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The current study examines the extent to which religiosity account for ideological orientations in 16 countries from five continents (Australia, Brazil, Chile, Germany, Greece, Finland, Israel, Italy, Japan, Poland, Slovakia, Spain, Turkey, Ukraine, the United Kingdom, and the United States). Results showed that religiosity was consistently related to right and conservative ideologies in all countries, except Australia. This relation held across different religions, and did not vary across participant’s demographic conditions (i.e., gender, age, income, and education). After controlling for basic personal values, the contribution of religiosity on ideology was still significant. However, the effect was substantial only in countries where religion has played a prominent role in the public sphere, such as Spain, Poland, Greece, Italy, Slovakia, and Turkey. In the other countries, the unique contribution of religiosity was marginal or small.

The current study examines the contribution of right-left (or conservative-liberal) ideology to voting, as well as the extent to which basic values account for ideological orientation. Analyses were conducted in 16 countries from 5 continents (Europe, North-America, South-America, Asia, and Oceania), most of which have been neglected by previous studies. Results showed that left-right (or liberal-conservative) ideology predicted voting in all countries except Ukraine. Basic values exerted a considerable effect in predicting ideology in most countries, especially in established democracies like Australia, Finland, Italy, UK, and Germany. Pattern of relations with the whole set of ten values revealed that the critical trade-off underlying ideology is between values concerned with tolerance and protection for the welfare of all people (universalism) versus values concerned with preserving the social order and status quo (security). A noteworthy exception was found in European post-communist countries, where relations of values with ideology were small (Poland) or near to zero (Ukraine, Slovakia).

We studied a Japanese family with type I antithrombin (AT) deficiency and identified a novel in-frame deletion mutation (-ATG at nucleotide position of 2771-2773) in the AT gene, which predicted loss of a methionine (Met) at amino acid number of 103. In addition, we found a single base replacement of G to A at nucleotide position of 67 (4 base upstream to the initial codon) in the mutant allele. Since the G67A substitution in the AT gene was very rare, this family was the second case, in which the nucleotide change was transmitted. To elucidate the mechanism of AT deficiency, we transiently expressed wild type and the mutant AT (DeltaM103) in HuH-7 human hepatoma cells and performed pulse-chase studies. The experiments revealed that the mutant AT (DeltaM103) hardly secreted into the medium and underwent partial intracellular degradation. In addition, we performed luciferase reporter assay to examine the effect of G67A substitution on the AT gene expression, and found that the substitution did not reduce the luciferase activity. These results suggested that secretion defect and intracellular degradation of the variant molecule with the deletion of Met 103 were responsible for AT deficiency in this family.

Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) of the elderly (EBV[+]DLBCL-E) is classified as a subtype of DLBCL. Until now, its molecular pathogenesis has remained unknown. To identify pathways characteristic of EBV(+)DLBCL-E, gene expression profiling of five EBV(+)DLBCL-E and seven EBV-negative DLBCL (EBV[-]DLBCL) cases was undertaken using human oligonucleotide microarray analysis. Gene set enrichment analysis and gene ontology analysis showed that gene sets of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) and nuclear factor kappa B (NF-κB) pathways were enriched in EBV(+)DLBCL-E cases. To confirm the results of the expression profiles, in vitro analysis was performed. Expression profiling analysis showed that high activation of the JAK-STAT and NF-κB pathways was induced by EBV infection into DLBCL cell lines. Activation of the NF-κB pathway was confirmed in EBV-infected cell lines using an electrophoretic mobility shift assay. Western blot analysis revealed an increased protein expression level of phosphorylated signal transducer and activator of transcription 3 (STAT3) in an EBV-infected cell line. Protein expression of phosphorylated STAT3 was frequently observed in lymphoma cells of EBV(+)DLBCL-E clinical samples using immunohistochemistry (EBV[+]DLBCL-E: 80.0% [n = 20/25] versus EBV[-]DLBCL: 38.9% [n = 14/36]; P = 0.001). The results of the present study suggest that activation of the JAK-STAT and NF-κB pathways was characteristic of EBV(+)DLBCL-E, which may reflect the nature of EBV-positive tumor cells. Targeting these pathways as therapies might improve clinical outcomes of EBV(+)DLBCL-E.

The purpose of this article is to study interpersonal cognition of resource allocation and individual differences in the cognition. Sixty subjects participated in an experimental game, and 18 individualists and 16 cooperators were selected according to their tendency in resource allocation, which is called social values. Then, they rated resource allocating behavior. Major findings were as follows: (1) Both groups rated “allocating more resource to the partner” as more socially desirable and friendly. (2) Individualists rated “allocating more resource to self, ” which was consistent with their social values, as more socially desirable. They also rated “equal allocation with own resource adjusted” as more socially desirable but less dynamic. (3) Cooperators rated “equal allocation with own resource adjusted, ” which was consistent with their social values, as more socially desirable and friendly. (4) Both groups rated “more resource to self” and “less resource to the partner” as dynamic (active and assertive). The relation between interpersonal cognition and social values is discussed.

NK cell neoplasms are lymphoid malignancies with an aggressive clinical course. In the present study, we analyzed gene expression profiling of NK cell neoplasms and attempted to identify important molecular pathways and new effective drugs. Pathway analysis of gene expression profiles suggested the important roles of the JAK-STAT pathway, NF-κB pathway or Wnt pathways in NK cell neoplasms. Notably, western blot analysis revealed that STAT3 was expressed and phosphorylated at a higher level in NK cell lines than in normal NK cells or other cell lines. These findings indicate the occurrence of JAK-STAT activation in NK cell neoplasms. Connectivity Map (CMAP) analysis of gene expression profiles identified candidate drugs against NK cell neoplasms. Among the drugs suggested by CMAP analysis, we focused on puromycin, phenoxybenzamine, LY294002, wortmannin, vorinostat and trichostatin A because they exhibited high enrichment scores. We added these drugs to NK cell lines and other cell lines. Among the drugs, vorinostat suppressed NK cell line proliferation at a significantly lower concentration compared to other cell lines. Suppression of the JAK-STAT pathway appeared to contribute to this effect. Vorinostat may be a good candidate for use in the therapy against NK cell neoplasms.

Introduction: Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of non-Hodgkin lymphomas noted for their poor prognosis. Their molecular pathogenesis has not been entirely elucidated. We previously found that primary thyroid T-cell lymphoma (PTTL) is a distinct entity among heterogeneous PTCLs and that this disease is characterized by the genomic loss of 6q24 (Br J Haematol., 161:214-223). In this study, we extended the analysis to other types of PTCLs and performed functional assays to identify causative genes located on 6q24. Methods: Focusing on chromosome 6q loss, we reexamined previous comparative genomic hybridization data from 267 PTCL cases comprising 6 PTTLs, 51 PTCLs-not otherwise specified (NOS), 62 adult T-cell leukemias/lymphomas, 35 natural killer (NK)-cell lymphomas, 39 angioimmunoblastic T-cell lymphomas (Genes Chromosomes Cancer, 46:37-44), and 74 anaplastic large cell lymphomas (Br J Haematol., 140:516-526). Gene expression levels were determined by using published gene expression profiling (GEP) data (GSE6338 and GSE19069) and quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). Subsequently, we established Tet-Off cell lines belonging to several lineages (6 T-cell lines, 1 NK-cell line, 4 B-cell lines, 1 myeloid cell line, and 3 epithelial cell lines) for functional analyses. Results: Genomic loss of 6q24 was observed in 8% (n = 267) of PTCL cases, and it occurred most frequently in PTTL cases (67%; n = 6). All the genomic losses were heterozygous; homozygous loss of this region was not observed in our analysis. The smallest region of deletion, observed in a PTTL case, was considered the minimal common region (MCR) of 6q24 loss. The MCR contained 2 known coding genes, STX11 and UTRN. Combined GEP data and quantitative RT-PCR analyses showed that the expression of STX11, but not UTRN, was markedly lower in PTCL than in normal T-cells. We therefore regarded STX11 as the most probable candidate gene located in 6q24. Syntaxin 11, encoded by STX11, is a t-SNARE protein that plays a role in binding vesicles to cell membranes, and alteration of STX11 in the germline causes familial hemophagocytic syndrome type 4. To further evaluate genomic alteration of STX11, mutation analysis was performed on PTCL-NOS and PTTL cases as well as T-cell lines, for which adequate DNA was available. This revealed STX11 mutations in 2 cases (1 PTCL-NOS case and 1 T-cell line). Wild-type STX11 expression suppressed the proliferation of T-cell lines bearing genomic alterations at the STX11 locus only, and it did not show suppressive effects on other lineage cell lines (Fig. 1). Expression of STX11 induced cellular apoptosis in the cell line, although the number of apoptotic cells induced was relatively small. Interestingly, expression of a novel STX11 mutant (p.Arg78Cys), observed in a T-cell line, did not exert suppressive effects on the induced cell lines suggesting that there was a loss-of-function mutation (Fig. 2). Finally, we evaluated the clinical impact of STX11 alteration in PTTL and PTCL-NOS cases where data were available. This showed that PTCL-NOS cases with genomic alterations of STX11 tended to have a poorer prognosis than those without (Fig. 3; P = 0.069). Conclusion: In the present study, we examined the MCR of 6q24 loss and showed that STX11 acts as a tumor suppressor gene in PTCLs only. These findings provide a novel approach for understanding the molecular pathogenesis of PTCLs, and they may contribute to the future development of new drugs for the treatment of PTCLs. Disclosures No relevant conflicts of interest to declare.

Age-related EBV-associated B-cell lymphoproliferative disorder (AR-EBVLPD) is newly classified as a subtype of diffuse large cell lymphoma (DLBCL) according to the WHO classification. AR-EBVLPD cases have poor prognosis compared to that of EBV-negative DLBCL patients. Until now, its molecular pathogenesis remains largely unknown. We investigated gene expression profiling to identify molecular genetic characterization of AR-EBVLPD. Total RNA was extracted from fresh-frozen tumor samples of five AR-EBVLPD and eight EBV-negative DLBCL cases. Expression profiling was studied using the Agilent 44K human oligonucleotide microarray. Genes highly expressed in AR-EBVLPD included inflammatory and immune-related genes. Gene set enrichment analysis and gene ontology analysis showed that gene sets of the JAK-STAT and NF-kB pathways were enriched in AR-EBVLPD cases. In vitro analysis showed that high activation of JAK-STAT and NF-kB pathways was induced by EBV infection into DLBCL cell lines. The immunoprecipitation assay confirmed that the NF-kB pathway was activated in EBV-infected cell lines compared to EBV-naïve cell lines. The protein expression level of phosphorylated STAT3 increased in an EBV-infected cell line according to western blot analysis. A total of 61 patients (25 AR-EBVLPD and 36 EBV-negative DLBCL) were analyzed immunohistochemically for pSTAT3. Protein expression of phospho-STAT3 was frequently observed in lymphoma cells of AR-EBVLPD clinical samples using immunohistochemistry [AR-EBVLPD: (80.0%, n=20/25) vs. EBV-negative DLBCL: (38.9%, n=22/36), p=0.001]. These results suggested that STAT3 and NF-kB activation was characteristic of AR-EBVLPD, which may reflect the nature of EBV-positive tumor cells. Targeting these pathways as therapies might improve clinical outcomes of AR-EBVLPD. Citation Format: Harumi Kato, Kazuhito Yamamoto, Kennosuke Karube, Jun Takizawa, Shinobu Tsuzuki, Yasushi Yatabe, Teru Kanda, Miyuki Katayama, Yukiyasu Ozawa, Kenji Ishitsuka, Masataka Okamoto, Tomohiro Kinoshita, Koichi Oshima, Shigeo Nakamura, Yasuo Morishima, Masao Seto. Gene expression profiling identifies characteristic oncogenetic pathways in age-related Epstein-Barr virus (EBV)-positive B-cell lymphoproliferative disorders. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2014. doi:10.1158/1538-7445.AM2013-2014

Although self-disclosure after a negative experience may be good for our adjustment, we also feel hesitant to do so. This study investigated the relationship between self-esteem and hesitancy to disclose negative information about one's self. One hundred and fifty-five undergraduates imagined self-disclosure to a friend of high or low intimacy. They then answered a questionnaire concerning hesitancy to self-disclose negative information to friends, as well as expected negative consequences of such self disclosure. Main results were: (1) Low intimacy strongly affected the hesitancy. (2) Factor analysis of the negative consequences found three factors: interpersonal and intra-personal negative-effect, and no positive expectation. (3) Hesitancy of high self-esteem students was most affected by the interpersonal factor. Impression management may be the reason. (4) On the other hand, low students tended to feel hurt after negative self-disclosure. Theirs was affected by the intra-personal and no positive expectation factors. Defensiveness may be the reason. The results were discussed from the viewpoint of adjustment when people have had a negative experience.

Abstract 3448 Age-related EBV-associated B-cell lymphoproliferative disorder (AR-EBLPD) is classified as a subtype of diffuse large cell lymphoma (DLBCL) according to the WHO classification. However, molecular genetic characterization of AR-EBLPD remains largely unknown. We studied expression profiles of 5 AR-EBLPD and 8 EB-negative DLBCL samples using the Agilent 44K human oligonucleotide microarray. Total RNA was extracted from fresh-frozen tumor samples. Each microarray slide was converted into datasets using the Agilent Micro Array Scanner and Feature extractions. Data was standardized with Z-scores. Differences in mRNA expression levels between two sample groups were calculated using a two-sided t-test. A total of 1973 probes showed a p-value less than 0.05 with less than a 25% false discovery rate (FDR). These probes included 1688 genes. The number of probes showing high expression in AR-EBLPD and EB-negative DLBCL was 804 (693 genes) and 1169 (995 genes), respectively. First, we selected the top 300 differentially expressed genes. Genes highly expressed in AR-EBLPD included IL6, TNFAIP3, HOPX, and SLAMF1. IL6 is known as a gene encoding a cytokine which functions in inflammation and the maturation of B lymphocytes, and TNFAIP3 is known as a negative regulatory gene of the NF-kB pathway. HOPX and SLAMF1 are reported as genes related to lymphocyte function or the immune system (Schwartzberg et al. Nature immunology 2009, Hawiger et al. Nature immunology 2011). For better characterization, we next performed Gene Ontology Analysis using the WEB-based GEne SeT AnaLysis Toolkit and found that categories of external stimulus and inflammatory responses were enriched in AR-EBLPD. The Kyoto Encyclopedia of Genes and Genomes (KEGG)-signaling analyses showed that pathways of the NOD-like receptor (p-value =1.30e-06), JAK-STAT (p-value =9.01e-06), and Toll-like receptor (p-value =0.0002) were characteristic of AR-EBLPD. These results implied that inflammation would be prominent in AR-EBLPD cases. For validation, we next performed Gene Set Enrichment Analysis (GSEA) using all the database of KEGG pathways (186 gene sets). Dominant gene sets in AR-EBLPD included the cytokine-cytokine receptor interaction [Normalized Enrichment Score (NES) =2.66, p-value (Figure 1) Gene Set Enrichment Analysis of 5 AR-EBLPD and 8 EB-negative DLBCL samples. The NF-kB signature reported from an NIH group (Puente et al. Nature 2011) was enriched in AR-EBLPD [Normalized Enrichment Score (NES) =2.20, p-value Disclosures: No relevant conflicts of interest to declare.