Single-molecule quantum dot as a Kondo simulator.

Structural flexibility of molecule-based systems is key to realizing the novel functionalities. Tuning the structure in the atomic scale enables us to manipulate the quantum state in the molecule-based system. Here we present the reversible Hamiltonian manipulation in a single-molecule quantum dot consisting of an iron phthalocyanine molecule attached to an Au electrode and a scanning tunnelling microscope tip. We precisely controlled the position of Fe2+ ion in the molecular cage by using the tip, and tuned the Kondo coupling between the molecular spins and the Au electrode. Then, we realized the crossover between the strong-coupling Kondo regime and the weak-coupling regime governed by spin-orbit interaction in the molecule. The results open an avenue to simulate low-energy quantum many-body physics and quantum phase transition through the molecular flexibility.

Apoptosis-mediated seasonal testicular regression in the Japanese Jungle Crow (Corvus macrorhynchos).

The present study investigated effects of apoptosis observed during seasonal testicular regression in Japanese Jungle Crows. The study was conducted during January to June 2008, 2009. Testes from adults captured during non-breeding (January), prebreeding (February to mid-March), main-breeding (late March to early May), transition (mid-May to late May), and post-breeding (June) seasons were analyzed. Apoptosis was assessed by in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. Paired-testis volume increased 95-fold from the non-breeding to the main-breeding season (P < 0.05), and subsequently decreased 26-fold from the main breeding to the post-breeding season (P < 0.05). Testicular activity was evaluated from the total germ cell count and sperm index, which increased 42- and 5-fold, respectively, in the main-breeding season, and subsequently decreased 33- and 5-fold in the post-breeding season. In testes, TUNEL-positive germ cells were at low levels in the non-breeding season, absent in the prebreeding and the main-breeding seasons, and highest in mid-May (P < 0.05). In contrast, TUNEL-positive Sertoli cells occurred only in late-April. In addition, TUNEL-positive fibroblast-like cells were observed in the outer zone of the tunica albuginea in the post-breeding season. Collectively, these data suggested that the seasonal rise in the testicular competence occurred slowly in Japanese Jungle Crows; however, testis function was terminated rapidly after the breeding season. Furthermore, we concluded, similar to other avian species, Sertoli cell apoptosis followed by massive germ cell death was responsible for rapid testicular regression in Jungle Crows.

Lateral displacement by transient mobility in chemisorption of CO on Pt(997).

We investigated adsorbed states of CO on Pt(997) at 11 K using infrared reflection absorption spectroscopy. At 11 K, thermal migration is suppressed and thus the initial chemisorption at terrace sites and step sites is controlled by the transient mobility of the adsorbing molecule. The initial occupation ratio between atop CO on the terrace and atop CO at the step is directly determined to be 3.6:1. With a simple isotropic migration model, we estimated the mean lateral displacement from the first impact point to the initial chemisorption site to be 6.8 A. We also discuss the origin of transient mobility of CO on metal surfaces.

[Calcium intake and osteoporosis in many countries].

From the viewpoint of preventing the life-style related diseases, daily diet and nutrient intake are important. In particular, an adequate intake of calcium is one of the important means of preventing osteoporosis. Calcium intake is much lower in Asia and Africa than in the United States and Europe, mainly due to the exceedingly low intake of milk and dairy products. However, although the prevalence of osteoporosis, especially hip fracture, is currently much higher in Western countries than in developing Asian countries, in the rapidly industrializing countries of Asia and other areas, the prevalence of osteoporosis is rapidly approaching the level in Western countries. As the world population continues to age, it is necessary to consider the prevention of osteoporosis from the viewpoint of a global problem.

[Nutritional therapy].

Osteoporosis is one of the life style related diseases. Therefore, from the viewpoint of prevention, daily diet and nutrient intake are important. An adequate intake of calcium together with nutrient balance plays an essential role in maintaining and promoting health and preventing osteoporosis. Moreover, prior to nutritional therapy, it is essential to understand the current nutritional status and dietary habits of the individual.

Borrelidin is an angiogenesis inhibitor; disruption of angiogenic capillary vessels in a rat aorta matrix culture model.

Borrelidin, an antibiotic from Streptomyces rochei, was found to be an angiogenesis inhibitor in a rat aorta matrix culture model which forms capillary vessels in vitro. Borrelidin strongly inhibited capillary tube formation with a 50%-inhibitory concentration value of 0.8 nM, and decreased the number of capillary tubes within 24 hours when added after maturation of tube formation. Borrelidin remarkably disrupted capillary tubes in a dose-dependent manner, by inducing apoptosis of the tube-forming cells.

Effects of physical characteristics and dietary habits on bone mineral density in adolescent girls.

In the health management of bone, of most importance is how to spend the period until peak bone mass, that is appropriate self management for bone health. Therefore, we evaluated the effects of physical characteristics and dietary habits on the bone mineral density (BMD) of the second metacarpal bone (sigma GS/D: BMD) by the digital image processing method (DIP) in 197 healthy adolescent girls (Japanese students at a junior high school, aged 12-15 y), an important period of physical and bone growth. Concerning the physical characteristics of the subjects according to age group, body height in each age group was higher than the standard values for Japanese according to age, but body weights in the 14-year-old and 15-year-old groups were significantly lower than the standard values for Japanese. Compared with the standard BMD values for Japanese according to age, BMD in the subjects was high in the 12-year-old, 13-year-old and 14-year-old groups but low in the 15-year-old group (-7.3%). Concerning the nutritional state, energy, calcium (Ca), and iron intakes were insufficient in every age group. BMD relative to the standard BMD value for Japanese (standard value was regarded as 0%) was evaluated according to the ingestion frequency of Ca-rich foods. The relative BMD value (%) increased with the ingestion frequency of Ca-rich foods. These results suggest that maintenance of an appropriate physique and adequate intake of nutrients such as Ca are important for bone growth during adolescence. Active promotion of educational guidance mainly on the effects of diet on bone health in adolescents in necessary.

Cross-sectional and longitudinal studies on the effect of water exercise in controlling bone loss in Japanese postmenopausal women.

The effects of water exercise, as a form of daily physical activity (water exercise in a warm water pool), on bone loss in healthy Japanese postmenopausal women have been cross-sectionally and longitudinally investigated from the viewpoint of preventing osteoporosis. In the cross-sectional study, the bone mineral density (BMD) of the lumbar spine (Z-score (%)) in the Veterans group (N = 27), who had been exercising for 35.2 months on average, was significantly higher than that in the Newcomers (N = 40), who had only begun to exercise 3 or 4 weeks before, and that in the Non-exercisers (N = 30), serving as a control group. The rate of change in the BMD of the lumbar spine was -0.92%/year in the Non-exercisers (N = 30), +1.55%/year in the Veterans (N = 20), and +2.16%/year in the Newcomers (N = 15), based on BMD Z-scores. In the Exercisers groups, it was found that the rate of change in the BMD showed a slight increase rather than a decrease irrespective of the duration of menopause. On the other hand, in the Non-exercisers group, the rate of change in the BMD decreased slightly. The results of questionnaires showed that the subjects' general awareness of health and fitness in daily life was enhanced after starting the water exercise program. These results suggest that consistently participating in water exercise is an important factor in preventing bone loss, and moreover, appears not only to indirectly improve awareness of daily physical activity but also to promote health and improve daily life.

Noninvasive evaluation of the magnitude of aortic and mitral regurgitation by means of Doppler two-dimensional echocardiography.

Using transmitral flow velocity and left ventricular ejection flow velocity, we measured left ventricular inflow volume (LVIV) and left ventricular outflow volume (LVOV) by pulsed Doppler echocardiography in 73 patients who had mitral valve regurgitation (MR), aortic valve regurgitation (AR), or no valvular regurgitation. Doppler-determined regurgitant volume (DOPRV), Doppler-determined regurgitant fraction (DOPRF), total stoke volume, and forward stroke volume were calculated to compare the severity assessed by angiographic scoring and the regurgitant fraction determined by radionuclide angiography (RIRF). In 17 patients with MR, LVIV (84.4 +/- 20.4 ml) was significantly greater (p less than 0.01) than LVOV (52.5 +/- 15.7 ml). LVOV, which is equivalent to forward stroke volume, was lower in patients with MR (52.2 +/- 15.7 ml) than in normal subjects (67.0 +/- 15.7 ml). In 15 patients with AR, LVOV (121.7 +/- 61.1 ml) was significantly greater (p less than 0.01) than LVIV (75.1 +/- 28.1 ml) and LVOV, which is equivalent to total stroke volume, was greater in patients with AR (121.7 +/- 61.1 ml) than in normal subjects (64.0 +/- 14.4 ml). DOPRF correlated with RIRF (r = 0.79, p less than 0.01, n = 11). DOPRV (mild: 10.5 +/- 8.5 ml; moderate: 28.8 +/- 13.6 ml; severe: 74.5 +/- 36.7 ml) and DOPRF (mild: 13.7% +/- 11.5%; moderate: 33.1% +/- 14.2%; severe: 52.6% +/- 15.3%) increased markedly with the severity of regurgitation as assessed by cineangiography. In AR, total stroke volume influenced both forward stroke volume and regurgitant volume, and in MR, regurgitant volume influenced both total stroke volume and forward stroke volume. Total stroke volume in AR and regurgitant volume in MR may play a key role in valvular regurgitation.

Synaptic plasticity in the red nucleus and learning.

Pairing of the stimulus to the cerebral peduncle (CP) with that to the forearm skin leads cats to flex their forearms within a 10-day training period in response to stimulus to CP, which was initially ineffective. Behavioral study and extracellular unit analysis suggested that the cellular mechanism for this conditioning lies at the corticorubral (CR) synapses. Since formation of new CR synapses occurs in parallel with the recovery from behavioral deficits after brain damage and peripheral nerve cross-innervation, we explored the possibility that the formation of new CR synapses underlies conditioning. We investigated the time course of the CR excitatory postsynaptic potentials (EPSPs) as well as the distribution of the CR synapses on the somadendritic membrane of the red nucleus neurons and compared them with those observed in control animals. In conditioned animals, the times-to-peak of the CR EPSPs were significantly shorter than those in control animals. Electron microscopic studies demonstrated that more CR synapses make contact with large, i.e. proximal, dendrites and somata of red nucleus neurons in conditioned cats than in control ones. These results support the view that the formation of new synapses on the proximal dendrites and soma underlies classical conditioning in the cat.

Formation of new cortico-rubral synapses as a possible mechanism for classical conditioning mediated by the red nucleus in cat.

1.) By extracellular and intracellular recordings of the red nucleus (RN) cell activity, we investigated enhancement of signaling effectiveness at the cortico-rubral synapses underlying the establishment of classical conditioning mediated by RN in the cat. The classical conditioning of forelimb flexion was produced by pairing the conditioned stimulus (CS) to the cerebral peduncle (CP) with the unconditioned stimulus (US) to the forelimb skin at an interval of 100 msec for about a week. 2.) The increased responsiveness of RN cells to the CS was correlated with acquisition of the conditioned forelimb flexion, i.e. RN cells responded to the CS with higher firing probability in the animals which received the paired conditioning than those in the animals which received the CS alone or pairing of the CS and the US at random intervals or those in the naive animals which did not receive any training. 3.) Monosynaptic excitation of RN cells in response to the single pulse to CP was most enhanced in the animals which received the paired conditioning. By contrast, response of RN cells, as well as the behavioral response, induced by stimulation of the cerebellar interpositus nucleus (IP) was not enhanced after the paired conditioning. The difference between the responses to the stimulation of CP and IP suggested that the primary site of neuronal change is the cortico-rubral synapses. 4.) In the animals that received the paired conditioning, the excitatory postsynaptic potentials (EPSPs) induced by stimulation of CP had fast-rising components superimposed on the normal slow-rising EPSPs. On the other hand, most of the CP-EPSPs recorded in the naive animals showed a slow time course. The slow time course of the CP-EPSPs has been attributed to the peripheral localization of the cortico-rubral synapses on the dendrites of RN cells. 5.) The electrotonic length of RN cells in the animals which received the paired conditioning was not shorter than that in the naive animals. Therefore, it was suggested that the appearance of the fast-rising component in the CP-EPSPs is cause by formation of the new cortico-rubral synapses on proximal portions of the soma-dendritic membrane of RN cells. 6.) Since it has been established that new synapses formed by collateral sprouting are retained for more than several months, the formation of new synaptic connections could underlie long-lasting behavioral modification.

Rhythmic slow wave observed on nocturnal sleep encephalogram in children with idiopathic nocturnal enuresis.

All-night sleep polygraphs, except the first night, were recorded for 15 patients with idiopathic nocturnal enuresis and 10 normal controls. Relations between sleep and the mechanism by which nocturnal enuresis is caused, with special emphasis on the occurrence of rhythmic slow waves (RSW), was studied. The following results were obtained. (a) There was no significant difference between the two groups in the proportions of the electroencephalographic (EEG) sleep stages, under the same conditions. (b) Nocturnal enuresis occurred with almost the same frequency in all sleep stages except stage 1 sleep and was higher in the second and third cycles. (c) Immediately before a nocturnal enuretic event, 6-7 Hz RSW continued for as long as 15-40 s in NREM sleep, or 3-5 Hz RSW was observed in REM sleep. (d) RSW was observed in enuretics and controls, and decreased with increase in age. However, RSW occurred more often, and age-related decrease was delayed in enuretic children. (e) RSW was induced by stimuli such as changes in sleep stages or body movement. During RSW, the variance of heart rate and respiration tended to be low. These results and the similarity between RSW and diffuse rhythmic theta suggest that RSW may be an expression of the process of maintaining a given sleep stage in children. These results may also be caused by the immaturity of the sleep mechanism in enuretic children. The long-lasting RSW on the sleep EEG was considered to be a sign of the onset of nocturnal enuresis.

Dendritic and somatic appendages of identified rubrospinal neurons of the cat.

Giant neurons of the red nucleus of the cat were stained intracellularly with horseradish peroxidase and examined using light microscopy, electron microscopy of thin sections, and high voltage electron microscopy of thick sections (2-5 microns). Special attention was paid to the arrangement of dendritic spines and other appendages relative to the distribution of synaptic contacts from known sources. In the region of the neuron known to receive synaptic contacts from the nucleus interpositus of the cerebellum (soma and proximal 200-300 microns of dendrites), the dendrites were relatively unbranched, and free of long spines or complex appendages. The surface of the neurons in this region was covered with a dense layer of short thin appendages that invaginated or penetrated between the synaptic terminals that cover this part of the cells. The small spines received synapses of the types associated both with the cerebellar afferent fibers and with the local inhibitory interneurons. These same terminals made synaptic contacts directly onto the surface of the neurons and onto the lateral surfaces of the spines, suggesting that the spines may serve primarily to increase the available synaptic surface area. The more distal portion of the dendritic field, where cerebellar afferents do not make synaptic contacts, exhibited a dramatically different appearance. The dendrites were much more branched, and exhibited many and varied dendritic appendages. The appendages were of three general types. One was a large protrusion with a cup-shaped head that formed the principal postsynaptic component of a glomerular arrangement also involving an axon terminal and usually a presynaptic dendrite. A second was a long thin filiform process that usually occurred around the glomeruli. This appendage was occasionally postsynaptic. The third was a spherical appendage containing many lysosomal organelles resembling residual bodies. The glomerular dendritic protrusions were very common in the distal portion of the dendritic field, numbering at least 1000 per cell. At least some of the glomeruli are specialized for receipt of synaptic input from the corticorubral pathway, since lesions of sensorimotor cortex resulted in degeneration of the central synaptic terminal in some glomeruli on horseradish peroxidase-injected rubrospinal neurons. These specializations of dendritic structure may contribute to the differences in excitatory postsynaptic potential wave shape between cortical and cerebellar inputs, and they may play a role in the changes in the cortical excitatory postsynaptic potential that develop after lesions of cerebellar inputs.(ABSTRACT TRUNCATED AT 250 WORDS)

Sprouting of GABAergic synapses in the red nucleus after lesions of the nucleus interpositus in the cat.

An immunocytochemical study using anti-GAD serum was performed to examine the plastic changes of GABAergic inhibitory synapses in the red nucleus (RN) after lesions of the nucleus interpositus (IP) of the cat. Light-microscopic analyses revealed that 20-175 d after the unilateral lesion of the IP, somatic profiles of large neurons in the magnocellular RN contralateral to the lesion were more densely covered with GAD-immunoreactive puncta than those in the ipsilateral RN. Electron-microscopic analyses demonstrated that the GAD-immunoreactive puncta observed with the light microscope were synaptic terminals and that the number of GAD-immunoreactive synaptic terminals per unit length of somatic membrane of RN neurons was increased on the deafferented side. The GAD-immunoreactive terminals on somata of RN neurons made symmetric synaptic contacts with somatic membranes on both the deafferented and control sides. The number of immunoreactive synapses on somata of RN neurons was markedly increased on the deafferented side following IP lesion, whereas that of the unlabeled asymmetric synapses was decreased. These observations indicate that new GABAergic synapses were formed on somata of RN neurons after deafferentation from the IP.

Synaptic currents at interpositorubral and corticorubral excitatory synapses measured by a new iterative single-electrode voltage-clamp method.

A new iterative single-electrode voltage clamp method was applied to the measurement of synaptic currents in the red nucleus (RN) neuron of the cat. Voltage clamp was attained within 10 repetitions with great stability and the new algorithm was demonstrated to be superior to the original algorithm of iterative voltage clamp. With a conventional microelectrode, it was possible to measure the synaptic current with the time resolution of 50 microseconds. The synaptic currents evoked by stimulation of the contralateral interpositus nucleus (IP) had time-to-peak ranging from 200 to 540 microseconds and fitted well to alpha functions. Corticorubral (CR) synaptic current was also measured by making use of synaptic plasticity. The stimulation of the ipsilateral cerebral peduncle in cats with chronic lesion of the contralateral IP evoked fast rising EPSPs, as reported previously. The CR-EPSPs with times-to-peak less than 1 ms were subjected to voltage clamp. The CR synaptic currents had times-to-peak ranging from 350 to 880 microseconds. Since most of the interpositorubral (IR) synapses and a part of the CR synapses in IP-lesioned cats are situated on the somatic membrane of RN neurons and some of the CR synaptic currents were as rapid as the IR synaptic currents, the observed synaptic currents evoked by stimulation of the IP and those of the fast-rising CR-EPSPs were taken to originate from the synaptic membrane under space-clamp, i.e. soma. The present study provided additional evidence for the sprouting of the CR fibers as well as the time course of the synaptic current at the dendritic synapses remote from the soma, for the first time.

Morphological and electrophysiological study of sprouting of corticorubral fibers after lesions of the contralateral cerebrum in kitten.

The appearance of crossed corticorubral projections following ablations of the ipsilateral cortex is shown to result from the formation of new connections and is not due to the preservation of pre-existing bilateral connections. At least some of these crossed projections are collaterals of the pyramidal tract. Post-tetanic potentiation can be demonstrated both intra- and extracellularly following ipsilateral cerebral peduncle stimulation whereas no changes in excitatory postsynaptic potential amplitude are observed following contralateral cerebral peduncle stimulation.

Anatomical and physiological properties of the projection from the sensory cortex to the motor cortex in normal cats: the difference between corticocortical and thalamocortical projections.

Details of the distribution of terminal sites of the projection fibers from area 2 of the sensory cortex to the motor cortex were studied and compared with the distribution of terminals from the ventrolateral (VL) nucleus of the thalamus to the motor cortex. The results obtained were as follows: Intracortical microstimulation (ICMS) in area 2 produced measurable short-latency EPSPs only in neurons located in layers II and III of the motor cortex, whereas VL stimulation produced short-latency EPSPs in neurons throughout the depths of the motor cortex. The time from the beginning to the peak of the EPSPs was not significantly different for area 2- and VL-elicited EPSPs suggesting that there was no systematic difference between effective terminal sites for both inputs. However, there was a difference when a given neuron received both inputs suggesting that there was a segregation between the two inputs within a given cell. The majority of area 2-elicited EPSPs were smooth and monophasic, but some (40%) of them showed double peaks indicating that some neurons received mono- and disynaptic inputs from area 2. Intracellular injections of HRP suggested that neurons receiving input from area 2 were predominantly multipolar non-pyramidal neurons in layers II and III whereas neurons receiving thalamic input were pyramidal as well as non-pyramidal cells. Field potentials in the motor cortex evoked by area 2 stimulation did not change polarity in the depths of the cortex and therefore, differed from the VL-evoked potentials suggesting differences in the mechanisms of generating the electrical fields. It is concluded that association fibers effective for producing EPSPs terminate primarily on non-pyramidal cells in layer II and III whereas VL fibers terminate not only on pyramidal but also on non-pyramidal cells in layers III and V. This study provided a basis for examining the modifiability of association fibers after elimination of VL input to the motor cortex which is reported in the following paper.

Modification of the projection from the sensory cortex to the motor cortex following the elimination of thalamic projections to the motor cortex in cats.

Examination of the projection from area 2 of the sensory cortex to the motor cortex revealed substantial changes following lesion of the ventrolateral nucleus of the thalamus. These observed changes were as follows. (1) The polarity of the evoked potentials elicited by area 2 stimulation reversed in the depth of the motor cortex whereas in normal animals, there was no reversal. (2) The amplitude of area 2-elicited EPSPs in the motor cortical neurons became greater following the lesion of VL. (3) The shape of the observed EPSPs was characterized by multiple peaks whereas in normal animals, the EPSPs were generally smooth and monophasic. (4) Neurons receiving a short-latency input from area 2 were distributed throughout the depths of the motor cortex whereas in normal animals, they were located only in the upper layers (layers II and III). (5) Intracellular injection of HRP revealed that the neurons receiving short-latency input were not restricted to typical stellate type cells, but also included bipolar or bitufted neurons with elongated cell bodies and polarized arborizations. These neurons were located in the superficial (II and III) as well as in the deep (V) layer. It is concluded that the elimination of thalamic input resulted in the reinforcement of the corticocortical input to the motor cortex. The subsequently observed corticocortical projection extended to neurons did not originally innervated by the association fibers. The results suggested that functional recovery following thalamic lesion is partly due to reorganization of projections from the sensory cortex to the motor cortex.