人类TCRαβ家族V基因的进化研究

目的：了解人类TCRα家族V基因（TCRAV）和TCRβ家族V基因（TCRBV）的进化特征。方法：采用MEGA3．1软件对人类TCRAV和TCRBV基因分别构建进化树，并估算基因复制的发生时间；采用FEL法检测TCRAV和TCRBV编码序列正选择和负选择位点。结果：进化树显示TCRAV和TCRBV的基因分组在进化过程中已经维持了相当长的时间。TCRAV已经不受正选择作用，TCRBV基因序列的CDR8区域检测到两个正选择位点。结论：人类TCRαβ家族V基因的进化特征为研究TCR基因在机体免疫及疾病防治提供了理论分析基础。     

父母不同教养倾向对高中生心理健康的影响

目的探讨父母积极教养倾向和消极教养倾向对高中生心理健康的影响。方法采用中学生心理健康量表和父母教养方式评价量表(EMBU)对开封某重点高中二年级177名学生进行调查,并对结果进行了相应的处理分析。结果父母的情感温暖、理解是保护其子女免受抑郁和焦虑侵扰的有效方法;父母对子女过多的拒绝否认、过分干涉、过度保护、惩罚、严厉、偏爱被试是导致其子女形成偏执、敌对、人际关系敏感与紧张、学习压力感、适应不良、情绪不稳定和心理不平衡等不健康心理品质的主要因素。结论高中生的心理健康水平欠佳;父母应给予子女多一些情感温暖和理解,少一些惩罚严厉、拒绝否认和过分干涉过度保护,父母应公平对待自己的每个子女。     

Components in the P300: Don’t forget the Novelty P3!

This study investigated stimulus-response patterns of temporal principal components analysis (PCA)–derived event-related potential (ERP) components in a classical auditory habituation paradigm with long interstimulus intervals. The skin conductance response (SCR) was included as the “gold standard” model of the Orienting Reflex. Thirty participants were presented with a single series of 10 identical 60 dB tones, followed by a change trial at a different frequency. Single-trial, electrooculography-corrected ERPs were submitted to temporal PCA. The main focus was on the components expected in the P300/Late Positive Complex (LPC), and their electromagnetic tomography–derived cortical sources. Nine components were identified between 90 and 470 ms poststimulus (in temporal order): three N1 subcomponents, P2, four LPC components, and a negative Slow Wave (SW). The expected order of P3a, P3b, Novelty P3 (nP3), and positive Slow Wave (+SW) in the LPC was confirmed. SCR demonstrated strong exponential decay and recovery. P3b and nP3 each showed exponential decrement over trials, but only nP3 showed recovery at the change trial. Novelty effects failed to reach significance for the other LPC components, and were not apparent in non-LPC components. Frontal lobe activity in Brodmann areas 6, 8, and 9 was common to P3a, P3b, nP3, and +SW, consistent with the functional integration of these components in the LPC. Individual components had specific sources, although some sources overlapped between components or were reactivated later in the LPC. These data provide a fresh perspective on the components of the LPC and their cortical sources, and offer a processing model for the P300 in a habituation task, potentially generalizable to other paradigms.     

Association between genomic heterogeneity of hepatitis B virus and intrauterine infection

Hepatitis B virus (HBV) intrauterine infection remains to be an important cause for a large number of persistent hepatitis B surface antigen (HBsAg) positive carriers in areas with a high HBV prevalence, particularly in China and Southeast Asia. In this study, the possible association between the HBV genomic heterogeneity and intrauterine infection was investigated by comparing the quasi species isolated from eight pairs of HBsAg-positive mothers and their neonates, who were infected intrauterinely with HBV, with clones from eight HBsAg-positive mothers whose neonates were not infected with HBV. The proportion of clones with specific mutations was compared among different subject groups, and phylogenetic analysis was performed to evaluate the significance of specific mutations. It was observed that the core promoter with conserved major functional regions and conserved hepatitis B e antigen (HBeAg) might be beneficial to HBV maternal-fetal transmission. Particularly, A1762T/G1764A mutations seemed to be disadvantageous for fetal infection. It was also shown that amino acid substitutions located in the immune epitopes of HBsAg were strongly associated with intrauterine HBV transmission. The clones with mutations such as amino acid P110S in preS1 region, P36L in preS2 region and C107R in S region might infect fetuses more readily. In addition, positively selected site analysis confirmed the above results.     

Linkage of human cytomegalovirus glycoprotein gO variant groups identified from worldwide clinical isolates with gN genotypes, implications for disease associations and evidence for N-terminal sites of positive selection

Previously, we identified the glycoprotein gO gene, UL74, as a hypervariable locus in the human cytomegalovirus (HCMV) genome [Virology 293 (2002) 281]. Here, we analyze gO from 50 isolates from congenitally infected newborns, transplant recipients, and HIV/AIDS patients from Italy, Australia, and UK. These are compared to four gO groups described from USA transplantation patients [J. Virol. 76 (2002) 10841]. Phylogenetic analyses identified seven genotypes. Divergence between genotypes was up to 55% and within 3%. Discrete linkage was shown between seven hypervariable gO and gN genotypes, but not with gB. This suggests interactions, while gN and gO are known to form complexes with distinct conserved glycoproteins gM, gH/gL, respectively, both are involved in fusogenic entry and exit. Codon-based maximum likelihood models showed evidence for sites of positive selection. Further analyses of disease relationships should take into account these newly defined gO/gN groups.     

Permissive recognition during positive selection

In the periphery αβ T lymphocytes recognize antigens in conjunction with major histocompatibility complex (MHC) molecules. In the thymus immature T cells are positively selected on MHC molecules in the apparent absence of cognate peptides. Thus, at different developmental stages a T cell responds to different epitopes, yet uses the identical αβ T cell antigen receptor (TcR). To explain this paradox it has been hypothesized that during positive selection immature T cells see peptides/ligands unique to the thymus, are selected by specific antagonists related to their cognate peptides, or are driven by lowered affinity thresholds of their TcR. Though different in detail, these theories rely on defined peptides uniquely matched to select certain TcR. However, we find that in a TcR-transgenic (TcR_trans⁺) mouse severely limiting the diversity of peptides does not impair positive selection. We show that many unrelated peptides, including some naturally occurring on the cell surface, induce maturation of CD4^?CD8⁺TcR^high thymocytes. The same peptides when presented in conjunction with the selecting MHC molecule, are not recognized by peripheral T cells expressing the same TcR_trans. Therefore, these findings point to a promiscuous rather than discriminate recognition mode used by immature T cells.     

高师生社会支持、自尊与积极/消极情感的关系研究

目的探讨高师生社会支持、自尊和积极/消极情感的关系。方法采用社会支持评定量表、自尊量表与积极/消极情感量表对340名高师生进行调查。结果①相关分析表明,社会支持、自尊与积极/消极情感均两两呈显著正相关(r=-0.16～0.36,P<0.05);②层级回归分析表明,自尊是影响积极情感的不完全中介(t=3.43～-7.37,P<0.01);③层级回归分析表明,自尊是影响消极情感的完全中介(t=-2.19～-6.24,P<0.05)。结论中介效应检验表明,自尊是高师生社会支持与积极/消极情感间的中介变量。     

大学生积极心理资本与主观幸福感的关系

目的探讨大学生积极心理资本与主观幸福感的关系。方法采用积极心理资本问卷和主观幸福感问卷,对重庆市3所大学的235名大学生进行调查。结果①大学生积极心理资本状况总体较好,自我效能因子存在显著生源地差异(F=15.38,P<0.001);自我效能因子存在显著专业类型差异(F=5.07,P<0.05);希望因子存在显著专业类型差异(F=12.71,P<0.001);希望因子存在显著年级差异(F=3.84,P<0.05),进一步多重比较表明,四年级大学生的希望水平显著高于三年级大学生;②大学生主观幸福感状况总体不够理想,生活满意度因子存在显著生源地差异(F=11.22,P<0.01);消极情感因子存在显著专业类型差异(F=8.27,P<0.01);③大学生的积极心理资本和主观幸福感正相关,前者对后者各因子有显著的预测作用(预测效应介于16.2%～29%之间)。结论大学生积极心理资本对主观幸福感有积极影响。     

T-cell selection in the thymus: New routes toward the identification of the self-peptide ligandome presented by thymic epithelial cells

Within the thymus, thymic epithelial cells (TECs) provide a dedicated niche for the selection of functional T cells expressing a highly variable and self-tolerant T-cell receptor (TCR) repertoire. In this minireview, we start by summarizing recent studies that have improved our understanding on the composition of cortical TEC and medullary TEC microenvironments. Next, we focus on the molecular processes that control the function of TECs in T-cell selection. In particular, we discuss the role of cortical TECs in positive selection and the pathways employed by these cells to generate and present selecting self-peptides:MHC II complexes. Several studies have underscored the role of the β5t-containing thymoproteasome in the production of unique MHC I-bound peptides critical for CD8 T-cell selection. Contrarily, the identity of the molecular determinants that regulate the generation of MHC II-bound self-peptides capable of positive selecting CD4 T cells is far more uncertain. We highlight recent advances that interconnect the autophagy-lysosomal pathway, the presentation of specific sets of self-peptide:MHC II complexes, and the diversification of CD4 TCR repertoire. Lastly, we discuss how these findings may open up new avenues for deciphering the identity of the MHC I and MHC II ligandome in the thymus.     

Aiding risk information learning through simulated experience (ARISE): Using simulated outcomes to improve understanding of conditional probabilities in prenatal Down syndrome screening

ObjectiveTo determine whether the use of visually-presented simulated experiences to communicate statistical information can improve an individual’s understanding of conditional probabilities—specifically the positive predictive value (PPV) of prenatal screening tests for Down syndrome.MethodsIn Experiment 1 (N = 64) and Experiment 2 (N = 180) participants were asked to estimate the PPV of a prenatal screening test for Down syndrome based on either (1) explicit statistics regarding the prevalence of Down syndrome and the sensitivity and specificity of a prenatal screening test for Down syndrome, or (2) experiencing up to 5000 simulated test results over a short time.ResultsParticipants’ estimates of the PPV were more accurate when they had learned via simulated experiences (79% accuracy) compared with estimates based on explicitly described statistics (14%). Participants in the simulated experience condition also reported decreased interest in screening and decreased concern with a positive test result.ConclusionA visual paradigm presenting simulated experiences improves PPV estimates, compared to estimates derived from explicitly provided statistics, while also shifting attitudes away from screening.Practice implicationsThe use of simulated experiences may prove to be simple but powerful tool to communicate complex statistical information to patients in medical decision making situations.