Interference with reelin signaling in the lateral entorhinal cortex impairs spatial memory

Entorhinal neurons receive extensive intracortical projections, and form the primary input to the hippocampus via the perforant pathway. The glutamatergic cells of origin for the perforant pathway are distinguished by their expression of reelin, a glycoprotein involved in learning and synaptic plasticity. The functional significance of reelin signaling within the entorhinal cortex, however, remains unexplored. To determine whether interrupting entorhinal reelin signaling might have consequences for learning and memory, we administered recombinant receptor-associated protein (RAP) into the lateral entorhinal cortex (LEC) of young Long-Evans rats. RAP prevents reelin from binding to its receptors, and we verified the knockdown of reelin signaling by quantifying the phosphorylation state of reelin’s intracellular signaling target, disabled-1 (DAB1). Effective knockdown of reelin signaling was associated with impaired performance in the hippocampus-dependent version of the water maze. Moreover, inhibition of reelin signaling induced a localized loss of synaptic marker expression in the LEC. These observations support a role for entorhinal reelin signaling in spatial learning, and suggest that an intact reelin signaling pathway is essential for synaptic integrity in the adult entorhinal cortex.     

A socio-emotional relational framework for infidelity: the relational justice approach

Current clinical models for addressing infidelity tend not to make social context issues a central focus; yet, societal gender and power structures, such as female responsibility for relationships and limited male vulnerability, affect the etiology of affairs and create power imbalances in intimate relationships. How therapists respond to these societal influences may either limit or enhance the mutual healing of both persons in the relationship. Thus attention to these societal processes is an ethical issue. This paper presents one perspective, the Relational Justice Approach, for working with infidelity. It places gender, power, and culture at the center of intervention in couple therapy, and includes three stages: (1) creating an equitable foundation for healing, (2) placing the infidelity in a societal context, and (3) practicing mutuality. Each stage is illustrated with case examples and contrasted with current practice regarding infidelity.     

甲型H1N1流感普通型与重症型的处理

本文回顾性总结历史上几次世界性甲型流感流行和2009年H1N1流感流行情况。概述了2009年H1N1流感普通型病例的临床处理。重点阐述2009年H1N1流感重症型病例的高危人群、发生的危险因素以及临床表现。特别强调重症型流感抗病毒治疗的重要性及适应证。同时提醒关注神经氨酸酶抑制剂应用的耐药问题。     

言语和非言语信号加工的早期分离——来自ERP研究的证据

利用128导事件相关电位技术,对19名正常被试在言语、峰鸣声和音乐刺激上产生的脑电早期外源性成分N1进行了考察。实验结果发现,在音素条件和蜂鸣声条件下,左侧额叶N1波幅显著高于右侧。偶极子溯源分析发现音素条件和蜂鸣声条件下的偶极子都位于左脑额叶,而音乐条件下的两个偶极子位于右脑额叶。证明范畴属性对信号加工大脑半球优势的影响在加工的早期就开始发挥作用。     

Enhanced learning by posttrial injection of H1-but not H2-histaminergic antagonists into the nucleus basalis magnocellularis region

The aim of this study was to examine the effects of histaminergic antagonists on memory upon injection into the region of the nucleus basalis magnocellularis (NBM). In experiment 1, rats with chronically implanted cannulae were trained on the uphill avoidance task, which involves a punishment of a high-probability turning response on a tilted platform (negative geotaxis). Immediately after the training trial, that is, after a tail shock was administered upon performing the response, rats received one microinjection (0.5 microliter) of H1-receptor blocker chlorpheniramine (dose range 0.1 to 20 microgram) or the H2-receptor blocker ranitidine (same dose range) or saline into the NBM region. When tested 24 h later, rats treated with chlorpheniramine (20 micrograms) had significantly longer uphill latencies than vehicle controls and ranitidine-treated animals, indicative of superior learning of the avoidance response. In experiment 2, a test for possible proactive effects of posttrial chlorpheniramine on performance during the retention trial was performed. Animals were injected with either 20 micrograms chlorpheniramine or saline immediately after the training trial of the uphill task. One chlorpheniramine control group was treated with a delay of 5 h. Additional groups which received chlorpheniramine or vehicle after the training trial but no trail shock were included. When tested 24 h later, rats injected with 20 micrograms chlorpheniramine again exhibited significantly longer uphill latencies than did vehicle-injected rats. Retention latencies for the rats of the chlorpheniramine 5-h delayed group did not differ from those of the vehicle-injected rats, ruling out proactive effects of chlorpheniramine on performance. In summary, the histaminergic H1-blocker chlorpheniramine can enhance mnemonic functioning in addition to its reinforcing effects upon NBM injection as reported previously.     

应激性抑郁样行为发生中海马5-羟色胺1A受体的作用及其对NMDA受体和AMPA受体的调节

为探讨慢性不可预见性温和应激(chronic unpredictable mild stress, CUMS)诱发抑郁样行为发生中海马5-羟色胺1A受体(5-hydroxytryptamine receptor 1A, 5-HT1AR)表达与作用, 及其对谷氨酸N-甲基-D-天冬氨酸(N-methyl-D-aspartic acid, NMDA)受体和α-氨基羟甲基异恶唑丙酸(α-amino-3-hydroxy-5- methylisoxazole-4-propionic acid, AMPA)受体的影响。通过建立CUMS动物模型, 给应激抑郁模型大鼠海马微量注射5-HT1A受体激动剂、给正常大鼠海马微量注射5-HT1A受体拮抗剂, 测量大鼠体重变化率, 并采用糖水偏爱测试、旷场实验和悬尾实验等方法对大鼠进行行为学检测, 运用Western blot和ELISA方法检测大鼠海马组织中5-HT1AR和NMDAR和AMPAR的关键亚基的表达以及磷酸化水平。结果显示, 与对照组相比, CUMS组大鼠表现出抑郁样行为, 海马5-HT1AR、AMPA受体的GluR2/3亚基表达及磷酸化明显降低, NMDA受体的NR1和NR2B亚基表达及磷酸化显著增加; 正常大鼠海马微量注射5-HT1A受体拮抗剂WAY100635, 动物行为学表现及AMPA受体、NMDA受体表达及磷酸化水平均与CUMS组相同; 注射5-HT1A受体激动剂8-OH-DPAT能逆转应激诱导的上述改变。以上结果表明, CUMS诱发抑郁样行为与海马5-HT1AR表达下降, AMPAR表达量及磷酸化水平降低, NMDAR表达量及磷酸化水平升高有关。5-HT通过5-HT1AR产生抗抑郁作用。5-HT1AR激动剂抗抑郁作用与降低NMDAR表达量及磷酸化水平, 提高AMPAR表达量及磷酸化水平密切相关。     

糖尿病高血压和糖尿病肾病患者血清MMP-2及TIMP-1的表达及意义

为了探讨MMP-2、TIMP-1在DMEH和DN发病中的意义,随机收集T2DM患者146例,其中SDM 57例,DMEH 38例,DN 51例,健康对照38例。用ELISA法测定MMP-2、TIMP-1的含量。结果显示,DM患者尤其是DMEH和DN患者血清MMP-2明显低于健康对照组,P均〈0.01,且随病情发展呈逐渐降低趋势。而血清TIMP-1随病情的发展则呈现明显的上升趋势,SDM、DMEH组和DN组与健康对照组比较,分别为P〈0.05,P〈0.01和P〈0.01。因此,MMP-2和TIMP-1可能参与了DMEH和DN的发生发展过程,定期检测DM患者血清MMP-2和TIMP-1的含量变化有助于DM并发症的早期诊断和疗效观察。     

Taxicab Correspondence Analysis

Taxicab correspondence analysis is based on the taxicab singular value decomposition of a contingency table, and it shares some similar properties with correspondence analysis. It is more robust than the ordinary correspondence analysis, because it gives uniform weights to all the points. The visual map constructed by taxicab correspondence analysis has a larger sweep and clearer perspective than the map obtained by correspondence analysis. Two examples are provided. This research was financed by the Natural Sciences and Engineering Research Council of Canada. The author thanks Serge Vienneau for his help regarding the graphical displays, and also thanks the editor, associate editor, and two reviewers for their constructive comments.     

Attitudes Toward Fragile X Mutation Carrier Testing from Women Identified in a General Population Survey

Fragile X syndrome is primarily due to a CGG repeat expansion found in the FMR1 X-linked gene. In a previous study, we conducted focus groups with women to assess their attitudes towards fragile X carrier screening. In this follow-up study, we conducted in-depth interviews of general population reproductive-age women who were identified as carriers. We explored their attitudes toward testing for carrier status of the fragile X mutation. These women underwent screening primarily to participate in a research project rather than in search of a diagnosis for specific symptoms. As such, these women were wholly unprepared for positive carrier results. Their responses about their results and carrier screening, in many cases, were being worked out over the course of the interview itself. The most salient finding of this work is the apparent lack of relevance of carrier status to these women. Many expressed that although the information could be relevant in the future, it is not relevant at this stage of their lives in terms of family planning (either with respect to having unaffected offspring or to premature ovarian failure) and personal relationships. Although issues of abortion seemed prominent in the focus groups, we found that carrier status did not have an apparent effect on women’s attitudes about termination. We hypothesize this may be related to the fact that women had not processed their new carrier status and had not related it to previously-formed personal opinions. The findings of this work have significant implications for genetic counseling and population screening. Genetic counselors should be mindful that general population women may not recognize the immediate importance of their carrier status even when literature is provided and discussed prior to providing a sample. As part of comprehensive genetic counseling, counselors should identify the reproductive life stage of the woman receiving the new information and help her identify when this information would be more meaningful in her life. Counselors can assist in setting up a personalized road map with specific types of services that will be more applicable to the woman as her carrier status becomes more relevant.     

Living with Multiple Endocrine Neoplasia Type 1: Decent Care-Insufficient Medical and Genetic Information A Qualitative Study of MEN 1 Patients in a Swedish Hospital

This qualitative study explores how 29 Swedish patients with Multiple Endocrine Neoplasia type 1 (MEN1) experience living with the condition, appraisal of the clinical follow-up program, and surveys their future expectations. The aim of this study is to build knowledge about this patient group in order to provide optimal care. The participants describe physical, psychological, and social limitations in their daily activities and how these limitations influence quality of life. Our findings indicate that a majority of patients have adjusted to their situation, describing themselves as being healthy despite physical symptoms and treatment. The participants received decent care in the clinical follow-up program, - however, greater effort should be put into patient information. These patients might benefit from genetic counseling. Health professionals involved should recognize their potential impact and influence on a patient’s ability to adjust to these circumstances. Antonovsky`s Sense of Coherence theory is used to discuss these findings.