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We present an optimization-based approach for autonomous parking. Building on recent advances in the area of optimization-based collision avoidance (OBCA), we show that the autonomous parking problem can be formulated as a smooth non-convex optimization problem. Unfortunately, such problems are numerically challenging to solve in general and require appropriate warm-starting. To address this limitation, we propose a novel algorithm called Hierarchical OBCA (H-OBCA). The main idea is to first use a generic path planner, such as Hybrid A*, to compute a coarse trajectory using a simplified vehicle model and by discretizing the state-input space. This path is subsequently used to warm-start the OBCA algorithm, which optimizes and smoothens the coarse path using a full vehicle model and continuous optimization. Our studies indicate that the proposed H-OBCA parking algorithm combines Hybrid A*'s global path planning capability with OBCA's ability to generate smooth, collision-free, and dynamically feasible paths. Extensive simulations suggest that the proposed H-OBCA algorithm is robust and admits realtime parking for autonomous vehicles. Sample code is provided at https://github.com/XiaojingGeorgeZhang/H-OBCA.

The impacts of the self-heating and autonomous hole supply adjustment on the short-circuit (SC) behavior of narrow mesa Si-IGBTs are investigated. As reported previously, non-saturated output characteristics of very narrow mesa IGBT, which is originatedfrom so-called CIBL effect, leads to larger current peak and lattice temperature rising during SC pulse. Newly introduced "GGEE" structure does not show non-saturated output curves thanks to autonomous hole supply adjustment by parasitic pMOS operation. 3D TCAD simulation shows MOS channel mobility degradation besides the parasitic pMOS plays an important role to establish the built-in negative feed-back loop against the thermally induced nearly instantaneous failure.

Acute compartment syndrome (ACS) is a surgical emergency that requires urgent fasciotomy to prevent irreversible sequelae. We report two cases of unidentified ACS, which did not result from traumatic injuries such as fractures or crush injury, iatrogenic injury or diseases such as haematological malignancies. Both patients complained of severe pain and swelling of their extremity. No bite marks, blisters or skin necrosis was noted. They also complained of marked symptoms of third cranial nerve injury, including divergent squint and diplopia. The diagnosis of ACS was made following continuous intracompartmental pressure measurement, and both patients underwent urgent fasciotomy with partial incision. Considering the season and location of the injuries, together with the rapid progression of signs and symptoms that included thrombocytopaenia, acute renal failure, rhabdomyolysis and especially that of third cranial nerve injury, we postulate that these two cases may have developed following mamushi (Gloydiusblomhoffii) bites.

The crystal-packing structures of seven derivatives of diaroylmethanatoboron difluoride (1 a-gBF2 ) are characterized by no overlap of the π-conjugated main units of two adjacent molecules (type I), overlap of the benzene ring π-orbitals of two adjacent molecules (type II), and overlap of the benzene and dihydrodioxaborinine rings π-orbitals of adjacent molecules (type III). The crystal-packing structures govern the fluorescence (FL) properties in the crystalline states. The FL domain that is present in type I crystals, in which intermolecular orbital interactions are absent, leads to excited monomer-like FL properties. In the case of the type II crystals, the presence of intermolecular overlap of the benzene rings π-orbitals generates new FL domains, referred to as "excited multimers", which possess allowed S0 -S1 electronic transitions and, as a result, similar FL lifetimes at longer wavelengths than the FL of the type I crystals. Finally, intermolecular overlap of the benzene and dihydrodioxaborinine ring π-orbitals in the type III crystals leads to "excited multimer" domains with forbidden S0 -S1 electronic transitions and longer FL lifetimes at similar wavelengths as that in type I crystals.

We examined the link between trajectories of television contact time at ages 1–5 and externalizing problems at age 5, using data from a Japanese longitudinal study of media use and child development (N = 1,189). Despite the American Academy of Pediatrics recommendation for no television contact before age 2, growth mixture modeling identified 3 trajectory classes, comprising heavy-start contact (8%, mean contact time at age 0 = 331.44 min/day), characterized by remarkably long television contact time in infancy and maintenance of longer contact, while mild contact (51%, 147.57 min/day) and moderate contact (41%, 236.64 min/day) had relatively shorter contact in infancy and moderate declines in later years. The findings suggest that both infant temperamental difficulties and family characteristics predicted trajectory classification of television contact time. Scores for attention problems and conduct problems at age 5 did not significantly differ among trajectory groups, nor did regression coefficients.

Several sacoglossan sea slugs utilise chloroplasts ingested from algae for photosynthesis (kleptoplasty), a unique trophic strategy unknown in other animals. Its adaptive significance, especially the behavioural adaptations involved in this phenomenon, has not been fully explored. To address this issue, the effects of kleptoplasty on phototaxis were investigated, both across and within species, using sacoglossans collected along Japanese coasts in 2012 and 2013. First, the presence of phototaxis and preferred light intensity was studied in five sacoglossans with various photosynthetic capabilities using an I-maze with a light gradient (4–330 μmol photons m−2 s−1). Each individual was allowed to move for 30 min to choose the optimal light intensity. Elysia hamatanii, E. trisinuata, and Plakobranchus ocellatus, all with high photosynthetic activity (i.e. kleptoplastic), showed positive phototaxis. Among them, E. hamatanii preferred the highest light intensity followed by P. ocellatus and E. trisinuata, and the order corresponded with the shallowness of their habitats. Conversely, Stiliger ornatus and Placida sp., with virtually no photosynthetic activity (non-kleptoplastic), showed neutral and negative phototaxis, respectively. Next, the phototaxis of E. hamatanii individuals with (fed) and without (starved) functional chloroplasts was compared to examine the effects of the presence of kleptoplasts on phototaxis within a species. Both fed and starved individuals showed positive phototaxis, but the preferred light intensity of starved individuals was lower than that of fed individuals. These results suggest that sacoglossans with functional chloroplasts exhibit positive phototaxis towards a preferred light intensity which may benefit photosynthesis efficiency.

Background and Purpose The locus coeruleus (LC) is the principal nucleus containing the noradrenergic neurons and is a major endogenous source of pain modulation in the brain. Glial cell line-derived neurotrophic factor (GDNF), a well-established neurotrophic factor for noradrenergic neurons, is a major pain modulator in the spinal cord and primary sensory neurons. However, it is unknown whether GDNF is involved in pain modulation in the LC.

Bischofia javanica is a non-native tree species in Japan’s Ogasawara Islands, where it threatens native tree species due to its rapid propagation and growth. An effective method is needed to limit the expansion of B. javanica populations and to conserve the natural forest ecosystem of the islands. For this purpose, we examined the effectiveness of a new application technique for the herbicide glyphosate on B. javanica. In this method, glyphosate solution is directly injected into holes drilled in the stem, and each hole is then plugged with a cork stopper to prevent loss of the solution, namely the drill-and-plug method. We also developed an allometric regression model linking stem diameter with total aboveground biomass (AGB) to estimate the necessary herbicide dosage. Our results suggest that between 0.1 and 0.5 g kg−1 (active ingredient per unit AGB) is required to control most B. javanica trees. Verification of the drill-and-plug method using the minimum dosage (0.1 g kg−1) showed that most of the herbicide-treated trees were killed. These results suggest that the drill-and-plug method can help control the B. javanica invasion of the Ogasawara Islands.

Background and purpose Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a strong genetic basis. Although anxiety is a common major psychiatric condition in ASD, the underlying mechanisms of the anxiety are poorly understood. In individuals with ASD, evidence indicates a structural abnormality in the amygdala, a key component involved in anxiety and social behavior. Microglia, which are central nervous system-resident immune cells implicated in neurodevelopmental processes, are also reportedly altered in ASD. In the present study, we examined the involvement of microglia in the anxiety-related behaviors of ASD model mouse. Methods Mice that have a 6.3-Mb paternal duplication (patDp/+) corresponding to human chromosome 15q11-q13 were used as an ASD model. Iba1, a microglial activation marker, was examined in the amygdala using immunofluorescence. Effects of perinatal treatment with minocycline, a microglial modulator, on anxiety-related behaviors were examined in neonatal and adolescent patDp/+ mice. Results In patDp/+ mice, Iba1 was decreased in the basolateral amygdala at postnatal day 7, but not at postnatal days 37-40. Perinatal treatment with minocycline restored the Iba1 expression and reduced anxiety-related behaviors in patDp/+ adolescent mice. Conclusions Perinatal microglia in the basolateral amygdala may play a pathogenic role in the anxiety observed in a mouse model of ASD with duplication of human chromosome 15q11-q13.

This paper proposes a simple and efficient method to improve hot carrier (HC) immunity of p-channel LDMOSFET without degrading typical figure of merits such as breakdown voltage BV and specific on-resistance R sp . The superiority of a novel STI-based p-channel LDMOSFET with a hot electron cooling (HEC) layer against the conventional method to improve HC immunity (i.e. extending the p-drift length) is confirmed by TCAD simulation.

Blood serum from immunized humans or animals (e.g., horses) contains relevant antibodies and has been used as serum therapy to treat many diseases or envenomation events. The effectiveness of blood serum was initially discovered in 1890 when Kitasato and von Behring observed the effectiveness of this type of therapy against diphtheria and tetanus. Serum therapies played an important role in the advancement of modern medicine prior to the development of penicillin and steroids. At present, several types of serum therapy remain in clinical use. However, some physicians have a limited understanding of the nature and the benefits of serum therapy and the factors that require particular attention. In this review, we set out to clarify the benefits, cautions, and potential applications of serum therapy in the context of conditions such as gas gangrene, diphtheria, botulism, and tetanus and bites from three snake species (mamushi, habu, and yamakagashi) and the redback spider. It is hoped that this review will help clinicians to learn about clinical serum therapies and become familiar with their applications.

The morphogenesis of snake embryos is an elusive yet fascinating research target for developmental biologists. However, few data exist on development of early snake embryo due to limited availability of pregnant snakes, and the need to harvest early stage embryos directly from pregnant snakes before oviposition without knowing the date of fertilization. We established an ex vivo culture method for early snake embryos using the Japanese striped snake, Elaphe quadrivirgata. This method, which we named "sausage-style (SS) culture", allows us to harvest snake embryos at specific stages for each experiment. Using this SS culture system, we calculated somite formation rate at early stages before oviposition. The average somite formation rate between 6/7 and 12/13 somite stages was 145.9 min, between 60/70 and 80/91 somite stages 42.4 min, and between 113-115 and 126/127 somite stages 71 min. Thus, somite formation rate that we observed during early snake embryogenesis was changed over time. We also describe a developmental staging series for E. quadrivirgata. This is the first report of a developmental series of early snake embryogenesis prior to oviposition by full-color images with high-resolution. We propose that the SS culture system is an easy method for treating early snake embryos ex vivo.

Case A healthy 40-year-old man was admitted with severe coagulopathy that developed after Rhabdophis tigrinus bites. On admission, he showed significantly elevated levels of thrombin–antithrombin III complex (60 ng/mL), plasmin–alpha 2-plasmin inhibitor complex (22.3 μg/mL), and fibrinogen degradation products (592 μg/mL). He subsequently developed severe hypofibrinogenemia (50 mg/dL). Outcome Antivenom was given 28 h after the patient was bitten, following which his hemorrhagic symptoms resolved. By day 3 of admission, scabs had formed over the bite wounds. Furthermore, his fibrinogen levels increased to >100 mg/dL, while his thrombin–antithrombin III complex, plasmin–alpha 2-plasmin inhibitor complex, and fibrinogen degradation product levels normalized. He was discharged on day 6 of admission. Conclusion Rhabdophis tigrinus bites induced disseminated intravascular coagulation with a fibrinolytic phenotype, which completely recovered with antivenom treatment.

Sacoglossans use chloroplasts taken from algal food for photosynthesis (kleptoplasty), but the adaptive significance of this phenomenon remains unclear. Two con-generic sacoglossans (Elysia trisinuata and E. atroviridis) were collected in 2009–2011 from Shirahama (33.69°N, 135.34°E) and Mukaishima (34.37°N, 133.22°E), Japan, respectively. They were individually maintained for 16 days under four experimental conditions (combination of light/dark and with/without food), and their survival rate and relative (=final/initial) weights were measured. Both light and food had positive effects on the survival in E. trisinuata, whereas no positive effects of light or food on survival were detected in E. atroviridis. Both light and food had positive effects on relative weights in both species, but light had smaller effects than food. A significant interaction term between light and food was detected in E. trisinuata (but not in E. atroviridis) in that only the presence of both resulted in weight gains. This result suggests that E. trisinuata can obtain sufficient additional energy from photosynthesis for sustaining growth when fresh chloroplasts are continuously supplied from algal food. In addition, fluorescence yield measurements showed that unfed individuals of both E. trisinuata and E. atroviridis lost photosynthetic activity soon (

Fluorescence (FL) properties of a novel donor–acceptor dyad, comprised of mesitylene and 1,4-dicyano-2-methylnaphthalene (DCMN) subunits connected by FL,Can ether linkage, were elucidated. The dyad in cyclohexane exhibits FL arising from an intramolecular exciplex. In the crystalline state, the dyad does not emit light from intra- and inter-molecular exciplexes but rather displays FL that is nearly equivalent to that of 2-methoxymethyl-substituted DCMN. However, the emission spectrum of the crystalline dyad contains a 361shoulder in the 0.39long wavelength region, suggesting that weak intercolumnar charge-transfer interactions take place between columns consisting of the mesitylene and DCMN subunits. An exciplex is an electronically-excited state complex comprised of two different molecules. 1 Mechanisms for inter- 2 and intra-molecular 3 formations and the photo-physical 4 and -chemical properties 5 of a number of exciplexes in solution have been studied. On the other hand, exciplexes in the crystalline states have gained much less attention. In a previous effort, we studied the fluorescence (FL) behavior of dyads containing a 1,4-dicyano-2-methylnaphthalene (DCMN) electron acceptor tethered to 4-methyl-, 4-methoxy

Aims: There are contradictory views on whether mangroves are obligate halophytes or facultative halophytes. In this study, we examined :(1)if seedlings of a mangrove, Rhizophorastylosa, require NaCl for theiand (2) whether the growth response of R. stylosaseedlings under varying salinities was explained from the context of carbon economics. Methodology: Seedlings ofR. stylosawere hydroponically grown under varying salinities (0-480 mMNaCl) and their growth, mortality, photosynthetic and respiration rates were analyzed. Results:Most of the seedlings grown under NaCl -free condition died during the 34 -week culture, demonstrating their salt dependency. The best growth was accomplished under moderate salinity (240 mMNaCl) with highest stem elongation, maximum biomass gain and lowest leaf mortality. Whole -plant photosynthetic production was highest under the moderate salinity anddeclined towards high and low salinity ranges whereas wholeplant respiration did not increase towards high and low salinity ranges. The lower photosynthetic production under high salinity involved reductions in both leaf area and Original ResearchArticle

To develop silvicultural methods for dipterocarp species in degraded lands in a tropical monsoon climate, we examined uneven-aged forest management, in which dipterocarp trees were planted under nurse trees, by monitoring their growth for 20 years. In 1989, seedlings of four dipterocarp species (Dipterocarpus alatus, D. turbinatus, Hopea odorata and Shorea henryana) were planted beneath a 3-year-old Leucaena leucocephala plantation and in an open site in Sakaerat, north-east Thailand. The survival rate and tree size of the dipterocarp seedlings were monitored at both sites until 1995. Surand svival rates of the dipterocarp trees were significantly better under the Leucaena plantation. However, no apparent difference was observed in basal area between both sites, since saw vigorous growth of the surviving seedlings compensated for the loss of dead seedlings at the open site. Our results showed that D. alatus and H. odorata could be planted in an open site due to the vigorous growth of the seedlings, but that it was preferable to plant D. turbinatus beneath nurse trees. The Leucaena plantation was partially thinned to 50, 75 and 100% (clear-cut) in 1993, and the survival rate and growth of the dipterocarps was monitored until 2009. Thinning had no apparent effect on the survival rates of the dipterocarp seedlings. Although relative growth rates (RGR) of the dipterocarps reduced after thinning, thinning rates did not affect the growth of the dipterocarps. After thinning, dipterocarp trees overtook Leucaena in height at all thinning rates, possibly from 1999. An uneven-aged system combining Leucaena and dipterocarp trees is likely to be applicable to several dipterocarp species.

The components of children’s trust in same-gender peers (trust beliefs, ascribed trustworthiness, and dyadic reciprocal trust) were examined in samples of 8–11-year-olds from the UK, Italy, and Japan. Trust was assessed by children’s ratings of the extent to which same-gender classmates kept promises and kept secrets. Social relations analyses confirmed that children from each country showed significant: (a) actor variance demonstrating reliable individual differences in trust beliefs, (b) partner variance demonstrating reliable individual differences in ascribed trustworthiness, and (c) relationship variance demonstrating unique relationships between interaction partners. Cultural differences in trust beliefs and ascribed trustworthiness also emerged and these differences were attributed to the tendency for children from cultures that value societal goals to share personal information with the peer group.

The fluorescence (FL) and structural properties of dibenzoylmethanatoboron difluoride (1aBF2) and its diisopropyl derivative (1bBF2) in the crystalline state were investigated. Both 1aBF2 and 1bBF2 in their crystalline states have FL spectra that contain similar emission in the ca. 450–600 nm region, which correspond to emission of green light. However, the FL lifetimes (τFL) of these substances in their crystalline states are markedly different. Based on the results of wave deconvolution and decay profile analyses, we tentatively supposed that the FL band of 1aBF2 with average τFL = 47.7 ns is mainly comprised of FL band from an excited multimer, an emitting domain consisting of three or more molecules. In contrast, an excimer with average τFL = 5.3 ns is likely the emitting species in the crystalline state of 1bBF2. The results of X-ray crystallographic analyses support the conclusion that these contrasting properties derive from a difference in molecular overlap, especially between the benzene (B) and dioxaborinine (D) rings in the crystalline states of 1aBF2 and 1bBF2. Specifically, molecules in crystals of 1aBF2 are aligned having B-on-B and B-on-D overlap with respective short face-to-face distances (3.50 and 3.42 A) while those in 1bBF2 are aligned in a single B-on-B overlap mode with a longer face-to-face distance (3.82 A).

Neuronal damage in the somatosensory system causes intractable chronic neuropathic pain. Plastic changes in sensory neuron excitability are considered the cellular basis of persistent pain. Non-coding microRNAs modulate specific gene translation to impact on diverse cellular functions and their dysregulation causes various diseases. However, their significance in adult neuronal functions and disorders is still poorly understood. Here, we show that miR-7a is a key functional RNA sustaining the late phase of neuropathic pain through regulation of neuronal excitability in rats. In the late phase of neuropathic pain, microarray analysis identified miR-7a as the most robustly decreased microRNA in the injured dorsal root ganglion. Moreover, local induction of miR-7a, using an adeno-associated virus vector, in sensory neurons of injured dorsal root ganglion, suppressed established neuropathic pain. In contrast, miR-7a overexpression had no effect on acute physiological or inflammatory pain. Furthermore, miR-7a downregulation was sufficient to cause pain-related behaviours in intact rats. miR-7a targeted the β2 subunit of the voltage-gated sodium channel, and decreased miR-7a associated with neuropathic pain caused increased β2 subunit protein expression, independent of messenger RNA levels. Consistently, miR-7a overexpression in primary sensory neurons of injured dorsal root ganglion suppressed increased β2 subunit expression and normalized long-lasting hyperexcitability of nociceptive neurons. These findings demonstrate miR-7a downregulation is causally involved in maintenance of neuropathic pain through regulation of neuronal excitability, and miR-7a replenishment offers a novel therapeutic strategy specific for chronic neuropathic pain. * Abbreviations : AAV : adeno-associated virus DRG : dorsal root ganglion EGFP : enhanced green fluorescent protein

Neuropathic pain is intractable chronic pain caused by damage to the somatosensory system. Peripheral nerve injury of the primary sensory neurons changes expressions of multiple microRNAs that affect many aspects of cellular functions by regulating specific gene expressions. miR-21, a well-characterized oncogenic miRNA, is consistently upregulated after peripheral nerve injury in the dorsal root ganglion (DRG), where cell bodies of primary sensory neurons exist. However, their causal relationship to the pain is fully unknown. In this study, we therefore investigated the miR-21 expression in the DRGs along with the time course of neuropathic pain and its involvement in the neuropathic pain. Neuropathic pain was induced in rats by specific ligation of the left fifth lumbar spinal nerve. After the injury, miR-21 expression in the injured DRG neurons, but not in the neighboring uninjured DRG neurons, was persistently upregulated following the pain development. Intrathecal administration of interleukin-1β also increased the miR-21 expression in the DRG. Both mechanical allodynia and thermal hyperalgesia in the neuropathic pain were attenuated by intrathecal administration of miR-21 inhibitor. miR-21 is specifically upregulated in the injured DRG neurons and causally involved in the late phase of neuropathic pain. Therefore, miR-21 and its modulatory system may be a therapeutic target for intractable chronic neuropathic pain.

The core histone proteins (H2A, H2B, H3 and H4) are nuclear-localised proteins that play a central role in the formation of nucleosome structure. They have long been considered to be absent from extra-nuclear, DNA-containing organelles; that is plastids and mitochondria. Recently, however, the targeting of core histone H3 to mitochondria, and the presence of nucleosome-like structures in mitochondrial nucleoids, were proposed in cauliflower and tobacco respectively. Thus, we examined whether histone H3 was present in plant organelles and participated in the organisation of nucleoid structure, using highly purified organelles and organelle nucleoids isolated from BY-2 cultured tobacco cells. Immunofluorescence microscopic observations and Western blotting analyses demonstrated that histone H3 was absent from organelles and organelle nucleoids, consistent with the historical hypothesis. Thus, the organisation of organelle nucleoids, including putative nucleosome-like repetitive structures, should be constructed and maintained without participation of histone H3.

Heavy thinning may provide a feasible means to convert single-species coniferous plantations to broadleaved or mixed forests. To assess this possibility, we monitored tree seedling dynamics of other tree species, the understory microenvironment, and seed availability following heavy thinning (50 % by volume) in two hinoki (Chamaecyparis obtusa) plantations in Shikoku, southwestern Japan. Conventional (35 % by volume) and row thinning (50 % by volume) treatments were also applied at one of the sites. Diffuse transmittance in the understory dramatically increased after all thinning treatments then rapidly decreased, except after row thinning. Heavy thinning accelerated recruitment of small seedlings (with stems

Si interposer technology has the potential to enable highbandwidth and low-power image processing devices of the future, because a very high density system with an ultra-fine pitch (≤5um) wiring can be fabricated. However, the ultrafine pitch wiring may adversely affect the electrical performance of devices. This paper discusses the signal propagation properties of ultra-fine coplanar interconnects on Si interposers. A design chart of the interconnects, obtained from the viewpoint of maximum line length versus target operating frequency, is presented. © 2009 IEEE.

The very narrow mesa structures based on our 7th generation IGBT process are fabricated and it is found that the device with the narrowest mesa shows very poor short circuit (SC) withstand capability although it suppresses the conduction loss considerably. This poor SC capacity is caused by non-saturated output characteristics which are originated by collector bias induced barrier lowering in the middle of Si mesa. The current filamentation is observed in the 3D multi-cell short circuit simulation with self-heating and the SC capacity degradation due to the filamentation is enhanced in the narrower mesa structure.

The thermally backward reaction involved in the mechanofluorochromism of dibenzoylmethanatoboron difluoride (BF2DBM) derivatives, accompanied by an amorphous–crystalline phase transition, was quantitatively evaluated based on kinetics and thermodynamics. The kinetics was discussed by evaluation of the effect of temperature on the time-dependent changes of the fluorescence intensity for amorphous samples obtained by mechanical grinding. The thermodynamics was discussed based on data for the amorphous–crystalline phase transition obtained by differential scanning calorimetry. The enthalpy of activation (ΔH‡) of BF2DBM derivatives with MeO groups (2aBF2) was larger than that of derivatives with alkyl groups (2b-dBF2), whereas the entropy of activation (ΔS‡) was smaller than that of the derivatives with alkyl groups. It is proposed that the reaction dynamics of 2aBF2 will be governed by rotational motion around the C(methyl)–O bond. Interestingly, the Gibbs energies of activation (ΔG‡) were comparable for the reactions of all members of the BF2DBM series, though ΔH‡ and ΔS‡ were strongly dependent on the identity of the substituent. It is proposed that the substituent-dependent ΔS‡ term is one of the key parameters for understanding the mechanofluorochromism of BF2DBM derivatives associated with the amorphous–crystalline phase transition. These findings will also provide important insights into the process of formation of crystal nuclei in moving from the melted to the crystalline state., Article, PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES.15(3):420-430(2016)

The dorsal raphe nucleus (DRN) is the origin of the central serotonin [5-hydroxytryptamine (5-HT)] system and plays an important role in the regulation of many physiological functions such as sleep/arousal, food intake and mood. In order to understand the regulatory mechanisms of 5-HT system, characterization of the types of neurons is necessary. We performed electrophysiological recordings in acute slices of glutamate decarboxylase 67-green fluorescent protein knock-in mice. We utilized this mouse to identify visually GABAergic cells. Especially, we examined postsynaptic responses mediated by 5-HT receptors between GABAergic and serotonergic cells in the DRN. Various current responses were elicited by 5-HT and 5-HT(1A) or 5-HT(2A/2C) receptor agonists in GABAergic cells. These results suggested that multiple 5-HT receptor subtypes overlap on GABAergic cells, and their combination might control 5-HT cells. Understanding the postsynaptic 5-HT feedback mechanisms may help to elucidate the 5-HT neurotransmitter system and develop novel therapeutic approaches.

Many sacoglossan sea slugs utilize chloroplasts ingested from food algae for photosynthesis (functional kleptoplasty), and the extent and duration of kleptoplast retention differs greatly among sacoglossan species. Although most recent studies focus on the genetic, microscopic, or physiological mechanisms responsible for this unique phenomenon, its effects on the life history traits of sacoglossans have not been fully explored. To study the effects of light conditions on survival and weight retention, adult individuals of two sacoglossan species, Elysia trisinuata and Plakobranchus ocellatus (‘black type'), were reared under light conditions (a 14-hour light: 10-hour dark photoperiod with an irradiance level of 28 µmol m−2s−1) or complete darkness for 21 days. There was no significant difference in the survival rate between the light and dark treatments for E. trisinuata, and its wet weight relative to the initial weight was smaller in the light than in the dark. However, both the survival and relative weights were greater in the light than dark for P. ocellatus. Based on the fluorescent yield measurement using pulse-amplitude-modulated fluorometry, the retention duration of functional chloroplasts was longer (>17 days) for P. ocellatus than E. trisinuata (P. ocellatus benefits from photosynthesis for survival and growth, whereas E. trisinuata does not under starved conditions. This interspecific difference is likely related to the period of functional chloroplast retention.

Background and purpose The locus coeruleus (LC) is a major source of noradrenergic projections to the dorsal spinal cord, and thereby plays an important role in the modulation of nociceptive information. The LC receives inputs from substance P (SP)-containing fibres from other regions, and expresses the NK(1) tachykinin receptor, a functional receptor for SP. In the present study, we investigated the roles of SP in the LC in neuropathic pain. Experimental approach Chronic constriction injury (CCI) of the left sciatic nerve was performed in rats to induce neuropathic pain. After development of neuropathic pain, SP was injected into the LC and the nocifensive behaviours were assessed. The involvement of noradrenergic descending inhibition in SP-induced analgesia was examined by i.t. administration of yohimbine, an α(2) -adrenoceptor antagonist. NK(1) receptor expression in the LC was examined by immunohistochemistry. Key results In CCI rats, mechanical allodynia was alleviated by SP injection into the LC. These effects were abolished by prior injection of WIN 51708, an NK(1) receptor antagonist, into the LC or i.t. treatment with yohimbine. NK(1) receptor-like immunoreactivity was observed in noradrenergic neurons throughout the LC in intact rats, and remained unchanged after CCI. Conclusion and implications SP in the LC exerted analgesic effects on neuropathic pain through NK(1) receptor activation and resulted in facilitation of spinal noradrenergic transmission. Accordingly, manipulation of the SP/NK(1) receptor signalling pathway in the LC may be a promising strategy for effective treatment of neuropathic pain.

Rheumatoid arthritis (RA) is a chronic multisystem disease characterized by persistent joint inflammation associated with severe pain. Because RA is an immune-mediated joint disease and because type II collagen is considered an autoantigen, rodent models of arthritis using collagen type II-specific monoclonal antibodies are valuable for studying the pathogenesis of autoimmune arthritis and for evaluating therapeutic strategies. The tachykinin family peptides, substance P (SP) and hemokinin-1 (HK-1), are expressed in the nervous systems and in many peripheral organs and immunocompetent cells and activate tachykinin NK1 receptors with similar affinities. NK1 receptors are involved in the inflammation and hyperalgesia associated with a variety of inflammatory diseases. In the present study, we examined the involvement of SP and HK-1 in the joint inflammation and hyperalgesia in a collagen antibody-induced arthritis (CAIA) model in mice. The messenger RNA expression levels of the TAC1 gene encoding SP and of the TAC4 gene encoding HK-1 were decreased in the dorsal root ganglia and spinal cord at the peak of the inflammatory symptoms in CAIA. Systemic injection of an NK1 receptor antagonist, WIN 51708, significantly inhibited the joint swelling, but not the mechanical allodynia, on day 7 in CAIA mice. The messenger RNA expression levels of TAC1 and TAC4 in the dorsal root ganglia and dorsal spinal cord were unaffected by treatment with WIN 51708. These findings suggest that tachykinins and NK1 receptors play a key role in joint inflammation, rather than in nociceptive sensitization, in CAIA.

Persistent pain associated with inflammatory arthritis is an aggravating factor that decreases patients' quality of life. Current therapies for joint pain have limited effectiveness and produce unwanted negative side effects. Although the involvement of substance P and its cognate tachykinin receptor, NK(1), in joint inflammation has been extensively documented through animal experiments, the development of oral tachykinin NK(1) receptor antagonists against arthritis-induced pain has been unsuccessful in humans to date. To explore the possibility of using tachykinin NK(1) receptor antagonists as local therapeutic agents for inflammatory arthritis, we examined the effects of tachykinin NK(1) receptor antagonists administered into the rat ankle joint on hyperalgesia in complete Freund's adjuvant (CFA)-induced inflammatory monoarthritis. Administration of the tachykinin NK(1) receptor antagonist WIN 51708 or GR 82334 into the affected ankle joint at day 3 following intra-articular CFA injection reduced the mechanical hyperalgesia 12 h after the tachykinin NK(1) receptor antagonist injection and their analgesic effects persisted for at least 2 days. Histological examinations revealed that intra-articular WIN 51708 reduced the CFA-induced destructive changes in the cartilage. These findings suggest that intra-articular injection of tachykinin NK(1) receptor antagonists is a promising strategy for relieving the hyperalgesia that occurs in inflammatory arthritis.

The mechanism of theca cell layer formation in mammalian ovaries has not been elucidated. In the present study, we examined the roles of THY1 and integrin beta3 in theca cell layer formation during mouse folliculogenesis. The localization pattern of THY1 and integrin beta3 in adult mouse ovary was investigated immunohistochemically. The strongest THY1 signal was observed in theca cell layers from secondary to preantral follicles, at which time theca cells have begun to participate in follicle formation. Integrin beta3 also localized to the theca cell layer of secondary to preantral follicles and showed a localization pattern similar to that of THY1. Moreover, the role of THY1 in theca cell layer formation was examined using a follicle culture system. When anti-THY1 antibody was added to this culture, no theca cell layers were formed, and the granulosa cells were distanced from each other. Because a THY1 signal was not observed in ovaries at stages earlier than prepuberty, THY1 localization also appeared to be affected by mouse development. This possibility was examined by determining the effect of administering follicle-stimulating hormone, luteinizing hormone, and 17beta-estradiol to 7-day-old mice on THY1 localization in the ovary 3 days later. Only follicle-stimulating hormone induced a THY1 signal in 10-day-old mouse ovaries. No THY1 signal was observed in untreated 10-day-old ovaries. In conclusion, THY1 might play a role in cell adhesion via binding to integrin beta3 in mouse ovaries. The present results suggest that THY1 localization may be affected by follicle-stimulating hormone in mouse ovaries.

Volatile monoterpenes such as 1,8-cineole inhibit the growth of Brassica campestris seedlings in a dose-dependent manner, and the growth-inhibitory effects are more severe for roots than hypocotyls. The preferential inhibition of root growth may be explained if the compounds inhibit cell proliferation more severely than cell elongation because root growth requires both elongation and proliferation of the constituent cells, whereas hypocotyl growth depends exclusively on elongation of existing cells. In order to examine this possibility, BY-2 suspension-cultured tobacco (Nicotiana tabacum) cells were treated with 1,8-cineole, and the inhibitory effects on cell proliferation and on cell elongation were assessed quantitatively. Treatment with 1,8-cineole lowered both the mitotic index and elongation of the cells in a dose-dependent manner, and the half-maximal inhibitory concentration (IC₅₀) for cell elongation was lower than that for cell proliferation. Moreover, 1,8-cineole also inhibited starch synthesis, with IC₅₀ lower than that for cell proliferation. Thus, the inhibitory effects of 1,8-cineole were not specific to cell proliferation; rather, 1,8-cineole seemed inhibitory to a variety of physiological activities when it was in direct contact with target cells. Based on these results, possible mechanisms for the mode of action of 1,8-cineole and for its preferential inhibition on root growth are discussed.

With the aim of establishing silvicultural techniques for tree species indigenous to monsoon tropical areas, we examined the survivorship and growth performance of three tree species under different light conditions. A 23-year-old Acacia mangium plantation was thinned in different ways: group selection thinning (gap creation, 50 m by 60 m in size), 2/3 random selection thinning based on basal area, 1/3 random selection thinning, and no thinning (control). The seedlings of Hopea odorata, H. ferrea, and Xylia xylocarpa var. kerrii were planted in each treatment area with three replications. At 30 months after planting, all species achieved a high survival rate (>90%) in all treatments, perhaps owing to intensive tending in the experimental plots. Both stem thickening and height growth were promoted as light conditions improved: most in the gap plot and least in the control plot for all species. H. ferrea grew to a large height even in dark conditions, suggesting that this species is considerably shade-tolerant. In contrast, X. xylocarpa var. kerrii was light-demanding owing to vigorous growth in the gap plot. The growth of the seedlings seemed to be associated with regeneration patterns in their natural habitats. The group selection thinning seemed to be most suitable for the growth of indigenous tree species.

Glycyrrhetinic acid (GA), an aglycone of glycyrrhizin, isolated from the licorice root (Glycyrrhizia), and its semi-synthetic derivatives have a wide range of pharmacological effects. To investigate whether GA derivatives may be used as a new class of analgesics, we examined the effects of these compounds on human tachykinin receptors expressed in CHO-K1 cells. Among the GA derivatives examined, the disodium salt of olean-11,13(18)-dien-3β,30-O-dihemiphthalate inhibited the mobilization of [Ca2+]i induced by substance P, neurokinin A, and neurokinin B in CHO-K1 cells expressing the human NK1, NK2, and NK3 tachykinin receptors, respectively. In an inflammatory pain model, Compound 5 suppressed the capsaicin-induced flinching behavior in a dose-dependent manner. Compound 5 was also effective in suppressing pain-related behaviors in the late phase of the formalin test and reducing thermal hyperalgesia in the neuropathic pain state caused by sciatic nerve injury. Collectively, Compound 5 may be an analgesic candidate via tachykinin receptor antagonism. Keywords:: glycyrrhetinic acid, inflammatory pain, neuropathic pain, substance P, tachykinin receptor

Sirt3, a member of the sirtuin family, is known to control cellular mitochondrial function. Furthermore, because sirtuins require NAD for their deacetylase activity, nicotinamide phosphoribosyltransferase (Nampt), which is a rate-limiting enzyme in the intracellular NAD biosynthetic pathway, influences their activity. We examined the effects of exercise training and normal postural contractile activity on Sirt3 and Nampt protein expression in rat skeletal muscles. Male rats were trained by treadmill running at 20 m/min, 60 min/day, 7 days/wk for 4 wk. This treadmill training program increased the Sirt3 protein expression in the soleus and plantaris muscles by 49% and 41%, respectively ( P < 0.05). Moreover, a 4-wk voluntary wheel-running program also induced 66% and 95% increases in Sirt3 protein in the plantaris and triceps muscles of rats, respectively ( P < 0.05). Treadmill-running and voluntary running training induced no significant changes in Nampt protein expression in skeletal muscles. In resting rats, the soleus muscle, which is recruited during normal postural activity, possessed the greatest expression levels of the Sirt3 and Nampt proteins, followed by the plantaris and triceps muscles. Furthermore, the Sirt3, but not Nampt, protein level was reduced in the soleus muscles from immobilized hindlimbs compared with that shown in the contralateral control muscle. These results demonstrated that 1) Sirt3 protein expression is upregulated by exercise training in skeletal muscles and 2) local postural contractile activity plays an important role in maintaining a high level of Sirt3 protein expression in postural muscle.

Serotonergic antidepressant drugs have been commonly used to treat mood and anxiety disorders, and increasing evidence suggests potential use of these drugs beyond current antidepressant therapeutics. Facilitation of adult neurogenesis in the hippocampal dentate gyrus has been suggested to be a candidate mechanism of action of antidepressant drugs, but this mechanism may be only one of the broad effects of antidepressants. Here we show a distinct unique action of the serotonergic antidepressant fluoxetine in transforming the phenotype of mature dentate granule cells. Chronic treatments of adult mice with fluoxetine strongly reduced expression of the mature granule cell marker calbindin. The fluoxetine treatment induced active somatic membrane properties resembling immature granule cells and markedly reduced synaptic facilitation that characterizes the mature dentate-to-CA3 signal transmission. These changes cannot be explained simply by an increase in newly generated immature neurons, but best characterized as “dematuration” of mature granule cells. This granule cell dematuration developed along with increases in the efficacy of serotonin in 5-HT 4 receptor-dependent neuromodulation and was attenuated in mice lacking the 5-HT 4 receptor. Our results suggest that serotonergic antidepressants can reverse the established state of neuronal maturation in the adult hippocampus, and up-regulation of 5-HT 4 receptor-mediated signaling may play a critical role in this distinct action of antidepressants. Such reversal of neuronal maturation could affect proper functioning of the mature hippocampal circuit, but may also cause some beneficial effects by reinstating neuronal functions that are lost during development.

This study proposes a simple method for stand volume estimation by combining low laser-sampling density Light Detection and Ranging (LiDAR) data (i.e. 1 hit per 4 m2) with high-resolution optical imagery (i.e. 0.6 m) in coniferous plantations. The study area was in closed-canopy, mountainous, Japanese cedar (Cryptomeria japonica) plantations on undulating terrain at an elevation of 135-391 m above sea level. A total of 25 circular plots (0.04 ha) were established and stand volumes within plots were investigated in the field. The field-measured, plot-level stand volume ranged from 262.8 to 984.0 m3 ha-1 and the average value was 555.7 m3 ha-1. We used the measurements as validation data to evaluate estimates derived from an empirical regression model that was constructed on the basis of the allometry between crown diameter and diameter at breast height (DBH) from previous research. As a result, stand volume at various stand conditions could be estimated precisely regardless of different laser footprint sizes of 0.16-0.47 m when combining low-density LiDAR data with QuickBird panchromatic imagery. The maximum random error and root mean square error (RMSE) in stand volume estimates by data combination were 10% and 39% of the average stand volume, respectively. Thus, this method based on allometry and using low-density LiDAR data and high-resolution optical imagery could be capable of offering precise stand volume estimates in coniferous forests in different localities.