Animal Models Relevant to Schizophrenia and Autism: Validity and Limitations

Development of animal models is a crucial issue in biological psychiatry. Animal models provide the opportunity to decipher the relationships between the nervous system and behavior and they are an obligatory step for drug tests. Mouse models or rat models to a lesser extent could help to test for the implication of a gene using gene targeting or transfecting technologies. One of the main problem for the development of animal models is to define a marker of the psychiatric disorder. Several markers have been suggested for schizophrenia and autism, but for the moment no markers or etiopathogenic mechanisms have been identified for these disorders. We examined here animal models related to schizophrenia and autism and discussed their validity and limitations after first defining these two disorders and considering their similarities and differences. Animal models reviewed in this article test mainly behavioral dimensions or biological mechanisms related to autistic disorder or schizophrenia rather than providing specific categorical models of autism or schizophrenia. Furthermore, most of these studies focus on a behavioral dimension associated with an underlying biological mechanism, which does not correspond to the complexity of mental disorders. It could be useful to develop animal models relevant to schizophrenia or autism to test a behavioral profile associated with a biological profile. A multi-trait approach seems necessary to better understand multidimensional disorders such as schizophrenia and autism and their biological and clinical heterogeneity. Finally, animal models can help us to clarify complex mechanisms and to study relationships between biological and behavioral variables and their interactions with environmental factors. The main interest of animal models is to generate new pertinent hypotheses relevant to humans opening the path to innovative research. Edited by Gene Fisch     

Genetic and Environmental Influences on Schizotypy among Adolescents in Taiwan: A Multivariate Twin/sibling Analysis

This study aimed to examine the relative contribution of genes and environment to psychometrically measured schizotypy and the causes for the covariation between different dimensions of schizotypy in a total of 330 pairs of twins and 36 same-sex sib-pairs aged 12–16 and systematically recruited from junior high schools in Taipei. Twins’ zygosity was determined by a combination of DNA typing and physical similarity. Schizotypy was measured using the Perceptual Aberration Scale (PAS) as well as the Schizotypal Personality Questionnaire (SPQ) and its three factors (Cognitive-perceptual Dysfunction, Disorganization, and Interpersonal Dysfunction). Univariate analyses of structural equation modeling using Mx program showed that scores on these schizotypal measures were substantially heritable (h ² ranging from 41 to 49%), with some genetic effects being non-additive. Multivariate analyses revealed common genetic factors linking between various traits of schizotypy, with bivariate heritability ranging from 50 to 65%. The proportion of the genetic contributions not shared with the other measures of schizotypy ranged from 24% for the Disorganization to 49% for the PAS scores. We concluded that there exist both common and specific genetic factors between the various dimensions of schizotypy, and at least half of their correlations were genetic in nature. Edited by Peter McGuffin     

Orbital marginal zone lymphomas: an immunohistochemical, polymerase chain reaction, and fluorescence in situ hybridization study

Many studies have been performed on chromosomal aberrations of extranodal marginal zone lymphomas. However, only a few have been published so far on ocular adnexal marginal zone lymphomas. We studied 18 cases of orbital lymphoid cell infiltrates. Using fluorescence in situ hybridization (FISH), we studied some of the most common chromosomal aberrations found in extranodal marginal zone lymphomas as: trisomies 3, and rearrangements of the 18q21 MALTI gene to detect the translocations t(11;18)(q21;q21) and t(14;18)(q32;q21)MALT1. Our goals were as follows: (1) study those aberrations in our material and compare them with the literature, (2) check their prognostic significance, and (3) check whether studying those aberrations with FISH can be used as a diagnostic tool to differentiate reactive from neoplastic infiltrates, in addition to immunohistochemistry and polymerase chain reaction. We found a high frequency of trisomies 3 (68%) and 18 (56.6%), the highest published so far in orbital lymphomas. On the other hand, no rearrangement was seen in any of our cases. The histologic picture and the clinical course were the same when there was one or more aberrations. As for the diagnostic significance, the presence of a prior, concurrent, or subsequent lymphoma in almost all the positive for aberrations cases suggests that either the orbital infiltrates in these cases are lymphomas, or they have, at least, a malignant potential or a genetic instability. Therefore, the demonstration of these numerical aberrations by FISH may be an additional sensitive, reliable, and relatively simple tool to differentiate reactive from neoplastic orbital lymphoid cell infiltrates when the immunohistochemistry and polymerase chain reaction, performed in a busy and routine-based histopathology laboratory, are unsatisfactory.     

大学生网络成瘾影响因素分析

目的探讨大学生网络成瘾的原因。方法采用中文网络成瘾量表、自尊量表、孤独量表、大学生日常生活压力调查表、自编大学生网络使用行为调查问卷，对1450名大学生进行了调查，回收有效问卷1038份。结果对大学生网络成瘾的现状、网络使用特征及心理特征进行调查，建立大学生网络成瘾影响因素模型。结论①大学生网络成瘾呈轻度、重度两种水平，这两种水平总流行率达到14．84％；②网络使用时间、娱乐上网、交易上网、人际上网与网络成瘾存在着显著正相关关系；③自尊、孤独、大学生日常生活压力对网络成瘾有很好的预测作用；④网络成瘾是特定的个体心理特征与特定的网络使用行为、外部环境交互作用的结果。     

父母-子女人格相似性对教养行为与青少年抑郁关系的调节作用

目的:考查父母-子女人格相似性对教养行为与青少年抑郁关系的调节作用。方法:采用中国科学院心理研究所全国青少年心理健康数据库中2009年的横断数据,对其中4474名11岁到22岁的在校学生数据进行分析。父母和子女人格均为自评,教养行为采用父母自评,抑郁由青少年自评。结果:父亲-子女在神经质维度上的相似性与父亲各项教养行为的交互作用均显著;母亲-子女在外向性维度上的相似性与母亲说理的交互作用显著,母亲-子女在神经质维度上的相似性与母亲各项教养行为的交互作用均显著,母亲-子女在精神质维度上的相似性与母亲监控交互作用显著。结论:父母-子女人格相似性对教养行为与青少年抑郁的关系具有显著的调节作用。     

An Automated Self‐Similarity Analysis of the Pulmonary Tree of the Sprague–Dawley Rat

We present the results of an automated analysis of the morphometry of the pulmonary airway trees of the Sprague–Dawley rat. Our work is motivated by a need to inform lower‐dimensional mathematical models to prescribe realistic boundary conditions for multiscale hybrid models of rat lung mechanics. Silicone casts were made from three age‐matched, male Sprague–Dawley rats, immersed in a gel containing a contrast agent and subsequently imaged with magnetic resonance (MR). From a segmentation of this data, we extracted a connected graph, representing the airway centerline. Segment statistics (lengths and diameters) were derived from this graph. To validate this MR imaging/digital analysis method, airway segment measurements were compared with nearly 1,000 measurements collected by hand using an optical microscope from one of the rat lung casts. To evaluate the reproducibility of the MR imaging/digital analysis method, two lung casts were each imaged three times with randomized orientations in the MR bore. Diameters and lengths of randomly selected airways were compared among each of the repeated imaging datasets to estimate the variability. Finally, we analyzed the morphometry of the airway tree by assembling individual airway segments into structures that span multiple generations, which we call branches. We show that branches not segments are the fundamental repeating unit in the rat lung and develop simple mathematical relationships describing these structures for the entire lung. Our analysis shows that airway diameters and lengths have both a deterministic and stochastic character. Anat Rec, 2008. © 2008 Wiley‐Liss, Inc.     

Amino acid substitutions in the structural or nonstructural proteins of a vaccine strain of equine arteritis virus are associated with its attenuation

Comparative sequence analysis of a series of strains of equine arteritis virus (EAV) of defined virulence for horses, ranging from the horse-adapted virulent Bucyrus (VB) strain to a fully attenuated vaccine strain derived from it, identified 13 amino acid substitutions associated with attenuation. These include 4 substitutions in the replicase proteins and 9 in the structural proteins. Using reverse genetic techniques, these amino acid substitutions were introduced into a virulent infectious cDNA clone pEAVrVBS derived from the VB strain of EAV. Inoculation of horses with the recombinant viruses clearly demonstrated that changes in either the replicase (nsp1, nsp2 and nsp7) or structural proteins (GP2, GP4, GP5 and M) resulted in attenuation of the virulent VB strain. The recombinant virus with substitutions in the structural proteins was more attenuated than the recombinant virus with substitutions only in the replicase proteins.     

Targeting EGFR/HER2 heterodimerization with a novel anti-HER2 domain II/III antibody

HER2, a ligand-free tyrosine kinase receptor of the HER family, is frequently overexpressed in breast cancer. The anti-HER2 antibody trastuzumab has shown significant clinical benefits in metastatic breast cancer. Despite the effectiveness of trastuzumab, its efficacy remains variable and often modest. Thus, there is an urgent need to improve ErbB2-targeting therapy. Here, we describe a novel anti-HER2 antibody, 7C3, which was developed using hybridoma technique. Structural analysis confirms that the epitope of this antibody is in domain II/III of HER2. Moreover, a structural conformation change was observed in HER2 in complex with 7C3. Interestingly, this novel anti-HER2 antibody exhibits efficacy in blocking HER2/EGFR heterodimerization and signaling. The results highlight the different function role of HER2 domains and the unique potential of 7C3 to inhibit the HER2/EGFR heterodimer, which may complement current anti-HER2 treatments.     

GFD-Net: A novel semantic similarity methodology for the analysis of gene networks

Since the popularization of biological network inference methods, it has become crucial to create methods to validate the resulting models.Here we present GFD-Net, the first methodology that applies the concept of semantic similarity to gene network analysis. GFD-Net combines the concept of semantic similarity with the use of gene network topology to analyze the functional dissimilarity of gene networks based on Gene Ontology (GO). The main innovation of GFD-Net lies in the way that semantic similarity is used to analyze gene networks taking into account the network topology. GFD-Net selects a functionality for each gene (specified by a GO term), weights each edge according to the dissimilarity between the nodes at its ends and calculates a quantitative measure of the network functional dissimilarity, i.e. a quantitative value of the degree of dissimilarity between the connected genes.The robustness of GFD-Net as a gene network validation tool was demonstrated by performing a ROC analysis on several network repositories. Furthermore, a well-known network was analyzed showing that GFD-Net can also be used to infer knowledge.The relevance of GFD-Net becomes more evident in Section “GFD-Net applied to the study of human diseases” where an example of how GFD-Net can be applied to the study of human diseases is presented.GFD-Net is available as an open-source Cytoscape app which offers a user-friendly interface to configure and execute the algorithm as well as the ability to visualize and interact with the results(http://apps.cytoscape.org/apps/gfdnet).     

Heterologous structure of coating antigen on sensitivity of ELISA for sulfamethazine: evidence from molecular similarity analysis

Six structurally similar sulfonamide haptens have been linked to ovalbumin by diazo-method used as coating antigen. An enzyme-linked immunosorbent assay (ELISA) was developed to investigate heterologous structure of coating haptens on sensitivity of ELISA for sulfamethazine. The sensitivities of ELISA, expressed as IC₅₀ values, ranged from 94 to 877 ng mL^{? 1} when six coating antigens were employed. The results suggested that the structural heterology of coating hapten had significant effect on ELISA sensitivity. In order to evaluate the relationship between the degree of hapten heterology and ELISA sensitivity, we used molecular similarity methods to qualitatively represent the degree of coating hapten heterology. The Molecular Access System (MACCS) structural keys and the Tanimoto similarity coefficient were used to calculate and compare the degree of coating hapten's similarity, and the authors found that the sensitivity of ELISA was not in direct proportion with degree of coating hapten heterology in the case of study.