An investigation of the role of ADAM-like Decysin 1 in intestinal mucosal inflammation

ADAM-like decysin 1 (ADAMDEC1) is a highly conserved metalloprotease which is exclusively expressed in the gastrointestinal (GI) tract, under healthy state, in various mammalian species including human. The physiological function and catalytical substrate of ADAMDEC1 remain unknown. However, a reduction in its normally high expression is seen within the tissue of GI inflammatory diseases and cancer, such as inflammatory bowel disease and colorectal cancer, which suggests that ADAMDEC1 is likely to play a vital role in physiology and potentially pathogenesis of GI diseases. Previous studies utilising dextran sodium sulfate (DSS) colitis model in Adamdec1 knockout (Adamdec1-/-) mice demonstrated an exaggerated mucosal inflammation during experimental colitis in these mice, thus the protective role of ADAMDEC1 in mucosal inflammation. However, the mechanism through which ADAMDEC1 mediates such a role in inflammation remains unknown. This project primarily aimed to characterise the role of ADAMDEC1 during intestinal mucosal inflammation. By utilising DSS-colitis model, the components of mucosal defence and immune response in which ADAMDEC1 might potentially be involved to mediate its protective role were narrowed down to: antigen presenting cell - T cell interaction, monocyte to macrophage differentiation, phenotype of monocytes and macrophages, polarisation of Th17 and Treg cells, susceptibility of epithelial cells to DSS, and inhibitory effect of ADAMDEC1 on bacterial enzymes. Furthermore, analysis of the gut microbiome of the Adamdec1-/- and WT mice revealed that ADAMDEC1’s role in mucosal inflammation was unlikely to be mediated via interaction with the microbiome. Finally, the marked impact of the environment on the gut microbiome and its impact on the expressivity of genotype were demonstrated. In conclusion, an advance was made in defining the potential role of ADAMDEC1 during mucosal inflammation. The project also demonstrated important challenges relating to environmental control when designing experiments to examine the phenotype of transgenic animals

言語行動分析の観点 : 「行動の仕方」を形づくる諸要素について

国立国語研究所The National Language Research Institute同じ目的をもつ言語行動でも,その実現の仕方はさまざまであり得る。本稿では,言語行動の行われ方を記述し,その特徴を多角的にとらえるための分析の観点を提案する。観点の収集にあたっては,大量調査資料を用いて同一場面におけるさまざまな話者の言語行動を分析し,バリエーションがあらわれる諸側面を考察した。そして,その所見をもとに,言語行動一般の特徴分析に有効と思われる以下の観点を抽出した。○全体的な構成:長さと複雑さ,はたらきかけの組み合せ,表現類型の組み合せ,「核」となるはたらきかけのあり方○はたらきかけの表現:表現類型,インパクトの強さや情報伝達の明確さを調節する表現,スピーチレベル,各種伝達手段(言話,パラ言語,非言語)の使い方○行動上の指向性:日的達成指向/対人配慮指向のあらわれ方This paper proposes factors to be considered in the multidimensional analysis of interpersonal linguistic behaviors. A linguistic behavior may be realized in a variety of ways, depending upon the speakers, the context, etc. This paper attempts to elucidate the linguistic and behavioral factors involved in the production of various linguistic behaviors; it also explores the possibility of characterizing the factors that might permit one to objectively explain everyday descriptions of linguistic behaviors, such as "a businesslike request", "warm advice", etc. Based upon an examination of the data (discourse-completion-type answers from 397 Japanese informants) from a sociolinguistic survey conducted by the National Language Research Institute, variation was observed in the use of interactional moves, sentence patterns, expressions (words and phrases), honorifics, and paralinguistic and nonverbal communication. Based upon observations made of the data, the following factors were extracted to be applied to the multidimensional analysis of linguistic behaviors in general. ・ overall structure of linguistic behaviors - length and complexity - combination of interactional moves - combination of sentence patterns - type and position of the "nuclear" move ・ expressions - sentence patterns - hedges and intensifiers - mode of providing information - speech levels - paralinguistic and nonverbal communication ・ orientation - goal achievement vs. politenes

The Role of Diet and Gut Microbiota in Regulating Gastrointestinal and Inflammatory Disease

Diet is an important lifestyle factor that is known to contribute in the development of human disease. It is well established that poor diet plays an active role in exacerbating metabolic diseases, such as obesity, diabetes and hypertension. Our understanding of how the immune system drives chronic inflammation and disease pathogenesis has evolved in recent years. However, the contribution of dietary factors to inflammatory conditions such as inflammatory bowel disease, multiple sclerosis and arthritis remain poorly defined. A western diet has been associated as pro-inflammatory, in contrast to traditional dietary patterns that are associated as being anti-inflammatory. This may be due to direct effects of nutrients on immune cell function. Diet may also affect the composition and function of gut microbiota, which consequently affects immunity. In animal models of inflammatory disease, diet may modulate inflammation in the gastrointestinal tract and in other peripheral sites. Despite limitations of animal models, there is now emerging evidence to show that anti-inflammatory effects of diet may translate to human gastrointestinal and inflammatory diseases. However, appropriately designed, larger clinical studies must be conducted to confirm the therapeutic benefit of dietary therapy

三者面接調査における回答者間の相互作用 : 同性の友人同士の場合

国立国語研究所国際交流基金日本語国際センターThe National Institute for Japanese LanguageThe Japan Foundation Japanese-Language Institute本稿では,三者間談話の一つとして2名の回答者に対する面接調査を取り上げ,そこに見られる回答者間の相互作用を分析した。調査者と回答者の間の質問-回答という基本的枠組みを持つ面接調査において,回答者間の相互作用は逸脱的行動にもなり得るが,実際には回答行動として機能していた。相互作用の種類としては,同意要求・情報確認とそれへの応答,もう一人の回答へのコメントとそれに対する応答・反応,互いの発話をふまえた回答,もう一人の回答への相づち・反応が観察された。本稿では,これらの相互作用が,回答行動のパターンに「調査者の質問に各々の回答者が個別に答える」以外の各種のサブタイプを出現させると同時に,回答者による談話行動においても回答以外のサブタイプを可能にしていたことを指摘する。In this paper, we analyze the interaction between the respondents in three survey interviews of two respondents each, as instances of three-party discourse. Given the basic question-answer structure of the survey interview, interaction between the respondents has the potential of becoming disruptive behavior. However, we found that on the contrary it functioned as answering behavior. We observed the following types of utterance functions: 1) opinion confirmation (agreement requests) /information confirmation requests and responses to these confirmation requests, 2) comments on the other respondent\u27s answers, and answers/responses to these comments, 3) answers based on the other respondent\u27s utterances, and 4) back channel and responses to the other respondent\u27s answers. We also demonstrate that these interactions gave rise to subtypes of answering behavior other than "each respondent answering questions separately," as well as subtypes of respondents\u27 communicational behavior other than answering

Effects of the order of exposure to antimicrobials on the incidence of multidrug-resistant Pseudomonas aeruginosa

Multidrug-resistant Pseudomonas aeruginosa (MDRP) is one of the most important pathogens in clinical practice. To clarify the mechanisms contributing to its emergence, we isolated MDRPs using the P. aeruginosa PAO1, the whole genome sequence of which has already been elucidated. Mutant strains resistant to carbapenems, aminoglycosides, and new quinolones, which are used to treat P. aeruginosa infections, were isolated; however, none met the criteria for MDRPs. Then, PAO1 strains were exposed to these antimicrobial agents in various orders and the appearance rate of MDRP varied depending on the order of exposure; MDRPs more frequently appeared when gentamicin was applied before ciprofloxacin, but were rarely isolated when ciprofloxacin was applied first. Exposure to ciprofloxacin followed by gentamicin increased the expression of MexCD-OprJ, an RND-type multidrug efflux pump, due to the NfxB mutation. In contrast, exposure to gentamicin followed by ciprofloxacin resulted in more mutations in DNA gyrase. These results suggest that the type of quinolone resistance mechanism is related to the frequency of MDRP and that the risk of MDRP incidence is highly dependent on the order of exposure to gentamicin and ciprofloxacin

Cyclin D1 activation through ATF-2 in Reg-induced pancreatic β-cell regeneration

AbstractRegenerating gene product (Reg) is induced in pancreatic β-cells and acts as an autocrine/paracrine growth factor for regeneration via a cell surface Reg receptor. However, the manner by which Reg induces β-cell regeneration was unknown. In the present study, we found that Reg increased phospho-ATF-2, which binds to −57 to −52 of the cyclin D1 gene to activate the promoter. The Reg/ATF-2-induced cyclin D1 promoter activation was attenuated by PI(3)K inhibitors such as LY294002 and wortmannin. In Reg knockout mouse islets, the levels of phospho-ATF-2, cyclin D1, and phospho-Rb were greatly decreased. These results indicate that the Reg–Reg receptor system stimulates the PI(3)K/ATF-2/cyclin D1 signaling pathway to induce β-cell regeneration

Genetic polymorphisms related to muscular strength and flexibility are associated with artistic gymnastic performance in the Japanese population

departmental bulletin pape

Poly ADP-ribose Polymerase (PARP) Staining for Immunohistological Investigation of Primary Breast Cancer

Given that clinical trials of poly ADP-ribose polymerase (PARP) 1 inhibitors are underway, in the present study we investigated the prevalence of triple-negative breast cancer and PARP1 expression in patients with primary invasive breast cancer. Immunohistological studies plus PARP staining were performed on samples from 206 primary breast cancer patients undergoing surgery at Showa University Hospital between January 2010 and May 2011. Fifteen patients (7.3%) were found to have triple-negative breast cancer. Hormone receptor-positive patients were significantly more likely to be PARP1 negative. There were no PARP1-negative patients in the triple-negative group. However, there was no significant difference in the rate of PARP1 negativity between patients with triple-negative breast cancer and those with other breast cancer subtypes. There were no PARP1-negative patients in the triple-negative breast cancer group. Given that the effectiveness of PARP inhibitors has not been sufficiently established in clinical trials, a more in-depth analysis is required to determine the factors contributing to effective treatment. Future studies should include more subjects with triple-negative breast cancer and those with BRCA mutations