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Variation in the CACNA1C gene has been associated with bipolar disorder in several genome-wide association studies. This gene encodes the alpha 1C subunit of L-type voltage-gated calcium channels, which play an essential role in neurons. We analysed 39 biomarkers in either cerebrospinal fluid or serum in relation to six different CACNA1C variants in 282 patients with bipolar disorder and 90 controls. We report associations of CACNA1C risk alleles with serum levels of BDNF as well as tissue plasminogen activator, which converts pro-BDNF to mature BDNF. This sheds light on links between CACNA1C genetic variants and pathophysiological mechanisms in bipolar disorder.
Although alterations in the dendritic spine density in the brain regions may play a role in the stress-induced depression-like phenotype, the precise mechanisms are unknown. The aim was to investigate the role of spine density in the brain regions after chronic social defeat stress (CSDS).
We examined dendritic spine density in the medial prefrontal cortex (mPFC), CA1, CA3, dentate gyrus (DG) of hippocampus, nucleus accumbens (NAc), and ventral tegmental area (VTA) of susceptible and resilient mice after CSDS.
Spine density in the prelimbic area of mPFC, CA3, and DG in the susceptible group, but not resilient group, was significantly lower than control group. In contrast, spine density in the NAc and VTA in the susceptible group, but not resilient group, was significantly higher than control group.
The results suggest that regional differences in spine density may contribute to resilience versus susceptibility in mice subjected to CSDS.
The product of the G72 gene is an activator of d-amino acid oxidase and has been suggested to play a role in the pathogenesis of schizophrenia. Increased G72 protein levels may be associated with disturbed glutamatergic transmission and increased reactive oxygen species. Only one pilot study by Lin et al. has investigated the potential role of serum G72 protein levels as a biomarker for schizophrenia. In this study, we aimed to compare serum G72 protein levels between patients with schizophrenia and healthy controls, and to retest the results of the previous pilot study.
Materials and methods
In total, 107 patients with a diagnosis of schizophrenia according to the inclusion and exclusion criteria and 60 age–sex-matched healthy controls were included in the study. The groups were compared regarding serum G72 protein levels.
The mean serum G72 protein values were 495.90±152.03 pg/ml in the schizophrenia group and 346.10±102.08 pg/ml in the healthy control group. The mean serum G72 protein level was significantly increased in the schizophrenia group compared with the healthy control group (t=−3.89, p<0.001). A receiver operating characteristics analysis was performed to compare the schizophrenia and healthy control groups. It was determined that the cut-off value was 141.51 pg/ml with a sensitivity of 0.991 and a specificity of 0.821.
We suggest that serum G72 protein levels may represent a candidate biomarker for schizophrenia and have confirmed the results of the previous preliminary study. Additional studies with larger sample sizes and the inclusion of first episode schizophrenia patients are required to clarify the reliability and validity of serum G72 protein levels as a biomarker for schizophrenia.
Glutamatergic neurotransmission via the N-methyl-d-aspartate (NMDA) receptor is integral to the pathophysiology of depression. This study was performed to examine whether amino acids related to NMDA receptor neurotransmission are altered in the serum of patients with depression.
We measured the serum levels of d-serine, l-serine, glycine, glutamate and glutamine in patients with depression (n=70), and age-matched healthy subjects (n=78).
Serum levels of d-serine and l-serine in patients with depression were significantly higher than those of healthy controls (p<0.001). In contrast, serum levels of glycine, glutamate and glutamine did not differ between the two groups. Interestingly, the ratio of l-serine to glycine in patients was significantly higher than that of healthy controls (p<0.001).
This study suggests that serine enantiomers may be peripheral biomarkers for depression, and that abnormality in the d-serine-l-serine-glycine cycle plays a role in the pathophysiology of depression.
Treatment-resistant depression is a challenging problem in the clinical setting. Tipepidine has been used as a non-narcotic antitussive in Japan since 1959.
We administered tipepidine to 11 patients with treatment-resistant depression. Tipepidine was given for 8 weeks as an augmentation.
Tipepidine significantly improved depression scores on the Hamilton Rating Scale for depression. Add-on treatment with tipepidine significantly improved scores on the trail making test and Rey auditory verbal learning test. However, no changes were observed in blood concentrations of stress-related hormones (adrenocorticotropic hormone, cortisol, dehydroepiandrosterone sulphate) with tipepidine augmentation.
Tipepidine might be a potential therapeutic drug for treatment-resistant depression.
Accumulating evidences suggest that pro-inflammatory cytokines such as interleukin-6 (IL-6) play a role in the pathophysiology of depression. In the learned helplessness (LH) paradigm, ~35% rats are resilient to inescapable stress.
Levels of IL-6 in the serum and medial prefrontal cortex (mPFC) of LH rats (susceptible) and non-LH rats (resilience) were measured using enzyme-linked immunosorbent assay and western blot analysis, respectively.
Serum levels of IL-6 in the LH rats were significantly higher than those of control and non-LH rats. In contrast, tissue levels of IL-6 in the mPFC were not different among three groups.
The results suggest that peripheral IL-6 may contribute to resilience versus susceptibility to inescapable stress.
A recent clinical study demonstrated that sodium benzoate (SB), a prototype competitive d-amino acid oxidase inhibitor, was effective in the treatment of several symptoms, such as positive and negative symptoms, and cognitive impairment in medicated patients with schizophrenia. The objective of the study was to examine the effects of SB on behavioural abnormalities such as pre-pulse inhibition (PPI) deficits and hyperlocomotion in mice after a single administration of the N-methyl-d-aspartate (NMDA) receptor antagonist, phencyclidine (PCP).
The effects of SB on behavioural abnormalities (PPI deficits and hyperlocomotion) in mice after PCP administration were examined. Furthermore, effects of SB on tissue levels of amino acids were also examined.
A single oral dose of SB (100, 300, or 1000 mg/kg) attenuated PPI deficits in mice after administration of PCP (3.0 mg/kg, s.c.) in a dose-dependent manner. In contrast, L-701,324 (10 mg/kg), an antagonist at the glycine site of the NMDA receptor, did not affect the effect of SB (1000 mg/kg) on PCP-induced PPI deficits. Furthermore, a single oral dose of SB (1000 mg/kg) significantly attenuated the hyperlocomotion in mice after administration of PCP (3.0 mg/kg, s.c.). However, a single oral dose of SB (1000 mg/kg) caused no changes to d-serine levels in plasma or in the frontal cortex, hippocampus, and striatum of these animals.
This study suggests that SB induced antipsychotic effects in the PCP model of schizophrenia, although it did not increase d-serine levels in the brain.
We developed a portable ozone-mist sterilization system to exterminate pests (harmful insects) in agricultural field and greenhouse. The system is composed of an ozone generator, an ozone-mist spray and a small container of ozone gas. The ozone generator can supply highly concentrated ozone using the surface dielectric barrier discharge. Ozone-mist is produced using a developed nozzle system. We studied the effects of ozone-mist spray sterilization on insects and agricultural plants. The sterilization conditions are estimated by monitoring the behavior of aphids and observing the damage of the plants. It was shown that aphids were exterminated in 30 s without noticeable damages of the plant leaves. The reactive radicals with strong oxidation potential such as hydroxyl radical (*OH), hydroperoxide radical (*HO2), the superoxide ion radical (*O2‒) and ozonide radical ion (*O3‒) can increase the sterilization rate for aphids.
In this paper, we study finite symplectic actions on K3 surfaces X, that is, actions of finite groups G on X which act on H2,0(X) trivially. We show that the action on the K3 lattice H2(X, ℤ) induced by a symplectic action of G on X depends only on G up to isomorphism, except for five groups.
Hydrogen gas evolution from water dispersing nanoparticles induced by 60Co gamma-ray irradiation was studied. Nanoparticle of TiO2 with average size of 30 nm was examined. It was indicated that the hydrogen yields were affected significantly by pH of the dispersion. Difference in agglomeration could explain the difference in hydrogen yields. Reactions that enhance the hydrogen yields were discussed, and it was concluded that the radiolysis process is dominant in the total enhancement mechanism.
The underlying GaN layers on which laser diodes are fabricated have been improved through two steps. In the first step, GaN single layer on sapphire was investigated. The residual strain and etch pit density were measured. We found that they reflect the optical quality. We found that the threading dislocation can be reduced to 4 × 108 cm−2. The optical quality depends on the residual strain and dislocation density. In the next step, we have utilized epitaxial lateral overgrowth ELO) technique. The optimized GaN layer on sapphire with the smallest dislocation density was used as seed layer. In the wing region of ELO-GaN, the threading dislocation density was reduced to 1 × 106 cm−2. On the other hand, in the seed region, dislocation density remained 4 × 108 cm−2. Photoluminescence intensity in the wing region was three times as large as that in the seed. The laser diodes were fabricated on the ELO-GaN layer, so that the ridge stripe was fabricated over the wing region, and its properties were compared with those of laser diodes on sapphire. It was found that the lifetime can be increased by using the ELO-GaN layer as the underlying layer.
Mechanism and dynamics of the ordering process in oriented crystallization of polymers were investigated by time-resolved small-angle X-ray scattering (SAXS) and wide-angle X-ray diffraction (WAXS). As a model system for the oriented crystallization, a cross-linked polybutadiene rubber with a high cis-1,4-linkage was chosen, and the structure evolution during the isothermal crystallization was investigated under constant elongations by real time and in situ analyses of the microscopic observables such as long spacing, crystallite size, SAXS integrated intensity, WAXS crystallinity and WAXS line width as well as a macroscopic observable such as stress. The isothermal ordering processes were explored in three different crystallization regimes: crystallization from (i) unoriented melts, (ii) weakly-to-moderately oriented melts and (iii) highly oriented melts.
Ammonothermal growth of GaN was studied to determine its eventual utility for mass production of GaN bulk crystals. Dissolution of GaN in supercritical ammonia with 1 M NaNH2 was investigated through a weight loss method. The time dependence of the weight loss was examined at 500°C and 525°C. Since the weight loss did not reach saturation as a function of time, the solubility limit was not realized. However, experiments demonstrate that GaN has a negative temperature dependence of solubility in supercritical ammonobasic solutions. Based on this result, GaN was grown via fluid transport from metallic Ga to a free-standing GaN single crystal seed by placing the seed crystal in a higher temperature zone and the nutrient in a lower temperature zone. GaN films with thickness of 5 μm (Ga face) and 4 μm (N face) were simultaneously grown on the seed in three days. The surface morphology, optical property, and defect density were found to be different for films on Ga face and N face.
Immune dysfunction has been proposed as a mechanism for the pathophysiology
of autistic-spectrum disorders. The selectin family of adhesion molecules
plays a prominent role in immune/inflammatory responses. We determined the
serum levels of three types of soluble-form selectin (sP, sL and sE) in 15
men with high-functioning autism and 22 age-matched healthy controls by
enzyme-linked immunosorbent assay. Levels of sP-selectin and sL-selectin
were significantly lower in patients than in controls. Furthermore,
sP-selectin levels were negatively correlated with impaired social
development during early childhood.
To confirm the presence of apneusis in patients with hypoxic–ischemic encephalopathy and to clarify which factors influence their respiratory patterns, polygraphic studies were performed on two patients. Apneusis was clinically suspected in both patients who had severe brainstem damage. In one subject, inputs of vagal afferents from the gastrointestinal tract and the urinary bladder often resulted in extreme tachypnea instead of apneusis. Lung inflation facilitated expiration during inspiratory arrest. Expiration preceded a periodic inhibition of rigospastic discharge in the right biceps muscle. In the other subject, prolonged inspiratory pauses with cyanosis occurred with or without preceding epileptic seizure. Both phenytoin dose reduction and treatment with tandospirone, a serotonin-1A agonist, were effective in improving the respiratory distress in this subject.
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