable phone (KEITAI) unit with multiple functions. This research focuses on users' knowledge of cellular phone usage and design and practice of the information transfer method for users who need more information. In this article, we conducted several surveys and their data analysis to determine the necessary knowledge about KEITAI's potential and possible risks for the improvement of KEITAI's usability as well as the operation of successful workshop. We further focus on how KEITAI users gain the knowledge of cellular phones (as information tool), and which functions they have concerns about by comparing the results of nationwide Internet survey and regional survey. Based on these results, we review the knowledge users need, as well as the appropriate area and scale of a trial experiment of the workshop for the effective provision of KEITAI knowledge for "not advanced KEITAI user". We also found that users concerns are focused on security-related functions such as service suspension in case of theft and electric money, regardless of user type. As a solution to bridge such gap, we held a workshop for providing information on a cellular phone including a quiz game and one-on-one lecture, etc. The repetitive training effectively contributed to the users' satisfaction and the improvement of their understandings.
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