Transient Receptor Potential 1 Regulates Capacitative Ca2+ Entry and Ca2+ Release from Endoplasmic Reticulum in B Lymphocytes〉

Capacitative Ca2+ entry (CCE) activated by release/depletion of Ca2+ from internal stores represents a major Ca2+ influx mechanism in lymphocytes and other nonexcitable cells. Despite the importance of CCE in antigen-mediated lymphocyte activation, molecular components constituting this mechanism remain elusive. Here we demonstrate that genetic disruption of transient receptor potential (TRP)1 significantly attenuates both Ca2+ release-activated Ca2+ currents and inositol 1,4,5-trisphosphate (IP3)-mediated Ca2+ release from endoplasmic reticulum (ER) in DT40 B cells. As a consequence, B cell antigen receptor–mediated Ca2+ oscillations and NF-AT activation are reduced in TRP1-deficient cells. Thus, our results suggest that CCE channels, whose formation involves TRP1 as an important component, modulate IP3 receptor function, thereby enhancing functional coupling between the ER and plasma membrane in transduction of intracellular Ca2+ signaling in B lymphocytes

Ancient Jomon genome sequence analysis sheds light on migration patterns of early East Asian populations

Anatomically modern humans reached East Asia more than 40,000 years ago. However, key questions still remain unanswered with regard to the route(s) and the number of wave(s) in the dispersal into East Eurasia. Ancient genomes at the edge of the region may elucidate a more detailed picture of the peopling of East Eurasia. Here, we analyze the whole-genome sequence of a 2,500-year-old individual (IK002) from the main-island of Japan that is characterized with a typical Jomon culture. The phylogenetic analyses support multiple waves of migration, with IK002 forming a basal lineage to the East and Northeast Asian genomes examined, likely representing some of the earliest-wave migrants who went north from Southeast Asia to East Asia. Furthermore, IK002 shows strong genetic affinity with the indigenous Taiwan aborigines, which may support a coastal route of the Jomon-ancestry migration. This study highlights the power of ancient genomics to provide new insights into the complex history of human migration into East Eurasia

Clinical and immunological evaluation of anti-apoptosis protein, survivin-derived peptide vaccine in phase I clinical study for patients with advanced or recurrent breast cancer

<p>Abstract</p> <p>Background</p> <p>We previously reported that survivin-2B, a splicing variant of survivin, was expressed in various types of tumors and that survivin-2B peptide might serve as a potent immunogenic cancer vaccine. The objective of this study was to examine the toxicity of and to <b>c</b>linically and immunologically evaluate survivin-2B peptide in a phase I clinical study for patients with advanced or recurrent breast cancer.</p> <p>Methods</p> <p>We set up two protocols. In the first protocol, 10 patients were vaccinated with escalating doses (0.1–1.0 mg) of survivin-2B peptide alone 4 times every 2 weeks. In the second protocol, 4 patients were vaccinated with the peptide at a dose of 1.0 mg mixed with IFA 4 times every 2 weeks.</p> <p>Results</p> <p>In the first protocol, no adverse events were observed during or after vaccination. In the second protocol, two patients had induration at the injection site. One patient had general malaise (grade 1), and another had general malaise (grade 1) and fever (grade 1). Peptide vaccination was well tolerated in all patients. In the first protocol, tumor marker levels increased in 8 patients, slightly decreased in 1 patient and were within the normal range during this clinical trial in 1 patient. With regard to tumor size, two patients were considered to have stable disease (SD). Immunologically, in 3 of the 10 patients (30%), an increase of the peptide-specific CTL frequency was detected. In the second protocol, an increase of the peptide-specific CTL frequency was detected in all 4 patients (100%), although there were no significant beneficial clinical responses. ELISPOT assay showed peptide-specific IFN-γ responses in 2 patients in whom the peptide-specific CTL frequency in tetramer staining also was increased in both protocols.</p> <p>Conclusion</p> <p>This phase I clinical study revealed that survivin-2B peptide vaccination was well tolerated. The vaccination with survivin-2B peptide mixed with IFA increased the frequency of peptide-specific CTL more effectively than vaccination with the peptide alone, although neither vaccination could induce efficient clinical responses. Considering the above, the addition of another effectual adjuvant such as a cytokine, heat shock protein, etc. to the vaccination with survivin-2B peptide mixed with IFA might induce improved immunological and clinical responses.</p

表現における主観性と間主観性

金田 晋: (研究代表者)刊行にあたって 1 金田 晋: 表現の間主観性への現象学的問い(1) 2 古東 哲明: ウーティスの永遠 12 高橋 憲雄: 表現・対話・理性 30 安西 信一: 「開かれた庭」のパラドックス 37 斎藤 稔: 絵画表現における間主観性 53 圀府寺 司: ファン・ゴッホ神話 65 永田 雄次郎: 江戸時代狩野派の絵画教育と制作活動 72 幣原 映智: J. A. Berard: L'Art du chantに見られる演奏家の資質 82 原 正幸: 《准南子》の音楽観 91 青木 孝夫: 能楽のレトリック その1 102 水島 裕雅: 「空の色」の表現についての一考察 114研究期間:平成3-4年度 ; 研究種目:一般研究B ; 課題番号: 0345100

表現におけるアイコニシティと意味作用

金田 晋: 美と時間性 1 高橋 憲雄: 「書く」ことの意味 17 古東 哲明: 逆説コレクション 47 品川 哲彦: 類似による把握と人格概念 61 水島 裕雅: 『万葉集』における「空(そら)」の転義について 75 圀府寺 司: ファン・ゴッホ《烏の群れ飛ぶ麦畑》 : 物語の結びとしての「絶筆」 90 原 正幸: 生と〈リズム〉 : アウグスティヌス《音楽論》第VI巻再考 99 青木 孝夫: 演劇の類像的表現について : 「天満屋の場面」(『曾根崎心中』より)の分析を例に 110研究期間:平成5-7年度 ; 研究種目:一般研究B ; 課題番号: 0545101