Characterization of Functional Multiplicity of an Activation Site by the Interaction Among Neuro-Circuits as Probed by fMRI Responses to Different Stimulus Inputs

It is known that a functional site is often activated by various stimuli of different characteristics and that it is hard to determine the functional specificity of such a site. We used a paired stimulus paradigm to probe characteristics of processing activities of various sites in fusiform areas in the ventral visual pathway where the shape of a visual object is recognized. The processing activities induced by a pair of stimuli at a site interact each other if the neural events are temporally close. The interaction appears in most cases as suppression of the neural response to the second inputs of the pair. We observed areas where fairly strong interaction was present between the activities induced by stimuli of different categories such as face and building. On the other hand, those areas known to be very specific to these categories showed very weak interaction in the processing activities by the paired stimuli of the same category but with different contents such as different faces or different buildings. The observation indicates that these category specific sites contain loosely connected sub-sites or neuro-circuits, which work on particular contents in the inputs.     

SFRP2与Periostin的相互作用在瘢痕疙瘩形成机制中的研究

目的利用pull-down技术验证凋亡相关蛋白基因SFRP2（Secreted frizzled-related protein 2）和骨母细胞特异性因子-2 Periostin（Osteoblast-specific factor2）间的相互作用。方法构建能在哺乳动物细胞中表达带HA标签的Periostin融合蛋白（HA—Periostin）的重组载体pCMV—HA—Periostin,经酶切鉴定正确后,和表达带Myc标签的融合蛋白（Myc—SFRP2）的重组真核表达载体pCMV—HA—SFRP2,单独或共转染人293细胞,利用pull-down技术验证Periostin与SFRP2间的相互作用。结果成功构建重组载体pCMV—HA-Periostin．与抗Myc单克隆抗体沉淀Myc—SFRP2相互作用蛋白复合物后,可以检测到HA—PeMostin的表达。通过体外蛋白质结合实验证实了Periostin与SFRP2间的相互作用。结论成功构建带HA标签的Periostin融合蛋白（HA-Periostin）的重组载体,利用pull—down技术证实了Periostin与SFRP2间的存在相互作用。     

Interaction models of CYP1A1, GSTM1 polymorphisms and tobacco smoking in intestinal gastric cancer

AIM: To explore the interaction models of the cytochrome P-450 (CYP) 1A1 Val variant and glutathione S-transferase (GST) M1 null polymorphisms with tobacco smoking in the occurrence of intestinal gastric cancer. METHODS: A community-based case-control study was conducted in Yangzhong. Subjects included 114 intestinal types of gastric cancer with endoscopic and pathological diagnosis during January 1997 and December 1998, and 693 controls selected from their spouse, siblings or siblings-in-law who had no history of digestive system cancer. Logistic regression was used to estimate the interaction models. RESULTS: The frequency of the CYP1A1 Val variant allele in cases did not differ from that in controls. The OR of GSTM1 null genotype was 2.0 (95% confidence interval (95%CI): 1.2-3.1, P<0.01). It showed a significant type 2 form of interaction model when both CYP1A1 Val variant allele and former tobacco smoking existed (i.e., among the multiplicative effects, the disease risk is increased by the tobacco exposure alone but not by the CYP1A1 variant alone). The interaction index gamma was 2.8, and OR(eg) (95%CI) was 5.0 (1.9-13.4). GSTM1 null genotype and former tobacco smoking were significant in a type 4 interaction model (i.e., the disease risk is increased by GSTM1 null genotype or tobacco exposure alone among the multiplicative effects). The interaction index gamma and OR(eg) (95%CI) were 3.4 and 8.4 (3.4-20.9), respectively. CONCLUSION: Different interaction models of CYP1A1 Val variant allele and GSTM1 null genotype with tobacco smoking will contribute to understanding carcinogenic mechanism, but there is a need to further investigate in larger scale studies.     

Metabolic studies on the possible mode of action of isoniazid tumorigenicity

Summary Data on tumorigenicity and mutagenicity of INH show that INH is tumorigenic in mice but not in rats. The metabolic studies on the two species denote that rats are rapid inactivators whereas mice are slow inactivators of INH. Rats are also resistant to the immediate inhibitory effect of INH on DNA biosynthesis. Using Ames test it was observed that INH is mutagenic to salmonella typhimurium strains TA 100 and 1535 and this effect is abolished in presence of 59 mixture. In vivo and in vitro studies on INH interaction with macromolecules reveal that there is a greater interaction with RNA than with DNA and the site of interaction is the cytidine and deoxycytidine, respectively. A preliminary study is undertaken to see if healed TB cases have a higher risk for cancer. It is found that cancer incidence in this group is higher as compared to noncancer patients.     

钙离子信号调节亲环素配体研究进展

钙离子信号调节亲环素配体(CAML)作为亲环素B的结合蛋白于1994年被首次发现,尽管其具体作用机制目前还不十分清楚,但许多研究已证实其在T细胞受体及钙离子信号转导、细胞凋亡、免疫调节以及病毒感染等方面具有重要作用.目前已经报道与其相互作用的蛋白主要有:跨膜激活剂及钙调亲环素配体相互作用分子(transmembrane activator and CAML interactor,TACI)、EGF受体,血管紧张素ⅡⅠ型受体相关蛋白(AT1 receptorassociated protein,ATRAP)、人立早基因(immediate early gene X-1,IEX-1)、淋巴细胞特异蛋白质酪氨酸激酶(p56Lck)、常染色体隐性遗传性多囊肾疾病的相关基因PKHD1编码的蛋白fibrocystin,以及霍普金氏肉瘤相关疱疹病毒K7蛋白(KSHV)等.本文就CAML相关研究进展作简要综述.     

砷与5-氮胞苷对人淋巴细胞DNA损伤的联合作用

为探讨砷和5－氮胞苷对人淋巴细胞DNA损伤及修复的联合作用，应用单细胞凝胶电泳（SCGE）技术比较研究了5－氮胞苷与砷同时和前后作用于人类淋巴细胞产生的联合毒性，结果显示10μmol/L5-氮胞苷和10μmol/L砷单独处理人淋巴细胞2h引起明显的DNA泳动（彗星尾），但两试剂引起的DNA泳动（彗星尾）间无显差异，5－氮胞苷前处理与砷后处理2h引起的彗星尾与其单独处理组比较非常显，砷前处理与5－氮胞苷后处理引起的彗星尾与其单独处理组比较无显性差异，但较对照组差异显，10μmol/L5-氮胞苷和10μmol/L砷分别单独处理2h引起了人淋巴细胞显的DNA损伤（链断裂），5－氮胞苷与砷在对淋巴细胞DNA的损伤上表现为单纯相加作用。5－氮胞苷前处理显增加了细胞对砷的基因毒性的敏感性，或砷后处理显增加了5－氮胞苷引起的DNA损伤，5－氮胞苷后处理2h显抑制了细胞对砷所致DNA损伤的修复。     

Standardization for Subgroup Analysis in Randomized Controlled Trials

Randomized controlled trials (RCTs) emphasize the average or overall effect of a treatment (ATE) on the primary endpoint. Even though the ATE provides the best summary of treatment efficacy, it is of critical importance to know whether the treatment is similarly efficacious in important, predefined subgroups. This is why the RCTs, in addition to the ATE, also present the results of subgroup analysis for preestablished subgroups. Typically, these are marginal subgroup analysis in the sense that treatment effects are estimated in mutually exclusive subgroups defined by only one baseline characteristic at a time (e.g., men versus women, young versus old). Forest plot is a popular graphical approach for displaying the results of subgroup analysis. These plots were originally used in meta-analysis for displaying the treatment effects from independent studies. Treatment effect estimates of different marginal subgroups are, however, not independent. Correlation between the subgrouping variables should be addressed for proper interpretation of forest plots, especially in large effectiveness trials where one of the goals is to address concerns about the generalizability of findings to various populations. Failure to account for the correlation between the subgrouping variables can result in misleading (confounded) interpretations of subgroup effects. Here we present an approach called standardization, a commonly used technique in epidemiology, that allows for valid comparison of subgroup effects depicted in a forest plot. We present simulations results and a subgroup analysis from parallel-group, placebo-controlled randomized trials of antibiotics for acute otitis media.     

Bayesian Assessment of the Influence and Interaction Conditions in Multipopulation Tailoring Clinical Trials

Multipopulation tailoring trials provide a trial design option that supports the realization of tailored therapeutics or personalized medicine. Several recent publications have focused on statistical and clinical considerations that arise in these trials that are designed to study the overall treatment effect in a population of interest as well as one or more prospectively defined subpopulations. Millen et al. (2012 Millen , B. A. , Dmitrienko , A. , Ruberg , S. , Shen , L. ( 2012 ). A statistical framework for decision making in confirmatory multipopulation tailoring clinical trials . Drug Information Journal 46 : 647 – 656 .[Web of Science ®] , [Google Scholar]) introduced the influence and interaction conditions as part of a general framework to facilitate decision making in multipopulation trials. This article provides Bayesian methods for assessing the influence and interaction conditions. The methods introduced are illustrated using case studies based on clinical trials with biomarker-driven designs.     

Exploring interaction effects in small samples increases rates of false-positive and false-negative findings: results from a systematic review and simulation study

ObjectiveTo give a comprehensive comparison of the performance of commonly applied interaction tests.MethodsA literature review and simulation study was performed evaluating interaction tests on the odds ratio (OR) or the risk difference (RD) scales: Cochran Q (Q), Breslow–Day (BD), Tarone, unconditional score, likelihood ratio (LR), Wald, and relative excess risk due to interaction (RERI)-based tests.ResultsReview results agreed with results from our simulation study, which showed that on the OR scale, in small sample sizes (eg, number of subjects ≤ 250) the type 1 error rates of the LR test was 0.10; the BD and Tarone tests showed results around 0.05. On the RD scale, the LR and RERI tests had error rates around 0.05. On both scales, tests did not differ regarding power. When exposure prevented the outcome RERI-based tests were relatively underpowered (eg, N = 100; RERI power = 5% vs. Wald power = 18%). With increasing sample size, difference decreased.ConclusionIn small samples, interaction tests differed. On the OR scale, the Tarone and BD tests are recommended. On the RD scale, the LR and RERI-based tests performed best. However, RERI-based tests are underpowered compared with other tests, when exposure prevents the outcome, and sample size is limited.