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The role of processing bodies (P-bodies), key sites of post-transcriptional control, in adult stem cells remains poorly understood. Here, we report that adult Drosophila intestinal stem cells, but not surrounding differentiated cells such as absorptive enterocytes (ECs), harbor P-bodies that contain Drosophila orthologs of mammalian P-body components DDX6, EDC3, EDC4, and LSM14A/B. A targeted RNAi screen in intestinal progenitor cells identified 39 previously known and 64 novel P-body regulators, including Patr-1, a gene necessary for P-body assembly. Loss of Patr-1-dependent P-bodies leads to a loss of stem cells that is associated with inappropriate expression of EC-fate gene nubbin. Transcriptomic analysis of progenitor cells identifies a cadre of such weakly transcribed pro-differentiation transcripts that are elevated after P-body loss. Altogether, this study identifies a P-body-dependent repression activity that coordinates with known transcriptional repression programs to maintain a population of in vivo stem cells in a state primed for differentiation.

Pathological osteolysis is associated with excessive bone resorption by activated osteoclasts. Given that receptor activator of NF-kB and its ligand (RANKL) are key players in the differentiation and activation of osteoclasts, the RANKL/RANK signaling pathway is considered a promising target for the development of effective osteoclastogenesis inhibitors. We previously found that the orally available compound, AS2690168, suppresses RANKL-induced osteoclastogenesis of RAW264 cells. In this report, we further characterized the pharmacological profiles of AS2690168 in vitro and in vivo. AS2690168 suppressed soluble RANKL (sRANKL)-induced NFATc1 mRNA expression in RAW264 cells at 0.3 and 3.0 μM. It also suppressed calcium release from parathyroid hormone-stimulated mouse calvaria with an IC

In eukaryotes, specific DNA-protein structures called telomeres exist at linear chromosome ends. Telomere stability is maintained by a specific capping protein complex. This capping complex is essential for the inhibition of the DNA damage response (DDR) at telomeres and contributes to genome integrity. In Drosophila, the central factors of telomere capping complex are HOAP and HipHop. Furthermore, a DDR protein complex Mre11-Rad50-Nbs (MRN) is known to be important for the telomere association of HOAP and HipHop. However, whether MRN interacts with HOAP and HipHop, and the telomere recognition mechanisms of HOAP and HipHop are poorly understood. Here, we show that Nbs interacts with Mre11 and transports the Mre11-Rad50 complex from the cytoplasm to the nucleus. In addition, we report that HOAP interacts with both Mre11 and Nbs. The N-terminal region of HOAP is essential for its co-localization with HipHop. Finally, we reveal that Nbs interacts with the N-terminal region of HOAP.

This study aims to elucidate 1-year clinical outcomes using this technique for patients with stage 4 or 5 advanced chronic kidney disease (CKD). Research has proven that imaging-guided percutaneous coronary intervention (PCI) reduces contrast volume significantly; however, only short-term clinical benefits have been reported. Minimum-contrast (MINICON) studies are based on the registry design pattern to enroll PCI results in patients with advanced CKD stage 4 or 5 comorbid with coronary artery disease. We excluded cases of emergency PCI or maintenance dialysis from this study. In this study, we compared the intravascular ultrasound (IVUS)-guided MINICON PCI group (n = 98) with the angiography-guided standard PCI group (n = 86). Enrollment of the MINICON studies started in 2006. Before 2012, IVUS-guided MINICON PCI was performed only in 14% (stage 1), but it was 100% after 2012 (stage 2). The enrollment finished in 2016. The IVUS-guided MINICON PCI group exhibited a significantly reduced contrast volume (22 ± 20 vs. 130 ± 105 mL; P

Transposable elements not only can change genomic positions and disperse across the gene pool, but also can jump to another species through horizontal transmission. Of late, the P element, a DNA transposon in insects, was shown to cross the genetic boundary from Drosophila melanogaster to D. simulans in Europe around 2006. To understand the dynamics of transposable elements, especially in the early stages of invasion, we examined 63 lines of D. simulans from 11 natural populations in Japan established in 1976-2015. Based on PCR analyses, P elements were demonstrated to exist in Japan in 2008 and later. One copy of the full-length P element was identified and mapped to a site on chromosome 3 L in a genome. All of 18 copies of P elements examined shared "A" at the nucleotide position 2040, which is representative of the direct descendants of the original P element that invaded in D. simulans. We also found that some lines having P elements can induce intensive gonadal dysgenesis in D. simulans at 29°C. Our present results imply that P elements in D. simulans arrived at the east end of Asia just a few years later than or almost simultaneously to the initial invasion in Europe, Africa, and North America, suggesting a more astonishingly rapid spread than previously assumed.

本研究では京都市と大阪市という二つの都市の都心区のマンション住民に質問紙調査を行い、その比較分析を行った。関西を代表するこれらの都市の都心区で起こったことは、1990年頃まで減少していた人口が大規模なマンションの建設により増加を始めたことである。両都市の「都心回帰」のジエントリファイヤーであるマンション住民が増加することによって、①専門的・技術的職業従事者が増加し、事務職やサービス職従業者は漸増、生産工程従事者や運輸関係従事者は減少しており、地域社会の階層構造が大きく変化している。また、彼らは、②交通の利便性や通勤・通学の便を求めて都心に移住してきたことが共通点であった。他方で、マンション住民の近隣交際や地域活動への参与は大阪市では低くなっており、京都市ではある程度はなされていた。また、町内会などの地域住民組織の加入は大阪市では京都に比べてかなり低かった。そして、彼らのコミュニティ意識は、京都市では「共同体」意識が、大阪市では「コミュニティ」意識が相対的に高かった。, This study aims at a comparative analysis between the urban condominium residents of Kyoto city and Osaka city by conducting a questionnaire survey in a central ward of each city. Due to the large-scale developments of condominiums, the central wards of the two cities have experienced population growth since around 1990, after several decades of population decline. The influx of new residents has altered the social composition of the central wards; the number of professional workers has increased, while the number of blue-collar workers has decreased. Our analysis reveals that in both cities, the most important reason why those gentrifiers, have migrated to the areas is traffic accessibility to places of works/schools, residents of Osaka have less social connections in their neighborhood than those of Kyoto. And residents of Kyoto tend to respect and obey local rules/traditions compared with those of Osaka who aspire to improve their community through cooperation with neighbors., 論文(Article)

The continuity of life depends on mechanisms in the germline that ensure the integrity of the genome. The DNA damage response/checkpoint kinases ATM and ATR are essential signaling factors in the germline. However, it remains unknown how a downstream transducer, Checkpoint Kinase 1 (CHEK1 or CHK1), mediates signaling in the male germline. Here, we show that CHEK1 has distinct functions in both the mitotic and meiotic phases of the male germline in mice. In the mitotic phase, CHEK1 is required for the resumption of prospermatogonia proliferation after birth and the maintenance of spermatogonia. In the meiotic phase, we uncovered two functions for CHEK1: one is the stage-specific attenuation of DNA damage signaling on autosomes, and the other is coordination of meiotic stage progression. On autosomes, the loss of CHEK1 delays the removal of DNA damage signaling that manifests as phosphorylation of histone variant H2AX at serine 139 (γH2AX). Importantly, CHEK1 does not have a direct function in meiotic sex chromosome inactivation (MSCI), an essential event in male meiosis, in which ATR is a key regulator. Thus, the functions of ATR and CHEK1 are uncoupled in MSCI, in contrast to their roles in DNA damage signaling in somatic cells. Our study reveals stage-specific functions for CHEK1 that ensure the integrity of the male germline.

大都市では2000年前後より、人口の「都心回帰」が起こっている。本論では都心の地域社会の変容を、大阪市北区菅南地区を事例として探った。当地区は、大阪の都心地域の中でも、曽根崎や堂島などの最都心部に隣接する住商混合地域である。また大阪天満宮を中心とした伝統行事を継承している地域でもある。産業構造の変化や高齢化によって旧住民は減少する一方だが、地域に急増したマンションの新住民の地域社会への関わりは薄い。このような都心社会の問題状況と可能性を考察した。, Since around 2000, metropolitan regions including the City of Osaka, have experienced rapid population growth, so called "back to the city movement." In this thesis, the impact of urban core revival in Kannan district in Kita Ward, one of the central districts of Osaka, has been examined by census data and interview data of the community leaders. The characteristic of the area is to be the mixture of residential and commercial areas and also it is a traditional district strongly influenced by the culture of the Osaka Tenmangu Shrine. While long-tern residents are decreasing, new condominium residents are dramatically increasing. Although they tend not to involve in the local communities, some cases seem to open up the possibilities., 論文(Article)

The spatial and temporal availability of cytokines, and the microenvironments this creates, is critical to tissue development and homeostasis. Creating concentration gradients in vitro using soluble proteins is challenging as they do not provide a self-sustainable source. To mimic the sustained cytokine secretion seen in vivo from the extracellular matrix (ECM), we encapsulated a cargo protein into insect virus-derived proteins to form nanoparticle co-crystals and studied the release of this cargo protein mediated by matrix metalloproteinase-2 (MMP-2) and MMP-8. Specifically, when nerve growth factor (NGF), a neurotrophin, was encapsulated into nanoparticles, its release was promoted by MMPs secreted by a PC12 neuronal cell line. When these NGF nanoparticles were spotted onto a cover slip to create a uniform circular field, movement and alignment of PC12 cells via their extended axons along the periphery of the NGF nanoparticle field was observed. Neural cell differentiation was confirmed by the expression of specific markers of tau, neurofilament, and GAP-43. Connections between the extended axons and the growth cones were also observed, and expression of connexin 43 was consistent with the formation of gap junctions. Extensions and connection of very fine filopodia occurred between growth cones. Our studies indicate that crystalline protein nanoparticles can be utilized to generate a highly stable cytokine gradient microenvironment that regulates the alignment and differentiation of nerve cells. This technique greatly simplifies the creation of protein concentration gradients and may lead to therapies for neuronal injuries and disease.

Objectives The fractional flow reserve (FFR) is an index of the severity of coronary stenosis that has been clinically validated in several studies. The instantaneous wave-free ratio (iFR) and the resting distal coronary artery pressure/aortic pressure (Pd/Pa) are nonhyperemic pressure-derived indices of the severity of stenosis. This study sought to examine the diagnostic accuracy of the iFR and resting Pd/Pa with respect to hyperemic FFR. Methods Following an intracoronary injection of papaverine, the iFR, resting Pd/Pa, and FFR were continuously measured in 123 lesions in 103 patients with stable coronary disease. Results The iFR and resting Pd/Pa values were strongly correlated with the FFR (R=0.794, p0.89 and a Pd/Pa value of >0.92 were defined as double-negative lesions. In these 109 lesions, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 92.3%, 82.9%, 75.0%, 95.1%, and 86.2%, respectively. Conclusion This analysis demonstrated that the iFR and resting Pd/Pa were strongly correlated with the FFR and that the diagnostic accuracy of the iFR was similar to that of the resting Pd/Pa. The diagnostic accuracy can be improved with the use of both the iFR and the resting Pd/Pa.

2000年前後より，大都市都心部に生じている人口の「都心回帰」による地域コミュニティの変化を探るために，京都市都心部の中京区で行ったコミュニティ調査の結果を事例として分析し，都心住民の生活実態と社会意識を大阪都心区との比較の視点も加えて分析した。その結果，コミュニティ意識の全体的な高さ，地域住民組織とのつながり，政治的信頼感の高さなどに「京都の」都心居住を志向する住民の特徴があることがわかった。, Since around 2000, Japanese major cities have witnessed urban core revival, which have changed local communities in various ways. The author examined on the lifestyle and social consciousness by analyzing questionnaire survey in Nakagyo Ward in Kyoto conducted in 2014 as a case study. The author found that some aspects characterized urban core residents of Kyoto such as higher sense of community, more connectedness to local community associations, and more confidence in politics compare to a case of urban core residents in Osaka., 論説(Article)

名古屋市でも1990年代後半以降、人口の「都心回帰」が顕著になった。都心の地域コミュニティはどのような変化を経験し、人口の再増加を牽引しているマンションの新住民の社会的背景にはどのような特徴があるのか。統計分析、都心部の学区でのインタビュー調査、中区内のマンション住民への質問紙調査の結果、増加は主に単身世帯や夫婦世帯で、居住満足度や定住志向は高いが、地域住民組織への参加は低調である、しかしコミュニティ形成の契機は一定程度あるため、今後のとりくみが重要であることが明らかになった。, Since the late 1990s, Nagoya has experienced the changing trend of the urban core population resulting from rapid increase of middle- and high-rise condominiums in the district like other major cities. In this condition, what changes have local communities faced? What is the social character and consciousness of new condominium residents? With interviews and a questionnaire survey in the Naka ward of Nagoya, we found that the population increase can be attributed to that of single-person and married-couple households, and that the socio-economic status of new condominium residents is higher than that of the long-term residents, and that most of the residents are not actively involved in the neighborhood association although some of them participate. Consequently, many of the existing neighbourhood associations struggle with ageing and decreasing active members., 論文(Article)

In order to investigate genetic impact of a large amount of radionuclides released by the Fukushima Dai-ichi Nuclear Power Plant accident in 2011, we surveyed 2,304 haploid genomes of Drosophila melanogaster collected in three localities in Fukushima in 2012 and 2013 for chromosomal inversions. No unique inversion was found in 298 genomes in 2012 and only two in 2,006 genomes in 2013. The observed frequencies were even lower than the long-term average frequency of unique inversions in Japan. The common cosmopolitan inversions were also examined in Fukushima, Kyoto, and Iriomote (Okinawa) in 2012. Among three samples in Fukushima, the flies in Iizaka, where environmental radiation level was the highest, showed the lowest frequency of In(2L)t, but the highest frequency of In(3R)P, contrary to the expectation of decreasing of their frequencies in higher polluted areas. These results suggest that, at this level of genetic analysis, Fukushima populations of D. melanogaster would not have been negatively impacted following the release of radionuclides. Transposable P-element mobility was not likely to induce DNA damage solely or synergistically with radioactivity, because their transposition activity was totally repressed in the Fukushima strains. However, it should be noted that, because of limitations in access to the exclusion zone, we could only sample the populations in areas of relatively low radioactive contamination (0.39-0.63 μSv/h). Therefore, the present study is likely to be underpowered to detect any effects that might be expected in heavily contaminated areas.

Transposable elements not only can change genomic positions and disperse across the gene pool, but also can jump to another species through horizontal transmission. Of late, the P element, a DNA transposon in insects, was shown to cross the genetic boundary from Drosophila melanogaster to D. simulans in Europe around 2006. To understand the dynamics of transposable elements, especially in the early stages of invasion, we examined 63 lines of D. simulans from 11 natural populations in Japan established in 1976–2015. Based on PCR analyses, P elements were demonstrated to exist in Japan in 2008 and later. One copy of the full‐length P element was identified and mapped to a site on chromosome 3 L in a genome. All of 18 copies of P elements examined shared “A” at the nucleotide position 2040, which is representative of the direct descendants of the original P element that invaded in D. simulans. We also found that some lines having P elements can induce intensive gonadal dysgenesis in D. simulans at 29°C. Our present results imply that P elements in D. simulans arrived at the east end of Asia just a few years later than or almost simultaneously to the initial invasion in Europe, Africa, and North America, suggesting a more astonishingly rapid spread than previously assumed.

Objective Measuring the fractional flow reserve (FFR) requires the induction of coronary hyperemia, usually with adenosine, adenosine triphosphate (ATP), or papaverine. However, adenosine can induce rhythmic complications, and intracoronary boluses of papaverine that prolong the QT interval can cause ventricular tachycardia. Injection of contrast media, which is routinely performed to validate the FFR guidewire placement, also induces hyperemia and may be an alternative method of measuring the FFR. We evaluated the diagnostic accuracy of the FFR after contrast hyperemia (FFRcont) compared to FFR evaluated after intracoronary papaverine (FFRpp). Methods This study included 109 lesions in 93 patients (mean age 70.4±8.7 years) with stable coronary disease. The FFR was measured as follows: 1) baseline pressure value; 2) FFRcont after intracoronary contrast injection (iopamidol, 8 mL for left coronary artery [LCA] or 6 mL for right coronary artery [RCA]); 3) FFRpp after intracoronary injection of papaverine (12 mg for LCA or 8 mg for RCA). Results FFRcont values were strongly correlated with FFRpp (R=0.940, p

日本の大都市では1990年代後半から都心人口が減少から増加に転じたが,なかでも東京都中央区の変化は急激である。都心人口の再増加が地域社会に与えるインパクトを解明する前段階として,東京都中央区を対象に官庁統計およびマンション住民に対する質問紙調査のデータ資料によって分析を行った。その結果、都心マンション急増によって今までとは異なるアッパーミドル層が集住し,地域のネットワークや近隣商業,政治を変えていく可能性が示唆された。, Since the late 1990s Japanese major cities have witnessed a shift from decline to growth of its population in urban core areas and Chuo ward in Tokyo demonstrated a particularly high increase. This study aims to examine the impact of resurgence in urban core population growth on local communities with two materials such as analysis of census data in Chuo ward, and the questionnaire survey of new condominium residents in Chuo ward. The findings suggest that increased condominium construction in urban core areas can promote inflow of upper-middle class residents, what consequently brings a possibility of changes in local networks, neighborhood commercial zones and urban politics., 論文(Article)

米国の1990年代の都心回帰の現象によって生じたジェントリフィケーションの主体、ジェントリファイヤーに注目した。彼らは一般的には低所得者を都心から追い出す者として否定的に語られることが多い。本稿ではシカゴ市都心で行われた都心回帰高齢者へのインタビュー調査から彼らの社会的役割を考察した。その結果、彼らは非常に活動的で貢献的活動を含む多くの社会活動に参加していることを発見し、都心社会に一定の貢献をしていると結論づけた。, The back to the city movement was occurred in 1990s in the U.S., which gave rise to phenomenon of gentrification. Author focused the actors, gentrifiers, who were generally described as negative character in that they ran low-income residents out of the cities. In this paper however, author examined gentrifiers' social roles using interview data got by seniors who moved into a downtown Chicago. Author concluded that gentrifiers contributed to their urban communities to certain extent as author found that they were very active and participated lots of social activities including contributory activities., 論文(Article)

The major role of BRCA1 in meiosis is not in meiotic recombination but instead in promotion of the dramatic chromatin changes required for formation and function of the XY body., During meiosis, DNA damage response (DDR) proteins induce transcriptional silencing of unsynapsed chromatin, including the constitutively unsynapsed XY chromosomes in males. DDR proteins are also implicated in double strand break repair during meiotic recombination. Here, we address the function of the breast cancer susceptibility gene Brca1 in meiotic silencing and recombination in mice. Unlike in somatic cells, in which homologous recombination defects of Brca1 mutants are rescued by 53bp1 deletion, the absence of 53BP1 did not rescue the meiotic failure seen in Brca1 mutant males. Further, BRCA1 promotes amplification and spreading of DDR components, including ATR and TOPBP1, along XY chromosome axes and promotes establishment of pericentric heterochromatin on the X chromosome. We propose that BRCA1-dependent establishment of X-pericentric heterochromatin is critical for XY body morphogenesis and subsequent meiotic progression. In contrast, BRCA1 plays a relatively minor role in meiotic recombination, and female Brca1 mutants are fertile. We infer that the major meiotic role of BRCA1 is to promote the dramatic chromatin changes required for formation and function of the XY body.

Introduction Aspirin inhibits both the cyclooxygenase (COX)-1-dependent production of thromboxane A2 (TXA2) in platelets and COX-2-dependent production of anti-aggregatory prostaglandin I2 (PGI2) in vessel walls, resulting in “aspirin dilemma.” Our objective is to investigate whether ASP6537 can overcome aspirin dilemma and exert a potent antithrombotic effect without a concurrent ulcerogenic effect. Methods We evaluated the inhibitory effects of ASP6537 on recombinant human COX-1 (rhCOX-1) and rhCOX-2 activities using a COX-1/2 selectivity test. To determine whether ASP6537 induces aspirin dilemma, we examined the effects of ASP6537 on in vitro TXA2 and PGI2 metabolite production from platelets and isolated aorta of guinea pigs, and on plasma concentrations of TXA2 and PGI2 metabolites in aged rats. Finally, we evaluated the antithrombotic effects and ulcerogenic activity of ASP6537 using an electrically induced carotid arterial thrombosis model and a gastric ulcer model in guinea pigs. Results The IC50 ratios of rhCOX-2 to rhCOX-1 for ASP6537 and aspirin were > 142,000 and 1.63 fold, respectively. ASP6537 inhibited TXA2 production more selectively than aspirin in in vitro and in vivo TXA2/PGI2 production studies. ASP6537 exerted a significant antithrombotic effect at ≥ 3 mg/kg, while aspirin tended to inhibit thrombosis at 300 mg/kg but it was not statistically significant. Further, ASP6537 did not induce ulcer formation at 100 mg/kg, whereas aspirin exhibited an ulcerogenic effect at doses of ≥ 100 mg/kg. Conclusions ASP6537 functions as a highly selective COX-1 inhibitor with a superior ability to aspirin for normalizing TXA2/PGI2 balance, and exerts antithrombotic effect without ulcerogenic effect.

Bovine trypsin was modified with glucose through the Maillard reaction at 50°C and 65% RH for various periods (1 to 8 days). Tryptic activity against both benzoyl-L-arginine-p-nitroanilide and two protein substrates was enhanced with increases in the reaction period, and reached the maximum after a 4-day reaction. Although there were no big differences in pH dependency of trypsin activity between native and modified trypsins, the Km of the modified trypsin decreased to about half the native one. The modified trypsin retained its original activity almost completely after incubation in a buffer solution of pH 8.0 at 37°C for 72 h, while native trypsin was greatly inactivated. Furthermore, tryptic acitivity at high temperature, residueal activity after heating, and differential scanning calorimetric analysis showed that the modified trypsin was more heat-stable than native trypsin.

Background Generally, newly progressed coronary lesions (NPCLs) are considered to be composed of lipid-rich plaques. In case of vulnerable plaque rupture, they may quickly become culprit lesions responsible for acute coronary syndromes. Methods Between September 2011 and September 2015, 2034 patients underwent scheduled follow-up coronary angiography (CAG) after percutaneous coronary intervention (PCI) in Tsuchiya General Hospital. Patients with NPCLs found by CAG during the follow-up period were evaluated by optical coherence tomography (OCT). NPCLs were defined as the lesions with less than 50% diameter stenosis, which progressed to more than 75% diameter stenosis within 3years after the previous CAG. Patients with restenosis after PCI were excluded. We compared OCT findings of NPCLs between symptomatic and asymptomatic patients. Results The follow-up CAG showed NPCLs in 64 patients (3.2%). OCT revealed fibrous plaque in 42 patients (65.6%) and thin-cap fibroatheroma in one patient. Thirteen patients had chest symptoms for one month before CAG and the remaining 51 patients were asymptomatic. The prevalence of fibrous plaque and intimal disruption or plaque rupture were not significantly different between symptomatic and asymptomatic patients (61.5% vs. 66.7%, p=0.752 and 30.8% vs. 11.8%, p=0.213, respectively). However, thrombi were more frequently observed in symptomatic patients (61.5% vs. 13.7%, p Conclusions The majority of NPCLs found in asymptomatic patients at follow-up CAG were not vulnerable; however, those found in symptomatic patients might be vulnerable. In clinical practice, NPCLs found in asymptomatic patients should be evaluated for functional severity of stenosis in order to determine the need for coronary revascularization.

Introduction: We assessed whether QT interval was still different between male and female patients with primary aldosteronism. We also assessed the gender difference in the relation between serum potassium level and QT interval. Materials and methods: The study population consisted of 80 patients with newly diagnosed primary aldosteronism. There were 39 male and 41 female patients. Results: There were no significant (ns) differences in serum potassium (3.6±0.7 mEq/l vs 3.8±0.5mEq/l, p =ns) and QTc interval (423±26 msec vs 427±23 msec, p =ns) between male and female patients. In overall patients, serum potassium level was inversely associated with QTc interval significantly ( r =−0.36, p

Residual risk of cardiovascular events after treatment with stain might be explained in part because patients have low levels of n−3 polyunsaturated fatty acids (PUFA). We examined how lipid-lowering therapy with strong statin affected serum PUFA levels in patients with coronary artery disease. The study population consisted of 46 patients with coronary artery disease whose low-density lipoprotein (LDL) cholesterol was more than 100 mg/dl. Lipid-lowering therapy was performed with a strong statin including atorvastatin (n = 22), rosuvastatin (n = 9) or pitavastatin (n = 15). Serum PUFA levels were determined by gas chromatography. The treatment with strong statin decreased the sum of dihomo-γ-linolenic acid (DGLA) and arachidonic acid (AA) levels (195 ± 41 to 184 ± 44 μg/ml, P < 0.05) as well as the sum of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels (233 ± 71 to 200 ± 72 μg/ml, P < 0.001). These effects of strong statin resulted in a significant decrease in ratio of the sum of EPA and DHA levels to the sum of DGLA and AA levels (1.20 ± 0.27 to 1.10 ± 0.35, P < 0.05). The percent decrease in the LDL cholesterol level correlated significantly with that in the sum of EPA and DHA levels (r = 0.38, P < 0.01). In conclusion, our results showed that lipid-lowering therapy with strong statin mainly reduced n−3 PUFAs in proportion to the decrease in the LDL cholesterol level in patients with coronary artery disease.

Intracellular mRNA localization and translation are ways to achieve asymmetric protein sorting in polarized cells, and they play fundamental roles in cell-fate decisions and body patterning during animal development. These processes are regulated by the interplay between cis-acting elements and trans-acting RNA-binding proteins that form and occur within a ribonucleoprotein (RNP) complex. Recent studies in the Drosophila oocyte have revealed that RNP complex assembly in the nucleus is critical for the regulation of cytoplasmic mRNA localization and translation. Furthermore, several trans-acting factors promote the reorganization of target mRNAs in the cytoplasm into higher-order RNP granules, which are often visible by light microscopy. Therefore, RNA localization and translation are likely to be coupled within these RNP granules. Notably, diverse cytoplasmic RNP granules observed in different cell types share conserved sets of proteins, suggesting they have fundamental and common cellular functions.

Aliskiren is a novel blood pressure-lowering agent acting as an oral direct renin inhibitor. We evaluated the effects of aliskiren on the fibrinolytic system in patients with coronary artery disease who were receiving angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II type 1 receptor blockers (ARBs). We studied 17 patients with coronary artery disease whose systolic blood pressure was more than 130 mmHg despite treatment with ACEIs or ARBs. Aliskiren (150 mg) was added to ACEIs or ARBs, and was continued for 6 weeks. Aliskiren significantly decreased systolic blood pressure (140 ± 6-128 ± 8 mmHg, P < 0.001) and plasma renin activity (1.8 ± 2.3-0.6 ± 0.9 ng/ml/h, P < 0.01) after 6 weeks. However, it did not affect plasminogen activator inhibitor-1 (28.8 ± 14.5-30.6 ± 13.6 ng/ml, P = 0.84), fibrinogen (305 ± 72 vs 301 ± 71 mg/dl, P = 0.33), or D-dimer (0.49 ± 0.24-0.51 ± 0.28 μg/ml, P = 0.70) levels. Our data suggested that patients receiving ACEIs or ARBs would not be expected to have any changes in biomarkers of the fibrinolytic system with additional pharmacologic inhibition of the renin-angiotensin-aldosterone system.

Background: Several reports have recently described the variant form of takotsubo cardiomyopathy exhibiting midventricular ballooning. The purpose of this study was to assess electrocardiographic (ECG) findings on admission in patients with midventricular ballooning. Hypothesis: ECG findings are different between the midventricular ballooning form and apical ballooning form of takotsubo cardiomyopathy. Methods: We reviewed ECGs on admission in 6 patients with midventricular ballooning and 20 patients with apical ballooning. The sum of ST segment elevation in leads V1 to V3 or in leads V4 to V6 was obtained. The number of leads showing ST segment elevation and/or T wave inversion was also obtained. These ECG findings were compared between the 2 groups. Results: In midventricular ballooning, ECG changes including ST segment elevation and/or T wave inversion were observed frequently in leads V2 and V3, and were not observed in leads II, III, −aVR, aVF, V5, and V6. On the other hand, in apical ballooning, they were found in all leads. They were most common in leads V4 and V5. The sum of ST segment elevation in leads V1 to V3 was similar (2.6 ± 2.0 mm vs 2.7 ± 2.0 mm, P = not significant), and the sum of ST segment elevation in leads V4 to V6 was significantly lower in midventricular ballooning than apical ballooning (0.4 ± 0.8 mm vs 3.5 ± 3.0 mm, P

Background: The transradial approach has several pitfalls that include problems regarding the radial puncture and difficulties with the catheter technique. We evaluated whether external side-compression of radial artery was helpful to yield the success rate for advancement of guidewires under the presence of side branches or arterial tortuosity. Methods and Results: The study population consisted of 11 patients with unsuccessful advancement of guidewires into the brachial artery. In 7 patients, the J-tip hydrophilic guidewire was not advanced into the brachial artery because it always directed into the side branch. During external side-compression of radial artery at the culprit site with a finger of the second operator, the guidewire was successfully advanced into the brachial artery in all patients. In 4 patients, the guidewire was not advanced into the brachial artery because the radial artery was tortuous. During external side-compression of radial artery at the culprit site, the guidewire was successfully advanced into the brachial artery in 2 patients. In the remaining 2 patients in whom this attempt was unsuccessful, coronary angiography was performed through the right brachial artery. Overall success rate of this technique was 82%. Conclusion: External side-compression of radial artery is an easy and feasible technique for difficulties in the advancement of guidewires due to the presence of side branches or arterial tortuosity. (J Interven Cardiol 2011;24:397–400)

Throughout life, new neurons are added and old ones eliminated in the adult mouse olfactory bulb. Previous studies suggested that olfactory experience controls the process by which new neurons are integrated into mature circuits. Here we report novel olfactory-experience-dependent mechanisms of neuronal turnover. Using two-photon laser-scanning microscopy and sensory manipulations in adult live mice, we found that the neuronal turnover was dynamically controlled by olfactory input in a neuronal subtype-specific manner. Olfactory input enhanced this turnover, which was characterized by the reiterated use of the same positions in the glomeruli by new neurons. Our results suggest that olfactory-experience-dependent modification of neuronal turnover confers structural plasticity and stability on the olfactory bulb.

Drosophila pole (germ) plasm contains germline and abdominal determinants. Its assembly begins with the localization and translation of oskar (osk) RNA at the oocyte posterior, to which the pole plasm must be restricted for proper embryonic development. Osk stimulates endocytosis, which in turn promotes actin remodeling to form long F-actin projections at the oocyte posterior pole. Although the endocytosis-coupled actin remodeling appears to be crucial for the pole plasm anchoring, the mechanism linking Osk-induced endocytic activity and actin remodeling is unknown. Here, we report that a Golgi-endosomal protein, Mon2, acts downstream of Osk to remodel cortical actin and to anchor the pole plasm. Mon2 interacts with two actin nucleators known to be involved in osk RNA localization in the oocyte, Cappuccino (Capu) and Spire (Spir), and promotes the accumulation of the small GTPase Rho1 at the oocyte posterior. We also found that these actin regulators are required for Osk-dependent formation of long F-actin projections and cortical anchoring of pole plasm components. We propose that, in response to the Osk-mediated endocytic activation, vesicle-localized Mon2 acts as a scaffold that instructs the actin-remodeling complex to form long F-actin projections. This Mon2-mediated coupling event is crucial to restrict the pole plasm to the oocyte posterior cortex.

研究ノート(Research note)

Background: ω-5 Gliadin is known as a major allergen in wheat-dependent exercise-induced anaphylaxis. The characteristics that make ω-5 gliadin an allergen remain unclear. Methods: Mice were sensitized by means of intraperitoneal injection of gliadin fractions together with the adjuvant alum. Anaphylactic responses were assessed by measuring body temperature and voluntary physical activity. Specific IgE levels in mouse serum were evaluated by ELISA. After oral administration of proteins to mice, concentrations of administered proteins in their portal blood were also analyzed by competitive inhibition ELISA. Results: Oral administration of ω-5 gliadin evoked significant decreases in body temperature and physical activity of sensitized mice, whereas the gliadin fraction did not induce these effects at the same dose. These responses were exercise independent. ELISA analysis revealed that IgE antibodies from sensitized mice react to ω-5 gliadin with great efficacy. After oral administration of either the gliadin fraction or ω-5 gliadin, blood levels of ω-5 gliadin were much higher than those of the gliadin fraction. Conclusions: ω-5 Gliadin caused anaphylaxis in sensitized mice, whereas the gliadin fraction did not at the same dose. The anaphylactic response was exercise independent. It is likely that IgE of sensitized mice reacts strongly to ω-5 gliadin and that ω-5 gliadin is better absorbed from the gastrointestinal tract than other components of the gliadin fraction. These results indicated that ω-5 gliadin has prominent characteristics as an allergen and that exercise might be an indirect factor in anaphylaxis induction.

The sirolimus-eluting stent (SES) has dramatically reduced restenosis in patients with most types of coronary lesions, but bifurcation lesions remain a predictor of poor prognosis even in SES implantation. We aimed to determine the clinical outcomes of the left main trunk (LMT) side branches (SB) treated with a single SES strategy. SES implantation was successfully performed on 70 patients with LMT stenosis from August 2005 to August 2008. Of the 70 patients, 55 patients (59 SB) were treated with a single SES and a jailed SB. The 56 SB were divided into two groups according to percent diameter stenosis immediately following percutaneous coronary intervention (PCI) (Group 1: >50%; Group 2

Stressful exercise results in temporary immune depression. However, the impact of exercise on the immune responses via toll-like receptor (TLR) 7, which recognizes the common viral genomic feature, single-stranded RNA, remains unclear. To clarify the effect of stressful exercise on immune function in response to viral infection, we measured the changes in the plasma concentration of tumor necrosis factor (TNF)-α and interferon (IFN)-α, which are induced downstream from the TLR-ligand interaction, in exhaustive-exercised mice immediately after treatment with the imidazoquinoline R-848, which can bind to and activate TLR7. Both exhaustive-exercised (EX) and non-exercised (N-EX) male C3H/HeN mice were injected with R-848 (5 mg kg(-1)), and blood samples were collected. In addition, RAW264 cells, which are mouse macrophage cells, were cultured 30 min after epinephrine (10 μM) or norepinephrine (10 μM) treatments, and were then stimulated with R-848 (10 μg ml(-1)). In addition, the effect of propranolol (10 mg kg(-1)) as blockade of β-adrenergic receptors on R-848-induced TNF-α and IFN-α production in the exercised mice was examined. Both the TNF-α and IFN-α concentrations in the plasma of EX were significantly lower than those in the plasma of N-EX after R-848 injection (P < 0.05 and P < 0.01, respectively), although the R-848 treatment increased the plasma TNF-α and IFN-α concentrations in both groups (P < 0.01, respectively). The R-848-induced TNF-α production in RAW264 cells was significantly inhibited by epinephrine and norepinephrine pre-treatment, although IFN-α was not detected. The propranolol treatment completely inhibited exercise-induced TNF-α and IFN-α suppression in response to R-848 in the mice. These data suggest that EX induces a reduction in TNF-α and IFN-α production in response to R-848, and that these phenomena might be regulated by an exercise-induced elevation of the systemic catecholamines.

日本の大都市では2000年を画期として都心回帰がみられる。その原因は、不況によりオフィス需要が減少し、大型マンションが建てられ、新住民の居住が促進されたためである。大阪市特有の地域住民組織「地域振興会」へのインタビューを通して、大阪市における新住民と旧住民との関係について調査した。その結果から、新住民のそれへの参加は少なく、旧住民中心の振興町会側も対応に苦慮し、新旧住民間の交流やコミュニティの形成が課題となっていることが判明した。, Japanese metropolises have regained population and experienced re-urbanization ever since 2000. The construction of large scale condominiums brought huge numbers of new residents into the areas. We conducted research in Osaka's central city areas and examined how the demographic transformation in the areas affected local communities, focusing on the relationships between new residents and old residents. In Osaka city, the Tiikishinkokai serves as the community-based organization. We found new residents tend to have little concern for the community and cherish privacy while old residents involve themselves deeper in the community. This discord makes it difficult to nurture better understanding between them. The leaders of the associations are now facing these challenges., 論文(Article)

Mitochondrial beta-oxidation is an important system involved in the energy production of various cells. In this system, the function of L-carnitine is essential for the uptake of fatty acids to mitochondria. However, it is unclear whether or not endogenous respiration, ADP-induced O(2) consumption without substrates, is caused by L-carnitine treatment. In this study, we investigated whether L-carnitine is essential to the beta-oxidation of quarried fatty acids from the mitochondrial membrane by phospholipase A(2) (PLA(2)) using isolated mitochondria from the liver of rats. Intact mitochondria were incubated in a medium containing Pi, CoA and L-carnitine. The effect of L-carnitine treatment on ADP-induced mitochondrial respiration was observed without exogenous respiratory substrate. Increase in mitochondrial respiration was induced by treatment with L-carnitine in a concentration-dependent manner. Treatment with rotenone, a complex I blocker, completely inhibited ADP-induced oxygen consumption even in the presence of L-carnitine. Moreover, the L-carnitine dependent ADP-induced mitochondrial oxygen consumption did not increase when PLA(2) inhibitors were treated before ADP treatment. The L-carnitine-dependent ADP-induced oxygen consumption did contribute to ATP productions but not heat generation via an uncoupling system. These results suggest that L-carnitine might be essential to the beta-oxidation of quarried fatty acids from the mitochondrial membrane by PLA(2).

Objective: Stressful exercise reduces the plasma pro-inflammatory cytokine concentration in response to lipopolysaccharide (LPS). The aim of this study was to clarify the mechanism of exhaustive exercise-induced suppression of the plasma tumor necrosis factor (TNF)-α concentration in response to LPS. Methods: Male C3H/HeN mice (n = 66) were randomized to treadmill running to exhaustion (Ex) or a sedentary (Non-Ex) condition. Monocytes and splenic macrophages were collected from some animals, and other animals were injected with LPS (1 mg/kg) immediately after the exercise. The liver, lung and spleen tissues in the mice were removed 30 min after the LPS injection for determination of TNF-α mRNA expression. Blood and tissue samples were collected for determination of TNF-α and TNF receptors (TNFR) 1 h after the LPS injection. Results: Although there was a significant suppression in LPS-induced plasma TNF-α in the Ex mice when compared to the Non-Ex mice (p < 0.01), soluble TNFR in plasma was not affected by the exercise. There was no change in cell-surface expression of Toll-like receptor 4 (TLR4) and in LPS-induced TNF-α mRNA expression and TNFR content in tissues between the Ex and Non-Ex groups. Interestingly, TNF-α contents in the liver, lung and spleen of the Ex mice were significantly lower than those of the Non-Ex group (p < 0.01, p < 0.01 and p < 0.05, respectively). Conclusion: These data suggest that exhaustive exercise-induced suppression of the plasma TNF-α concentration despite LPS stimulation might depend on translation of TNF-α in tissues.

【目 的】 食道癌・肺癌患者の放射線食道炎の状況と対応を調査・比較し, 症状緩和のための看護介入法を検討する. 【対象と方法】 放射線治療を行った食道癌・肺癌患者を対象に, 治療前日から終了日までの症状出現時期, 嚥下スコア・嚥下障害のGradeの変化, 投薬状況の項目についてデータを診療録から収集した. 【結 果】 食道癌患者の半数以上が治療前から症状があった. 両疾患を比較して治療終了時のスコアの上昇は同程度であったが, 食道癌患者では早期にスコア・Gradeが上昇する傾向であった. 食道癌患者には症状自覚時期とほぼ同時期に粘膜保護剤の投与を開始していたが, 肺癌患者は投薬が遅い傾向であった. 両疾患共に粘膜保護剤の予防投与はなく, 約25％の患者が鎮痛剤を使用していた. 【結 語】 放射線治療を受ける患者のQOLの維持には, 十分な症状観察と早期対応が重要であり, 適切な看護介入のための前向き研究が必要であることが示唆された.

Background: In previous studies, the minimal luminal diameter (MLD) of lesions treated with a bare metal stent (BMS) was shown to improve from 6 months to 3 years. However, the long-term response to a sirolimus-eluting stent (SES) implantation remains unclear. Methods and Results: To evaluate 6-month, 12-month and 3-year outcomes, clinical and angiographic follow-up data were analyzed for 367 consecutive patients (506 de novo lesions) who underwent successful SES implantation compared to follow-up data for 617 consecutive patients (802 de novo lesions) who underwent BMS implantation. Clinical follow-up information was obtained for 363 SES-treated patients (98.9%) and 581 BMS-treated patients (94.2%) at 1 year, and 334 SES-treated patients (91.0%) and 566 BMS-treated patients (91.7%) at 3 years. At 3 years, there were no significant differences in the cumulative cardiac death and myocardial infarction. Target lesion revascularization (TLR) rates were significantly higher in BMS-treated patients than in SES-treated patients. In BMS-treated patients, most TLR was performed within 450 days, however, after 450 days, the TLR rate was significantly lower than that for the SES-treated patients. In quantitative coronary angiographic data, among lesions that required no revascularization at the initial 12-month follow up, MLD increased significantly from the 12-month to the 3-year follow-up angiography in BMS-treated lesions. However, MLD decreased significantly in SES-treated lesions. Conclusions: From a 12-month follow-up to a 3-year follow-up, stenosis in BMS-treated lesions regressed, but stenosis in SES-treated lesions progressed. And late TLR was more frequently required in the SES-treated patients. (Circ J 2010; 74: 1104 - 1110)

Membrane permeability transition (MPT) of mitochondria has an important role in apoptosis of various cells. The classic type of MPT is characterized by increased Ca(2+) transport, membrane depolarization, swelling, and sensitivity to cyclosporin A. In this study, we investigated whether L-carnitine suppresses oleic acid-induced MPT using isolated mitochondria from rat liver. Oleic acid-induced MPT in isolated mitochondria, inhibited endogenous respiration, caused membrane depolarization, and increased large amplitude swelling, and cytochrome c (Cyt. c) release from mitochondria. L-Carnitine was indispensable to beta-oxidation of oleic acid in the mitochondria, and this reaction required ATP and coenzyme A (CoA). In the presence of ATP and CoA, L-carnitine stimulated oleic acid oxidation and suppressed the oleic acid-induced depolarization, swelling, and Cyt. c release. L-Carnitine also contributed to maintaining mitochondrial function, which was decreased by the generation of free fatty acids with the passage of time after isolation. These results suggest that L-carnitine acts to maintain mitochondrial function and suppresses oleic acid-mediated MPT through acceleration of beta-oxidation.