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Effects of Category-Learning on Categorization An Analysis of Inference-Based and Classification-Based Learning
It is widely acknowledged that categories have many functions, but few studies have actually addressed the impact of these functions on the way categories are learned. For instance, many categorization experiments predominantly rely on classification-based incremental learning. The problem with this approach is that it implicitly assumes that the function of categorization is separable from the way that categories are learned. In this study, we examined the relation between learning and the subsequent use of categories by contrasting three types of category-learning methods — inference-based, classification-based, and a combination of these methods. The results of the experiment indicate that there is an intricate relationship between category-learning and subsequent use of the category. The results further suggest that different processing modes may have been adopted by subjects in the different learning conditions
Protein phosphatase 1 is involved in the dissociation of Ca2+/calmodulin-dependent protein kinase II from postsynaptic densities
AbstractAutophosphorylation-dependent translocation of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) to postsynaptic densities (PSDs) from cytosol may be a physiologically important process during synaptic activation. We investigated a protein phosphatase responsible for dephosphorylation of the kinase. CaM kinase II was shown to be targeted to two sites using the gel overlay method in two-dimensional gel electrophoresis. Protein phosphatase 1 (PP1) was identified to dephosphorylate CaM kinase II from its complex with PSDs using phosphatase inhibitors and activators, and purified phosphatases. The kinase was released from PSDs after its dephosphorylation by PP1
Two spatially distinct kinesin-14 proteins, Pkl1 and Klp2, generate collaborative inward forces against kinesin-5 Cut7 in S. pombe
Kinesin motors play central roles in bipolar spindle assembly. In many eukaryotes, spindle pole separation is driven by kinesin-5, which generates outward force. This outward force is balanced by antagonistic inward force elicited by kinesin-14 and/or dynein. In fission yeast, two kinesin-14 proteins, Pkl1 and Klp2, play an opposing role against the kinesin-5 motor protein Cut7. However, how the two kinesin-14 proteins coordinate individual activities remains elusive. Here, we show that although deletion of either pkl1 or klp2 rescues temperature-sensitive cut7 mutants, deletion of only pkl1 can bypass the lethality caused by cut7 deletion. Pkl1 is tethered to the spindle pole body, whereas Klp2 is localized along the spindle microtubule. Forced targeting of Klp2 to the spindle pole body, however, compensates for Pkl1 functions, indicating that cellular localizations, rather than individual motor specificities, differentiate between the two kinesin-14 proteins. Interestingly, human kinesin-14 (KIFC1 or HSET) can replace either Pkl1 or Klp2. Moreover, overproduction of HSET induces monopolar spindles, reminiscent of the phenotype of Cut7 inactivation. Taken together, this study has uncovered the biological mechanism whereby two different Kinesin- 14 motor proteins exert their antagonistic roles against kinesin-5 in a spatially distinct manner.This work was supported by the Japan Society for the Promotion of Science (JSPS) [KAKENHI Scientific Research (A) 16H02503 to T.T., a Challenging Exploratory Research grant 16K14672 to T.T., Scientific Research (C) 16K07694 to M.Y.], the Naito Foundation (T.T.) and the Uehara Memorial Foundation (T.T)
The nanoparticulation by octaarginine-modified liposome improves α-galactosylceramide-mediated antitumor therapy via systemic administration
AbstractAlpha-galactosylceramide (αGC), a lipid antigen present on CD1d molecules, is predicted to have clinical applications as a new class of adjuvant, because αGC strongly activates natural killer T (NKT) cells which produce large amounts of IFN-γ. Here, we incorporated αGC into stearylated octaarginine-modified liposomes (R8-Lip), our original delivery system developed for vaccines, and investigated the effect of nanoparticulation. Unexpectedly, the systemic administered R8-Lip incorporating αGC (αGC/R8-Lip) failed to improve the immune responses mediated by αGC compared with soluble αGC in vivo, although αGC/R8-Lip drastically enhanced αGC presentation on CD1d in antigen presenting cells in vitro. Thus, we optimized the αGC/R8-Lip in vivo to overcome this inverse correlation. In optimization in vivo, we found that size control of liposome and R8-modification were critical for enhancing the production of IFN-γ. The optimization led to the accumulation of αGC/R8-Lip in the spleen and a positive therapeutic effect against highly malignant B16 melanoma cells. The optimized αGC/R8-Lip also enhanced αGC presentation on CD1d in antigen presenting cells and resulted in an expansion in the population of NKT cells. Herein, we show that R8-Lip is a potent delivery system, and size control and R8-modification in liposomal construction are promising techniques for achieving systemic αGC therapy
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