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type:Article, Low-branching soybean cultivars have few nodes per plant, and there have been many cases in northern Japan where growing these cultivars at high plant densities did not improve yield. Soybean cultivar ‘Tokei 1122ʹ (T22), which has a long terminal raceme, was bred to improve the yield of low-branching cultivars under dense planting conditions. To elucidate the effects of long racemes on the suitability of T22 for dense planting, we compared the yield and yield components of T22 and ‘Toyoharuka’ (TH), which is a low-branching cultivar, at various planting densities. There was no significant difference in the seed yield of these cultivars at low planting densities, whereas the seed yield of T22 was significantly greater than that of TH under dense planting conditions. The increase in the number of seeds per unit area was greater for T22 than for TH. An analysis of variance revealed a significant interaction between cultivar and planting density for seed yield, number of pods, and number of pods per node. Moreover, the low-branching cultivar ‘Tokei 1122ʹ with long terminal racemes produced a higher yield under non-lodging conditions than the conventional low-branching cultivar at planting densities of 33 plants m^<−2> or higher. The greater yield of T22 is likely because of its long terminal raceme, which increases the number of pods per node and the sink capacity (number of seeds) at high planting densities.

type:Article, To elucidate the effects of maturity and the stem growth habit on the planting density-dependent branching plasticity of soybean cultivars, we studied the branch traits of 12 cultivars or lines planted at different densities (8.3, 16.7, and 22.2 plants m^<−2>) in Sapporo (2012) and Ebetsu (2013). The 12 cultivars and lines consisted of three determinate cultivars from Hokkaido, three indeterminate cultivars from the northern US, and near-isogenic lines with the backgrounds of Canadian, US, and Japanese cultivars exhibiting diverse stem growth habits. We investigated the relationship between the maturity or stem growth habit and branching plasticity, which was calculated based on the ratios of different branch traits under sparse and dense planting conditions. The use of the ratios of the total branch length and the number of nodes per branch under sparse and dense planting conditions as a measure of branching plasticity revealed varietal differences across years. For the determinate and indeterminate cultivars in both years, branching plasticity was positively correlated with the number of days until stage R5 (onset of seed filling), which is when branches cease to elongate. Comparisons of Japanese and US cultivars and near-isogenic lines for the Dt1 gene (mediating the stem growth habit) indicated that the branching plasticity of indeterminate cultivars and lines is greater than that of determinate cultivars, with a large variation among backgrounds and cultivars. The results of this study imply that branching plasticity is greater in late-maturing soybean cultivars. Moreover, the indeterminate growth habit substantially enhances branching plasticity.

Nobuhiro Fujioka,1 Masahiro Kitabatake,2 Noriko Ouji-Sageshima,2 Takahiro Ibaraki,1 Makiko Kumamoto,1 Yukio Fujita,1 Shigeto Hontsu,1 Motoo Yamauchi,1 Masanori Yoshikawa,1 Shigeo Muro,1 Toshihiro Ito2 1Department of Respiratory Medicine, Nara Medical University, Kashihara, Nara, Japan; 2Department of Immunology, Nara Medical University, Kashihara, Nara, JapanCorrespondence: Toshihiro ItoDepartment of Immunology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, JapanTel +81-744-22-3051Fax +81-744-29-7503Email toshi-ito@naramed-u.ac.jpPurpose: Chronic obstructive pulmonary disease (COPD) is a worldwide problem because of its high prevalence and mortality. However, there is no fundamental treatment to ameliorate their pathological change in COPD lung. Recently, adipose-derived mesenchymal stem cells (ADSCs) have attracted attention in the field of regenerative medicine to repair damaged organs. Moreover, their utility in treating respiratory diseases has been reported in some animal models. However, the detailed mechanism by which ADSCs improve chronic respiratory diseases, including COPD, remains to be elucidated. We examined whether human ADSCs (hADSCs) ameliorated elastase-induced emphysema and whether hADSCs differentiated into alveolar epithelial cells in a murine model of COPD.Methods: Female SCID-beige mice (6 weeks old) were divided into the following four groups according to whether they received an intratracheal injection of phosphate-buffered saline or porcine pancreatic elastase, and whether they received an intravenous injection of saline or hADSCs 3 days after intratracheal injection; Control group, hADSC group, Elastase group, and Elastase-hADSC group. We evaluated the lung function, assessed histological changes, and compared gene expression between hADSCs isolated from the lung of Elastase-hADSC group and naïve hADSCs 28 days after saline or elastase administration.Results: hADSCs improved the pathogenesis of COPD, including the mean

type:Article, The broadening of genetic diversity is essential to improving soybean [Glycine max (L.) Merr.] seed yields, and exotic germplasms can be a source of new alleles that improve yield. The stem termination habit is an important trait affecting seed yield in soybean, and this habit can be used to classify soybean into indeterminate, semi‐determinate, and determinate phenotypes. The genetic background and environment determine whether indeterminate phenotypes have a higher yield than determinate phenotypes. Most soybean cultivars developed in high latitude countries such as Canada, Switzerland, and Poland have an indeterminate growth habit, but this is not found in any of the commercial Japanese cultivars. This study investigated high‐yielding Canadian soybean cultivars growing in Hokkaido, northern Japan. Five Canadian cultivars, Haroson, RCAT Angora, Block, RCAT Alliance, and OAC Dorado, produced significantly greater than Hokkaido's leading cultivar Yukihomare in the preliminary screening tests. OAC Dorado also produced a significantly greater yield than Yukihomare in the trials (116%). OAC Dorado had six characteristics that were distinct from the Hokkaido cultivars: an indeterminate growth habit; high pod number, especially on branches; high seed number per pod; long reproductive period; low protein content; and short lower internodes. Our findings indicate that OAC Dorado is an important germplasm for high‐yield breeding and suggest that it may be possible to breed a high‐yielding cultivar with an indeterminate growth habit in Hokkaido.

type:Article

Influenza-associated encephalopathy (IAE) is a serious complication that can follow influenza virus infection. Once a cytokine storm is induced during influenza virus infection, tight junction protein disruption occurs, which consequently leads to blood-brain barrier (BBB) breakdown. However, the details of IAE pathogenesis are not well understood. Here, we established a murine IAE model by administration of lipopolysaccharide following influenza virus infection. Brains from IAE model mice had significantly higher expression of type I interferons and inflammatory cytokines. In addition, the expression of Caveolin-1, one of the key proteins that correlate with protection of the BBB, was significantly lower in brains from the IAE group compared with the control group. We also found that, among 84 different histone modification enzymes, only SET domain bifurcated 2 (Setdb2), one of the histone methyltransferases that methylates the lysine 9 of histone H3, showed significantly higher expression in the IAE group compared with the control group. Furthermore, chromatin immunoprecipitation revealed that methylation of histone H3 lysine 9 was correlated with repression of the Caveolin-1 promoter region. These studies identify Caveolin-1 as a key regulator of BBB permeability in IAE and reveal that it acts through histone modification induced by Setdb2., 博士（医学）・甲第706号・平成31年3月15日, © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/., © 2018 Springer Nature Publishing AG

Influenza-associated encephalopathy (IAE) is a serious complication that can follow influenza virus infection. Once a cytokine storm is induced during influenza virus infection, tight junction protein disruption occurs, which consequently leads to blood-brain barrier (BBB) breakdown. However, the details of IAE pathogenesis are not well understood. Here, we established a murine IAE model by administration of lipopolysaccharide following influenza virus infection. Brains from IAE model mice had significantly higher expression of type I interferons and inflammatory cytokines. In addition, the expression of Caveolin-1, one of the key proteins that correlate with protection of the BBB, was significantly lower in brains from the IAE group compared with the control group. We also found that, among 84 different histone modification enzymes, only SET domain bifurcated 2 (Setdb2), one of the histone methyltransferases that methylates the lysine 9 of histone H3, showed significantly higher expression in the IAE group compared with the control group. Furthermore, chromatin immunoprecipitation revealed that methylation of histone H3 lysine 9 was correlated with repression of the Caveolin-1 promoter region. These studies identify Caveolin-1 as a key regulator of BBB permeability in IAE and reveal that it acts through histone modification induced by Setdb2., 博士（医学）・甲第706号・平成31年3月15日, © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/., © 2018 Springer Nature Publishing AG

This study evaluates the basic characteristics of smart structures composed of dielectric elastomer actuators (DEAs) to suppress vibrations. A DEA, which is a lightweight, flexible polymer that can induce high deformations, should realize next-generation actuators. Additionally, DEA can achieve vibration control of structures with complex shapes or curved surfaces. Herein the performance and efficacy of DEAs are evaluated as an actuator for vibration control at high frequencies. First, the appropriate DEA structure is considered. Second, the control system for the smart structure using the DEA is modeled and designed as an actuator. Third, a method to determine DEA's optimum arrangement and shape is discussed by focusing on the structure's strain energy. Finally, a control simulation and a control experiment validate the vibration suppression effects and the efficacy of the DEA.

The extratropical transition (ET) of tropical cyclones often has an important impact on the nature and predictability of the midlatitude flow. This review synthesizes the current understanding of the dynamical and physical processes that govern this impact and highlights the relationship of downstream development during ET to highimpact weather, with a focus on downstreamregions. It updates a previous review from2003 and identifies new and emerging challenges and future research needs. First, the mechanisms through which the transitioning cyclone impacts the midlatitude flow in its immediate vicinity are discussed. This ‘‘direct impact’’manifests in the formation of a jet streak and the amplification of a ridge directly downstream of the cyclone. This initial flow modification triggers or amplifies amidlatitude Rossby wave packet,which disperses the impact ofETinto downstream regions (downstream impact) and may contribute to the formation of high-impact weather. Details are provided concerning the impact of ET on forecast uncertainty in downstream regions and on the impact of observations on forecast skill. The sources and characteristics of the following key features and processes thatmay determine the manifestation of the impact of ET on the midlatitude flow are discussed: the upper-tropospheric divergent outflow, mainly associated with latent heat release in the troposphere below, and the phasing between the transitioning cyclone and the midlatitude wave pattern. Improving the representation of diabatic processes during ET in models and a climatological assessment of the ET’s impact on downstream high-impact weather are examples for future research directions.

This study evaluates the basic characteristics of smart structures composed of dielectric elastomer actuators (DEAs) to suppress vibrations. A DEA, which is a lightweight, flexible polymer that can induce high deformations, should realize next-generation actuators. Additionally, DEA can achieve vibration control of structures with complex shapes or curved surfaces. Herein the performance and efficacy of DEAs are evaluated as an actuator for vibration control at high frequencies. First, the appropriate DEA structure is considered. Second, the control system for the smart structure using the DEA is modeled and designed as an actuator. Third, a method to determine DEA's optimum arrangement and shape is discussed by focusing on the structure's strain energy. Finally, a control simulation and a control experiment validate the vibration suppression effects and the efficacy of the DEA.

Cellular translation should be precisely controlled in response to extracellular cues. However, knowledge is limited concerning signal transduction-regulated translation. In the present study, phosphorylation was identified in the 40S small subunit ribosomal protein uS7 (Yjr123w/previously called as Rps5) by Ypk1 and Pkc1, AGC family protein kinases in yeast Saccharomyces cerevisiae. Serine residue 223 (Ser223) of uS7 in the conserved C-terminal region was crucial for this phosphorylation event. S223A mutant uS7 caused severe reduction of small ribosomal subunit production, likely due to compromised interaction with Rio2, resulting in both reduced translation and reduced cellular proliferation. Contrary to optimal culture conditions, heat stressed S223A mutant cells exhibited increased heat resistance and induced heat shock proteins. Taken together, an intracellular signal transduction pathway involving Ypk1/Pkc1 seemed to play an important role in ribosome biogenesis and subsequent cellular translation, utilizing uS7 as a substrate.

The mechanistic/mammalian target of rapamycin complex 1 (mTORC1) regulates cellular function in various cell types. Although the role of mTORC1 in skeletogenesis has been investigated previously, here we show a critical role of mTORC1/4E-BPs/SOX9 axis in regulating skeletogenesis through its expression in undifferentiated mesenchymal cells. Inactivation of Raptor, a component of mTORC1, in limb buds before mesenchymal condensations resulted in a marked loss of both cartilage and bone. Mechanistically, we demonstrated that mTORC1 selectively controls the RNA translation of Sox9, which harbors a 5′ terminal oligopyrimidine tract motif, via inhibition of the 4E-BPs. Indeed, introduction of Sox9 or a knockdown of 4E-BP1/2 in undifferentiated mesenchymal cells markedly rescued the deficiency of the condensation observed in Raptor-deficient mice. Furthermore, introduction of the Sox9 transgene rescued phenotypes of deficient skeletal growth in Raptor-deficient mice. These findings highlight a critical role of mTORC1 in mammalian skeletogenesis, at least in part, through translational control of Sox9 RNA.

Extratropical transition (ET) is the process by which a tropical cyclone, upon encountering a baroclinic environment and reduced sea surface temperature at higher latitudes, transforms into an extratropical cyclone. This process is influenced by, and influences, phenomena from the tropics to the midlatitudes and from themeso- to the planetary scales to extents that vary between individual events. Motivated in part by recent high-impact and/or extensively observed events such as NorthAtlanticHurricane Sandy in 2012 and western North Pacific Typhoon Sinlaku in 2008, this review details advances in understanding and predicting ET since the publication of an earlier review in 2003. Methods for diagnosing ETin reanalysis, observational, andmodel-forecast datasets are discussed.New climatologies for the eastern North Pacific and southwest Indian Oceans are presented alongside updates to western North Pacific and North Atlantic Ocean climatologies. Advances in understanding and, in some cases, modeling the direct impacts of ET-related wind, waves, and precipitation are noted. Improved understanding of structural evolution throughout the transformation stage of ET fostered in large part by novel aircraft observations collected in several recent ET events is highlighted. Predictive skill for operational and numerical model ET-related forecasts is discussed along with environmental factors influencing posttransition cyclone structure and evolution. Operational ET forecast and analysis practices and challenges are detailed. In particular, somechallenges of effective hazard communication for the evolving threats posed by a tropical cyclone during and after transition are introduced. This review concludes with recommendations for future work to further improve understanding, forecasts, and hazard communication.

Nontuberculous mycobacteria (NTM), including Mycobacterium avium complex (MAC), cause opportunistic chronic pulmonary infections. Notably, MAC susceptibility is regulated by various factors, including the host immune system. Persimmon (Ebenaceae Diospyros kaki Thunb.) tannin is a condensed tannin composed of a polymer of catechin groups. It is well known that condensed tannins have high antioxidant activity and bacteriostatic properties. However, it is hypothesized that condensed tannins might need to be digested and/or fermented into smaller molecules in vivo prior to being absorbed into the body to perform beneficial functions. In this study, we evaluated the effects of soluble persimmon-derived tannins on opportunistic MAC disease. Soluble tannins were hydrolyzed and evaluated by the oxygen radical absorbance capacity (ORAC) method. The ORAC value of soluble tannin hydrolysate was approximately five times greater than that of soluble tannin powder. In addition, soluble tannin hydrolysate exhibited high bacteriostatic activity against MAC in vitro. Furthermore, in an in vivo study, MAC infected mice fed a soluble tannin-containing diet showed significantly higher anti-bacterial activity against MAC and less pulmonary granuloma formation compared with those fed a control diet. Tumor necrosis factor α and inducible nitric oxide synthase levels were significantly lower in lungs of the soluble tannin diet group compared with the control diet group. Moreover, proinflammatory cytokines induced by MAC stimulation of bone marrow-derived macrophages were significantly decreased by addition of soluble tannin hydrolysate. These data suggest that soluble tannin from persimmons might attenuate the pathogenesis of pulmonary NTM infection., 博士（医学）・乙第1408号・平成29年11月24日, Copyright: © 2017 Matsumura et al. This is an open access article distributed under the terms of the Creative Commons Attribution License(http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information files.

Nontuberculous mycobacteria (NTM), including Mycobacterium avium complex (MAC), cause opportunistic chronic pulmonary infections. Notably, MAC susceptibility is regulated by various factors, including the host immune system. Persimmon (Ebenaceae Diospyros kaki Thunb.) tannin is a condensed tannin composed of a polymer of catechin groups. It is well known that condensed tannins have high antioxidant activity and bacteriostatic properties. However, it is hypothesized that condensed tannins might need to be digested and/or fermented into smaller molecules in vivo prior to being absorbed into the body to perform beneficial functions. In this study, we evaluated the effects of soluble persimmon-derived tannins on opportunistic MAC disease. Soluble tannins were hydrolyzed and evaluated by the oxygen radical absorbance capacity (ORAC) method. The ORAC value of soluble tannin hydrolysate was approximately five times greater than that of soluble tannin powder. In addition, soluble tannin hydrolysate exhibited high bacteriostatic activity against MAC in vitro. Furthermore, in an in vivo study, MAC infected mice fed a soluble tannin-containing diet showed significantly higher anti-bacterial activity against MAC and less pulmonary granuloma formation compared with those fed a control diet. Tumor necrosis factor α and inducible nitric oxide synthase levels were significantly lower in lungs of the soluble tannin diet group compared with the control diet group. Moreover, proinflammatory cytokines induced by MAC stimulation of bone marrow-derived macrophages were significantly decreased by addition of soluble tannin hydrolysate. These data suggest that soluble tannin from persimmons might attenuate the pathogenesis of pulmonary NTM infection., 博士（医学）・乙第1408号・平成29年11月24日, Copyright: © 2017 Matsumura et al. This is an open access article distributed under the terms of the Creative Commons Attribution License(http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information files.

Thaumatin is an intensely sweet-tasting protein that elicits sweet taste at a concentration of 50 nM, a value 100, 000 times larger than that of sucrose on a molar basis. Here we attempted to produce a protein with enhanced sweetness by removing negative charges on the interacting side of thaumatin with the taste receptor. We obtained a D21N mutant which, with a threshold value 31 nM is much sweeter than wild type thaumatin and, together with the Y65R mutant of single chain monellin, one of the two sweetest proteins known so far. The complex model between the T1R2-T1R3 sweet receptor and thaumatin, derived from tethered docking in the framework of the wedge model, confirmed that each of the positively charged residues critical for sweetness is close to a receptor residue of opposite charge to yield optimal electrostatic interaction. Furthermore, the distance between D21 and its possible counterpart D433 (located on the T1R2 protomer of the receptor) is safely large to avoid electrostatic repulsion but, at the same time, amenable to a closer approach if D21 is mutated into the corresponding asparagine. These findings clearly confirm the importance of electrostatic potentials in the interaction of thaumatin with the sweet receptor.

Nonfunctional mutant ribosomal RNAs in 40S or 60S subunits are selectively degraded in eukaryotic cells (nonfunctional rRNA decay, NRD). We previously reported that NRD of 25S rRNA required cullin-E3 ligase Rtt101 and its associating factor Mms1, both of which are involved in DNA repair. Although Mms22, an accessory component of the E3 complex, was suggested to direct the E3 complex to DNA repair, the factor that directs the complex to 25S NRD currently remains unknown. We herein demonstrated that another accessory component, Crt10 was required for 25S NRD, but not for DNA repair, suggesting that this accessory component specifies the function of the E3 complex differently. We also identified two distinct Crt10-containing E3 complexes, one of which contained the Paf1 complex, a Pol-II binding complex that modulates the transcription of stress-related genes. Our results showed the convergence of multiple pathways for stresses that harm nucleic acids and provided a molecular framework for the substrate diversity of the E3 complex.

In this study, the indigenous alcoholic beverages in a rural village of Cameroon were investigated. The technique for producing alcoholic beverages in the village was observed, and the concentrations of ethanol, glucose and lactic acid and the pH values during the course of production were measured using portable devices at the field site. Eight different kinds of alcoholic beverage (palm wine, palm spirits, raffia wine, cassava spirits, maize turbid beer, maize spirits, plantain wine and plantain spirits) were produced and consumed in the village. Of these beverages, palm wine, made from palm sap, was the most important alcoholic beverage in a villager's daily life. In addition, starch-based alcoholic beverages were distilled rather than drunk directly. As germinated maize, which has a relatively low amylase activity, was used as an amylase source in production, starch-based alcoholic beverages might need to be distilled to enhance the ethanol concentration. During the course of production, the pH was reduced using local techniques, which proved to be effective in preventing bacterial contamination.

Asumi Iesato,1 Takaaki Oba,1 Mayu Ono,1 Toru Hanamura,1 Takayuki Watanabe,1 Tokiko Ito,1 Toshiharu Kanai,1 Kazuma Maeno,1 Katsuhiko Ishizaka,2 Hiroyuki Kitabatake,3 Daisuke Takeuchi,4 Akira Suzuki,4 Jun Nakayama,5 Ken-ichi Ito11Division of Breast and Endocrine Surgery, Department of Surgery, Shinshu University School of Medicine, Matsumoto, 2Department of Surgery, Iiyama Red Cross Hospital, Iiyama, 3Department of Gastroenterology, Iiyama Red Cross Hospital, Iiyama, 4Department of Gastrointestinal Surgery, Shinshu University School of Medicine, Matsumoto, 5Department of Molecular Pathology, Shinshu University Graduate School of Medicine, Matsumoto, Nagano, JapanAbstract: It is occasionally difficult to diagnose breast metastasis of gastric carcinoma because of its rarity. However, to appropriately treat patients with breast tumors without delay, it is important to distinguish metastatic cancer from primary breast cancer. We report two cases of breast metastasis of gastric carcinoma and review the literature. The first case was a 41-year-old female diagnosed with bilateral pelvic tumors who visited the outpatient clinic because of pain and enlargement of both breasts. Ultrasonography showed diffuse hypoechoic lesions, which were enhanced on gadolinium-enhanced magnetic resonance imaging in the bilateral mammary gland. Core needle biopsy of the right breast revealed signet-ring cells, which were also identified in the resected bilateral pelvic tumors. Subsequent upper gastrointestinal endoscopy revealed signet-ring cell carcinoma in the stomach, and the bilateral breast lesions were diagnosed as metastases of gastric carcinoma. The second case was a 34-year-old female diagnosed with cervical metastasis of signet-ring cell carcinoma who was referred to the breast cancer clinic because of a nodule in the left breast detected by computed tomography. Ultrasonography showed a hypoechoic nodule that was enhanced on gadolinium-enhanced magnetic resonance imaging. Because the

Thaumatin, a sweet-tasting plant protein, elicits a sweet taste sensation at 50 nM in humans but not rodents. Although it was shown that the cysteine-rich domain (CRD) of human T1R3 (hT1R3) is important for the response to thaumatin, the amino acid residues within CRD critical for response are still unknown. A comparison of the amino acid sequence (69 amino acid residues) of CRD between hT1R3 and mouse T1R3 (mT1R3) revealed sixteen amino acids that differ. In the present study, we converted each of these sixteen amino acids in hT1R3 to their mouse counterpart and examined the response to thaumatin and sucralose using a cell-based assay. No significant decrease in the response to sucralose was seen among any of the sixteen mutants. However, five mutants (Q504K, A537T, R556P, S559P, and R560K) exhibited a significantly diminished response to thaumatin. The five critical residues involved in the response to thaumatin were dispersed in the CRD of hT1R3 and widely distributed when compared to brazzein. The unique intense sweet-taste of thaumatin might be attributed to the different receptor activation mechanism compared to the small molecule sweetener sucralose.

Eukaryotic cells have quality control systems that eliminate nonfunctional rRNAs with deleterious mutations (nonfunctional rRNA decay, NRD). We have previously reported that 25S NRD requires an E3 ubiquitin ligase complex, which is involved in ribosomal ubiquitination. However, the degradation process of nonfunctional ribosomes has remained unknown. Here, using genetic screening, we identified two ubiquitin-binding complexes, the Cdc48-Npl4-Ufd1 complex (Cdc48 complex) and the proteasome, as the factors involved in 25S NRD. We show that the nonfunctional 60S subunit is dissociated from the 40S subunit in a Cdc48 complex-dependent manner, before it is attacked by the proteasome. When we examined the nonfunctional 60S subunits that accumulated under proteasome-depleted conditions, the majority of mutant 25S rRNAs retained their full length at a single-nucleotide resolution. This indicates that the proteasome is an essential factor triggering rRNA degradation. We further showed that ribosomal ubiquitination can be stimulated solely by the suppression of the proteasome, suggesting that ubiquitin-proteasome-dependent RNA degradation occurs in broader situations, including in general rRNA turnover.

Background : Tenascin-C (TN-C), an extracellular matrix glycoprotein, is specifically expressed at high levels during embryonic development, but not in the adult heart. TN-C reappears at sites of inflammatory tissue remodeling or wound healing under various pathologic conditions, such as acute myocardial infarction, acute myocarditis, and some cases of cardiomyopathy. Therefore, the expression of TN-C might be useful for detecting the clinical characteristics of, and ventricular remodeling in, dilated cardiomyopathy (DCM). Methods and Results : Circulating serum TN-C levels in 107 patients with DCM were measured using an ELISA kit. Clinical data were also assessed by Pearson's or Spearman's correlation analysis to estimate correlations between variables. Serum TN-C levels in DCM patients were higher than those in normal controls (p<0.001). TNC levels showed a significantly positive correlation with New York Heart Association functional class (p<0.001), B-type natriuretic peptide level (p<0.001), cardiothoracic ratio on chest X-ray (p<0.01), left ventricular end-diastolic diameter (p<0.05) and left ventricular end-systolic diameter (p<0.01), and a significantly negative correlation with left ventricular ejection fraction (p<0.01). Conclusions : The findings suggest that increased serum TN-C levels indicate the severity of heart failure, left ventricular dysfunction and remodeling in patients with DCM.

筑波大学博士 (工学) 学位論文・平成9年3月24日授与 (乙第1272号)

Background: There are few biological markers, which strictly show the severity of congestive heart failure (CHF). Methods and Results: Lymphocyte G-protein coupled receptor kinase (GRK) mRNA expression was measured by quantitative reverse transcription-polymerase chain reaction in 15 CHF patients: 5 patients classified as New York Heart Association class-II treated with angiotensin converting enzyme inhibitor (ACEI) (IIA), 5 patients in class-II without ACEI (IIC), and 5 patients in class-III treated with ACEI (IIIA). GRK mRNA level in IIIA was significantly higher than those in IIA (p<0.05). GRK mRNA level in IIA were significantly lower than those in IIC (p<0.05). Conclusions: The expression level of lymphocyte GRK might show the severity of CHF, and ACEI treatment could reduce the level of GRK in CHF patients. (Circ J 2006; 70: 362 - 363)

Background: There are few biological markers, which strictly show the severity of congestive heart failure (CHF). Methods and Results: Lymphocyte G-protein coupled receptor kinase (GRK) mRNA expression was measured by quantitative reverse transcription-polymerase chain reaction in 15 CHF patients: 5 patients classified as New York Heart Association class-II treated with angiotensin converting enzyme inhibitor (ACEI) (IIA), 5 patients in class-II without ACEI (IIC), and 5 patients in class-III treated with ACEI (IIIA). GRK mRNA level in IIIA was significantly higher than those in IIA (p<0.05). GRK mRNA level in IIA were significantly lower than those in IIC (p<0.05). Conclusions: The expression level of lymphocyte GRK might show the severity of CHF, and ACEI treatment could reduce the level of GRK in CHF patients. (Circ J 2006; 70: 362 - 363)

A 72-year-old woman was admitted to our institution because of sudden chest pain. Emergency coronary angiography revealed thrombotic occlusion of the distal right coronary artery. A large cylindrical thrombus was retrieved from her distal right coronary artery using a thrombus aspiration catheter. IVUS showed minimal atherosclerosis and moderate ectatic change at the proximal right coronary artery. A reconstructed IVUS image also showed that a mural thrombus with abrupt ending was still retained at the ectatic segment. Based on this evidence, coronary ectasia was thought to be the primary cause for the thrombus formation and acute myocardial infarction in this case.

A 72-year-old woman was admitted to our institution because of sudden chest pain. Emergency coronary angiography revealed thrombotic occlusion of the distal right coronary artery. A large cylindrical thrombus was retrieved from her distal right coronary artery using a thrombus aspiration catheter. IVUS showed minimal atherosclerosis and moderate ectatic change at the proximal right coronary artery. A reconstructed IVUS image also showed that a mural thrombus with abrupt ending was still retained at the ectatic segment. Based on this evidence, coronary ectasia was thought to be the primary cause for the thrombus formation and acute myocardial infarction in this case.

Objectives: The purpose of this study was to identify risk markers in patients with Brugada syndrome. Background: Patients with Brugada syndrome who experience syncope or aborted sudden death are at high risk for recurrent lethal arrhythmias. The prognosis and therapeutic approaches in asymptomatic individuals with a Brugada-type ECG (asymptomatic Brugada syndrome) are controversial. Methods: We genetically screened 30 asymptomatic probands (29 men and 1 woman; mean age 47.1 years) exhibiting a spontaneous Brugada-type ECG. Family members of patients with Brugada syndrome were excluded from the study. Results: Twenty-nine of 30 patients (96.7%) remained symptom-free for at least 3 years. One patient (case 1) with a family history of sudden death died suddenly during sleep. Ventricular fibrillation was induced by programmed electrical stimulation in 14 of 18 subjects (78%), but none of these 18 subjects developed spontaneous ventricular arrhythmias. Genetic screening failed to identify SCN5A mutations in most cases but demonstrated a novel double missense mutation (K1527R and A1569P) located on the same allele in another asymptomatic subject (case 2). Heterologously expressed mutant Na channels exhibited a negative shift of steady-state inactivation (9.2 mV) and enhanced slow inactivation, suggesting this individual harbors a subclinical channel dysfunction compatible with symptomatic Brugada syndrome. Conclusions: Asymptomatic individuals with a Brugada-type ECG generally have a better prognosis than their symptomatic counterparts, but a subgroup of these individuals may have a poor prognosis. Severe Na channel dysfunction as a result of SCN5A mutations may not be sufficient to cause symptoms or arrhythmias in patients with Brugada syndrome, suggesting unknown factors or modifier genes influence arrhythmogenesis.

A 72-year-old woman was admitted to our institution because of sudden chest pain. Emergency coronary angiography revealed thrombotic occlusion of the distal right coronary artery. A large cylindrical thrombus was retrieved from her distal right coronary artery using a thrombus aspiration catheter. IVUS showed minimal atherosclerosis and moderate ectatic change at the proximal right coronary artery. A reconstructed IVUS image also showed that a mural thrombus with abrupt ending was still retained at the ectatic segment. Based on this evidence, coronary ectasia was thought to be the primary cause for the thrombus formation and acute myocardial infarction in this case.

Objectives: The purpose of this study was to identify risk markers in patients with Brugada syndrome. Background: Patients with Brugada syndrome who experience syncope or aborted sudden death are at high risk for recurrent lethal arrhythmias. The prognosis and therapeutic approaches in asymptomatic individuals with a Brugada-type ECG (asymptomatic Brugada syndrome) are controversial. Methods: We genetically screened 30 asymptomatic probands (29 men and 1 woman; mean age 47.1 years) exhibiting a spontaneous Brugada-type ECG. Family members of patients with Brugada syndrome were excluded from the study. Results: Twenty-nine of 30 patients (96.7%) remained symptom-free for at least 3 years. One patient (case 1) with a family history of sudden death died suddenly during sleep. Ventricular fibrillation was induced by programmed electrical stimulation in 14 of 18 subjects (78%), but none of these 18 subjects developed spontaneous ventricular arrhythmias. Genetic screening failed to identify SCN5A mutations in most cases but demonstrated a novel double missense mutation (K1527R and A1569P) located on the same allele in another asymptomatic subject (case 2). Heterologously expressed mutant Na channels exhibited a negative shift of steady-state inactivation (9.2 mV) and enhanced slow inactivation, suggesting this individual harbors a subclinical channel dysfunction compatible with symptomatic Brugada syndrome. Conclusions: Asymptomatic individuals with a Brugada-type ECG generally have a better prognosis than their symptomatic counterparts, but a subgroup of these individuals may have a poor prognosis. Severe Na channel dysfunction as a result of SCN5A mutations may not be sufficient to cause symptoms or arrhythmias in patients with Brugada syndrome, suggesting unknown factors or modifier genes influence arrhythmogenesis.

A 72-year-old woman was admitted to our institution because of sudden chest pain. Emergency coronary angiography revealed thrombotic occlusion of the distal right coronary artery. A large cylindrical thrombus was retrieved from her distal right coronary artery using a thrombus aspiration catheter. IVUS showed minimal atherosclerosis and moderate ectatic change at the proximal right coronary artery. A reconstructed IVUS image also showed that a mural thrombus with abrupt ending was still retained at the ectatic segment. Based on this evidence, coronary ectasia was thought to be the primary cause for the thrombus formation and acute myocardial infarction in this case.

A single-pinhole camera is usually used for X-rey imaging. In URA coded aperture camera, the pinhole is replaced by multi-pinhole arrays arranged in m-sequences. Since the URA camera can view the object with a large solid angle, it can also provide some tomographic resolution for three-dimensional objects. But a reconstructed image is blurred by defocus artifact. In this paper, we propose a new iterative algorithm to remove the defocus artifact. We show that the reconstructed image can be improved by using the proposed iterative algorithm.

In Africa, there are numerous traditional alcoholic beverages. Unavailability of literature on these beverages, particularly regarding their production, consumption and quality is a major constraint against industrial production. The rising prices of conventional alcoholic beverages call for more studies on these beverages. "Denge", one such beverage, was studied and analyzed in terms of total soluble solids, specific gravity, pH and titratable acidity changes during fermentation. Results showed that Kigelia africana and Aloe pluridens were used to prepare fermenting agents for subsequent production of "denge", acting primarily as a reservoir of micro-organisms for this fermentation. Slime formation in the raw cane juice was a common problem. Optimum time for heat sterilisation of the juice, a possible method to be used by ordinary households need to be established. Types and numbers of microorganisms in the fermentation need identification. Types and levels of residual toxicants from K. africana and A. pluridens in the wine need to be documented. The specific gravity, total soluble solids, pH and tritratable acidity studies have displayed the perishability of "denge" during storage. More shelflife studies are recommended.

Oriented spherulitic textures of a rod-shaped nylon 6.12 sample were crystallized by the temperature slope method. Crystallization conditions were compared by changing temperatures and growth rates. Three types of textures (negative spherulites, positive spherulites, and spherulitic aggregates) were observed by this method. The negative textures appeared when the growth rate was less than 0.1 mm/h. Crystalline orientation and mechanical properties of the textures were investigated by x-ray diffraction and microhardness measurements, respectively. The hydrogen-bonded (010) planes were perpendicular to the growth direction in the negative spherulite, while they were parallel to the growth direction in the positive spherulite. In the spherulitic aggregates, the b axis was parallel to the growth direction, while the (010) planes formed roughly an angle of 45° with the growth direction. Due to the orientation of the hydrogen-boned planes, the negative texture exhibited an anisotropy, with hardness values of 106 MPa and 137 MPa when measured perpendicular or parallel to the growth direction, respectively.