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Cr-Loaded iron oxide with a dendritic crystalline structure was synthesized and the reversible crystalline phase transition during redox cycling of the iron oxide was investigated. X-ray diffraction and transmission electron microscopy analyses revealed that Cr was well dispersed and loaded in the iron oxide dendrite crystals, whose lattice constant was dependent on the Cr loading. Temperature-programmed oxidation and reduction experiments revealed the reversible redox properties of the Cr-loaded iron oxide dendrites, whose redox temperature was found to be lower than that of Cr-free iron oxide dendrites. In situ Fe K-edge and Cr K-edge X-ray absorption near-edge structure (XANES) analysis indicated that Cr loading extended the redox reaction window for conversion between Fe3O4 and γ-Fe2O3 owing to compressive lattice strain in the iron oxide spinel structures.

Objective The aim of this study was to compare the image quality and the visibility of trigger angiography non-contrast enhanced (TRANCE) in diastolic phase and 3D balanced steady-state free precession (3D SSFP) sequences for the evaluation of pulmonary vein (PV) and left atrium (LA). Methods About 10 volunteers underwent TRANCE and 3D SSFP imaging on 1.5 T MRI. Axial images were reconstructed and regions of interest were positioned on the right superior pulmonary vein (RSPV), right inferior pulmonary vein (RIPV), left superior pulmonary vein (LSPV), left inferior pulmonary vein (LIPV), LA, and left atrial appendage (LAA). Contrast-to-noise ratio (CNR) between each part and muscle were calculated and compared between two sequences. The two observers independently scored the image quality of each image on the basis of PV, LA, and LAA anatomy and contour using a five-point scale, which scores were averaged and compared. Results CNRs on RSPV, RIPV, LSPV, LIPV, LA, and LAA were significantly higher in TRANCE sequence compared with 3D SSFP sequence. On visual assessment, TRANCE showed significantly higher scores in RSPV, RIPV, LSPV, LIPV compared with 3D SSFP sequence. Conclusions TRANCE provides higher image quality in PVs and LA compared with 3D SSFP on 1.5 T MRI. On visual assessment, TRANCE provides better visibility of PVs anatomy and contour compared with 3D SSFP.

Cr-Loaded iron oxide with a dendritic crystalline structure was synthesized and the reversible crystalline phase transition during redox cycling of the iron oxide was investigated. X-ray diffraction and transmission electron microscopy analyses revealed that Cr was well dispersed and loaded in the iron oxide dendrite crystals, whose lattice constant was dependent on the Cr loading. Temperature-programmed oxidation and reduction experiments revealed the reversible redox properties of the Cr-loaded iron oxide dendrites, whose redox temperature was found to be lower than that of Cr-free iron oxide dendrites. In situ Fe K-edge and Cr K-edge X-ray absorption near-edge structure (XANES) analysis indicated that Cr loading extended the redox reaction window for conversion between Fe3O4 and γ-Fe2O3 owing to compressive lattice strain in the iron oxide spinel structures.

Through cognitive task performance, we examined the functional role of finger writing (kūsho) in a Japanese patient with moderate sensory aphasia and reading difficulties. We hypothesized that the visual feedback of kūsho would improve visual language processing, which we tested with a "kanji construction task" using character subparts. Results showed a higher number of correct responses 1) when the patient used kūsho and 2) when visual feedback of finger movements was available. The results suggest that kūsho may not improve the retrieval of phonological information but does aid the visual processing necessary to assemble character subparts.

The hypochlorite anion (OCl−), a reactive oxygen species (ROS), is an important microbicidal agent in the immune system. Accurate and selective detection of OCl− in environmental and biological samples by a fluorescent molecular sensor is an important subject. All previously reported sensors, however, have suffered from tedious multi-step synthesis for the sensors and the use of large amounts of organic solvents for the analysis. Herein, we report that a coumarin–dihydroperimidine dye prepared by facile condensation behaves as a fluorescent sensor for OCl− in 99% water. The sensor exhibits weak fluorescence, but OCl−-selective dehydrogenation of its dihydroperimidine unit creates a strong blue fluorescence. This turn-on fluorescence response facilitates selective and sensitive detection of OCl− in the physiological pH range. Ab initio calculation revealed that the fluorescence enhancement by OCl− is triggered by intramolecular proton transfer from the coumarin –OH to the imine nitrogen of the formed perimidine moiety.

The amount of practice and time interval between practice sessions are important factors that influence motor learning efficiency. Here, we aimed to reveal the relationship between the retention and consolidation of a new internal model, and the amount of practice and time interval between practice sessions. We employed a visuomotor rotation tracking task to test the hypotheses that (1) a new internal model consolidates owing to extensive practice after reaching a task performance plateau and (2) a longer time interval between practice sessions makes it difficult to activate a new internal model. The participants were assigned to one of the four groups that differed in terms of the amount of practice and the time interval between practice sessions. They performed a tracking task in which they experienced 120° clockwise visuomotor rotation and were required to track a moving target on a computer display using a mouse cursor. To evaluate the retention and consolidation of a new internal model, we calculated the aftereffects and savings as measures of motor learning. To the best our knowledge, this is the first study to manipulate both the amount of practice and the time interval between practice sessions simultaneously in one experiment using a visuomotor tracking task. Our results support the previously reported idea that extensive practice is necessary for the consolidation of a new internal model.

A naphthalimide–dicyanoisophorone conjugate (1) was synthesized and used as a chemodosimeter for fluorometric and colorimetric detection of hypochlorous acid (HClO) and hypochlorite (OCl–) in aqueous media. This molecule shows a strong reddish-purple color and a weak fluorescence, but HClO/OCl–-selective oxidative decomposition of the dicyanoisophorone moiety promotes a color fading and a fluorescence enhancement. Ab initio calculation revealed that these responses to HClO/OCl– originate from the suppression of intramolecular electron transfer from the photoexcited naphthalimide moiety by the decomposition of the dicyanoisophorone moiety. These colorimetric and fluorometric responses facilitate relatively rapid (∼5 min), selective, and sensitive detection of HClO/OCl– as low as ∼1.3 μM under physiological conditions.

Hypochlorite anion (ClO&minus, ) is a widely-used disinfectant and a microbicidal agent in the immune system. Accurate detection of ClO&minus, in environmental and biological samples by simply prepared chemosensors/chemodosimeters is important. Herein, we report that a naphthalimide&ndash, sulfonylhydrazine conjugate with an imine (C=N) linker, prepared via simple condensation, acts as an effective fluorescent chemodosimeter for ClO&minus, The molecule exhibits a weak emission, but ClO&minus, selective cleavage of its C = N bond creates a strong green emission. Ab initio calculation showed that the emission enhancement by ClO&minus, originates from the suppression of intramolecular electron transfer from the photoexcited naphthalimide through the C = N linker. This response enables selective and sensitive detection of ClO&minus, at physiological pH range (7&ndash, 9) and allows fluorometric ClO&minus, imaging in the presence of cells.

Kūsho, which refers to a behavior in which one moves the index finger as a substitute for a pen in the air or on a surface, mostly used when trying to recall the shape of a written character or the spelling of a word, has been known to facilitate cognitive task performance among kanji writing-system users. This study investigates whether the facilitative effect of kūsho, the existence of which has been exclusively confirmed in younger adults, is present in old age. Moreover, to further understand the interaction between finger movement and cognitive processing, we analyzed the correlation between the kūsho effect and factors such as age, mini-mental state examination (MMSE) score, and number of years of education. The kūsho effect was assessed by a task where participants mentally assembled a set of kanji subparts to form an actual character. The results showed a significant facilitative effect of kūsho and a strong negative correlation between kūsho effect and education. This study confirms the benefits of finger movement for solving cognitive tasks involving visual processing of written language among older adults and suggests the kūsho effect may be mediated by education.

The present study investigated interactions between cognitive processes and finger actions called “kusho,” meaning “air-writing” in Japanese. Kanji-culture individuals often employ kusho behavior in which they move their fingers as a substitute for a pen to write mostly done when they are trying to recall the shape of a Kanji character or the spelling of an English word. To further examine the visualization role of kusho behavior on cognitive processing, we conducted a Kanji construction task in which a stimulus (i.e., sub-parts to be constructed) was simultaneously presented. In addition, we conducted a Kanji vocabulary test to reveal the relation between the kusho benefit and vocabulary size. The experiment provided two sets of novel findings. First, executing kusho behavior improved task performance (correct responses) as long as the participants watched their finger movements while solving the task. This result supports the idea that visual feedback of kusho behavior helps cognitive processing for the task. Second, task performance was positively correlated with the vocabulary score when stimuli were presented for a relatively long time, whereas the kusho benefits and vocabulary score were not correlated regardless of stimulus-presentation time. These results imply that a longer stimulus-presentation could allow participants to utilize their lexical resources for solving the task. The current findings together support the visualization role of kusho behavior, adding experimental evidence supporting the view that there are interactions between cognition and motor behavior.

Skeletal muscle atrophy caused by unloading is characterized by both decreased responsiveness to myogenic growth factors (e.g., insulin-like growth factor 1 [IGF-1] and insulin) and increased proteolysis. Here, we show that unloading stress resulted in skeletal muscle atrophy through the induction and activation of the ubiquitin ligase Cbl-b. Upon induction, Cbl-b interacted with and degraded the IGF-1 signaling intermediate IRS-1. In turn, the loss of IRS-1 activated the FOXO3-dependent induction of atrogin-1/MAFbx, a dominant mediator of proteolysis in atrophic muscle. Cbl-b-deficient mice were resistant to unloading-induced atrophy and the loss of muscle function. Furthermore, a pentapeptide mimetic of tyrosine(608)-phosphorylated IRS-1 inhibited Cbl-b-mediated IRS-1 ubiquitination and strongly decreased the Cbl-b-mediated induction of atrogin-1/MAFbx. Our results indicate that the Cbl-b-dependent destruction of IRS-1 is a critical dual mediator of both increased protein degradation and reduced protein synthesis observed in unloading-induced muscle atrophy. The inhibition of Cbl-b-mediated ubiquitination may be a new therapeutic strategy for unloading-mediated muscle atrophy.

Intact osteoactivin, a novel type I membrane glycoprotein, were shed at a dibasic motif in the juxtamembrane region in C2C12 myoblasts. Extracellular fragments were secreted into the culture media by a putative metalloprotease. Extracellular fragments of osteoactivin, but not control protein, induced matrix metalloprotease-3 (MMP-3) expression in NIH-3T3 fibroblasts. Epidermal growth factor (ERK) kinase inhibitors inhibited the osteoactivin-mediated MMP-3 expression, whereas the extracellular fragment of osteoactivin activated ERK1/2 and p38 in the mitogen-activated protein kinase pathway. Our results suggest that the extracellular fragments of osteoactivin produced by shedding act as a growth factor to induce MMP-3 expression via the ERK pathway in fibroblasts.

In rehabilitation, a robot is useful and effective for repetitive trainings. However, few rehabilitation robots have adaptability to personal difference. Therefore, an index for quantitative assessment of the difference is required to achieve the adaptability. In conventional research, a hand stiffness is used as one of the indeces, and a dynamic hand stiffness is measured only in 2 dimensions. Then, in this paper the dynamic hand stiffness of reaching motions is measured in 3 dimensions by using an arm robot. The experimental results are represented as stiffness ellipsoids. Moreover, the results are compared with the ellipsoids in 2 dimensions. From these results, it is revealed that the characteristics of the dynamic hand stiffness in 3 dimensions is different from that in 2 dimensions. The fact implicits that a human controlls his/her arm stiffness not in work space but in joint space.

The present study investigated the interactions between motor action and cognitive processing with particular reference to kanji-culture individuals. Kanji-culture individuals often move their finger as if they are writing when they are solving cognitive tasks, for example, when they try to recall the spelling of English words. This behavior is called kusho, meaning air-writing in Japanese. However, its functional role is still unknown. To reveal the role of kusho behavior in cognitive processing, we conducted a series of experiments, employing two different cognitive tasks, a construction task and a stroke count task. To distinguish the effects of the kinetic aspects of kusho behavior, we set three hand conditions in the tasks; participants were instructed to use either kusho, unrelated finger movements or do nothing during the response time. To isolate possible visual effects, two visual conditions in which participants saw their hand and the other in which they did not, were introduced. We used the number of correct responses and response time as measures of the task performance. The results showed that kusho behavior has different functional roles in the two types of cognitive tasks. In the construction task, the visual feedback from finger movement facilitated identifying a character, whereas the kinetic feedback or motor commands for the behavior did not help to solve the task. In the stroke count task, by contrast, the kinetic aspects of the finger movements influenced counting performance depending on the type of the finger movement. Regardless of the visual condition, kusho behavior improved task performance and unrelated finger movements degraded it. These results indicated that motor behavior contributes to cognitive processes. We discussed possible mechanisms of the modality dependent contribution. These findings might lead to better understanding of the complex interaction between action and cognition in daily life.

Unloading can prevent bone formation by osteoblasts. To study this mechanism, we focused on a ubiquitin ligase, Cbl-b, which was highly expressed in osteoblastic cells during denervation. Our results suggest that Cbl-b may mediate denervation-induced osteopenia by inhibiting IGF-I signaling in osteoblasts. Introduction: Unloading, such as denervation (sciatic neurectomy) and spaceflight, suppresses bone formation by osteoblasts, leading to osteopenia. The resistance of osteoblasts to growth factors contributes to such unloading-mediated osteopenia. However, a detailed mechanism of this resistance is unknown. We first found that a RING-type ubiquitin ligase, Cbl-b, was highly expressed in osteoblastic cells after sciatic neurectomy in mice. In this study, we reasoned that Cbl-b played an important role in the resistance of osteoblasts to IGF-I. Materials and Methods: Cbl-b–deficient (Cbl-b–/–) or wildtype (Cbl-b+/+) mice were subjected to sciatic neurectomy. Bone formation in these mice was assessed by calcein labeling and histomorphometric analyses. We examined IGF-I signaling molecules in femora of these mice by Western blot and immunohistochemical analyses. We also examined the mitogenic response of Cbl-b–overexpressing or –deficient osteoblastic cells to various growth factors. Results: In Cbl-b+/+ mice, denervation decreased femur mass and bone formation, whereas it increased the expression of Cbl-b protein in osteoprogenitor cells and in osteocalcin-positive cells (osteoblastic cells) in hindlimb bone. In contrast, in Cbl-b−/− mice, bone mass and bone formation were sustained during denervation. Denervation inhibited the mitogenic response of osteoprogenitor cells most significantly to IGF-I. Therefore, we focused on Cbl-b–mediated modification of IGF-I signaling. Denervation decreased the amounts of insulin receptor substrate-1 (IRS-1), phosphatidly inositol 3-phosphate kinase (PI3K), and Akt-1 proteins in femora of Cbl-b+/+ mice, whereas the amounts of these IGF-I signaling molecules in femora of Cbl-b–/– mice were constant after denervation. On a cellular level, primary osteoblastic cells from Cbl-b–/– mice were more stimulated to proliferate by IGF-I treatment compared with those from Cbl-b+/+ mice. Furthermore, overexpression of Cbl-b increased ubiquitination and degradation of IRS-1 in primary Cbl-b–/– osteoblastic cells, leading to their impaired mitogenic response to IGF-I. Conclusions: These results suggest that Cbl-b induces resistance of osteoblasts to IGF-I during denervation by increasing IRS-1 degradation and that Cbl-b–mediated modification of IGF-I signaling may contribute to decreased bone formation during denervation.

著者人数：13名, Accepted: 2006-12-15, 資料番号: SA1000616000

The senescence-accelerated mouse (SAM) is known to be a murine model for accelerated aging. A novel inbred SAMP10 has shown age-related brain atrophy and learning deficiency. In the present study, we investigated the changes in learning ability and in ligand binding with muscarinic acetylcholine (mACh) receptors, alpha adrenoceptors and protein kinase C in SAMP10. In Morris's water maze task, in a control strain of SAMR1 at 9 months, the escape latency and path length decreased with increasing trial days, in contrast, escape latency and path length did not decrease in SAMP10. These results indicate that SAMP10 exhibits learning deficiency. The ligand binding activity of mACh receptors decreased in the hippocampus of SAMP10 and the protein kinase C level in the hippocampus of SAMP10 was lower than that of SAMR1. On the other hand, there was no significant difference between SAMR1 and SAMP10 regarding ligand binding activity of alpha(1) and alpha(2) adrenoceptors. Thus, a reduction of mACh receptors and protein kinase C in the brain seems to underlie dysfunction of learning and memory in SAMP10.

The Ral GTPase is activated by RalGDS, which is one of the effector proteins for Ras. Previous studies have suggested that Ral might function to regulate the cytoskeleton; however, its in vivo function is unknown. We have identified a Drosophila homologue of Ral that is widely expressed during embryogenesis and imaginal disc development. Two mutant Drosophila Ral (DRal) proteins, DRalG20V and DRalS25N, were generated and analyzed for nucleotide binding and GTPase activity. The biochemical analyses demonstrated that DRalG20V and DRalS25N act as constitutively active and dominant negative mutants, respectively. Overexpression of the wild-type DRal did not cause any visible phenotype, whereas DRalG20V and DRalS25N mutants caused defects in the development of various tissues including the cuticular surface, which is covered by parallel arrays of polarized structures such as hairs and sensory bristles. The dominant negative DRal protein caused defects in the development of hairs and bristles. These phenotypes were genetically suppressed by loss of function mutations of hemipterous and basket, encoding Drosophila Jun NH2-terminal kinase kinase (JNKK) and Jun NH2-terminal kinase (JNK), respectively. Expression of the constitutively active DRal protein caused defects in the process of dorsal closure during embryogenesis and inhibited the phosphorylation of JNK in cultured S2 cells. These results indicate that DRal regulates developmental cell shape changes through the JNK pathway.

We studied the role of Ras signaling in the regulation of cell death during Drosophila eye development. Overexpression of Argos, a diffusible inhibitor of the EGF receptor and Ras signaling, caused excessive cell death in developing eyes at pupal stages. The Argos-induced cell death was suppressed by coexpression of the anti-apoptotic genes p35, diap1, or diap2 in the eye as well as by the Df(3L)H99 chromosomal deletion that lacks three apoptosis-inducing genes, reaper, head involution defective (hid) and grim. Transient misexpression of the activated Ras1 protein (Ras1V12) later in pupal development suppressed the Argos-induced cell death. Thus, Argos-induced cell death seemed to have resulted from the suppression of the anti-apoptotic function of Ras. Conversely, cell death induced by overexpression of Hid was suppressed by gain-of-function mutations of the genes coding for MEK and ERK. These results support the idea that Ras signaling functions in two distinct processes during eye development, first triggering the recruitment of cells and later negatively regulating cell death.

The number of lung cancer patients is increasing. One complication of particular concern after surgery for lung cancer is postoperative pneumonia. The present study examined the various effects of oral care cough reflexes (cough reflex test), oral health conditions (OAG and face scale), and immune function (NK cell activity) in patients who underwent surgery for lung cancer. Subjects included 60 patients aged 75 years old or younger who were scheduled to undergo surgery for stage I lung cancer. The average age was 65.3 +/- 6.0 years old. We randomly divided the subjects into an oral care group and a control group. In the oral care group, we observed a significant increase in the normal rate of cough reflex test postsurgery, relative to pre-surgery. In contrast, no significant change in the normal rate of cough reflex test was noted for patients in the control group. Oral health conditions showed similar results. While we observed no significant change in NK cell activity from between pre-surgery and post-surgery in the oral care group, we did note a significant decrease in the control group. Two cases of pneumonia after surgery were identified in the control group. The oral care group did not get postoperative pneumonia. Thus, it was shown that oral care is related to cough reflex, oral health conditions, and immune function.

While oral care is known to play an important role in the prevention of aspiration pneumonia, its influence on immune function is unclear. In this study, we performed oral care on ten dependent elderly individuals and examined its influence on NK cell activity. The study duration was 12 weeks. During the first six weeks, the subjects cleaned their mouths as usual (control period). In the last six weeks, a dental hygienist performed oral care and denture cleaning three times a week (intervention period). The outcome measure was the quantity of oral bacteria and the detection rate of the microbe in connection with an opportunistic infection and NK cell activity before and after the intervention. Samples were collected at three time points: the beginning of the study, after the control period and before the intervention period (i. e., after six weeks), and after the intervention period (i. e., after 12 weeks). There was no significant difference in the number of oral bacteria between the control period and the intervention period. In contrast, while NK cell activity did not change during the control period, activity increased during the intervention period (p = 0.03). This finding suggests that rather than decreasing the number of oral bacteria, oral care increases NK cell activity.

The small GTP-binding protein Ral is activated by RalGDS, one of the effector molecules for Ras. Active Ral binds to a GTPase activating protein for CDC42 and Rac. Although previous studies suggest a role for Ral in the regulation of CDC42 and Rac, which are involved in arranging the cytoskeleton, its in vivo function is largely unknown. To examine the effect of overexpressing Ral on development, transgenic Drosophila were generated that overexpress wild-type or mutated Ral during eye development. While wild-type Ral caused no developmental defects, expression of a constitutively activated protein resulted in a rough eye phenotype. Activated Ral did not affect cell fate determination in the larval eye discs but caused severe disruption of the ommatidial organization later in pupal development. Phalloidin staining showed that activated Ral perturbed the cytoskeletal structure and cell shape changes during pupal development. This phenotype is similar to that caused by RhoA overexpression. In addition, the phenotype was synergistically enhanced by the coexpression of RhoA. These results suggest that Ral functions to control the cytoskeletal structure required for cell shape changes during Drosophila development.