Search

More than 50% of the images captured by optical satellites are covered by clouds, which reduces the available information in the images and seriously affects the subsequent applications of satellite images. Therefore, the identification and segmentation of cloud regions come to be one of the most important problems in current satellite image processing. Due to the complexity and variability of satellite images, especially when the ground is covered with snow, the boundary information of cloud regions is difficult to be accurately identified. The fast and accurate segmentation of cloud regions is a difficult point in the current research. We propose a lightweight convolutional neural network. Firstly, channel attention is used to optimize the effective information in the feature maps as a way to improve the network's ability to extract semantic information at each scale. Then, we fuse high and low-dimensional feature maps to enhance the network's ability to obtain small-scale semantic information. In addition, the feature aggregation module automatically adjusts the input multi-level feature weights to highlight the details of different features. Finally, we design the fully connected conditional random field to solve the problem that some noise in the input image and local minima during training is passed to the output layer resulting in the loss of edge features. Experimental results show that the proposed method achieves 0.9695 and 0.8218 for overall accuracy and recall, respectively, which has higher segmentation accuracy with the shortest time consumption compared with other state-of-the-art methods.

Extracting features of retinal vessels from fundus images plays an essential role in computer-aided diagnosis of diseases, such as diabetes, hypertension, and cerebrovascular diseases. Although a number of deep learning-based methods have been used in this field, the accuracy of retinal vessel segmentation remains challenging due to limited densely annotated data, inter-vessel differences, and structured prediction problems, especially in areas of small blood vessels and the optic disk. In this paper, we propose an ARN model with a atrous block to address these issues, which can avoid the loss of data structure, and enlarge the receptive field, so that each convolution output contains a larger range of information. In addition, we also introduce residual convolution network to increase the network depth and improve the network performance.Some key parameters are used to measure the feasibility of the model, such as sensitivity (Se), specificity (Sp), F1-score (F1), accuracy (Acc), and area under each curve (AUC). Experimental results on two benchmark datasets demonstrate the effectiveness of the proposed methods, which accuracy are 0.9686 on the DRIVE and 0.9746 on the CHASE DB1. The segmentation structure can assist the doctor in diagnosis more effectively.

Tropical forests are one of the main carbon sinks on Earth, but the magnitude of CO2 absorbed by tropical vegetation remains uncertain. Terrestrial biosphere models (TBMs) are commonly used to estimate the CO2 absorbed by forests, but their performance is highly sensitive to the parameterization of processes that control leaf-level CO2 exchange. Direct measurements of leaf respiratory and photosynthetic traits that determine vegetation CO2 fluxes are critical, but traditional approaches are time-consuming. Reflectance spectroscopy can be a viable alternative for the estimation of these traits and, because data collection is markedly quicker than traditional gas exchange, the approach can enable the rapid assembly of large datasets. However, the application of spectroscopy to estimate photosynthetic traits across a wide range of tropical species, leaf ages and light environments has not been extensively studied. Here, we used leaf reflectance spectroscopy together with partial least-squares regression (PLSR) modeling to estimate leaf respiration (Rdark25), the maximum rate of carboxylation by the enzyme Rubisco (Vcmax25), the maximum rate of electron transport (Jmax25), and the triose phosphate utilization rate (Tp25), all normalized to 25°C. We collected data from three tropical forest sites and included leaves from fifty-three species sampled at different leaf phenological stages and different leaf light environments. Our resulting spectra-trait models validated on randomly sampled data showed good predictive performance for Vcmax25, Jmax25, Tp25 and Rdark25 (RMSE of 13, 20, 1.5 and 0.3 μmol m-2 s-1, and R2 of 0.74, 0.73, 0.64 and 0.58, respectively). The models showed similar performance when applied to leaves of species not included in the training dataset, illustrating that the approach is robust for capturing the main axes of trait variation in tropical species. We discuss the utility of the spectra-trait and traditional gas exchange approaches for enhancing tropical plant trait studies and improving the parameterization of TBMs.

The gently inclined medium-thick orebody is generally viewed as difficult to extract. This paper presents a sublevel open stoping using long-hole with back filling method, particularly for inclined medium-thick orebodies. This method not only changes the temporal sequence of ore stoping and realizes transportation using gravity and trackless devices, but also improves production capacity and efficiency. Nonetheless, this method also has some disadvantages; for example, the orebody has more contact with country rock, and the method has a more complex loss and dilution process. This paper starts with the analysis of the results of physical simulation experiments that examine the interactive relationship among the lower stope footwall dip angle, the footwall surface roughness, draw point interval and production blast ring and concludes their influence on the ore-recovery ratio in each production cycle. Secondly, based on physical simulation results, the multivariate linear fit was carried out on the SPSS using the dimensional analysis method. Thus a statistical model was developed for investigating the influence of gently inclined medium thick orebody, the footwall dip angle, the footwall roughness and interval of draw points on the recovery ratio, which can accurately forecast the ore-recovery ratio under different parameters in the physical simulation process. The optimal structural parameters obtained from physical simulation and statistical analysis was then applied to industrial experiments. Based on the 3D laser scanning during in-suit experiments, it was found that the lower stope had an 82% recovery ratio and an 18% dilution ratio, while the upper stope had a recovery ratio of 85% and a dilution ratio of 12%. Moreover, the production capacity could be up to 600t/d. The physical simulation and industrial experiments both demonstrate that the new mining method can be adopted for the safe and efficient mining of gently inclined medium-thick orebodies.

Cognitive impairment has been observed in patients with major depressive disorder (MDD). However, it remains unclear whether the deficits in specific cognitive domains are present in first-episode, drug-naïve patients or medicated patients. In the present study, using the CogState battery (CSB) Chinese language version, we evaluated the visual, working, and verbal memory in first-episode drug-naive patients and medicated patients with MDD in a Chinese population. We measured the cognitive function in first-episode drug-naïve patients (n = 36), medicated MDD patients (n = 71), and age- and sex-matched healthy control subjects (n = 59) in a Chinese population. The CSB composite scores in both first-episode drug-naive patients and medicated patients were significantly poorer than those in the healthy control subjects. The CSB sub-scores, including visual, working, and verbal memory were also significantly poorer in both patient groups than those in the healthy control subjects. In contrast, processing speed, attention/vigilance, executive function, spatial working memory, and social cognition were no different from healthy controls, whereas the executive function was significantly better in the medicated patients than in the healthy control subjects and first-episode drug-naïve patients. These findings suggest an impairment in the visual, working, and verbal memory in first-episode, drug-naive MDD patients in a Chinese population.

Failure detectors are one of the fundamental components for maintaining the high availability of vehicular cloud computing. In vehicular cloud computing, lots of RSUs are deployed along the road to improve the connectivity. Many of them are equipped with solar battery due to the unavailability or excess expense of wired electrical power. So it is important to reduce the battery consumption of RSU. However, the existing failure detection algorithms are not designed to save battery consumption RSU. To solve this problem, a new energy-efficient failure detector 2E-FD has been proposed specifically for vehicular cloud computing. 2E-FD does not only provide acceptable failure detection service, but also saves the battery consumption of RSU. Through the comparative experiments, the results show that our failure detector has better performance in terms of speed, accuracy and battery consumption.

Failure detectors are used to build high availability distributed systems as the fundamental component. To meet the requirement of a complicated large-scale distributed system, accrual failure detectors that can adapt to multiple applications have been studied extensively. However, several implementations of accrual failure detectors do not adapt well to the cloud service environment. To solve this problem, a new accrual failure detector based on Weibull Distribution, called the Weibull Distribution Failure Detector, has been proposed specifically for cloud computing. It can adapt to the dynamic and unexpected network conditions in cloud computing. The performance of the Weibull Distribution Failure Detector is evaluated and compared based on public classical experiment data and cloud computing experiment data. The results show that the Weibull Distribution Failure Detector has better performance in terms of speed and accuracy in unstable scenarios, especially in cloud computing.

Aquaporin 5 (AQP5) participates in the migration of endometrial cells. Elucidation of the molecular mechanisms associated with AQP5-mediated, migration of endometrial cells may contribute to a better understanding of endometriosis. Our objectives included identifying the estrogen-response element (ERE) in the promoter region of the AQP5 gene, and, investigating the effects of AQP5 on ectopic implantation of endometrial cells. Luciferase reporter assays and electrophoretic mobility shift assay (EMSA) identified the ERE-like motif in the promoter region of the AQP5 gene. After blocking and up-regulating estradiol (E2) levels, we analysed the expression of AQP5 in endometrial stromal (ES) cells. After blocking E2 /or phosphatidylinositol 3 kinase(PI3K), we analysed the role of AQP5 in signaling pathways. We constructed an AQP5, shRNA, lentiviral vector to knock out the AQP5 gene in ES cells. After knock-out of the AQP5 gene, we studied the role of AQP5 in cell invasion, proliferation, and the formation of ectopic endometrial implants in female mice. We identified an estrogen-response element in the promoter region of the AQP5 gene. Estradiol (E2) increased AQP5 expression in a dose-dependent fashion, that was blocked by ICI182,780(an estrogen receptor inhibitor). E2 activated PI3K /protein kinase B(AKT) pathway (PI3K/AKT), that, in turn, increased AQP5 expression. LY294002(PI3K inhibitor) attenuated estrogen-enhanced, AQP5 expression. Knock-out of the AQP5 gene with AQP5 shRNA lentiviral vector significantly inhibited E2-enhanced invasion, proliferation of ES cells and formation of ectopic implants. Estrogen induces AQP5 expression by activating ERE in the promoter region of the AQP5gene, activates the PI3K/AKT pathway, and, promotes endometrial cell invasion and proliferation. These results provide new insights into some of the mechanisms that may underpin the development of deposits of ectopic endometrium.

To investigate the soil heavy metal pollution characteristics and ecological risk factors, 42 samples and six typical soil profiles were collected from the Shenyang industrial district in northeast China and were analyzed for contents of titanium (Ti), copper (Cu), lead (Pb), zinc (Zn), cobalt (Co), nickel (Ni), chromium (Cr) and arsenic (As). Through statistical analysis, it was found that the mean concentrations were higher than their background values (Ti = 4.77>3.8g/kg, Cu = 33.75>22.6 mg/kg, Pb = 45.95>26 mg/kg, Zn = 81.54>74.2 mg/kg, Co = 12.91>12.7 mg/kg, Ni = 32.26>26.9 mg/kg, Cr = 83.36>61 mg/kg and As = 13.69>11.2 mg/kg) but did not exceed their corresponding pollution limits for the Chinese Environmental Quality Standard for Soils (State Environmental Protection Administration of China, 1995). There were contamination hotspots that may be caused by human activities such as smelting plants and sewage irrigation. The Enrichment Factor and Ecological Risk Index were used to identify the anthropogenic contamination and ecological risks of heavy metals. Soil in the study area could be considered lightly or partially polluted by heavy metals. According to clustering analysis, distinct groups of heavy metals were discriminated between natural or anthropogenic sources.

Proteus mirabilis isolates commonly have decreased susceptibility to imipenem. Previously, we found P. mirabilis hfq mutant was more resistant to imipenem and an outer membrane protein (OMP) could be involved. Therefore, we investigated the role of this OMP in carbapenem susceptibility. By SDS-PAGE we found this OMP (named ImpR) was increased in hfq mutant and LC-MS/MS revealed it to be the homologue of Salmonella YbfM, which is a porin for chitobiose and subject to MicM (a small RNA) regulation. We demonstrated that ImpR overexpression resulted in increased carbapenem MICs in the laboratory strain and clinical isolates. Chitobiose induced expression of chb (a chitobiose utilization operon). Real-time RT-PCR and SDS-PAGE were performed to elucidate the relationship of hfq, impR, chb and MicM in P. mirabilis. We found MicM RNA was decreased in hfq mutant and chbBC-intergenic region (chbBC-IGR) overexpression strain (chbIGRov), while impR mRNA was increased in hfq mutant, micM mutant and chbIGRov strain. In addition, mutation of hfq or micM and overexpression of chbBC-IGR increased ImpR protein level. Accordingly, chitobiose made wild-type have higher levels of ImpR protein and are more resistant to carbapenems. Hfq- and MicM-complemented strains restored wild-type MICs. Mutation of both impR and hfq eliminated the increase in carbapenem MICs observed in hfq mutant and ImpR-complementation of hfq/impR double mutant resulted in MICs as hfq mutant, indicating that the ImpR-dependent decreased carbapenem susceptibility of hfq mutant. These indicate MicM was antisense to impR mRNA and was negatively-regulated by chbBC-IGR. Together, overexpression of ImpR contributed to the decreased carbapenem susceptibility in P. mirabilis.

Inflammation is now believed to be responsible for coronary heart disease (CHD). This belief has stimulated the evaluation of various inflammatory markers for predicting CHD. This study was designed to investigate the association between four inflammatory cytokines (CD121a, interleukin [IL]-1β, IL-8, and IL-11) and CHD. Here, we evaluated 443 patients with CHD and 160 CHD-free controls who underwent coronary angiography. Cytokines were evaluated using flow cytometry, and statistical analyses were performed to investigate the association between cytokine levels and the risk of CHD. Patients with CHD had significantly higher levels of CD121a. The odds ratios for CHD according to increasing CD121a quartiles were 1.00, 1.47 [95% confidence interval (CI): 0.79-2.72], 2.67 (95% CI: 1.47-4.84), and 4.71 (95% CI: 2.65-8.37) in an age- and sex-adjusted model, compared to 1.00, 1.48 (95% CI: 0.70-3.14), 2.25 (95% CI: 1.10-4.62), and 4.39 (95% CI: 2.19-8.79) in a model that was adjusted for multiple covariates. A comparison of the stable angina, unstable angina, and acute myocardial infarction (AMI) subgroups revealed that patients with AMI had the highest CD121a levels, although IL-1β levels were similar across all groups. IL-8 levels were also increased in AMI patients, and IL-11 levels were higher in CHD patients than in non-CHD patients. Correlation analysis revealed a positive association between CD121a, IL-8, and the Gensini score. Together, the significant increase in CD121a levels among CHD patients suggests that it may be a novel inflammatory marker for predicting CHD.

The concentrations of heavy metals (mercury (Hg), cadmium (Cd), lead (Pb), chromium (Cr), copper (Cu) and arsenic (As)) in surface water and sediments were investigated in two adjacent drinking water reservoirs (Hongfeng and Baihua Reservoirs) on the Yunnan-Guizhou Plateau in Southwest China. Possible pollution sources were identified by spatial and statistical analyses. For both reservoirs, Cd was most likely from industrial activities, and As was from lithogenic sources. For the Hongfeng Reservoir, Pb, Cr and Cu might have originated from mixed sources (traffic pollution and residual effect of former industrial practices), and the sources of Hg included the inflows, which were different for the North (industrial activities) and South (lithogenic origin) Lakes, and atmospheric deposition resulting from coal combustion. For the Baihua Reservoir, the Hg, Cr and Cu were primarily derived from industrial activities, and the Pb originated from traffic pollution. The Hg in the Baihua Reservoir might also have been associated with coal combustion pollution. An analysis of ecological risk using sediment quality guidelines showed that there were moderate toxicological risks for sediment-dwelling organisms in both reservoirs, mainly from Hg and Cr. Ecological risk analysis using the Hakanson index suggested that there was a potential moderate to very high ecological risk to humans from fish in both reservoirs, mainly because of elevated levels of Hg and Cd. The upstream Hongfeng Reservoir acts as a buffer, but remains an important source of Cd, Cu and Pb and a moderately important source of Cr, for the downstream Baihua Reservoir. This study provides a replicable method for assessing aquatic ecosystem health in adjacent plateau reservoirs.

There is currently a wide variety of methods used to evaluate soil contamination. We present a discussion of the advantages and limitations of different soil contamination assessment methods. In this study, we analyzed seven trace elements (As, Cd, Cr, Cu, Hg, Pb, and Zn) that are indicators of soil contamination in Dexing, a city in China that is famous for its vast nonferrous mineral resources in China, using enrichment factor (EF), geoaccumulation index (Igeo), pollution index (PI), and principal component analysis (PCA). The three contamination indices and PCA were then mapped to understand the status and trends of soil contamination in this region. The entire study area is strongly enriched in Cd, Cu, Pb, and Zn, especially in areas near mine sites. As and Hg were also present in high concentrations in urban areas. Results indicated that Cr in this area originated from both anthropogenic and natural sources. PCA combined with Geographic Information System (GIS) was successfully used to discriminate between natural and anthropogenic trace metals.

BackgroundPliocene uplifting of the Qinghai-Tibetan Plateau (QTP) and Quaternary glaciation may have impacted the Asian biota more than any other events. Little is documented with respect to how the geological and climatological events influenced speciation as well as spatial and genetic structuring, especially in vertebrate endotherms. Macaca mulatta is the most widely distributed non-human primate. It may be the most suitable model to test hypotheses regarding the genetic consequences of orogenesis on an endotherm.Methodology and principal findingsUsing a large dataset of maternally inherited mitochondrial DNA gene sequences and nuclear microsatellite DNA data, we discovered two maternal super-haplogroups exist, one in western China and the other in eastern China. M. mulatta formed around 2.31 Ma (1.51-3.15, 95%), and divergence of the two major matrilines was estimated at 1.15 Ma (0.78-1.55, 95%). The western super-haplogroup exhibits significant geographic structure. In contrast, the eastern super-haplogroup has far greater haplotypic variability with little structure based on analyses of six variable microsatellite loci using Structure and Geneland. Analysis using Migrate detected greater gene flow from WEST to EAST than vice versa. We did not detect signals of bottlenecking in most populations.ConclusionsAnalyses of the nuclear and mitochondrial datasets obtained large differences in genetic patterns for M. mulatta. The difference likely reflects inheritance mechanisms of the maternally inherited mtDNA genome versus nuclear biparentally inherited STRs and male-mediated gene flow. Dramatic environmental changes may be responsible for shaping the matrilineal history of macaques. The timing of events, the formation of M. mulatta, and the divergence of the super-haplogroups, corresponds to both the uplifting of the QTP and Quaternary climatic oscillations. Orogenesis likely drove divergence of western populations in China, and Pleistocene glaciations are likely responsible for genetic structuring in the eastern super-haplogroup via geographic isolation and secondary contact.

BackgroundClinical studies demonstrate that the N-methyl-D-aspartate (NMDA) receptor antagonist, ketamine, induces rapid antidepressant effects in patients with refractive major depressive disorder and bipolar depression. This rapid onset of action makes ketamine a highly attractive drug for patients, particularly those who do not typically respond to therapy. A recent study suggested that glycogen synthase kinase (GSK)-3 may underlie the rapid antidepressant action of ketamine, although the precise mechanisms are unclear. In this study, we examined the effects of ketamine and GSK-3 inhibitor SB216763 in the unpredictable, chronic mild stress (CMS) mouse model of mice.Methodology/principal findingsAdult C57/B6 male mice were divided into 2 groups, a non-stressed control group and the unpredictable CMS (35 days) group. Then, either vehicle, ketamine (10 mg/kg), or the established GSK-3 inhibitor, SB216763 (10 mg/kg), were administered into mice in the CMS group, while vehicle was administered to controls. In the open field test, there was no difference between the four groups (control+vehicle, CMS+vehicle, CMS+ketamine, CMS+SB216763). In the sucrose intake test, a 1% sucrose intake drop, seen in CMS mice, was significantly attenuated after a single dose of ketamine, but not SB216763. In the tail suspension test (TST) and forced swimming test (FST), the increased immobility time seen in CMS mice was significantly attenuated by a single dose of ketamine, but not SB216763. Interestingly, the ketamine-induced increase in the sucrose intake test persisted for 8 days after a single dose of ketamine. Furthermore, a single administration of ketamine, but not SB216763, significantly attenuated the immobility time of the TST and FST in the control (non-stressed) mice.Conclusions/significanceThese findings suggest that a single administration of ketamine, but not GSK-3 inhibitor SB216763, produces a long-lasting antidepressant action in CMS model mice.

BackgroundCognitive impairment in patients with schizophrenia is a core symptom of this disease. The computerized CogState Battery (CSB) has been used to detect seven of the most common cognitive domains in schizophrenia. The aim of this study was to examine the reliability and validity of the Chinese version of the CSB (CSB-C), in Chinese patients with schizophrenia.Methodology/principal findingsSixty Chinese patients with schizophrenia and 58 age, sex, and education matched healthy controls were enrolled. All subjects completed the CSB-C and the Repeated Battery for the Assessment of Neuropsychological Status (RBANS). To examine the test-retest reliability of CSB-C, we tested 33 healthy controls twice, at a one month interval. The Cronbach α value of CSB-C in patients was 0.81. The test-retest correlation coefficients of the Two Back Task, Gronton Maze Learning Task, Social Emotional Cognition Task, and Continuous Paired Association Learning Task were between 0.39 and 0.62 (pConclusions/significanceThe CSB-C shows good reliability and validity in measuring the broad cognitive domains of schizophrenia in affected Chinese patients. Therefore, the CSB-C can be used as a cognitive battery, to assess the therapeutic effects of potential cognitive-enhancing agents in this cohort.

V. cholerae can form sessile biofilms associated with abiotic surfaces, cyanobacteria, zoo-plankton, mollusks, or crustaceans. Along with the vibrio polysaccharide, secreted proteins of the rbm gene cluster are key to the biofilm ultrastructure. Here we provide a thorough structural characterization of RbmA, a protein involved in mediating cell-cell and cell-biofilm contacts. We correlate our structural findings with initial ligand specificity screening results, NMR protein-ligand interaction analysis, and complement our results with a full biocomputational study.

ContextOn May 12(th) 2008, a devastating earthquake measuring 8.0 on the Richter scale, struck Wenchuan county and surrounding areas in China. The prevalence of mental illness among children and adolescents in a rural town far from the earthquake epicenter is unknown.ObjectiveTo assess the prevalence of posttraumatic stress disorder (PTSD) and depression among junior middle school students in a rural town Ningqiang county, 327 km from the earthquake epicenter.Design, setting, and participantsA population-based mental health survey was conducted in March, 2009.Main outcome measureSurvey Self-designed General Condition Survey Scale, Children's Revised Impact of Event Scale (CRIES-13), and the Depression Self-rating Scale for Children (DSRSC) were used to sample 1,841 junior middle school students in Ningqiang county, ten months after the Wenchuan earthquake.ResultsThe prevalence rate of a high-risk for PTSD was 28.4%, with 32.7% among females, 23.8% among males (female vs. male, pConclusionTraumatic events experienced during the earthquake were significantly associated with symptoms of PTSD and depression in children and adolescents, ten months after the Wenchuan earthquake. These data highlight a need for mental health services for children and adolescents in rural areas, far from earthquake epicenters.

BACKGROUND: Newcastle disease (ND) is a highly contagious viral disease of poultry caused by pathogenic strains of the Newcastle disease virus (NDV). Live NDV vaccines are administered by drinking water, eyedrops or coarse aerosol spray. To further enhance mucosal immune responses, chitosan nanoparticles were developed for the mucosal delivery of a live NDV vaccine. METHODOLOGY/PRINCIPAL FINDINGS: A lentogenic live-virus vaccine (strain LaSota) against NDV encapsulated in chitosan nanoparticles were developed using an ionic crosslinking method. Chitosan nanoparticles containing the lentogenic live-virus vaccine against NDV (NDV-CS-NPs) were produced with good morphology, high stability, a mean diameter of 371.1 nm, an encapsulation rate of 77% and a zeta potential of +2.84 mV. The Western blotting analysis showed that NDV structural proteins were detected in NDV-CS-NPs. The virus release assay results of NDV-CS-NPs indicated that NDV was released from NDV-CS-NPs. Chickens immunized orally or intranasally with NDV-CS-NPs were fully protected whereas one out of five chickens immunized with the LaSota live NDV vaccine and three out of five chickens immunized with the inactivated NDV vaccine were dead after challenge with the highly virulent NDV strain F48E9. CONCLUSIONS/SIGNIFICANCE: NDV-CS-NPs induced better protection of immunized specific pathogen free chickens compared to the live NDV vaccine strain LaSota and the inactivated NDV vaccine. This study lays a foundation for the further development of mucosal vaccines and drugs encapsulated in chitosan nanoparticles.

Glycine transporter-1 (GlyT-1) in glial cells regulates extracellular levels of glycine, which acts as an obligatory co-agonist at the N-methyl-D-aspartate (NMDA) receptors in the brain. In the present study, we developed a novel radioligand, [³H]3-chloro-N-((S)-((R)-1-methylpiperidin-2-yl)(thiophen- 3-yl)methyl)-4- (trifluoromethyl)picolinamide ([³H]CHIBA-3007), for studying GlyT-1 in the brain. The presence of a single saturable high-affinity binding component for [³H]CHIBA-3007 binding to the rat brain membranes was detected. Scatchard analysis revealed an apparent equilibrium dissociation constant (K(d)) of 1.61±0.16 nM and a maximal number of binding sites (B(max)) of 692.8±22.8 fmol/mg protein (mean ± SEM, n = 3). The specific binding of [³H]CHIBA-3007 was inhibited by a number of GlyT-1 inhibitors, such as CHIBA-3007, desmethyl-CHIBA-3007, CHIBA-3008, SSR504734, NFPS/ALX5407, LY2365109 and Org24598, consistent with the pharmacological profiles of GlyT-1 inhibitors. Interestingly, the potency of eight GlyT-1 inhibitors (CHIBA-3007, desmethyl-CHIBA-3007, NFPS/ALX5407, LY2365109, Org24598, SSR504734, sarcosine, and glycine) for blocking in vitro specific binding of [³H]CHIBA-3007 was significantly correlated with the potency of these inhibitors for inhibiting [¹⁴C]glycine uptake in the rat brain membranes. In contrast, the GlyT-2 inhibitor ALX1393 exhibited very weak for [³H]CHIBA-3007 binding. Furthermore, the regional distribution of [³H]CHIBA-3007 binding in the rat brain was similar to the previously reported distribution of GlyT-1. The present findings suggest that [³H]CHIBA-3007 would be a useful new radioligand for studying GlyT-1 in the brain.

BackgroundAccumulating epidemiological evidence shows that life event stressors are major vulnerability factors for psychiatric diseases such as major depression. It is also well known that social isolation in male mice results in aggressive behavior. However, it is not known how social isolation-induced aggression affects anxiety and depressive-like behavior in isolated male mice subjected to unpredictable chronic mild stress (CMS), an animal model of depression.Methodology/principal findingsC57/B6 male mice were divided into 3 groups; non-stressed controls, in Group I; isolated mice subjected to the CMS protocol in Group II and aggression by physical contact in socially isolated mice subjected to the CMS protocol in Group III. In the sucrose intake test, ingestion of a 1% sucrose solution by mice in Groups II and III was significantly lower than in Group I. Furthermore, intake of this solution in Group III mice was significantly lower than in Group II mice. In the open field test, mice in Group III, showed reduced locomotor activity and reduced entry and retention time in the central zone, compared to Groups I and II mice. Moreover, the distances moved in 1 hour by Group III mice did not differ between night and morning. In the light/black box test, Groups II and III animals spent significantly less time in the light box compared to Group I animals. In the tail suspension test (TST) and forced swimming test (FST), the immobility times of Group II and Group III mice were significantly longer than in Group I mice. In addition, immobility times in the FST were significantly longer in Group III than in Group II mice.Conclusions/significanceThese findings show that social isolation-induced aggression could potentiate anxiety and depressive-like behaviors in isolated male mice subjected to CMS.

BACKGROUND: Our previous study revealed that administration of syngeneic female BALB/c mice with excessive self activated lymphocyte-derived DNA (ALD-DNA) could induce systemic lupus erythematosus (SLE) disease, indicating that overload of self-DNA might exceed normal clearance ability and comprise the major source of autoantigens in lupus mice. Serum amyloid P component (SAP), an acute-phase serum protein with binding reactivity to DNA in mice, was proved to promote the clearance of free DNA and prevent mice against self-antigen induced autoimmune response. It is reasonable to hypothesize that SAP treatment might contribute to alleviation of SLE disease, whereas its role in ALD-DNA-induced lupus nephritis is not fully understood. METHODOLOGY/PRINCIPAL FINDINGS: The ratios of SAP to DNA significantly decreased and were negatively correlated with the titers of anti-dsDNA antibodies in ALD-DNA-induced lupus mice, indicating SAP was relatively insufficient in lupus mice. Herein a pcDNA3-SAP plasmid (pSAP) was genetically constructed and intramuscularly injected into BALB/c mice. It was found that SAP protein purified from the serum of pSAP-treated mice bound efficiently to ALD-DNA and inhibited ALD-DNA-mediated innate immune response in vitro. Treatment of ALD-DNA-induced lupus mice with pSAP in the early stage of SLE disease with the onset of proteinuria reversed lupus nephritis via decreasing anti-dsDNA autoantibody production and immune complex (IC) deposition. Further administration of pSAP in the late stage of SLE disease that had established lupus nephritis alleviated proteinuria and ameliorated lupus nephritis. This therapeutic effect of SAP was not only attributable to the decreased levels of anti-dsDNA autoantibodies, but also associated with the decreased infiltration of lymphocytes and the reduced production of inflammatory markers. CONCLUSION/SIGNIFICANCE: These results suggest that SAP administration could effectively alleviated lupus nephritis via modulating anti-dsDNA antibody production and the inflammation followed IC deposition, and SAP-based intervening strategy may provide new approaches for treating SLE disease.

BackgroundThe alpha7 nicotinic acetylcholine receptors (nAChRs) play an important role in the pathophysiology of neuropsychiatric diseases such as schizophrenia and Alzheimer's disease. The goal of this study was to evaluate the two carbon-11-labeled alpha7 nAChR agonists [(11)C]A-582941 and [(11)C]A-844606 for their potential as novel positron emission tomography (PET) tracers.Methodology/principal findingsThe two tracers were synthesized by methylation of the corresponding desmethyl precursors using [(11)C]methyl triflate. Effects of receptor blockade in mice were determined by coinjection of either tracer along with a carrier or an excess amount of a selective alpha7 nAChR agonist (SSR180711). Metabolic stability was investigated using radio-HPLC. Dynamic PET scans were performed in conscious monkeys with/without SSR180711-treatment. [(11)C]A-582941 and [(11)C]A-844606 showed high uptake in the mouse brain. Most radioactive compounds in the brain were detected as an unchanged form. However, regional selectivity and selective receptor blockade were not clearly observed for either compound in the mouse brain. On the other hand, the total distribution volume of [(11)C]A-582941 and [(11)C]A-844606 was high in the hippocampus and thalamus but low in the cerebellum in the conscious monkey brain, and reduced by pretreatment with SSR180711.Conclusions/significanceA nonhuman primate study suggests that [(11)C]A-582941 and [(11)C]A-844606 would be potential PET ligands for imaging alpha7 nAChRs in the human brain.

Glycine transporter-1 (GlyT-1) in glial cells regulates extracellular levels of glycine, which acts as an obligatory co-agonist at the N-methyl-D-aspartate (NMDA) receptors in the brain. In the present study, we developed a novel radioligand, [3H]3- chloro-N-((S)-((R)-1-methylpiperidin-2-yl)(thiophen- 3-yl)methyl)-4- (trifluoromethyl)picolinamide ([3H]CHIBA-3007), for studying GlyT-1 in the brain. The presence of a single saturable high-affinity binding component for [3H]CHIBA-3007 binding to the rat brain membranes was detected. Scatchard analysis revealed an apparent equilibrium dissociation constant (Kd) of 1.61±0.16 nM and a maximal number of binding sites (Bmax) of 692.8±22.8 fmol/mg protein (mean ± SEM, n = 3). The specific binding of [3H]CHIBA-3007 was inhibited by a number of GlyT-1 inhibitors, such as CHIBA-3007, desmethyl-CHIBA-3007, CHIBA-3008, SSR504734, NFPS/ALX5407, LY2365109 and Org24598, consistent with the pharmacological profiles of GlyT-1 inhibitors. Interestingly, the potency of eight GlyT-1 inhibitors (CHIBA-3007, desmethyl-CHIBA-3007, NFPS/ALX5407, LY2365109, Org24598, SSR504734, sarcosine, and glycine) for blocking in vitro specific binding of [3H]CHIBA-3007 was significantly correlated with the potency of these inhibitors for inhibiting [14C]glycine uptake in the rat brain membranes. In contrast, the GlyT-2 inhibitor ALX1393 exhibited very weak for [3H]CHIBA- 3007 binding. Furthermore, the regional distribution of [3H]CHIBA-3007 binding in the rat brain was similar to the previously reported distribution of GlyT-1. The present findings suggest that [3H]CHIBA-3007 would be a useful new radioligand for studying GlyT-1 in the brain. [ABSTRACT FROM AUTHOR]

Background: The α7 nicotinic acetylcholine receptors (nAChRs) play an important role in the pathophysiology of neuropsychiatric diseases such as schizophrenia and Alzheimer's disease. The goal of this study was to evaluate the two carbon-11-labeled α7 nAChR agonists [11C]A-582941 and [11C]A-844606 for their potential as novel positron emission tomography (PET) tracers. Methodology/Principal Findings: The two tracers were synthesized by methylation of the corresponding desmethyl precursors using [11C]methyl triflate. Effects of receptor blockade in mice were determined by coinjection of either tracer along with a carrier or an excess amount of a selective α7 nAChR agonist (SSR180711). Metabolic stability was investigated using radio-HPLC. Dynamic PET scans were performed in conscious monkeys with/without SSR180711-treatment. [11C]A-582941 and [11C]A-844606 showed high uptake in the mouse brain. Most radioactive compounds in the brain were detected as an unchanged form. However, regional selectivity and selective receptor blockade were not clearly observed for either compound in the mouse brain. On the other hand, the total distribution volume of [11C]A-582941 and [11C]A-844606 was high in the hippocampus and thalamus but low in the cerebellum in the conscious monkey brain, and reduced by pretreatment with SSR180711. Conclusions/Significance: A nonhuman primate study suggests that [11C]A-582941 and [11C]A-844606 would be potential PET ligands for imaging α7 nAChRs in the human brain. [ABSTRACT FROM AUTHOR]