The Relationship Between Cognitive Dysfunction and Symptom Dimensions Across Schizophrenia, Bipolar Disorder, and Major Depressive Disorder

Background: Cognitive dysfunction is considered a core feature among schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). Despite abundant literature comparing cognitive dysfunction among these disorders, the relationship between cognitive dysfunction and symptom dimensions remains unclear. The study aims are a) to identify the factor structure of the BPRS-18 and b) to examine the relationship between symptom domains and cognitive function across SZ, BD, and MDD.Methods: A total of 716 participants [262 with SZ, 104 with BD, 101 with MDD, and 249 healthy controls (HC)] were included in the study. One hundred eighty participants (59 with SZ, 23 with BD, 24 with MDD, and 74 HC) completed the MATRICS Consensus Cognitive Battery (MCCB), and 507 participants (85 with SZ, 89 with BD, 90 with MDD, and 243 HC) completed the Wisconsin Card Sorting Test (WCST). All patients completed the Brief Psychiatric Rating Scale (BPRS).Results: We identified five BPRS exploratory factor analysis (EFA) factors (“affective symptoms,” “psychosis,” “negative/disorganized symptoms,” “activation,” and “noncooperation”) and found cognitive dysfunction in all of the participant groups with psychiatric disorders. Negative/disorganized symptoms were the most strongly associated with cognitive dysfunctions across SZ, BD, and MDD.Conclusions: Our findings suggest that cognitive dysfunction severity relates to the negative/disorganized symptom domain across SZ, BD, and MDD, and negative/disorganized symptoms may be an important target for effective cognitive remediation in SZ, BD, and MDD

Role of Human-Mediated Dispersal in the Spread of the Pinewood Nematode in China

Background: Intensification of world trade is responsible for an increase in the number of alien species introductions. Human-mediated dispersal promotes not only introductions but also expansion of the species distribution via long-distance dispersal. Thus, understanding the role of anthropogenic pathways in the spread of invading species has become one of the most important challenges nowadays. Methodology/Principal Findings: We analysed the invasion pattern of the pinewood nematode in China based on invasion data from 1982 to 2005 and monitoring data on 7 locations over 15 years. Short distance spread mediated by long-horned beetles was estimated at 7.5 km per year. Infested sites located further away represented more than 90% of observations and the mean long distance spread was estimated at 111–339 km. Railways, river ports, and lakes had significant effects on the spread pattern. Human population density levels explained 87% of the variation in the invasion probability (P,0.05).Since 2001, the number of new records of the nematode was multiplied by a factor of 5 and the spread distance by a factor of 2. We combined a diffusion model to describe the short distance spread with a stochastic,individual based model to describe the long distance jumps. This combined model generated an error of only 13% when used to predict the presence of the nematode. Under two climate scenarios (stable climate or moderate warming), projections of the invasion probability suggest that this pest could expand its distribution 40–55% by 2025. Conclusions/Significance: This study provides evidence that human-induced dispersal plays a fundamental role in the spread of the pinewood nematode, and appropriate control measures should be taken to stop or slow its expansion. This model can be applied to Europe, where the nematode had been introduced later, and is currently expanding its distribution. Similar models could also be derived for other species that could be accidentally transported by humans

Functional expression of CCL8 and its interaction with chemokine receptor CCR3

Abstract Background Chemokines and their cognate receptors play important role in the control of leukocyte chemotaxis, HIV entry and other inflammatory diseases. Developing an effcient method to investigate the functional expression of chemokines and its interactions with specific receptors will be helpful to asses the structural and functional characteristics as well as the design of new approach to therapeutic intervention. Results By making systematic optimization study of expression conditions, soluble and functional production of chemokine C-C motif ligand 8 (CCL8) in Escherichia coli (E. coli) has been achieved with approx. 1.5 mg protein/l culture. Quartz crystal microbalance (QCM) analysis exhibited that the purified CCL8 could bind with C-C chemokine receptor type 3 (CCR3) with dissociation equilibrium constant (K D) as 1.2 × 10−7 M in vitro. Obvious internalization of CCR3 in vivo could be detected in 1 h when exposed to 100 nM of CCL8. Compared with chemokine C-C motif ligand 11 (CCL11) and chemokine C-C motif ligand 24 (CCL24), a weaker chemotactic effect of CCR3 expressing cells was observed when induced by CCL8 with same concentration. Conclusion This study delivers a simple and applicable way to produce functional chemokines in E. coli. The results clearly confirms that CCL8 can interact with chemokine receptor CCR3, therefore, it is promising area to develop drugs for the treatment of related diseases

Regulation of the Oligomeric Status of CCR3 with Binding Ligands Revealed by Single-Molecule Fluorescence Imaging

The relationship between the oligomeric status and functions of chemokine receptor CCR3 is still controversial. We use total internal reflection fluorescence microscopy at the single-molecule level to visualize the oligomeric status of CCR3 and its regulation of the membrane of stably transfected T-REx-293 cells. We find that the population of the dimers and oligomers of CCR3 can be modulated by the binding of ligands. Natural agonists can induce an increase in the level of dimers and oligomers at high concentrations, whereas antagonists do not have a significant influence on the oligomeric status. Moreover, monomeric CCR3 exhibits a stronger chemotactic response in the migration assay of stably transfected CCR3 cells. Together, these data support the notion that CCR3 exists as a mixture of monomers and dimers under nearly physiological conditions and the monomeric CCR3 receptor is the minimal functional unit in cellular signaling transduction. To the best of our knowledge, these results constitute the first report of the oligomeric status of CCR3 and its regulation

Single-Molecule Imaging Demonstrates Ligand Regulation of the Oligomeric Status of CXCR4 in Living Cells

The role of dimerization and oligomerization of G-protein-coupled receptors in their signal transduction is highly controversial. Delineating this issue can greatly facilitate rational drug design. With single-molecule imaging, we show that chemokine receptor CXCR4 exists mainly as a monomer in normal mammalian living cells and forms dimers and higher-order oligomers at a high expression level, such as in cancer cells. Chemotaxis tests demonstrate that the signal transduction activity of CXCR4 does not depend only on its expression level, indicating a close relation with the oligomeric status of CXCR4. Moreover, binding ligands can effectively upregulate or downregulate the oligomeric level of CXCR4, which suggests that binding ligands may realize their pivotal roles by regulating the oligomeric status of CXCR4 rather than by simply inducing conformational changes