155 research outputs found

    Distinct Situational Cue Processing in Individuals with Kleptomania: A Preliminary Study

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    「万引き」依存症のメカニズムを解明 --窃盗症が不適応な学習である証拠の発見--. 京都大学プレスリリース. 2023-02-16.BACKGROUND: Impulse control disorder has been suggested to meet the criteria of addiction and is often considered a behavioral addiction; however, few studies have examined whether the disorder involves altered responses to situational cues that are associated with symptoms. In this study, we examined behavioral and neural responses to situational cues among individuals with an impulse control disorder, i.e., kleptomania. METHODS: Healthy adults and kleptomania patients whose symptoms were characterized by repetitive, uncontrolled shoplifting of sales goods in stores were recruited. Images with and without situational cues (e.g., a grocery store) were presented, and gazing patterns for the images were detected with the eye-tracker. Additionally, prefrontal cortical (PFC) responses were measured using functional near-infrared spectroscopy. PFC activities were further examined while subjects were watching video clips in virtual reality with and without situational cues. RESULTS: Among kleptomania patients, the gazing pattern for an image with situational cues was distinct from gazing patterns for other images; such differences were not observed in healthy subjects. Consistent with gazing patterns, PFC local network responses by hemoglobin changes to images and videos with situational cues were substantially different from other images and videos in kleptomania patients, whereas PFC responses were consistent across all image and video presentations in healthy subjects. CONCLUSIONS: These results suggest that kleptomania patients may perceive situational cues associated with their problematic behaviors differently from healthy subjects

    Detection of Soluble Organic Matter in Antarctic Micrometeorites

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    The Tenth Symposium on Polar Science/Poster presentations: [OA] Antarctic meteorites, Wed. 4 Dec. / Entrance Hall (1st floor), National Institute of Polar Researc

    Development and Characterization of Novel Molecular Probes for Ca2+/Calmodulin-Dependent Protein Kinase Kinase, Derived from STO-609

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    Ca2+/calmodulin-dependent protein kinase kinase (CaMKK) activates particular multifunctional kinases, including CaMKI, CaMKIV, and 5′AMP-activated protein kinase (AMPK), resulting in the regulation of various Ca2+-dependent cellular processes, including neuronal, metabolic, and pathophysiological pathways. We developed and characterized a novel pan-CaMKK inhibitor, TIM-063 (2-hydroxy-3-nitro-7H-benzo[de]benzo[4,5]imidazo[2,1-a]isoquinolin-7-one) derived from STO-609 (7H-benzimidazo[2,1-a]benz[de]isoquinoline-7-one-3-carboxylic acid), and an inactive analogue (TIM-062) as molecular probes for the analysis of CaMKK-mediated cellular responses. Unlike STO-609, TIM-063 had an inhibitory activity against CaMKK isoforms (CaMKKα and CaMKKβ) with a similar potency (Ki = 0.35 μM for CaMKKα, and Ki = 0.2 μM for CaMKKβ) in vitro. Two TIM-063 analogues lacking a nitro group (TIM-062) or a hydroxy group (TIM-064) completely impaired CaMKK inhibitory activities, indicating that both substituents are necessary for the CaMKK inhibitory activity of TIM-063. Enzymatic analysis revealed that TIM-063 is an ATP-competitive inhibitor that directly targets the catalytic domain of CaMKK, similar to STO-609. TIM-063 suppressed the ionomycin-induced phosphorylation of exogenously expressed CaMKI, CaMKIV, and endogenous AMPKα in HeLa cells with an IC50 of ∼0.3 μM, and it suppressed CaMKK isoform-mediated CaMKIV phosphorylation in transfected COS-7 cells. Thus, TIM-063, but not the inactive analogue (TIM-062), displayed cell permeability and the ability to inhibit CaMKK activity in cells. Taken together, these results indicate that TIM-063 could be a useful tool for the precise analysis of CaMKK-mediated signaling pathways and may be a promising lead compound for the development of therapeutic agents for the treatment of CaMKK-related diseases

    Inductive Effect of Palmatine on Apoptosis in RAW 264.7 Cells

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    Osteoporosis is a serious public health problem characterized by low bone density and deterioration of the bone microarchitecture. Current treatment options target either osteoclast resorption or osteoblast formation. It has been reported that berberine, a close structural analog of palmatine, inhibited bone loss in an osteoporosis model. In this study, osseous metabolism was observed in vitro with osteoclast bone resorbing cells. We proved that mouse preosteoclastic cell line (RAW 264.7) has a higher sensitivity to palmatine than mouse osteoblastic cell line (MC3T3-E1); the cell survival rates significantly decreased at 40 μM palmatine. The NO2- level, a metabolic product of nitric monoxide (NO), and iNOS mRNA expression, an osteoclast with NO induced enzyme, also increased with higher dosage of palmatine. Furthermore, it was recognized that the cell viability decrease from palmatine was caused by apoptosis rather than necrosis. Additionally, osteoclast apoptosis from palmatine did not occur when iNOS was inhibited with NG-nitro-L-arginine methyl ester hydrochloride (pan NOS inhibitor). These results indicate that palmatine plays an important role in osteoclast apoptosis via the NOS system. Hence, palmatine could be considered as a viable pharmaceutical candidate for osteoporosis bone resorption inhibitor

    Automorphic Instanton Partition Functions on Calabi-Yau Threefolds

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    We survey recent results on quantum corrections to the hypermultiplet moduli space M in type IIA/B string theory on a compact Calabi-Yau threefold X, or, equivalently, the vector multiplet moduli space in type IIB/A on X x S^1. Our main focus lies on the problem of resumming the infinite series of D-brane and NS5-brane instantons, using the mathematical machinery of automorphic forms. We review the proposal that whenever the low-energy theory in D=3 exhibits an arithmetic "U-duality" symmetry G(Z) the total instanton partition function arises from a certain unitary automorphic representation of G, whose Fourier coefficients reproduce the BPS-degeneracies. For D=4, N=2 theories on R^3 x S^1 we argue that the relevant automorphic representation falls in the quaternionic discrete series of G, and that the partition function can be realized as a holomorphic section on the twistor space Z over M. We also offer some comments on the close relation with N=2 wall crossing formulae.Comment: 25 pages, contribution to the proceedings of the workshop "Algebra, Geometry and Mathematical Physics", Tjarno, Sweden, 25-30 October, 201

    Direct Imaging Explorations for Companions around Mid-Late M Stars from the Subaru/IRD Strategic Program

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    The Subaru telescope is currently performing a strategic program (SSP) using the high-precision near-infrared (NIR) spectrometer IRD to search for exoplanets around nearby mid/late-M~dwarfs via radial velocity (RV) monitoring. As part of the observing strategy for the exoplanet survey, signatures of massive companions such as RV trends are used to reduce the priority of those stars. However, this RV information remains useful for studying the stellar multiplicity of nearby M~dwarfs. To search for companions around such ``deprioritized" M~dwarfs, we observed 14 IRD-SSP targets using Keck/NIRC2 observations with pyramid wavefront sensing at NIR wavelengths, leading to high sensitivity to substellar-mass companions within a few arcseconds. We detected two new companions (LSPM~J1002+1459~B and LSPM~J2204+1505~B) and two new candidates that are likely companions (LSPM~J0825+6902~B and LSPM~J1645+0444~B) as well as one known companion. Including two known companions resolved by the IRD fiber injection module camera, we detected seven (four new) companions at projected separations between 220\sim2-20~au in total. A comparison of the colors with the spectral library suggests that LSPM~J2204+1505~B and LSPM~J0825+6902~B are located at the boundary between late-M and early-L spectral types. Our deep high-contrast imaging for targets where no bright companions were resolved did not reveal any additional companion candidates. The NIRC2 detection limits could constrain potential substellar-mass companions (1075 MJup\sim10-75\ M_{\rm Jup}) at 10~au or further. The failure with Keck/NIRC2 around the IRD-SSP stars having significant RV trends makes these objects promising targets for further RV monitoring or deeper imaging with JWST to search for smaller-mass companions below the NIRC2 detection limits.Comment: 16 pages, 8 figures, accepted for publication in A

    Myosin-driven peroxisome partitioning in S. cerevisiae

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    In Saccharomyces cerevisiae, the class V myosin motor Myo2p propels the movement of most organelles. We recently identified Inp2p as the peroxisome-specific receptor for Myo2p. In this study, we delineate the region of Myo2p devoted to binding peroxisomes. Using mutants of Myo2p specifically impaired in peroxisome binding, we dissect cell cycle–dependent and peroxisome partitioning–dependent mechanisms of Inp2p regulation. We find that although total Inp2p levels oscillate with the cell cycle, Inp2p levels on individual peroxisomes are controlled by peroxisome inheritance, as Inp2p aberrantly accumulates and decorates all peroxisomes in mother cells when peroxisome partitioning is abolished. We also find that Inp2p is a phosphoprotein whose level of phosphorylation is coupled to the cell cycle irrespective of peroxisome positioning in the cell. Our findings demonstrate that both organelle positioning and cell cycle progression control the levels of organelle-specific receptors for molecular motors to ultimately achieve an equidistribution of compartments between mother and daughter cells
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