Hippocampal excitation-inhibition balance underlies the 5-HT2C receptor in modulating depressive behaviours.

The implication of 5-hydroxytryptamine 2C receptor (5-HT2CR) in depression is a topic of debate, and the underlying mechanisms remain largely unclear. We now elucidate hippocampal excitation-inhibition (E/I) balance underlies the regulatory effects of 5-HT2CR in depression. Molecular biological analyses showed that chronic mild stress (CMS) reduced the expression of 5-HT2CR in hippocampus. We revealed that inhibition of 5-HT2CR induced depressive-like behaviors, reduced GABA release and shifted the E/I balance towards excitation in CA3 pyramidal neurons by using behavioral analyses, microdialysis coupled with mass spectrum, and electrophysiological recording. Moreover, 5-HT2CR modulated neuronal nitric oxide synthase (nNOS)-carboxy-terminal PDZ ligand of nNOS (CAPON) interaction through influencing intracellular Ca2+ release, as determined by fiber photometry and coimmunoprecipitation. Notably, disruption of nNOS-CAPON by specific small molecule compound ZLc-002 or AAV-CMV-CAPON-125C-GFP, abolished 5-HT2CR inhibition-induced depressive-like behaviors, as well as the impairment in soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex assembly-mediated GABA vesicle release and a consequent E/I imbalance. Importantly, optogenetic inhibition of CA3 GABAergic neurons prevented the effects of AAV-CMV-CAPON-125C-GFP on depressive behaviors in the presence of 5-HT2CR antagonist. Conclusively, our findings disclose the regulatory role of 5-HT2CR in depressive-like behaviors and highlight the hippocampal nNOS-CAPON coupling-triggered E/I imbalance as a pivotal cellular event underpinning the behavioral consequences of 5-HT2CR inhibition.

Improving the Accuracy of Direction of Arrival Estimation with Multiple Signal Inputs Using Deep Learning.

In this paper, an innovative cyclic noise reduction method and an improved CAPON algorithm (also the called minimum variance distortionless response (MVDR) algorithm) are proposed to improve the accuracy and reliability of DOA (direction of arrival) estimation. By processing the eigenvalues obtained from the covariance matrix of the received signal, the signal-to-noise ratio (SNR) can be increased by up to 5 dB by the cyclic noise reduction method, which will improve the DOA estimation accuracy. The improved CAPON algorithm has a convolution neural network (CNN) structure, whose input is the processed covariance matrix of the received signal, and the CAPON spectral value is used as the training label to obtain the estimated spatial spectrum. It retains the advantages of the CAPON algorithm, which can achieve blind source estimation, and simulations show that the proposed algorithm exhibits a better performance than the traditional algorithm in conditions of various SNRs and snapshot numbers. The simulation results show that, based on a certain SNR, the root mean square error (RMSE) of the improved CAPON algorithm can be reduced from 0.86° to 0.8° compared to traditional algorithms, and the angle estimation error can be decreased by up to about 0.3°. With the help of the cyclic noise reduction method, the angle estimation error decreases from 0.04° to 0.02°.

Disrupting the Interaction of nNOS with CAPON Prevents the Reinstatement of Morphine Conditioned Place Preference.

Drug abuse is a dramatic challenge for the whole society because of high relapse rate. Environmental cues are crucial for the preference memory of drug abuse. Extinction therapy has been developed to inhibit the motivational effect of drug cues to prevent the reinstatement of morphine abuse. However, extinction therapy alone only forms a new kind of unstable inhibitory memory. We found that morphine conditioned place preference (CPP) extinction training increased the association of nitric oxide synthase (nNOS) with its carboxy-terminal PDZ ligand (CAPON) in the dorsal hippocampus (dHPC) significantly and blocking the morphine-induced nNOS-CAPON association using Tat-CAPON-12C during and after extinction training reversed morphine-induced hippocampal neuroplasticity defect and prevented the reinstatement and spontaneous recovery of morphine CPP. Moreover, in the hippocampal selective ERK2 knock-out or nNOS knockout mice, the effect of Tat-CAPON-12C on the reinstatement of morphine CPP and hippocampal neuroplasticity disappeared, suggesting ERK2 is necessary for the effects of Tat-CAPON-12C. Together, our findings suggest that nNOS-CAPON interaction in the dHPC may affect the consolidation of morphine CPP extinction and dissociating nNOS-CAPON prevents the reinstatement and spontaneous recovery of morphine CPP, possibly through ERK2-mediated neuroplasticity and extinction memory consolidation, offering a new target to prevent the reinstatement of drug abuse.

NOS1AP Interacts with α-Synuclein and Aggregates in Yeast and Mammalian Cells.

The NOS1AP gene encodes a cytosolic protein that binds to the signaling cascade component neuronal nitric oxide synthase (nNOS). It is associated with many different disorders, such as schizophrenia, post-traumatic stress disorder, autism, cardiovascular disorders, and breast cancer. The NOS1AP (also known as CAPON) protein mediates signaling within a complex which includes the NMDA receptor, PSD-95, and nNOS. This adapter protein is involved in neuronal nitric oxide (NO) synthesis regulation via its association with nNOS (NOS1). Our bioinformatics analysis revealed NOS1AP as an aggregation-prone protein, interacting with α-synuclein. Further investigation showed that NOS1AP forms detergent-resistant non-amyloid aggregates when overproduced. Overexpression of NOS1AP was found in rat models for nervous system injury as well as in schizophrenia patients. Thus, we can assume for the first time that the molecular mechanisms underlying these disorders include misfolding and aggregation of NOS1AP. We show that NOS1AP interacts with α-synuclein, allowing us to suggest that this protein may be implicated in the development of synucleinopathies and that its aggregation may explain the relationship between Parkinson's disease and schizophrenia.

Underlying Topography Inversion Using Dual Polarimetric TomoSAR.

Underlying topography plays an important role in the national economic construction, military security, resource exploration and investigation. Since synthetic aperture radar tomography (TomoSAR) can achieve the three-dimensional imaging of forests, it has been widely used in underlying topography estimation. At present, there are two kinds of TomoSAR based on the applied datasets: single polarimetric TomoSAR (SP-TomoSAR) and fully polarimetric TomoSAR (FP-TomoSAR). However, SP-TomoSAR cannot obtain the underlying topography accurately due to the lack of enough observations. FP-TomoSAR can improve the estimation accuracy of underlying topography. However, it requires high-cost data acquisition for the large-scale application. Thus, this paper proposes the dual polarimetric TomoSAR (DP-TomoSAR) as another suitable candidate to estimate the underlying topography because of its wide swath and multiple polarimetric observations. Moreover, three frequently used spectral estimation algorithms, namely, Beamforming, Capon and MUSIC, are used in DP-TomoSAR. For validation, a series of simulated experiments was carried out, and the airborne P-band multiple polarimetric SAR data over the Lope, Gabon was also acquired to estimate the underlying topography. The results suggest that DP-TomoSAR in HH & HV combination is more suitable to estimate underlying topography over forest areas than other DP combinations. Moreover, the estimation accuracy of DP-TomoSAR is slightly lower than that of FP-TomoSAR but is higher than that of SP-TomoSAR.

Systemic administration of ZLc-002 exerts anxiolytic-like effects by dissociation of nNOS from CAPON in adult mice.

Anxiety is recognized as primary clinical phenotype of psychiatric disorders. However, many patients with anxiety have not yet received effective treatment. Our previous study demonstrated that hippocampal nNOS-CAPON interaction is implicated in anxiety-related behaviors, and blocking nNOS-CAPON interaction in the hippocampus produces anxiolytic-like effects. Here, ZLc-002, a small molecule inhibitor of nNOS-CAPON coupling, was evaluated for anxiolytic-like properties after systemic administered using anxiety behavioral tests, including open-field (OF), elevated plus maze (EPM), novelty-suppressed feeding (NSF) and light-dark (LD) tests. We reported that ZLc-002 when administered intraperitoneally at the dose of 40 or 80 mg/kg/d for 14 days produces anxiolytic-like effects. Furthermore, the similar effects of ZLc-002 were observed when administered intravenously at the dose of 10, 20 or 40 mg/kg/d for 7 days. More importantly, the mice dosing with 80 mg/kg/d ZLc-002 intraperitoneally or 40 mg/kg/d ZLc-002 intravenously for 3 days exerted significant behavioral effects. However, intragastric administration with ZLc-002 was devoid of effect on anxiety behaviors, even at high doses. Furthermore, intraperitoneal or intravenous treatment of ZLc-002 significantly disrupted the interaction between nNOS and CAPON in the hippocampus of adult mice, and there was a significant anxiolytic-like effect of ZLc-002 at day 3 after intrahippocampal microinjection. Our results verified that systemic administration of putative small molecule inhibitor of nNOS-CAPON can be used for the treatment of anxiety disorders.

Cascade AOA Estimation Algorithm Based on Flexible Massive Antenna Array.

The Angle-of-Arrival (AOA) has a variety of applications in civilian and military wireless communication fields. Due to the rapid development of the location-based service (LBS) industry, the importance of the AOA estimation technique has increased. Although a large antenna array is necessary to estimate accurate AOA information of many signals, the computational complexity of conventional AOA estimation algorithms, such as Multiple Signal Classification (MUSIC), is dramatically increased. In this paper, we propose a cascade AOA estimation algorithm employing CAPON and Beamspace MUSIC, based on a flexible (on/off) antenna array. First, this approach roughly finds AOA groups, including several signal AOAs using CAPON, by applying some of the antenna elements. Then, it estimates each signal AOA in the estimated AOA groups using Beamspace MUSIC by applying the full size of the antenna array. In addition to extremely low computational complexity, the proposed algorithm also has similar estimation performance to that of MUSIC. In particular, the proposed cascade AOA estimation algorithm is highly efficient when employing a massive antenna array. Representative computer simulation examples are provided to illustrate the AOA estimation performance of the proposed technique.

Dissociating nNOS (Neuronal NO Synthase)-CAPON (Carboxy-Terminal Postsynaptic Density-95/Discs Large/Zona Occludens-1 Ligand of nNOS) Interaction Promotes Functional Recovery After Stroke via Enhanced Structural Neuroplasticity.

Background and Purpose- Stroke is a major public health concern worldwide. Although clinical treatments have improved in the acute period after stroke, long-term therapeutics remain limited to physical rehabilitation in the delayed phase. This study is aimed to determine whether nNOS (neuronal NO synthase)-CAPON (carboxy-terminal postsynaptic density-95/discs large/zona occludens-1 ligand of nNOS) interaction may serve as a new therapeutic target in the delayed phase for stroke recovery. Methods- Photothrombotic stroke and transient middle cerebral artery occlusion were induced in mice. Adeno-associated virus (AAV)-cytomegalovirus (CMV)-CAPON-125C-GFP (green fluorescent protein)-3Flag and the other 2 drugs (Tat-CAPON-12C and ZLc-002) were microinjected into the peri-infarct cortex immediately and 4 to 10 days after photothrombotic stroke, respectively. ZLc-002 was also systemically injected 4 to 10 days after transient middle cerebral artery occlusion. Grid-walking task and cylinder task were conducted to assess motor function. Western blotting, immunohistochemistry, Golgi staining, and electrophysiology recordings were performed to uncover the mechanisms. Results- Stroke increased nNOS-CAPON association in the peri-infarct cortex in the delayed period. Inhibiting the ischemia-induced nNOS-CAPON association substantially decreased the number of foot faults in the grid-walking task and forelimb asymmetry in the cylinder task, suggesting the promotion of functional recovery from stroke. Moreover, dissociating nNOS-CAPON significantly facilitated dendritic remodeling and synaptic transmission, indicated by increased dendritic spine density, dendritic branching, and length and miniature excitatory postsynaptic current frequency but did not affect stroke-elicited neuronal loss, infarct size, or cerebral edema, suggesting that nNOS-CAPON interaction may function via regulating structural neuroplasticity, rather than neuroprotection. Furthermore, ZLc-002 reversed the transient middle cerebral artery occlusion-induced impairment of motor function. Conclusions- Our results reveal that nNOS-CAPON coupling can serve as a novel pharmacological target for functional restoration after stroke.

Effects of caponisation and age on the histology of the internal organs of Leghorn cockerels.

1. Poultry researchers seek the most efficient bird line to produce capons (castrated cockerels). The previous studies did not include results from histopathological analyses of internal organs after caponisation. No data have been published on whether adipose tissue accumulates in internal organs or if caponisation changes the structure of the lymphoid organs and the accumulation of lymphoid cells. 2. The aim of this study was to analyse the occurrence of histopathological lesions in internal organs from Leghorn (layer-type) capons and cockerels at different times of fattening. 3. Two hundred, one-day-old Leghorn cockerels were used in this experiment. At 8 weeks of age, the birds were randomly divided into a control group (100 uncastrated cockerels) and a second group consisting of 100 castrated birds. At 12, 16, 20, 24 and 28 weeks of age, six cockerels and six capons were slaughtered. Samples of all internal organs from six cockerels and six capons at each slaughter age were evaluated. 4. The main histopathological differences between capons and cockerels were related to the accumulation of adipose tissue, with higher values noted in capons, especially in the gizzard and the caecum submucosa and fatty degeneration in liver hepatocytes. 5. Additionally, differences were observed more often in cockerels than in capons with regard to depletion of lymphoid cells in lymphoid organs, including the thymus and bursa of Fabricius in 28-week-old birds and the spleen in 24-week-old birds. 6. These studies prove that caponisation causes the accumulation of fat in internal organs and changes the structure of lymphoid organs. 7. Age influences the occurrence of desirable lesions, such as the accumulation of adipose tissue within the examined organs, and older capons (24 and 28 weeks old) are better sources of high quality, potentially edible tissues.

Decreased testosterone levels after caponization leads to abdominal fat deposition in chickens.

BACKGROUND: Caponization results in reduced androgen levels, which leads to abdominal fat accumulation in capons. In this study, we sought to understand the molecular mechanisms behind this fat accumulation. RESULTS: Abdominal fat (AF) content increased significantly (P < 0.05) and serum and AF testosterone levels decreased significantly (P < 0.05 or P < 0.01) after caponization. In AF tissue, 90 differentially expressed genes related to lipid metabolism were screened by gene expression profiling in caponized and sham-treated chickens. Among these, six representative genes were significantly up-regulated (APOA1, SCD, FABP7, RXRG, and FADS2) or down-regulated (FABP3) (P < 0.05 or P < 0.01) and were strongly associated with the PPAR pathway. In addition, cell junction pathways were also enriched. In vitro, Fat content was significantly lower in cells treated with testosterone compared with control cells (P < 0.01), and mRNA levels of RXRG, FABP7, and FABP3 changed accordingly, confirming the effect of testosterone on fat deposition. CONCLUSIONS: The results of this study indicate that testosterone reduction likely regulates gene expression through PPAR and cell junction pathways resulting in increased fat accumulation. These results provide increase our understanding of the biological mechanisms by which caponization induces greater fat accumulation.

Hippocampal nuclear factor kappa B accounts for stress-induced anxiety behaviors via enhancing neuronal nitric oxide synthase (nNOS)-carboxy-terminal PDZ ligand of nNOS-Dexras1 coupling.

Anxiety disorders are associated with a high social burden worldwide. Recently, increasing evidence suggests that nuclear factor kappa B (NF-κB) has significant implications for psychiatric diseases, including anxiety and depressive disorders. However, the molecular mechanisms underlying the role of NF-κB in stress-induced anxiety behaviors are poorly understood. In this study, we show that chronic mild stress (CMS) and glucocorticoids dramatically increased the expression of NF-κB subunits p50 and p65, phosphorylation and acetylation of p65, and the level of nuclear p65 in vivo and in vitro, implicating activation of NF-κB signaling in chronic stress-induced pathological processes. Using the novelty-suppressed feeding (NSF) and elevated-plus maze (EPM) tests, we found that treatment with pyrrolidine dithiocarbamate (PDTC; intra-hippocampal infusion), an inhibitor of NF-κB, rescued the CMS- or glucocorticoid-induced anxiogenic behaviors in mice. Microinjection of PDTC into the hippocampus reversed CMS-induced up-regulation of neuronal nitric oxide synthase (nNOS), carboxy-terminal PDZ ligand of nNOS (CAPON), and dexamethasone-induced ras protein 1 (Dexras1) and dendritic spine loss of dentate gyrus (DG) granule cells. Moreover, over-expression of CAPON by infusing LV-CAPON-L-GFP into the hippocampus induced nNOS-Dexras1 interaction and anxiety-like behaviors, and inhibition of NF-κB by PDTC reduced the LV-CAPON-L-GFP-induced increases in nNOS-Dexras1 complex and anxiogenic-like effects in mice. These findings indicate that hippocampal NF-κB mediates anxiogenic behaviors, probably via regulating the association of nNOS-CAPON-Dexras1, and uncover a novel approach to the treatment of anxiety disorders.

DOA Estimation for Underwater Target by Active Detection on Virtual Time Reversal Using a Uniform Linear Array.

Aiming at addressing the problem caused by multipath effects in direction of arrival (DOA) estimation for underwater targets, a method based on the active detection on virtual time reversal (ADVTR) Capon algorithm is proposed. Unlike the conventional passive target estimation method ignoring the multipath effects but only considering the direct wave, the proposed method is closer to the actual situation in that the multipath signal propagation model is fully taken into account; in addition, active detection (AD) and virtual time reversal (VTR) processes are added, which use active detection to estimate channels, and virtual time reversal to realize focusing in a computer after the source-receive array (SRA) receives the reflected signal of the target. The combination of the two methods can greatly improve the energy of SRA and the precision of target direction estimation. With the popular acoustic field simulation tool Bellhop, the model proposed in this paper is verified. Compared with the conventional Capon method without time reversal, the simulation results show that the ADVTR Capon estimation method is far better, in terms of resolution and suppressing the sidelobes. It is suitable for the target DOA estimation under low signal-to-noise ratio (SNR) conditions. Further, we also show the ADVTR Capon estimation method works well in a real tank experiment.

The role of Capon in multiple myeloma.

Capon is a ligand protein of nitric oxide synthase 1. Recently, studies have shown that Capon is involved in the development of tumors. It is independent of the regulation of nitric oxide synthase 1 in this process. At the same time, studies have found that nitric oxide synthase 1 is expressed in multiple myeloma, but its role in the development and progression of myeloma remains unclear. In this study, we found that there was a different expression of Capon between the normal multiple myeloma cells and the adherent multiple myeloma cells. In the process of myeloma cell proliferation, the reduced expression of Capon reduces the arrest of the cell cycle in the G1 phase and promotes the proliferation of myeloma cells. Cell adhesion-mediated drug resistance is one of the most important factors, which affect the chemotherapy effect of multiple myeloma. If the expression of Capon is decreased, myeloma cells are adhered to fibronectin or bone marrow stromal cells (bone marrow mesenchymal stem cells). In addition, the sensitivity of the cell line to chemotherapeutic agents was reduced after silencing Capon in the myeloma cell line which was adhered to bone marrow mesenchymal stem cells. We also found that reduced expression of Capon resulted in the activation of the AKT signaling pathway. In conclusion, these results may be helpful in studying the role of Capon in multiple myeloma.

Unexpected Heterodivalent Recruitment of NOS1AP to nNOS Reveals Multiple Sites for Pharmacological Intervention in Neuronal Disease Models.

The protein NOS1AP/CAPON mediates signaling from a protein complex of NMDA receptor, PSD95 and nNOS. The only stroke trial for neuroprotectants that showed benefit to patients targeted this ternary complex. NOS1AP/nNOS interaction regulates small GTPases, iron transport, p38MAPK-linked excitotoxicity, and anxiety. Moreover, the nos1ap gene is linked to disorders from schizophrenia, post-traumatic stress disorder, and autism to cardiovascular disorders and breast cancer. Understanding protein interactions required for NOS1AP function, therefore, has broad implications for numerous diseases. Here we show that the interaction of NOS1AP with nNOS differs radically from the classical PDZ docking assumed to be responsible. The NOS1AP PDZ motif does not bind nNOS as measured by multiple methods. In contrast, full-length NOS1AP forms an unusually stable interaction with nNOS. We mapped the discrepancy between full-length and C-terminal PDZ motif to a novel internal region we call the ExF motif. The C-terminal PDZ motif, although neither sufficient nor necessary for binding, nevertheless promotes the stability of the complex. It therefore potentially affects signal transduction and suggests that functional interaction of nNOS with NOS1AP might be targetable at two distinct sites. We demonstrate that excitotoxic pathways can be regulated, in cortical neuron and organotypic hippocampal slice cultures from rat, either by the previously described PDZ ligand TAT-GESV or by the ExF motif-bearing region of NOS1AP, even when lacking the critical PDZ residues as long as the ExF motif is intact and not mutated. This previously unrecognized heterodivalent interaction of nNOS with NOS1AP may therefore provide distinct opportunities for pharmacological intervention in NOS1AP-dependent signaling and excitotoxicity.

The analysis of meat traits of Sussex cockerels and capons (S11) at different ages.

The aim of the study was to compare Sussex cockerels and capons as well as to estimate the influence of age on slaughter yield and meat quality. The tests were performed on cockerels and capons from strain S11 (Sussex). At 16, 18, and 20 wk of age, a dissection of the entire carcass was conducted. The breast and leg muscles were tested for physio-chemical traits, as well as chemical parameters. It was noted that, due to significant differences in BW of the eviscerated carcasses between wk 18 and 20 of slaughter, the best time to cease rearing S11 cockerels could be wk 20. However, for S11 capons, the optimal time for slaughter appeared to be wk 18 (no significant differences in BW and carcass weight or musculature between wk 18 and 20). The trait which did not differ between cockerels and capons slaughtered at different ages was slaughter yield. Fatness of the cockerels increased with age whilst the weight of capons' skin with subcutaneous fat was the same at wk 18 and 20 of evaluation. With increasing age, pH indicators of cockerels and capons' breast muscles were increasing; the water holding capacity of capons' breast muscles were also increasing. Both cockerels and capons showed darker color of breast muscle at wk 20 compared to wk 16 of evaluation. Redness of the breast muscle in the following periods of evaluation did not show significant differences, although with age, the yellowness of the cockerels and capons' breast muscle increased significantly. Among cockerels and capons, the water content in the breast and leg muscles were decreasing with age whilst the protein content was increasing. A significant growing tendency of the percentage of fat share in the breast and leg muscles with age was noted in the capon group. Conclusions for breeding practice are as follows: due to meat and quality traits, Sussex cockerels and capons can be used until wk 18 or 20 of life.

Physicochemical composition and sensory quality evaluation of capon and rooster meat.

The aim of the present study was to evaluate the effect of caponization on the physicochemical and sensory characteristics of rooster and capon meat (2 Portuguese autochthonous chicken breeds of roosters:Amarela and Pedrês), raised under the same production. The birds were castrated at 9 wk of age and bred until 140 d of age. Forty Amarela (20 roosters and 20 capons-castrated male) and 40 Pedrês Portuguesa (20 roosters and 20 capons) breed chickens, 5 free-range chickens, and 5 broilers were used. From the breast, leg, and wing muscles, physicochemical parameters such as pH, water activity (aw), physical color, moisture content, ash, CP, pigments, collagen, and total fat and fatty acids profile, were analyzed according to standard procedures. Caponization did not affect pH, aw, lightness (L*), yellowness (b*), ash, protein, collagen, saturated fatty acids (SFA), polyunsaturated fatty acids (PUFA), and the ratio of unsaturated fatty acids (UFA)/SFA. Results show that caponization decreased (P≤0.05) moisture content and increased (P≤0.05) pigments and intramuscular fat content. Capons showed higher (P≤0.001) redness (a*) and chroma (C*), and lower (P≤0.001) hue (H*) compared to roosters. Caponization increased (P≤0.05) monounsaturated fatty acids content and PUFA/SFA. The main fatty acids found were oleic (C18:1), palmitic (C16:0), and linoleic (C18:2). Capons had greater (P≤ 0.05) C18:1 content but lower (P≤0.01) butyric acid (C4:0), caprylic acid (C8:0), stearic acid (C18:0), and (P≤0.05) arachidonic acid (C20.4) content than roosters. The objective of sensory analysis was making the comparison of the Amarela and Pedrêsmeat with a free-range chicken and a broiler. Panelists classified the capon meat (Amarela and Pedrês) as juicier and less tough and fibrous than rooster meat. Broilers were in general juicier, tenderer, and less fibrous than the other chickens in this study. The results of sensory evaluation complement those obtained in physicochemical analysis, suggesting that caponization promotes an overall improvement in meat quality.

Low Expression of CAPON in Glioma Contributes to Cell Proliferation via the Akt Signaling Pathway.

CAPON is an adapter protein for nitric oxide synthase 1 (NOS1). CAPON has two isoforms in the human brain: CAPON-L (long form of CAPON) and CAPON-S (short form of CAPON). Recent studies have indicated the involvement of CAPON in tumorigenesis beyond its classical role in NOS1 activity regulation. In this study, we found that the protein levels of CAPON-S, but not than CAPON-L, were significantly decreased in glioma tissues. Therefore, we established lentivirus-mediated stable cell lines with CAPON-S overexpression or down-regulation, and investigated the role of CAPON-S in the proliferation of glioma cells by using CCK8, EdU, and flow cytometry assays. Overexpression of CAPON-S reduced the cell variability and the percentage of EdU-positive cells, and arrested the cells in the G1 phase in glioma cells. Silencing of CAPON by short-hairpin RNA showed the opposite effects. Furthermore, an intracellular signaling array revealed that overexpression of CAPON-S resulted in a remarkable reduction in the phosphorylation of Akt and S6 ribosomal protein in glioma cells, which was further confirmed by Western blot. These findings suggest that CAPON may function as a tumor suppressor in human brain glioma and that the inactivation of the Akt signaling pathway caused by CAPON-S overexpression may provide insight into the underlying mechanism of CAPON in glioma cell proliferation.

Physicochemical characteristics of meat from capons derived from the crossing of conserved breed hens and meat roosters.

The study aimed to determine the effect of castration on physicochemical properties of meat from capons derived from the crossing of Rhode Island Red (R-11) hens and meat roosters. Subjects were 100 crossbred cockerels, which were randomly assigned to 2 groups of 50 each. Group I (control) consisted of intact cockerels and birds from group II were subjected to castration. The castration was performed at 7 wk of age under local anesthesia by a veterinarian. All birds were fed ad libitum with the same feed mixtures and placed on litter under optimal environmental conditions at a stocking density of 5 birds/m2. At the end of fattening (20 wk of age), 10 birds whose body weight was similar to group average, were selected from each group for slaughter. After slaughter, the birds were analyzed for dressing percentage and physicochemical parameters of breast and leg muscles, which were subjected to sensory evaluation. The results demonstrated that compared to intact cockerels, capons were characterized by significantly higher body weight, dressing percentage and carcass muscle content. Both the breast and leg muscles of the capons showed better physicochemical parameters and higher sensory score. It is therefore concluded that the birds derived from the crossing of Rhode Island Red (R-11) hens and meat roosters are good material for capon production, their meat is a product of distinctly higher quality.

nNOS and Neurological, Neuropsychiatric Disorders: A 20-Year Story.

In the central nervous system, nitric oxide (NO), a free gas with multitudinous bioactivities, is mainly produced from the oxidation of L-arginine by neuronal nitric oxide synthase (nNOS). In the past 20 years, the studies in our group and other laboratories have suggested a significant involvement of nNOS in a variety of neurological and neuropsychiatric disorders. In particular, the interactions between the PDZ domain of nNOS and its adaptor proteins, including post-synaptic density 95, the carboxy-terminal PDZ ligand of nNOS, and the serotonin transporter, significantly influence the subcellular localization and functions of nNOS in the brain. The nNOS-mediated protein-protein interactions provide new attractive targets and guide the discovery of therapeutic drugs for neurological and neuropsychiatric disorders. Here, we summarize the work on the roles of nNOS and its association with multiple adaptor proteins on neurological and neuropsychiatric disorders.

Disrupting the nNOS/NOS1AP interaction in the medial prefrontal cortex impairs social recognition and spatial working memory in mice.

The neuronal isoform of nitric oxide synthase (nNOS) and its interacting protein NOS1AP have been linked to several mental disorders including schizophrenia and depression. An increase in the interaction between nNOS and NOS1AP in the frontal cortex has been suggested to contribute to the emergence of these disorders. Here we aimed to uncover whether disruption of their interactions in the frontal cortex leads to mental disorder endophenotypes. Targeting the medial prefrontal cortex (mPFC), we stereotaxically injected wild-type C57BL/6J mice with recombinant adeno-associated virus (rAAV) expressing either full-length NOS1AP, the nNOS binding region of NOS1AP (i.e. NOS1AP396-503), or the nNOS amino-terminus (i.e. nNOS1-133), which was shown to disrupt the interaction of endogenous nNOS with PSD-95. We tested these mice in a comprehensive behavioural battery, assessing different endophenotypes related to mental disorders. We found no differences in anxiety-related and exploratory behaviours. Likewise, social interaction was comparable in all groups. However, social recognition was impaired in NOS1AP and NOS1AP396-503 mice. These mice, as well as mice overexpressing nNOS1-133 also displayed impaired spatial working memory (SWM) capacity, while spatial reference memory (SRM) remained intact. Finally, mice overexpressing NOS1AP and nNOS1-133, but not NOS1AP396-503, failed to habituate to the startling pulses in an acoustic startle response (ASR) paradigm, though we found no difference in overall startle intensity or prepulse inhibition (PPI) of the ASR. Our findings indicate a distinct role of NOS1AP/nNOS/PSD-95 interactions in the mPFC to contribute to specific endophenotypic changes observed in different mental disorders.