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1.
Science ; 375(6584): 1011-1016, 2022 03 04.
Article in English | MEDLINE | ID: mdl-35143255

ABSTRACT

The Hayabusa2 spacecraft investigated the C-type (carbonaceous) asteroid (162173) Ryugu. The mission performed two landing operations to collect samples of surface and subsurface material, the latter exposed by an artificial impact. We present images of the second touchdown site, finding that ejecta from the impact crater was present at the sample location. Surface pebbles at both landing sites show morphological variations ranging from rugged to smooth, similar to Ryugu's boulders, and shapes from quasi-spherical to flattened. The samples were returned to Earth on 6 December 2020. We describe the morphology of >5 grams of returned pebbles and sand. Their diverse color, shape, and structure are consistent with the observed materials of Ryugu; we conclude that they are a representative sample of the asteroid.

2.
Sci Adv ; 6(47)2020 11.
Article in English | MEDLINE | ID: mdl-33219034

ABSTRACT

One of the most challenging issues among experts is how to improve motor skills that have already been highly trained. Recent studies have proposed importance of both genetic predisposition and accumulated amount of practice for standing at the top of fields of sports and performing arts. In contrast to the two factors, what is unexplored is how one practices impacts on experts' expertise. Here, we show that training of active somatosensory function (active haptic training) enhances precise force control in the keystrokes and somatosensory functions specifically of expert pianists, but not of untrained individuals. By contrast, training that merely repeats the task with provision of error feedback, which is a typical training method, failed to improve the force control in the experts, but not in the untrained. These findings provide evidence that the limit of highly trained motor skills could be overcome by optimizing training methods.

3.
Phys Rev Lett ; 125(2): 027204, 2020 Jul 10.
Article in English | MEDLINE | ID: mdl-32701328

ABSTRACT

We report low temperature electron spin resonance experimental and theoretical studies of an archetype S=1/2 strong-rung spin ladder material (C_{5}H_{12}N)_{2}CuBr_{4}. Unexpected dynamics is detected deep in the Tomonaga-Luttinger spin liquid regime. Close to the point where the system is half-magnetized (and believed to be equivalent to a gapless easy plane chain in zero field) we observed orientation-dependent spin gap and anomalous g-factor values. Field theoretical analysis demonstrates that the observed low-energy excitation modes in magnetized (C_{5}H_{12}N)_{2}CuBr_{4} are solitonic excitations caused by Dzyaloshinskii-Moriya interaction presence.

4.
Insect Mol Biol ; 29(1): 48-55, 2020 02.
Article in English | MEDLINE | ID: mdl-31294881

ABSTRACT

Phosphoserine phosphatase (PSP) catalyses the synthesis of l-serine via the phosphorylated pathway by facilitating the dephosphorylation of phosphoserine. A cDNA encoding PSP from the silkworm Bombyx mori (bmPSP) was isolated using reverse transcription-PCR and then sequenced. The resulting clone encoded 236 amino acids with a molecular weight of 26 150, exhibiting 14-60% sequence identity with other PSPs. The recombinant PSP was overexpressed in Escherichia coli and purified. Kinetic studies showed that bmPSP possessed activity toward l-phosphoserine, and Asp20, Asp22 and Asp204 in bmPSP were found to be critical for modulating bmPSP activity. Real-time PCR analysis provided evidence that the amount of bmpsp transcript was reduced in middle silk glands of a sericin-deficient silkworm strain. These findings revealed that bmPSP may play important roles in synthesizing one-carbon donors of l-serine, which is abundant in silk, as well as other cell metabolites in B. mori.


Subject(s)
Bombyx/enzymology , Phosphoric Monoester Hydrolases/chemistry , Serine/biosynthesis , Amino Acid Sequence , Animals , Bombyx/genetics , Bombyx/metabolism , Cloning, Molecular , DNA, Complementary/genetics , Escherichia coli , Insect Proteins/biosynthesis , Insect Proteins/metabolism , Larva/metabolism , Phosphoric Monoester Hydrolases/genetics , Phosphoric Monoester Hydrolases/metabolism , Silk
5.
J Thromb Haemost ; 15(5): 998-1008, 2017 05.
Article in English | MEDLINE | ID: mdl-28294559

ABSTRACT

Essentials Regeneration role of C-type lectin receptor-2 (CLEC-2) after 70% hepatectomy (HPx) was investigated. Wild-type or CLEC-2 deleted from platelets of chimeric mice (flKO) underwent HPx. The liver/body weight ratio was significantly lower in the flKO than in the wild-type. CLEC-2 plays an essential role in liver regeneration after HPx. SUMMARY: Background and aim The aim of the present study was to investigate the role of C-type lectin receptor (CLEC)-2 in liver regeneration following partial liver resection in mice. Materials and methods Irradiated chimeric mice transplanted with fetal liver cells from wild-type (WT) mice, CLEC-2-deleted (KO) mice or mice with CLEC-2 deleted specifically from platelets (flKO) were generated. Mice underwent 70% partial hepatectomy (PH). Immunohistochemical staining was performed to investigate the expression of the endogenous ligand for CLEC-2, podoplanin. The accumulation of platelets in the liver was also quantified. The hepatic expression of the IL-6/gp130 and STAT3, Akt and ERK1/2 was also examined. Results The liver/body weight ratio and expression of all cell proliferation markers were significantly lower in the flKO group than in the WT group. The expression of phosphorylated (p) Akt and pERK1/2 was similar in the WT and flKO groups. On the other hand, the expression of pSTAT3 and IL-6 was significantly stronger in the WT group than in the flKO group. The expression of podoplanin was detected in the hepatic sinusoids of both groups. However, the extent to which platelets accumulated in hepatic sinusoids was significantly less in the flKO group than in the WT group. Conclusion CLEC-2 was involved in hepatic regeneration after liver resection and CLEC-2-related liver regeneration was attributed to the interaction between platelets and sinusoidal endothelial cells.


Subject(s)
Blood Platelets/metabolism , Hepatectomy/methods , Lectins, C-Type/metabolism , Liver Regeneration , Liver/surgery , Animals , Cell Proliferation , Cyclin D1/metabolism , Cytokine Receptor gp130/metabolism , Endothelial Cells/metabolism , Extracellular Signal-Regulated MAP Kinases/metabolism , Hepatocytes/metabolism , Interleukin-6/metabolism , Lectins, C-Type/deficiency , Lectins, C-Type/genetics , Liver/metabolism , Liver/pathology , Liver/physiopathology , Male , Membrane Glycoproteins/metabolism , Mice, Inbred C57BL , Mice, Knockout , Organ Size , Phosphorylation , Platelet Activation , Proto-Oncogene Proteins c-akt/metabolism , STAT3 Transcription Factor/metabolism , Signal Transduction , Time Factors , Tumor Necrosis Factor-alpha/metabolism , Vascular Endothelial Growth Factor A/metabolism
6.
Oncogene ; 35(8): 1049-57, 2016 Feb 25.
Article in English | MEDLINE | ID: mdl-25961936

ABSTRACT

The epithelial-mesenchymal transition (EMT) is a crucial morphological event that occurs during the progression of epithelial tumors. EMT can be induced by transforming growth factor ß (TGF-ß) in certain kinds of cancer cells through the induction of Snail, a key regulator of EMT. We have previously found that TGF-ß remarkably induces Snail expression in cooperation with Ras signals; however, the underlying mechanism of this synergism has not yet been determined. Here, we demonstrate that signal transducer and activator of transcription 3 (STAT3) acts as a mediator that synergizes TGF-ß and Ras signals. The overexpression of STAT3 enhanced Snail induction, whereas siRNA-mediated knockdown of STAT3 inhibited it. The STAT3-YF mutant, which has Tyr 705 substituted with Phe, did not enhance Snail induction. Several STAT3 mutants lacking transcriptional activity also failed to enhance it; however, the putative STAT3-binding elements in the Snail promoter regions were not required for STAT3-mediated Snail induction. Protein inhibitor of activated STAT3 (PIAS3) inhibited the enhanced Snail promoter activity induced by TGF-ß and Ras. The interaction between PIAS3 and STAT3 was reduced by TGF-ß in cells harboring oncogenic Ras, whereas TGF-ß promoted the binding of PIAS3 to Smad3, a crucial mediator of TGF-ß signaling. Therefore, these findings suggest that STAT3 enhances Snail induction when it is dissociated from PIAS3 by TGF-ß in cooperation with Ras signals.


Subject(s)
STAT3 Transcription Factor/metabolism , Transcription Factors/metabolism , Transforming Growth Factor beta/metabolism , ras Proteins/metabolism , Cells, Cultured , HeLa Cells , Humans , Signal Transduction , Snail Family Transcription Factors
7.
Neuroscience ; 284: 643-652, 2015 Jan 22.
Article in English | MEDLINE | ID: mdl-25450962

ABSTRACT

Many everyday tasks such as typing, grasping, and object manipulation require coordination of dynamic movement across multiple joints and digits. Playing a musical instrument is also one such task where the precise movement of multiple digits is transformed into specific sounds defined by the instrument. Through extensive practice musicians are able to produce precisely controlled movements to interact with the instrument and produce specific sequences of sounds. The present study aimed to determine what aspects of these dynamic movement patterns differ between pianists who have achieved professional status compared to amateur pianists that have also trained extensively. Common patterns of movement for each digit strike were observed for both professional and amateur pianists that were sequence specific, i.e. influenced by the digit performing the preceding strike. However, group differences were found in multi-digit movement patterns for sequences involving the ring or little finger. In some sequences, amateur subjects tended to work against the innate connectivity between digits while professionals allowed slight movement at non-striking digits (covariation) which was a more economical strategy. In other sequences professionals used more individuated finger movements for performance. Thus the present study provided evidence in favor of enhancement of both movement covariation and individuation across fingers in more skilled musicians, depending on fingering and movement sequence.


Subject(s)
Fingers , Motor Skills , Music , Adult , Biomechanical Phenomena , Female , Finger Joint/physiology , Fingers/physiology , Humans , Male , Middle Aged , Motor Skills/physiology , Practice, Psychological , Professional Competence , Signal Processing, Computer-Assisted , Young Adult
8.
Neuroscience ; 275: 444-54, 2014 Sep 05.
Article in English | MEDLINE | ID: mdl-24973654

ABSTRACT

Individuated finger movements represent a key feature of hand dexterity. However, our understanding of mechanisms underlying the acquisition of this motor skill is limited. The present study aimed to identify the effects of daily motor training on acquisition of individuated finger movements. Ten musically naïve individuals performed piano practice for 4 successive days, and hand kinematics were evaluated using a motion capture system. The results showed a decrease in movement covariation across fingers with practice, particularly at the ring and little fingers. The decrease was more pronounced in the pair of fingers with lower independent control prior to the practice. Furthermore, a few finger pairs demonstrated facilitated movement independence when the subject was provided with visual feedback (VFB) regarding the rhythmic accuracy of motor actions following each practice. The results provide evidence for the enhancement of individuated finger movements through dexterous hand use during piano practice, which suggests plastic adaptation of the neuromuscular system associated with independent control of finger movement.


Subject(s)
Learning/physiology , Motor Skills/physiology , Neuronal Plasticity/physiology , Biomechanical Phenomena , Female , Fingers/innervation , Fingers/physiology , Humans , Male , Movement/physiology , Music , Young Adult
9.
Neuroscience ; 269: 290-8, 2014 Jun 06.
Article in English | MEDLINE | ID: mdl-24709043

ABSTRACT

Auditory information plays an important role in fine motor control such as speech and musical performance. The purpose of this study was to assess expertise-dependent differences in the role of temporal information of auditory feedback in the production of sequential movements. Differences in motor responses to the transient delay of tone production during musical performance between expert pianists and non-musicians were evaluated. Compared to expert pianists, non-musicians showed more pronounced movement disruptions following the delayed auditory feedback. For example, in response to a perturbation the inter-keystroke interval was prolonged and the key-press was longer in non-musicians, while the expert pianist marginally shortened both measures. These distinct differences between groups suggest that extensive musical training influences feedback control in sequential finger movements. Furthermore, there was a significant positive correlation between the age at which the expert pianists commenced their musical training and the amount of disruption. Overall, these findings suggest that expert pianists have a higher level of robustness against perturbations and depend less on auditory feedback during the performance of sequential movements.


Subject(s)
Auditory Perception , Feedback, Sensory , Motor Skills , Music , Professional Competence , Acoustic Stimulation/methods , Adult , Age Factors , Female , Fingers , Humans , Male , Psychoacoustics , Time Factors , Time Perception
10.
Neuroscience ; 247: 152-63, 2013 Sep 05.
Article in English | MEDLINE | ID: mdl-23707706

ABSTRACT

The loss of independent control of finger movements impairs the dexterous use of the hand. Focal hand dystonia is characterised by abnormal structural and functional changes at the cortical and subcortical regions responsible for individuated finger movements and by the loss of surround inhibition in the finger muscles. However, little is known about the pathophysiological impact of focal dystonia on the independent control of finger movements. Here we addressed this issue by asking pianists with and without focal dystonia to repetitively strike a piano key with one of the four fingers as fast as possible while the remaining digits kept the adjacent keys depressed. Using principal component analysis and cluster analysis to the derived keystroke data, we successfully classified pianists according to the presence or absence of dystonic symptoms with classification rates and cross-validation scores of approximately 90%. This confirmed the effects of focal dystonia on the individuated finger movements. Interestingly, the movement features that contributed to successful classification differed across fingers. Compared to healthy pianists, pianists with an affected index finger were characterised predominantly by stronger keystrokes, whereas pianists with affected middle or ring fingers exhibited abnormal temporal control of the keystrokes, such as slowness and rhythmic inconsistency. The selective alternation of the movement features indicates a finger-specific loss of the independent control of finger movements in focal dystonia of musicians.


Subject(s)
Dystonic Disorders/diagnosis , Dystonic Disorders/physiopathology , Fingers/physiology , Movement/physiology , Music , Psychomotor Performance/physiology , Adult , Female , Humans , Male , Middle Aged , Motor Skills/physiology , Young Adult
11.
J Neuroinflammation ; 8: 70, 2011 Jun 22.
Article in English | MEDLINE | ID: mdl-21696573

ABSTRACT

BACKGROUND: How glial cells and cytokines are associated with the progression of delayed neuronal death induced by transient global ischemia is still unclear. To further clarify this point, we studied morphological changes in glial cells (microglial cells and astrocytes), and cytokine protein levels, during the progression of neuronal cell loss in CA1 (Cornu Ammonis 1) of the hippocampus after transient global ischemia. METHODS: Morphological changes in glial cells were studied immuno-histochemically. Nine cytokines (IL-1α, IL-1ß, IL-2, IL-4, IL-6, IL-10, GM-CSF, IFN-γ and TNF-α) were simultaneously measured by a multiplexed bead-based immunoassay from 6 h to day21 after transient four vessel occlusion (4VO) in rats. RESULTS: During the process of neuronal loss, we observed four distinct phases: (1) lag phase day0-2 (no NeuN+ cell loss observed), (2) exponential phase day2-7 (NeuN+ cells reduced in number exponentially), (3) deceleration phase day7-14 (reduction rate of NeuN+ cells became low), (4) stationary phase day14 onward (NeuN+ cell loss progressed no longer). In the lag phase, activated glial cells were observed in the entire hippocampus but later were gradually restricted to CA1. Cytokine protein levels in the lag and exponential phases were lower than in the deceleration and stationary phases. IL-1α, IL-1ß, IL-4, IL-6 and IFN-γ in 4VO were significantly higher in all four phases than in sham. Compared with sham level, GM-CSF was significantly high in the deceleration phase. TNF-α was significantly high in both the deceleration and stationary phases. CONCLUSION: Ischemic stress in 4VO activated glial cells in areas beyond CA1 in the lag phase. Pyramidal neurons were injured in CA1 from the end of the lag phase and then neuronal cells reduced in CA1 in the exponential phase. After neuronal death began, the influence of dead cells on glial cells and cytokine expression gradually became stronger than the influence by ischemic stress. Therefore, from the deceleration phase, changes in glial cells and cytokine production were likely caused by dead cells. Cytokine interaction in the microenvironment may determine the functions of IL-1α, IL-1ß, IL-4, IL-6 and IFN-γ in all four phases. The function of GM-CSF and TNF-α in the deceleration phase may be neurotrophic.


Subject(s)
Cytokines/metabolism , Ischemic Attack, Transient/physiopathology , Nerve Degeneration/physiopathology , Neuroglia/cytology , Neuroglia/metabolism , Animals , CA1 Region, Hippocampal/cytology , CA1 Region, Hippocampal/metabolism , CA1 Region, Hippocampal/pathology , Ischemic Attack, Transient/pathology , Male , Nerve Degeneration/pathology , Rats , Rats, Wistar
12.
Neuroscience ; 164(2): 822-31, 2009 Dec 01.
Article in English | MEDLINE | ID: mdl-19698766

ABSTRACT

The present study investigated a skill-level-dependent interaction between gravity and muscular force when striking piano keys. Kinetic analysis of the arm during the downswing motion performed by expert and novice piano players was made using an inverse dynamic technique. The corresponding activities of the elbow agonist and antagonist muscles were simultaneously recorded using electromyography (EMG). Muscular torque at the elbow joint was computed while excluding the effects of gravitational and motion-dependent interaction torques. During descending the forearm to strike the keys, the experts kept the activation of the triceps (movement agonist) muscle close to the resting level, and decreased anti-gravity activity of the biceps muscle across all loudness levels. This suggested that elbow extension torque was produced by gravity without the contribution of agonist muscular work. For the novices, on the other hand, a distinct activity in the triceps muscle appeared during the middle of the downswing, and its amount and duration were increased with increasing loudness. Therefore, for the novices, agonist muscular force was the predominant contributor to the acceleration of elbow extension during the downswing. We concluded that a balance shift from muscular force dependency to gravity dependency for the generation of a target joint torque occurs with long-term piano training. This shift would support the notion of non-muscular force utilization for improving physiological efficiency of limb movement with respect to the effective use of gravity.


Subject(s)
Arm/physiology , Gravitation , Motor Skills/physiology , Music , Psychomotor Performance/physiology , Biomechanical Phenomena , Electromyography , Female , Humans , Kinetics , Male , Practice, Psychological , Pressure , Professional Competence , Sound , Torque , Young Adult
13.
Cell Prolif ; 42(5): 571-86, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19614678

ABSTRACT

OBJECTIVE: In Alzheimer's disease, toxic soluble and insoluble forms of amyloid beta (Abeta) cause synaptic dysfunction and neuronal loss. Given its potential role in producing a toxic host microenvironment for transplanted donor stem cells, we investigated the interaction between Abeta and proliferation, survival, and differentiation of bone marrow-derived mesenchymal stem cells (BM-MSC) in culture. MATERIALS AND METHODS: We used BM-MSC that had been isolated from mouse bone marrow and cultured, and we also assessed relevant reaction mechanisms using gene microarray, immunocytochemistry, and inhibitors of potential signalling molecules, such as mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK)1/2 and tyrosine protein kinase. RESULTS AND CONCLUSIONS: Interestingly, we found that treatment with aggregated (1-40 or 1-42) and oligomeric (1-42) Abeta promoted neuronal-like differentiation of BM-MSC without toxic effects. This was not dependent on soluble factors released from BM-MSC progeny nor solely on formation of Abeta fibrils. The effect of Abeta is mediated by G-protein coupled receptors, neuropeptide Y1 (NPY1R) and serotonin (5-hydroxytryptamine) receptor 2B, via phosphatidylinositol-3-OH kinase-dependent activation of the MAPK/ERK1/2. Our results lend support to the idea that reciprocal donor stem cell-host interactions may promote a regenerative response that can be exploited by epigenetic modulation of NPY/serotonergic gene expression, for stem cell therapy, in Alzheimer's disease.


Subject(s)
Amyloid beta-Peptides/metabolism , MAP Kinase Signaling System/physiology , Mesenchymal Stem Cells/metabolism , Neuronal Plasticity/physiology , Peptide Fragments/metabolism , Receptor, Serotonin, 5-HT2B/metabolism , Receptors, Neuropeptide Y/metabolism , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Amyloid beta-Peptides/pharmacology , Animals , Apoptosis/drug effects , Apoptosis/physiology , Bone Marrow Cells/cytology , Bone Marrow Cells/metabolism , Cell Differentiation/drug effects , Cell Differentiation/physiology , Cell Division/drug effects , Cell Division/physiology , Cell Survival/drug effects , Cell Survival/physiology , Cells, Cultured , Dynamins/metabolism , Mesenchymal Stem Cells/cytology , Mice , Mice, Inbred C57BL , Mice, Mutant Strains , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Neuropeptide Y/genetics , Neuropeptide Y/metabolism , Peptide Fragments/pharmacology , Phosphatidylinositol 3-Kinases/metabolism
14.
J Neuroimmunol ; 204(1-2): 43-51, 2008 Nov 15.
Article in English | MEDLINE | ID: mdl-18817984

ABSTRACT

The effects of MPTP on two mouse strains with different MPTP sensitivities and immunological backgrounds were compared: MPTP-sensitive C57BL/6 mice (B6) with a propensity for Th1 and less MPTP-sensitive BALB/c mice (BALB) with a propensity for Th2. It was found that acute MPTP treatment induced behavioral dysfunction, activated microglia/astrocytes, and increased the levels of IL-10, IL-12(p40) IL-13, IFN-gamma, and MCP-1 in CSF in B6, but not in BALB. This suggests that variances in immunological backgrounds might be a major contributing factor in sensitivity differences to MPTP.


Subject(s)
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/pharmacology , Astrocytes/drug effects , Cytokines/blood , Cytokines/cerebrospinal fluid , Microglia/drug effects , Neurotoxins/pharmacology , Analysis of Variance , Animals , Corpus Striatum/drug effects , Corpus Striatum/metabolism , Drug Administration Schedule , Male , Mice , Mice, Inbred Strains , Movement/drug effects , Nerve Growth Factors/metabolism , S100 Calcium Binding Protein beta Subunit , S100 Proteins/metabolism , Species Specificity , Time Factors , Tyrosine 3-Monooxygenase/metabolism
15.
Neuroscience ; 156(2): 390-402, 2008 Oct 02.
Article in English | MEDLINE | ID: mdl-18721863

ABSTRACT

The problem of skill-level-dependent modulation in the joint dynamics of multi-joint arm movements is addressed in this study using piano keystroke performed by expert and novice piano players. Using the measured kinematic and key-force data, the time varying net, gravitational, motion-dependent interaction (INT), key-reaction (REA), and muscular (MUS) torques at the shoulder, elbow, wrist, and metacarpophalangeal (MP) joints were computed using inverse dynamics techniques. INTs generated at the elbow and wrist joints, but not those at the MP joint, were greater for the experts as compared with the novices. REA at the MP joint, but not at the other joints, was less for the experts as compared with the novices. The MUSs at the MP, wrist, and elbow joints were smaller, and that at the shoulder joint was larger for the experts as compared with the novices. The experts also had a lesser inter-strike variability of key striking force and key descending velocity as compared with the novices. These findings indicated that the relationship among the INT, REA, and MUS occurring at the joints of the upper-extremity differed between the expert and novice piano players, suggesting that the organization of multi-joint arm movement is modulated by long-term motor training toward facilitating both physiological efficiency and movement accuracy.


Subject(s)
Movement/physiology , Muscle, Skeletal/physiology , Music , Professional Competence , Psychomotor Performance/physiology , Torque , Upper Extremity/physiology , Adolescent , Analysis of Variance , Biomechanical Phenomena , Female , Humans , Joints/physiology , Male , Nonlinear Dynamics , Prohibitins , Young Adult
16.
Phys Rev E Stat Nonlin Soft Matter Phys ; 78(6 Pt 2): 066104, 2008 Dec.
Article in English | MEDLINE | ID: mdl-19256902

ABSTRACT

An analysis to describe statistical properties of weighted complex networks is proposed. Effective structures of weighted networks depend on how strongly weights w are paid attention or which weights are relevant to the network problem. Defining the metaweight w;{q} with a real parameter q , we characterize systematically weighted complex networks depending on the level of importance of weights. It is found that power-law distribution functions R_{q}[s(q)] of metastrengths s(q) defined by s_{i}(q)= summation operator_{j}w_{ij};{q} , where i and j denote node indices for any q are characterized by only three exponents if the weight distribution is independent of network topology. We also examine the validity of our analytical arguments and the meaning of power-law forms of R_{q}[s(q)] for different q values by illustrating some examples.

17.
Ultramicroscopy ; 108(1): 11-6, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17403579

ABSTRACT

We have analyzed the effect of the tip atomic species on the tip-sample separation and the bias-voltage dependence of apparent barrier height (ABH) on an Al(100) surface using the boundary-matching scattering-state density functional method, which can be used to calculate electron states under applied bias voltages self-consistently within the density functional theory. We found that, from the dependence of the tip-sample separation, the difference between measurements with the two tip atomic species is larger in the ABH than in the maximum barrier height evaluated from the calculated potential profile. Furthermore, we found that the bias-polarity dependence of the ABH measured with the Na tip shows behavior opposite to that shown by the ABH measured with the Al tip. These results can be understood from the difference in the degree of lateral confinement of tunneling electrons in the tunneling barrier region between the two atomic species.

18.
Neuroscience ; 130(3): 657-66, 2005.
Article in English | MEDLINE | ID: mdl-15590150

ABSTRACT

Accumulating evidences indicate that ceramide is closely involved in apoptotic cell death in neurodegenerative disorders and aging. We examined ceramide levels in the cerebrospinal fluid (CSF) or brain tissues from patients with neurodegenerative disorders and the mechanism of how intra- and extracellular ceramide was regulated during neuronal apoptosis. We screened the ceramide levels in the CSF of patients with neurodegenerative disorders, and found that ceramide was significantly increased in patients with Alzheimer's disease (AD) than in patients with age-matched amyotrophic lateral sclerosis (ALS) and other neurological controls. With immunohistochemistry in AD brains, ceramide was aberrantly expressed in astroglia in the frontal cortices, but not detected in ALS and control brains. To explore for the regulation of ceramide in astroglia in Alzheimer's disease brains, we examined the metabolism of ceramide during neuronal apoptosis. In retinoic acid (RA)-induced neuronal apoptosis, RA slightly increased de novo synthesis of ceramide, but interestingly, RA dramatically inhibited conversion of [14C] ceramide to glucosylceramide (GlcCer), suggesting that the increase of ceramide mass is mainly due to inhibition of the ceramide-metabolizing enzyme GlcCer synthase. In addition, a significant increase of the [14C] ceramide level in the culture medium was detected by chasing and turnover experiments without alteration of extracellular [14C] sphingomyelin levels. A 2.5-fold increase of ceramide mass in the supernatant was also detected after 48 h of treatment with RA. These results suggest a regulatory mechanism of intracellular ceramide through inhibition of GlcCer synthase and a possible role of ceramide as an extracellular/intercellular mediator for neuronal apoptosis. The increased ceramide level in the CSF from AD patients, which may be derived from astroglia, raises a possibility of neuronal apoptosis by the response to intercellular ceramide in AD.


Subject(s)
Alzheimer Disease/metabolism , Apoptosis/physiology , Astrocytes/metabolism , Ceramides/biosynthesis , Neurons/pathology , Aged , Alzheimer Disease/cerebrospinal fluid , Alzheimer Disease/pathology , Amyotrophic Lateral Sclerosis/cerebrospinal fluid , Amyotrophic Lateral Sclerosis/metabolism , Animals , Cell Line, Tumor , Cells, Cultured , Ceramides/cerebrospinal fluid , Extracellular Space/metabolism , Glucosyltransferases/analysis , Glucosyltransferases/biosynthesis , Humans , Immunohistochemistry , Indicators and Reagents , Lipid Metabolism , Mice , Serine/metabolism , Solvents , Transferases (Other Substituted Phosphate Groups)/analysis , Transferases (Other Substituted Phosphate Groups)/biosynthesis , Tretinoin/metabolism , Tretinoin/pharmacology
19.
Neuroscience ; 122(4): 985-95, 2003.
Article in English | MEDLINE | ID: mdl-14643765

ABSTRACT

Cell surface glycoconjugates are thought to mediate cell-cell recognition and to play roles in neuronal development and functions. We demonstrated here that exposure of neuronal cells to nanomolar levels of glyco-chains with an N-acetylgalactosamine (GalNAc) residue at the non-reducing termini (GalNAc-S) such as GalNAcbeta4(Neu5Acalpha3)Galbeta4GlcCer (GM2) ganglioside, its oligosaccharide portion, GalNAcbeta4Galbeta4GlcCer (Gg(3)) Cer, GalNAcalpha3GalNAcbeta3Galalpha4Galbeta4GlcCer (Gb(5)) Cer (Forssman hapten) and alpha1-4 linked oligomers of GalNAc, induced a rapid and transient activation of cAMP-dependent protein kinase (PKA) in subplasmalemma. The treatment was accompanied by peripheral actin polymerization and filopodia formation in NG108-15 cells and primary cultured hippocampal neurons, but not in glial cells. A cAMP-dependent protein kinase (PKA) selective inhibitor and an adenylate cyclase inhibitor blocked both PKA activation and the subsequent filopodia formation. A small GTPase cdc42 was a potential downstream target of GalNAc-S-activated PKA. These results suggest that extracellular GalNAc-S serve as potential regulators of the filopodia formation in neuronal cells by triggering the activation of PKA followed by cdc42 up-regulation via a cell surface receptor-like component. Filopodia formation induced by GalNAc-S may have a physiological relevance because long-term exposure to GalNAc-S enhanced F-actin-rich dendrite generation of primary cultured hippocampal neurons, and PKA-dependent dendritic outgrowth and branch formation of primary cultured cerebellar Purkinje neurons, in which actin isoforms were localized to motile structures in dendrites. These findings provide evidence for a novel GalNAc/PKA-signaling cascade in regulating some neuronal maturation.


Subject(s)
Acetylgalactosamine/pharmacology , Actins/metabolism , Cyclic AMP-Dependent Protein Kinases/physiology , Hippocampus/enzymology , Neurons/enzymology , Animals , Cells, Cultured , Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors , Enzyme Inhibitors/pharmacology , Extracellular Fluid/drug effects , Extracellular Fluid/enzymology , Hippocampus/drug effects , Neurons/drug effects , Pseudopodia/drug effects , Pseudopodia/enzymology , Rats
20.
Phys Rev Lett ; 91(16): 163001, 2003 Oct 17.
Article in English | MEDLINE | ID: mdl-14611399

ABSTRACT

Angular distributions of C 1s photoelectrons from fixed-in-space CO molecules have been measured with vibrational resolution. A strong dependence of the angular distributions on the vibrational states of the residual molecular ion has been found for the first time in the region of the shape resonance. Calculations in the relaxed core Hartree-Fock approximation have reproduced the angular distributions fairly well in the general shapes of the angular distributions due to the correct description of nuclear motion as an average of the internuclear-distance-dependent dipole amplitudes.

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