Search

Multifunctional ceramics with the 0.93(Na 0.5 Bi 0.5) 1- x Pr3+ x TiO 3 -0.07BaTiO 3 (abbreviated as BNBT- x Pr, x = 0.00, 0.002, 0.004, 0.006, 0.008) were synthesized using the solid-phase reaction method. This study systematically investigated the phase structure, microstructure, dielectric, ferroelectric, piezoelectric, and photoluminescence properties. As the value of x increased, the ceramics underwent a transition from a co-existing rhombohedral (R) and tetragonal (T) phases to a T phase with a slight R distortion. In addition, the grain size decreased, and the relative density increased. The Pr3+ doping led to a decrease in the coercive field and an improved reversible phase transition, accompanied by a reduction in the depolarization temperature (T d) from 91 °C to 41 °C. The ceramic with x = 0.006 showed excellent piezoelectric properties, with a d 33 = 201 pC/N and k p = 30.6%. Such properties were ascribed to the appropriate R/T phase ratio, increased relative density, decreased coercive field, and improved reversible phase transition. Moreover, under excitation at 451 nm, the ceramics exhibited bright red emission bands at 611 nm and 655 nm, corresponding to the transitions of 1D 2 →3H 5 and 3P 0 →3F 2 , respectively. After polarization, the relative intensity of the emission peak at 655 nm significantly increased due to the changed lattice environment caused by the electric field. These Pr-doped BNBT ceramics demonstrated great potential in applications requiring electro-optic integration and coupling devices as multifunctional materials. [ABSTRACT FROM AUTHOR]

Using Langevin dynamics simulations, we investigate the dynamics of polymer translocation into a circular nanocontainer through a nanopore under a driving force F. We observe that the translocation probability initially increases and then saturates with increasing F, independent of [lowercase_phi_synonym], which is the average density of the whole chain in the nanocontainer. The translocation time distribution undergoes a transition from a Gaussian distribution to an asymmetric distribution with increasing [lowercase_phi_synonym]. Moreover, we find a nonuniversal scaling exponent of the translocation time as chain length, depending on [lowercase_phi_synonym] and F. These results are interpreted by the conformation of the translocated chain in the nanocontainer and the time of an individual segment passing through the pore during translocation. [ABSTRACT FROM AUTHOR]

The optimal path problem of graph data is a classical problem, but with the continuous development of information technology, the linguistic attributes of path descriptions are becoming more and more abundant. The nature of these attributes has uncertainty feature, which makes the choice of optimal path more difficult. Therefore, in order to solve this problem, this paper takes the path of large-scale graph and the uncertainty of linguistic attributes and the inconsistency of evaluation scale described as the research object and uses LWAA and landmark community technology to effectively solve the query problem of approximate optimal path. The efficiency of the algorithm is also verified by experiments. [ABSTRACT FROM AUTHOR]

Abstract Penaeidins are a unique family of antimicrobial peptides specific to penaeid shrimp and have been reported mainly function as anti-bacterial and anti-fungal. In order to investigate whether penaeidins could also respond to virus or not, we examined the effect of WSSV on MjPen-II (penaeidin in kuruma shrimp, Marsupenaeus japonicus ) expression. In the control group, MjPen-II transcript level can be detected in almost all test tissues but was expressed most strongly in hemocytes. After WSSV infection, MjPen-II transcript level was significantly downregulated in hemocytes. Moreover, the proportion of MjPen-II+ hemocytes was not significantly different between non-infected and WSSV-infected shrimp, but the number of MjPen-II+ highly expressing hemocytes decreased after infection. In addition, MjPen-II was observed in the cytoplasm of granule-containing hemocytes. These results suggest that WSSV suppresses MjPen-II expression in hemocytes. Highlights • MjPen-II transcript level can be detected in various tissues but was expressed most strongly in hemocytes. • MjPen-II was located in the cytoplasm of granule-containing hemocytes in Marsupenaeus japonicus. • MjPen-II transcript level was significantly downregulated after white spot syndrome virus (WSSV) infection. • The proportion of MjPen-II+ highly expressing hemocytes decreased after WSSV infection but not with MjPen-II+ hemocytes. [ABSTRACT FROM AUTHOR]

cDNA of a newly recognized white spot syndrome virus (WSSV)-induced gene (MjVIG1) was characterized from Marsupenaeus japonicus hemocytes; this gene encodes a protein that lack similarity to any known characterized protein. To identify this novel gene, we mainly conducted transcript level analysis, immunostaining and flow cytometry after WSSV infection. MjV1G1 transcript levels were also measured after Yellow head virus (YHV) and Vibrio parahaemolyticus infection tests. In non-infected and WSSV-infected shrimp, MjVIG1 was observed in granule-containing hemocytes. In addition, the MjVIG1 transcript level and ratio of MjVIG1-positive hemocytes both significantly increased, and number of MjVIG1-positive hemocytes slightly increased after WSSV infection. In contrast, MjVIG1 transcript level did not change after YHV and V. parahaemolyticus infection. These results indicated that MjVIG1 might be a WSSV-specific induced gene in M. japonicus hemocytes. [ABSTRACT FROM AUTHOR]

Working memory is regulated by neurotransmitters in prefrontal cortex (PFC), including dopamine and norepinephrine. Previous studies of dopamine function in working memory have focused on the D1 and D2 receptors, with most evidence suggesting a dominant role for the D1 receptor. Since the dopamine D4 receptor is highly expressed in PFC, we hypothesize that it may also contribute to working memory. To test this hypothesis, we examined behavioral effects of L-745,870, a highly selective, centrally active, D4 antagonist, using a delayed alternation task in rats. Task performance was dose-dependently affected by the D4 antagonist, depending on individual baseline functional status of working memory. In rats with good baseline performance, the D4 antagonist had no effects at low doses, whereas high doses disrupted working memory. In rats with poor baseline working memory, the D4 antagonist significantly improved working memory at low doses, and higher doses were not distinguishable from vehicle controls. Effects of the D4 antagonist among poor performers were most robust when task demand for working memory was high, with lesser effects at lower demand level, suggesting that such effects were selective for working memory. The present findings indicate a significant role of the D4 receptor in working memory, and suggest innovative, D4-based, treatment of cognitive deficits associated with neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]

Attention-deficit hyperactivity disorder (ADHD) involves clinically heterogeneous dysfunctions of sustained attention, with behavioral overactivity and impulsivity, of juvenile onset. Experimental models, in addition to mimicking syndromal features, should resemble the clinical condition in pathophysiology, and predict potential new treatments. One of the most extensively evaluated animal models of ADHD is the spontaneously hypertensive rat. Other models include additional genetic variants (dopamine transporter gene knock-out mouse, coloboma mouse, Naples hyperexcitable rat, acallosal mouse, hyposexual rat, and population-extreme rodents), neonatal lesioning of dopamine neurons with 6-hydroxydopamine, and exposure to other neurotoxins or hippocampal irradiation. None is fully comparable to clinical ADHD. The pathophysiology involved varies, including both deficient and excessive dopaminergic functioning, and probable involvement of other monoamine neurotransmitters. Improved models as well as further testing of their ability to predict treatment responses are required. [Copyright &y& Elsevier]

Neuronal nitric oxide synthase (nNOS) catalyzes the synthesis of neuronal nitric oxide from l-arginine. Behavioral and neurochemical studies implicate neuronal nitric oxide in the pathophysiology of schizophrenia and in the actions of standard antipsychotic drugs. However, involvement of nNOS in the actions of newer antipsychotic drugs requires further investigation. Accordingly, density levels of nNOS, a marker for neuronal nitric oxide production, were examined in rat forebrain regions by computed autoradiography after repeated treatment (28 days) with three newer antipsychotic agents, olanzapine, risperidone, and quetiapine. No significant differences in nNOS levels were detected in representative cortical, limbic, and extrapyramidal brain regions of drug-treated vs vehicle-treated animals. The findings suggest that nNOS plays a minimal role in mediating the long-term actions of newer antipsychotic drugs. [Copyright &y& Elsevier]

We examined serotonin (5-HT) transporters in rat forebrain using quantitative autoradiography at three distinct developmental stages after neonatal 6-hydroxydopamine lesions. The lesions substantially increased 5-HT transporter binding in both caudate-putamen and nucleus accumbens, but not cerebral cortex. The effects reached maximal levels as early as postnatal day (PD) 24, and were sustained until early adulthood. Behavioral analyses indicated that neonatal lesions resulted in motor hyperactivity on PD 24, but not on PD 36 or 59. These findings suggest that excess 5-HT transporters reflect serotonin hyperinnervation reported to occur in lesioned rats, and may modulate motor hyperactivity. [Copyright &y& Elsevier]

Rationale: Serotonin (5-HT) and its receptors have been implicated in various neuropsychiatric disorders. Altered serotonergic neurotransmission and interactions between 5-HT and dopamine (DA) systems may contribute to the pathophysiology of idiopathic psychotic or manic disorders. Interactions with 5-HT receptors may also contribute to special properties of modern antipsychotic drugs not yet evaluated for long-term effects on 5-HT receptors. Objective and methods: We surveyed effects of newer atypical antipsychotics on 5-HT receptor types 1A, 2A, and 2C in rat forebrain regions by quantitative receptor autoradiography with selective radioligands following 28 days of continuous infusion of drugs or control vehicle. Results: Infusion of olanzapine, risperidone, and quetiapine increased 1A, but decreased 2A receptor labeling in frontal cerebral cortex. Olanzapine decreased binding at 2C receptors in hippocampal CA[sub 1] and CA[sub 3] regions and perhaps entorhinal cortex; olanzapine, but neither risperidone nor quetiapine, also decreased 2C labeling in caudate-putamen. Conclusions: The findings suggest that altered 5-HT[sub 1A] and 5-HT[sub 2A ] receptor levels in frontal cortex, and 5-HT[sub 2C] receptors in other forebrain regions, may contribute to psychopharmacological properties of these novel atypical antipsychotic agents, perhaps including their antipsychotic or antimanic actions, and low risk of adverse extrapyramidal effects. [ABSTRACT FROM AUTHOR]

Genetic studies suggest that dopamine D4 receptor polymorphism is associated with attention deficit hyperactivity disorder (ADHD). We recently reported that motor hyperactivity in juvenile male rats with neonatal 6-hydroxydopamine lesions of the central dopamine system can be reversed by dopamine D4 receptor-selective antagonists. In this study, effects of such lesions on D4 as well as other dopamine receptors (D1 and D2) were autoradiographically quantified at selected developmental stages. Neonatal lesions resulted in motor hyperactivity at postnatal day (PD) 25, but not at PD 37 or 60. Correspondingly, D4 receptor levels in lesioned rats were substantially increased in caudate-putamen and decreased in nucleus accumbens at PD 25, but not at PD 37 or 60. Neonatal lesions also led to relatively minor changes in D1 and D2 receptor binding in various forebrain regions. However, the time-course of lesion-induced motor hyperactivity correlated only with changes in D4, but not D1 and D2 receptors. These results further support the hypothesis that D4 receptors may play a pivotal role in lesion-induced hyperactivity, and possibly in clinical ADHD. [Copyright &y& Elsevier]

Rationale: Dopamine D[sub 4] receptor gene polymorphism has been repeatedly associated with attention deficit hyperactivity disorder (ADHD) and related personality traits. We recently reported that motor hyperactivity in an animal model of ADHD was dose-dependently reversed by CP-293,019, a D[sub 4] receptor-selective antagonist. However, behavioral effects of this agent may not be attributed exclusively to D[sub 4] receptor blockade, since it interacts with other sites including serotonin receptors. Objectives: To test further the hypothesis that D[sub 4] receptor blockade can reduce motor hyperactivity, behavioral effects of three chemically and pharmacologically dissimilar D[sub 4] antagonists were compared to that of ketanserin, a serotonin 5-HT[sub 2A/2C] antagonist. Methods: Selective dopamine lesions were made in male rats at postnatal day (PD) 5 with intracisternal 6-hydroxydopamine (100 µg) after desipramine pretreatment (25 mg/kg, SC) to protect noradrenergic neurons. Effects of D[sub 4] receptor-selective antagonists and ketanserin on lesion-induced motor hyperactivity were examined during the periadolescent period (postnatal days 23–26) with an infrared photobeam activity system. Results: The D[sub 4] antagonists L-745,870 and U-101,958 dose-dependently inhibited motor hyperactivity in rats with neonatal lesions, whereas S-18126 lacked this effect at doses up to 30 mg/kg. None of these drugs affected motor behavior in sham control rats. In contrast, ketanserin produced apparent sedative effects in both lesioned and intact control rats without normalizing hyperactivity. Conclusions: Motor hyperactivity in this ADHD model was selectively antagonized by three of four dopamine D[sub 4] receptor antagonists evaluated, encouraging clinical assessment of D[sub 4] antagonists in patients with ADHD. [ABSTRACT FROM AUTHOR]

Presents a study which examined the stereoselective effects of methylphenidate on motor hyperactivity in juvenile rats induced by neonatal 6-hydroxydopamine lesioning. Characteristics of attention deficit-hyperactivity disorder; Experiment on the motor inhibiting effects of d-methylphenidate; Methodology and results.

Tripterygium wilfordii glycosides (TWG) is a traditional Chinese medicine with effectiveness against rheumatoid arthritis (RA), supported by numerous clinical trials. Lipid mediators (LM) are biomolecules produced from polyunsaturated fatty acids mainly by cyclooxygenases (COX) and lipoxygenases (LOX) in complex networks which regulate inflammation and immune responses and are strongly linked to RA. The mechanism by which TWG affects LM networks in RA treatment remains elusive. Employing LM metabololipidomics using ultra-performance liquid chromatography-tandem mass spectrometry revealed striking modulation of LM pathways by TWG in human monocyte-derived macrophage (MDM) phenotypes. In inflammatory M1-MDM, TWG (30 µg/mL) potently suppressed agonist-induced formation of 5-LOX products which was confirmed in human PMNL and traced back to direct inhibition of 5-LOX (IC50 = 2.9 µg/mL). TWG also efficiently blocked thromboxane formation in M1-MDM without inhibiting other prostanoids and COX enzymes. Importantly, in anti-inflammatory M2-MDM, TWG (30 µg/mL) induced pronounced formation of specialized pro-resolving mediators (SPM) and related 12/15-LOX-derived SPM precursors, without COX and 5-LOX activation. During MDM polarization, TWG (1 µg/mL) decreased the capacity to generate pro-inflammatory 5-LOX and COX products, cytokines and markers for M1 phenotypes. Together, suppression of pro-inflammatory LM but SPM induction may contribute to the antirheumatic properties of TWG. [ABSTRACT FROM AUTHOR]

The pentacyclic triterpenoid quinone methide celastrol (CS) from Tripterygium wilfordii Hook. F. effectively ameliorates inflammation with potential as therapeutics for inflammatory diseases. However, the molecular mechanisms underlying the anti-inflammatory and inflammation-resolving features of CS are incompletely understood. Here we demonstrate that CS potently inhibits the activity of human 5-lipoxygenase (5-LOX), the key enzyme in pro-inflammatory leukotriene (LT) formation, in cell-free assays with IC 50 = 0.19–0.49 µM. Employing metabololipidomics using ultra-performance liquid chromatography coupled to tandem mass spectrometry in activated human polymorphonuclear leukocytes or M1 macrophages we found that CS (1 µM) potently suppresses 5-LOX-derived products without impairing the formation of lipid mediators (LM) formed by 12-/15-LOXs as well as fatty acid substrate release. Intriguingly, CS induced the generation of 12-/15-LOX-derived LM including the specialized pro-resolving mediator (SPM) resolvin D5 in human M2 macrophages. Finally, intraperitoneal pre-treatment of mice with 10 mg/kg CS strongly impaired zymosan-induced LT formation and simultaneously elevated the levels of SPM and related 12-/15-LOX-derived LM in peritoneal exudates, spleen and plasma in vivo. Conclusively, CS promotes a switch from LT biosynthesis to formation of SPM which may underlie the anti-inflammatory and inflammation-resolving effects of CS, representing an interesting pharmacological strategy for intervention with inflammatory disorders. [Display omitted] • 5-LOX is a high affinity target for celastrol (CS) with IC 50 of 0.19–0.49 µM. • CS blocks 5-LOX-derived leukotriene formation in PMNL and M1 macrophages. • in M2 macrophages CS elicits specialized pro-resolving mediator (SPM) formation. • CS impairs the levels of leukotrienes but elevates SPM in murine peritonitis. [ABSTRACT FROM AUTHOR]

Background: Attentional deficits accompany many psychiatric disorders, underscoring the need for rodent models of attention to screen novel therapeutic agents and characterize the biological basis of attention. The five-choice serial reaction time task (5CSRTT) is one such model. Here, we characterized the effects of four standard psychotropic agents on performance in the 5CSRTT. Methods: Male Sprague-Dawley rats were trained in the 5CSRTT (5-sec inter-trial interval and .5-sec stimulus duration) until they reliably performed at > 60% accuracy and < 20% omissions. They were then treated systemically with the stimulant methylphenidate (MPH) (.063–2.0 mg/kg), the N-methyl-D-aspartate antagonist dizocilpine (MK-801) (.008–.25 mg/kg), the norepinephrine reuptake inhibitor desipramine (DMI) (.63–10 mg/kg), or the κ-receptor agonist U69,593 (.25–2.0 mg/kg) 30 min before testing. Results: Methylphenidate (.5 mg/kg) increased accuracy. Dizocilpine impaired accuracy (.25 mg/kg), increased premature responses (.063–.25 mg/kg), and increased omissions (.25 mg/kg). Desipramine decreased premature responses (5.0 mg/kg) but increased omissions (10 mg/kg), correct response latencies (5.0–10.0 mg/kg), and reward latencies (5.0–10.0 mg/kg). The κ-opioid agonist U69,593 (1.0–2.0 mg/kg) increased omissions and correct response latencies. Conclusions: In Sprague-Dawley rats, psychotropic drugs with distinct pharmacological profiles produced distinguishable effects in the 5CSRTT. The effects of these classes of drugs under our testing conditions are qualitatively similar to their effects in humans. [Copyright &y& Elsevier]

Abstract: The development of the serotonergic (5HT) and dopaminergic (DA) systems may contribute to the onset of psychotic disorders during late adolescence and early adulthood. Previous studies in our laboratory have suggested that these systems may compete for functional territory on neurons during development, as lesions of the serotonergic system at postnatal day 5 (P5) result in an increase in the density of dopaminergic fibers in rat medial prefrontal cortex (mPFC). In the present study, the dopaminergic system of P5 rats was lesioned with intracisternal injections of 6-hydroxydopamine (6-OHDA). Quantification of serotonin-immunoreactivity (5HT-IR) in mPFC at adulthood (P70) revealed a significant decrease in fiber density within layers II and III of the Cg3 subdivision of mPFC in lesioned rats compared to sham controls. We propose that the decrease in serotonergic fibers in mPFC in response to a neonatal depletion of dopamine may be due to the loss of a trophic effect of this system on 5HT neurons and/or fibers during development. Taken together with previous findings, our data suggest that there may be an “inverse trophic” relationship between the cortical DA and 5HT systems whereby dopamine facilitates the ingrowth of 5HT fibers, while serotonin suppresses the ingrowth of DA fibers. We present a model based on neurotrophic interactions at the cortical and brainstem levels that could potentially explain these unexpected results. [Copyright &y& Elsevier]

We synthesized several N-substituted-11-hydroxynoraporphines and their esters of varying chain length, evaluated their binding affinity at dopamine (DA) receptor sites in rat caudate-putamen membranes, and quantified their effects on motor activity in normal adult male rats. The 11-hydroxyaporphines showed similar neuropharmacological properties to the corresponding 10,11-catecholaporphines. At moderate doses, their esters proved to have more prolonged behavioral actions and superior oral bioavailability. [Copyright &y& Elsevier]

Abstract: We investigated acid-catalyzed rearrangement of thebaine 14 and its N-propyl analog 15 with methanesulfonic acid in the presence of the nucleophiles methanethiol and hydrogen sulfide. R(−)-2-methylthioapocodeine 16, R(−)-2-methylthioapomorphine 18, and their N-n-propyl analogs 17, 19 were obtained by rearrangement in the presence of methanethiol. However, with hydrogen sulfide, rearrangement of thebaine 14 and its N-n-propyl analog 15 produced sulfide-linked bis-aporphines 21–24 instead of expected R(−)-2-mercaptoapocodeines 12, 13 and R(−)-2-mercaptoapomorphines 10, 11. R(−)-2-Methylthio-N-n-propylnorapomorphine 19 had higher affinity (K i =3.7nM) at D2 receptors in rat forebrain tissue than other novel 2-substituted sulfur-containing aporphines (K i ⩾50nM). Behavioral testing of the novel agents in rat indicated moderate locomotor arousal after systemic injection, and none after intragastric administration, indicating poor oral bioavailability. [Copyright &y& Elsevier]

Antipsychotic drugs are often prescribed to juvenile psychiatric patients, though their cerebral effects during development are incompletely described. Accordingly, we studied the effects of repeated treatment with dissimilar antipsychotic drugs on dopamine (DA) receptors in juvenile vs. adult rats. Tissue levels of DA receptor types (D1, D2, D3, and D4) in forebrain regions of juvenile rats were quantified after 3 weeks of daily treatment with representative first- (fluphenazine) and second-generation (clozapine and olanzapine) antipsychotics, and compared with similarly treated adult rats examined in previous studies. Fluphenazine, clozapine, and olanzapine all decreased D1 receptors in dorsolateral frontal and medial prefrontal cortex (MPC) of juvenile, but not adult rats. Conversely, all three test agents increased D2 labeling in MPC of adult, but not young animals. Fluphenazine and olanzapine, but not clozapine, also increased D2 receptor levels in hippocampus, and D4 levels in nucleus accumbens (NAc) and caudate-putamen (CPu) in both juvenile and adult brain. D3 receptors were not altered by any treatment in any brain region at either age. Only some DA receptor adaptations to antipsychotic treatment are shared by developing and mature animals. Developmental differences in DA receptor responses may account for differences in clinical effects of antipsychotic drugs between young and adult psychiatric patients. Synapse 59:92-100, 2006. © 2005 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The preservation of the neuronal circuitry in rat cerebellar slice cultures provides an advantage in monitoring the development and characterizing the pharmacology of GABAA receptor subtypes. Sprague–Dawley rats, 8–11 days of age, were decapitated, their cerebella were cut into 400-μm slices and transferred into culture dishes. Cell viability and organotypic cerebellar organization of the culture remained well preserved up to 3 weeks. Autoradiographic procedures were introduced in these advanced culture technique and employed [3H]Ro 15-4513 in the absence and presence of 10 μM diazepam to visualize all benzodiazepine (BZD) and diazepam-insensitive (DIS) binding sites, respectively. Since expression of the α6 subunit variant of the GABAA/BZD receptor is restricted to the cerebellar granule cells and the BZD receptor agonist diazepam has very low affinity for this subunit, changes in DIS [3H]Ro 15-4513 binding sites during cultivation time can be attributed to changes in α6 subunit expression. A time-dependent development of total and DIS [3H]Ro 15-4513 binding sites were observed in the culture with a trend towards an increase in GABAA receptor α6 subunit levels during the first week. These findings suggest that explant preparations can be used to examine morphological changes in rat cerebellar slices. In addition, these preparations can be utilized to study the pharmacological effects of GABAA/BZD selective drugs on postnatal development of GABAA receptors in rat cerebellum. [Copyright &y& Elsevier]