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Sample records for coxsackievirus b3 infection

  1. Colchicine aggravates coxsackievirus B3 infection in mice

    NARCIS (Netherlands)

    Smilde, Bernard J.; Woudstra, Linde; Fong Hing, Gene; Wouters, Diana; Zeerleder, Sacha; Murk, Jean-Luc; van Ham, Marieke; Heymans, Stephane; Juffermans, Lynda J. M.; van Rossum, Albert C.; Niessen, Hans W. M.; Krijnen, Paul A. J.; Emmens, Reindert W.

    2016-01-01

    There is a clinical need for immunosuppressive therapy that can treat myocarditis patients in the presence of an active viral infection. In this study we therefore investigated the effects of colchicine, an immunosuppressive drug which has been used successfully as treatment for pericarditis

  2. Reversible Atrioventricular Block and Junctional Ectopic Tachycardia in Coxsackievirus B3-Induced Fetal–Neonatal Myocarditis without Left Ventricular Dysfunction

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    Hironori Takahashi

    2011-09-01

    Full Text Available We present a case of fetal–neonatal acute myocarditis caused by coxsackievirus B3 infection in a term neonate. The condition manifested as high-grade atrioventricular (A-V block prenatally. After delivery, various arrhythmias such as high-grade A-V block, ventricular tachycardia, and junctional ectopic tachycardia appeared, and we had difficulty managing these arrhythmias. This is the first report describing a case of acute myocarditis due to coxsackievirus infection presenting with fetal A-V block. This case is also unique in that it is extremely rare that various arrhythmias occur serially in one patient without left ventricular dysfunction.

  3. Coxsackievirus Infections (For Parents)

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    ... for a serious infection, including myocarditis, hepatitis, and meningoencephalitis (an inflammation of the brain and meninges). In ... feel more comfortable. Because antibiotics only work against bacteria, they can't be used to fight a ...

  4. The role of sex differences in autophagy in the heart during coxsackievirus B3-induced myocarditis.

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    Koenig, Andreas; Sateriale, Adam; Budd, Ralph C; Huber, Sally A; Buskiewicz, Iwona A

    2014-03-01

    Under normal conditions, autophagy maintains cardiomyocyte health and integrity through turnover of organelles. During stress, oxygen and nutrient deprivation, or microbial infection, autophagy prolongs cardiomyocyte survival. Sex differences in induction of cell death may to some extent explain the disparity between the sexes in many human diseases. However, sex differences in gene expression, which regulate cell death and autophagy, were so far not taken in consideration to explain the sex bias of viral myocarditis. Coxsackievirus B3 (CVB3)-induced myocarditis is a sex-biased disease, with females being substantially less susceptible than males and sex hormones largely determine this bias. CVB3 was shown to induce and subvert the autophagosome for its optimal viral RNA replication. Gene expression analysis on mouse and human, healthy and CVB3-infected, cardiac samples of both sexes, suggests sex differences in autophagy-related gene expression. This review discusses the aspects of sex bias in autophagy induction in cardiomyocytes.

  5. Coxsackievirus B3 VLPs purified by ion exchange chromatography elicit strong immune responses in mice.

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    Koho, Tiia; Koivunen, Minni R L; Oikarinen, Sami; Kummola, Laura; Mäkinen, Selina; Mähönen, Anssi J; Sioofy-Khojine, Amirbabak; Marjomäki, Varpu; Kazmertsuk, Artur; Junttila, Ilkka; Kulomaa, Markku S; Hyöty, Heikki; Hytönen, Vesa P; Laitinen, Olli H

    2014-04-01

    Coxsackievirus B3 (CVB3) is an important cause of acute and chronic viral myocarditis, and dilated cardiomyopathy (DCM). Although vaccination against CVB3 could significantly reduce the incidence of serious or fatal viral myocarditis and various other diseases associated with CVB3 infection, there is currently no vaccine or therapeutic reagent in clinical use. In this study, we contributed towards the development of a CVB3 vaccine by establishing an efficient and scalable ion exchange chromatography-based purification method for CVB3 virus and baculovirus-insect cell-expressed CVB3 virus-like particles (VLPs). This purification system is especially relevant for vaccine development and production on an industrial scale. The produced VLPs were characterized using a number of biophysical methods and exhibited excellent quality and high purity. Immunization of mice with VLPs elicited a strong immune response, demonstrating the excellent vaccine potential of these VLPs. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. TLR3 is required for survival following Coxsackievirus B3 infection by driving T lymphocyte activation and polarization: The role of dendritic cells

    National Research Council Canada - National Science Library

    Renata Sesti-Costa; Marcela Cristina Santiago Françozo; Grace Kelly Silva; José Luiz Proenca-Modena; João Santana Silva

    2017-01-01

    .... In the current study, we found that TLR3 expression in dendritic cells plays a role in their activation upon CVB3 infection in vitro, as TLR3-deficient dendritic cells up-regulate CD80 and CD86...

  7. α-Lipoic acid attenuates coxsackievirus B3-induced ectopic calcification in heart, pancreas, and lung.

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    Kim, Hyo Shin; Shin, Hong-In; Lim, Hyun-Sook; Lee, Tae Yoon; Lee, Kyunghee; Jeong, Daewon

    2013-03-08

    Ectopic mineralization of soft tissues is known to be a typical response to systemic imbalance of various metabolic factors as well as tissue injury, leading to severe clinical consequences. In this study, coxsackievirus B3 (CVB3) infection in mice resulted in significant tissue injury, especially in the heart and pancreas. Inflammatory damage and apoptotic cell death were observed in CVB3-infected heart and pancreas tissues. Along with tissue damage, substantial ectopic calcification was detected in CVB3-infected heart, pancreas, and lung tissues, as determined by von Kossa staining and calcium content quantification. In addition, CVB3 infection induced upregulation of osteogenic signals, including six genes (BMP2, SPARC, Runx2, osteopontin, collagen type I, and osterix) in the heart, three genes (SPARC, osteopontin, and collagen type I) in the pancreas, and two genes (BMP2 and alkaline phosphatase) in the lung, as determined by quantitative real-time PCR analysis. Intriguingly, we showed that α-lipoic acid diminished CVB3-mediated inflammatory and apoptotic tissue damage, subsequently ameliorating ectopic calcification via the suppression of osteogenic signals. Collectively, our data provide evidence that ectopic calcification induced by CVB3 infection is implicated in the induction of osteogenic propensity, and α-lipoic acid may be a potential therapeutic agent to ameliorate pathologic calcification. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Comparison of effects of ivabradine versus carvedilol in murine model with the Coxsackievirus B3-induced viral myocarditis.

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    Li Yue-Chun

    Full Text Available BACKGROUND: Elevated heart rate is associated with increased cardiovascular morbidity. The selective I(f current inhibitor ivabradine reduces heart rate without affecting cardiac contractility, and has been shown to be cardioprotective in the failing heart. Ivabradine also exerts some of its beneficial effects by decreasing cardiac proinflammatory cytokines and inhibiting peroxidants and collagen accumulation in atherosclerosis or congestive heart failure. However, the effects of ivabradine in the setting of acute viral myocarditis and on the cytokines, oxidative stress and cardiomyocyte apoptosis have not been investigated. METHODOLOGY/PRINCIPAL FINDINGS: The study was designed to compare the effects of ivabradine and carvedilol in acute viral myocarditis. In a coxsackievirus B3 murine myocarditis model (Balb/c, effects of ivabradine and carvedilol (a nonselective β-adrenoceptor antagonist on myocardial histopathological changes, cardiac function, plasma noradrenaline, cytokine levels, cardiomyocyte apoptosis, malondialdehyde and superoxide dismutase contents were studied. Both ivabradine and carvedilol similarly and significantly reduced heart rate, attenuated myocardial lesions and improved the impairment of left ventricular function. In addition, ivabradine treatment as well as carvedilol treatment showed significant effects on altered myocardial cytokines with a decrease in the amount of plasma noradrenaline. The increased myocardial MCP-1, IL-6, and TNF-α. in the infected mice was significantly attenuated in the ivabradine treatment group. Only carvedilol had significant anti-oxidative and anti-apoptoic effects in coxsackievirus B3-infected mice. CONCLUSIONS/SIGNIFICANCE: These results show that the protective effects of heart rate reduction with ivabradine and carvedilol observed in the acute phase of coxsackievirus B3 murine myocarditis may be due not only to the heart rate reduction itself but also to the downregulation of

  9. Epidemic pleurodynia caused by coxsackievirus B3 at a medical center in northern Taiwan.

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    Huang, Wan-Ting; Lee, Ping-Ing; Chang, Luan-Ying; Kao, Chuan-Liang; Huang, Li-Min; Lu, Chun-Yi; Chen, Jong-Ming; Lee, Chin-Yun

    2010-12-01

    Epidemic pleurodynia is seldom reported in Southeast Asia and there has been no report from Taiwan. We conducted a retrospective chart review of children = 18 years of age in the National Taiwan University Hospital from January 1 to December 31, 2005. Epidemic pleurodynia was defined as an acute illness characterized by sharp localized pain over the chest or upper abdomen. Patients with known heart diseases or pulmonary consolidations were excluded. In total, 28 patients met the case definition of epidemic pleurodynia. Coxsackievirus B3 (CB3) was isolated in 15 (60%) of the 25 throat swab specimens. Four (14%) of the 28 patients presented chest wall tenderness and only one (6%) of the 18 patients tested had an elevated creatinine kinase level. Twenty-one (75%) of the 28 patients described pleuritic chest pains and 10 (45%) of the 22 chest radiographies exhibited pulmonary infiltrates or pleural effusions. Six patients were observed with tonsillar exudates and one was confirmed to have a CB3 urinary tract infection. The clinical features and radiological findings suggest that CB3-associated epidemic pleurodynia might be a disease of the pleura and occasionally spreads to nearby tissues, resulting in chest wall myositis, pulmonary infiltrates and myopericarditis. Copyright © 2010 Taiwan Society of Microbiology. Published by Elsevier B.V. All rights reserved.

  10. Human cardiac-derived adherent proliferating cells reduce murine acute Coxsackievirus B3-induced myocarditis.

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    Kapka Miteva

    Full Text Available BACKGROUND: Under conventional heart failure therapy, inflammatory cardiomyopathy typically has a progressive course, indicating a need for alternative therapeutic strategies to improve long-term outcomes. We recently isolated and identified novel cardiac-derived cells from human cardiac biopsies: cardiac-derived adherent proliferating cells (CAPs. They have similarities with mesenchymal stromal cells, which are known for their anti-apoptotic and immunomodulatory properties. We explored whether CAPs application could be a novel strategy to improve acute Coxsackievirus B3 (CVB3-induced myocarditis. METHODOLOGY/PRINCIPAL FINDINGS: To evaluate the safety of our approach, we first analyzed the expression of the coxsackie- and adenovirus receptor (CAR and the co-receptor CD55 on CAPs, which are both required for effective CVB3 infectivity. We could demonstrate that CAPs only minimally express both receptors, which translates to minimal CVB3 copy numbers, and without viral particle release after CVB3 infection. Co-culture of CAPs with CVB3-infected HL-1 cardiomyocytes resulted in a reduction of CVB3-induced HL-1 apoptosis and viral progeny release. In addition, CAPs reduced CD4 and CD8 T cell proliferation. All CAPs-mediated protective effects were nitric oxide- and interleukin-10-dependent and required interferon-γ. In an acute murine model of CVB3-induced myocarditis, application of CAPs led to a decrease of cardiac apoptosis, cardiac CVB3 viral load and improved left ventricular contractility parameters. This was associated with a decline in cardiac mononuclear cell activity, an increase in T regulatory cells and T cell apoptosis, and an increase in left ventricular interleukin-10 and interferon-γ mRNA expression. CONCLUSIONS: We conclude that CAPs are a unique type of cardiac-derived cells and promising tools to improve acute CVB3-induced myocarditis.

  11. Age-Associated Changes in Estrogen Receptor Ratios Correlate with Increased Female Susceptibility to Coxsackievirus B3-Induced Myocarditis

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    Andreas Koenig

    2017-11-01

    Full Text Available Sexual bias is a hallmark in various diseases. This review evaluates sexual dimorphism in clinical and experimental coxsackievirus B3 (CVB3 myocarditis, and how sex bias in the experimental disease changes with increased age. Coxsackieviruses are major causes of viral myocarditis, an inflammation of the heart muscle, which is more frequent and severe in men than women. Young male mice infected with CVB3 develop heart-specific autoimmunity and severe myocarditis. Females infected during estrus (high estradiol develop T-regulatory cells and when infected during diestrus (low estradiol develop autoimmunity similar to males. During estrus, protection depends on estrogen receptor alpha (ERα, which promotes type I interferon, activation of natural killer/natural killer T cells and suppressor cell responses. Estrogen receptor beta has opposing effects to ERα and supports pro-inflammatory immunity. However, the sexual dimorphism of the disease is significantly ameliorated in aged animals when old females become as susceptible as males. This correlates to a selective loss of the ERα that is required for immunosuppression. Therefore, sex-associated hormones control susceptibility in the virus-mediated disease, but their impact can alter with the age and physiological stage of the individual.

  12. Heme Oxygenase-1 Mediates Oxidative Stress and Apoptosis in Coxsackievirus B3-Induced Myocarditis

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    Oana N. Ursu

    2014-01-01

    Full Text Available Background: Heme oxygenase-1 (HO-1, which is suggested to play a role in defending the organism against oxidative stress-mediated injuries, can be induced by diverse factors including viruses and iron. As coxsackievirus B3 (CVB3-infected SWR/J mice susceptible for chronic myocarditis were found to have a significant iron incorporation and HO-1 upregulation in the myocardium, we aimed to investigate the molecular interplay between HO-1 expression and iron homeostasis in the outcome of viral myocarditis. Methods and Results: In susceptible SWR/J mice, but not in resistant C57BL/6 mice, we observed at later stages of CVB3 myocarditis significant iron deposits in macrophages and also in cardiomyocytes, which were spatially associated with oxidative stress, upregulation of HO-1 and caspase-3 activation. HO-1, which is also expressed in cultivated RAW 264.7 macrophages upon incubation with iron and/or CVB3, could be downregulated by inhibition of NO/iNOS using L-NAME. Moreover, specific inhibition of HO-1 by tin mesoporphyrin revealed a suppression of superoxide production in iron and/or CVB3-treated macrophages. The molecular relationship of HO-1 and caspase-3 activation was proven by downregulation with HO-1 siRNA in iron- and/or CVB3-treated cultivated cells. Importantly, iron was found to increase viral replication in vitro. Conclusion: These results indicate that HO-1 induces a paracrine signalling in macrophages via reactive oxygen species production, mediating apoptosis of heart muscle cells at later stages of myocarditis. Notably, in genetically susceptible mice iron potentiates the detrimental effects of CVB3 by the NO/HO-1 pathway, thus increasing cardiac pathogenicity.

  13. Short hairpin RNA targeting 2B gene of coxsackievirus B3 exhibits potential antiviral effects both in vitro and in vivo

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    Yao Hailan

    2012-08-01

    Full Text Available Abstract Background Coxsackievirus B3 is an important infectious agent of viral myocarditis, pancreatitis and aseptic meningitis, but there are no specific antiviral therapeutic reagents in clinical use. RNA interference-based technology has been developed to prevent the viral infection. Methods To evaluate the impact of RNA interference on viral replication, cytopathogenicity and animal survival, short hairpin RNAs targeting the viral 2B region (shRNA-2B expressed by a recombinant vector (pGCL-2B or a recombinant lentivirus (Lenti-2B were tansfected in HeLa cells or transduced in mice infected with CVB3. Results ShRNA-2B exhibited a significant effect on inhibition of viral production in HeLa cells. Furthermore, shRNA-2B improved mouse survival rate, reduced the viral tissues titers and attenuated tissue damage compared with those of the shRNA-NC treated control group. Lenti-2B displayed more effective role in inhibition of viral replication than pGCL-2B in vivo. Conclusions Coxsackievirus B3 2B is an effective target of gene silencing against coxsackievirus B3 infection, suggesting that shRNA-2B is a potential agent for further development into a treatment for enterviral diseases.

  14. The innate immune response to coxsackievirus B3 predicts progression to cardiovascular disease and heart failure in male mice

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    Onyimba Jennifer A

    2011-02-01

    Full Text Available Abstract Background Men are at an increased risk of dying from heart failure caused by inflammatory heart diseases such as atherosclerosis, myocarditis and dilated cardiomyopathy (DCM. We previously showed that macrophages in the spleen are phenotypically distinct in male compared to female mice at 12 h after infection. This innate immune profile mirrors and predicts the cardiac immune response during acute myocarditis. Methods In order to study sex differences in the innate immune response, five male and female BALB/c mice were infected intraperitoneally with coxsackievirus B3 (CVB3 or phosphate buffered saline and their spleens were harvested 12 h later for microarray analysis. Gene expression was determined using an Affymetrix Mouse Gene 1.0 ST Array. Significant gene changes were verified by quantitative real-time polymerase chain reaction or ELISA. Results During the innate immune response to CVB3 infection, infected males had higher splenic expression of genes which are important in regulating the influx of cholesterol into macrophages, such as phospholipase A2 (PLA2 and the macrophage scavenger receptor compared to the infected females. We also observed a higher expression in infected males compared to infected females of squalene synthase, an enzyme used to generate cholesterol within cells, and Cyp2e1, an enzyme important in metabolizing cholesterol and steroids. Infected males also had decreased levels of the translocator protein 18 kDa (TSPO, which binds PLA2 and is the rate-limiting step for steroidogenesis, as well as decreased expression of the androgen receptor (AR, which indicates receptor activation. Gene differences were not due to increased viral replication, which was unaltered between sexes. Conclusions We found that, compared to females, male mice had a greater splenic expression of genes which are important for cholesterol metabolism and activation of the AR at 12 h after infection. Activation of the AR has been linked to

  15. Deletions within the 5'UTR of coxsackievirus B3: consequences for virus translation and replication.

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    Hunziker, Isabelle P; Cornell, Christopher T; Whitton, J Lindsay

    2007-03-30

    Key features of an ideal RNA-based vaccine against coxsackievirus B3 (CVB3) are (i) limited genome replication/virus production (to minimize vaccine-related pathology) and (ii) abundant virus protein synthesis (to maximize immunogenicity). These attributes may apply to CVB3 RNAs lacking up to 250 nucleotides (nt) from their 5' terminus; these RNAs do not give rise to infectious progeny, but they have been reported to retain the entire CVB3 IRES (mapped to nt approximately 432-639) and to produce large quantities of viral protein in transfected cells. Here, we constructed five 5' RNA deletion variants that, to our surprise, failed to protect against CVB3 challenge. We investigated the reasons for this failure and conclude that (i) a 5' terminal deletion as short as 32 nt abolishes CVB3 RNA replication in transfected cells; (ii) this deleted RNA, and others with longer deletions, do not direct abundant protein synthesis in transfected cells, probably as a consequence of their replicative incapacity; and (iii) the CVB3 IRES is substantially larger than previously thought, and its 5' boundary lies between residues 76 and 125, very closely approximating that of the poliovirus IRES.

  16. Bilateral idiopathic retinal vasculitis following coxsackievirus A4 infection: a case report.

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    Mine, Izumi; Taguchi, Manzo; Sakurai, Yutaka; Takeuchi, Masaru

    2017-07-19

    Coxsackieviruses are members of a group of viruses called the enteroviruses, which may cause respiratory and gastrointestinal symptoms, erythema, meningoencephalitis, myocarditis, pericarditis, and myositis. Unilateral acute idiopathic maculopathy caused by coxsackievirus A16 has been associated with hand, foot, and mouth disease, but only a few reports describe retinitis associated with coxsackievirus serotype B3 or B4. We report a case of bilateral multifocal obstructive retinal vasculitis that developed after coxsackievirus A4 infection. A 60-year-old woman was referred to our department with bilateral visual disturbance that developed following flu-like symptoms. At the initial examination, best corrected visual acuity was 20/200 in the right eye and 20/50 in the left eye. The critical flicker frequency (CFF) was 23 Hz in the right eye and 27 Hz in the left eye. Fine white keratic precipitates with infiltrating cells were presented in the anterior chamber of both eyes, and multifocal retinal ischemic lesions were observed in the macula and posterior pole of both eyes. The retinal lesions corresponded with scotomas observed in Goldmann visual field test. On spectral domain-optical coherence tomography (SD-OCT), retinal lesions were depicted as hyper-reflective regions in the inner retina layers in both eyes, and disruption of ellipsoid line in the left eye., Fluorescein angiography exhibited findings indicative of multifocal obstructive retinal vasculitis. The patient had a history of current hypertension treated with oral therapy and glaucoma treated with latanoprost eye drops. Blood test for coxsackievirus antibody titers revealed that A4, A6, A9, B1, B2, B3, and B5 were positive (titers: 8-32). Abdominal skin biopsy of necrotic tissue suggested vascular damage caused by coxsackievirus. The general symptoms improved after 6 weeks, and the multifocal retinal ischemic lesions were partially resolved with residual slightly hard exudates. Only coxsackievirus A4

  17. The antiviral effect of jiadifenoic acids C against coxsackievirus B3

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    Miao Ge

    2014-08-01

    Full Text Available Coxsackievirus B type 3 (CVB3 is one of the major causative pathogens associated with viral meningitis and myocarditis, which are widespread in the human population and especially prevalent in neonates and children. These infections can result in dilated cardiomyopathy (DCM and other severe clinical complications. There are no vaccines or drugs approved for the prevention or therapy of CVB3-induced diseases. During screening for anti-CVB3 candidates in our previous studies, we found that jiadifenoic acids C exhibited strong antiviral activities against CVB3 as well as other strains of Coxsackie B viruses (CVBs. The present studies were carried out to evaluate the antiviral activities of jiadifenoic acids C. Results showed that jiadifenoic acids C could reduce CVB3 RNA and proteins synthesis in a dose-dependent manner. Jiadifenoic acids C also had a similar antiviral effect on the pleconaril-resistant variant of CVB3. We further examined the impact of jiadifenoic acids C on the synthesis of viral structural and non-structural proteins, finding that jiadifenoic acids C could reduce VP1 and 3D protein production. A time-course study with Vero cells showed that jiadifenoic acids C displayed significant antiviral activities at 0–6 h after CVB3 inoculation, indicating that jiadifenoic acids C functioned at an early step of CVB3 replication. However, jiadifenoic acids C had no prophylactic effect against CVB3. Taken together, we show that jiadifenoic acids C exhibit strong antiviral activities against all strains of CVB, including the pleconaril-resistant variant. Our study could provide a significant lead for anti-CVB3 drug development.

  18. Structural and functional characterization of the coxsackievirus B3 CRE(2C): role of CRE(2C) in negative- and positive-strand RNA synthesis.

    NARCIS (Netherlands)

    Ooij, M.J. van; Vogt, D.A.; Paul, A.; Castro, C.; Kuijpers, J.M.; Kuppeveld, F.J.M. van; Cameron, C.E.; Wimmer, E.; Andino, R.; Melchers, W.J.G.

    2006-01-01

    A stem-loop element located within the 2C-coding region of the coxsackievirus B3 (CVB3) genome has been proposed to function as a cis-acting replication element (CRE). It is shown here that disruption of this structure indeed interfered with viral RNA replication in vivo and abolished uridylylation

  19. Coxsackievirus B3 induces the formation of autophagosomes in cardiac fibroblasts both in vitro and in vivo

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    Zhai, Xia, E-mail: zhai_xia_cool@126.com [Department of Microbiology and Wu Lien-Teh Institute, Harbin Medical University, 157 Baojian Road, Harbin 150081 (China); Qin, Ying, E-mail: qinyinggaofeng@163.com [Department of Microbiology and Wu Lien-Teh Institute, Harbin Medical University, 157 Baojian Road, Harbin 150081 (China); Chen, Yang, E-mail: cy_hmu@126.com [Department of Microbiology and Wu Lien-Teh Institute, Harbin Medical University, 157 Baojian Road, Harbin 150081 (China); Lin, Lexun, E-mail: linlexun@163.com [Department of Microbiology and Wu Lien-Teh Institute, Harbin Medical University, 157 Baojian Road, Harbin 150081 (China); Wang, Tianying, E-mail: wangty0929@163.com [Department of Microbiology and Wu Lien-Teh Institute, Harbin Medical University, 157 Baojian Road, Harbin 150081 (China); Zhong, Xiaoyan, E-mail: littlerock712@163.com [Department of Microbiology and Wu Lien-Teh Institute, Harbin Medical University, 157 Baojian Road, Harbin 150081 (China); Wu, Xiaoyu, E-mail: xiaoyu_wu2006@163.com [Department of Cardiology, The First Hospital of Harbin Medical University, 23 Youzheng Street, Harbin 150001 (China); Chen, Sijia, E-mail: chensj0802@163.com [Department of Microbiology and Wu Lien-Teh Institute, Harbin Medical University, 157 Baojian Road, Harbin 150081 (China); Li, Jing, E-mail: jing070822@163.com [Center of Electron Microscopy, Harbin Medical University, 157 Baojian Road, Harbin 150081 (China); Wang, Yan, E-mail: wangyan@hrbmu.edu.cn [Department of Microbiology and Wu Lien-Teh Institute, Harbin Medical University, 157 Baojian Road, Harbin 150081 (China); Zhang, Fengmin, E-mail: fengminzhang@ems.hrbmu.edu.cn [Department of Microbiology and Wu Lien-Teh Institute, Harbin Medical University, 157 Baojian Road, Harbin 150081 (China); Zhao, Wenran, E-mail: zhaowenran2002@aliyun.com [Department of Cell Biology, Harbin Medical University, 157 Baojian Road, Harbin 150081 (China); and others

    2016-12-10

    Coxsackievirus group B (CVB) is one of the common pathogens that cause myocarditis and cardiomyopathy. Evidence has shown that CVB replication in cardiomyocytes is responsible for the damage and loss of cardiac muscle and the dysfunction of the heart. However, it remains largely undefined how CVB would directly impact cardiac fibroblasts, the most abundant cells in human heart. In this study, cardiac fibroblasts were isolated from Balb/c mice and infected with CVB type 3 (CVB3). Increased double-membraned, autophagosome-like vesicles in the CVB3-infected cardiac fibroblasts were observed with electron microscope. Punctate distribution of LC3 and increased level of LC3-II were also detected in the infected cardiac fibroblasts. Furthermore, we observed that the expression of pro-inflammatory cytokines, IL-6 and TNF-α, was increased in the CVB3-infected cardiac fibroblasts, while suppressed autophagy by 3-MA and Atg7-siRNA inhibited cytokine expression. Consistent with the in vitro findings, increased formation of autophagosomes was observed in the cardiac fibroblasts of Balb/c mice infected with CVB3. In conclusion, our data demonstrated that cardiac fibroblasts respond to CVB3 infection with the formation of autophagosomes and the release of the pro-inflammatory cytokines. These results suggest that the autophagic response of cardiac fibroblasts may play a role in the pathogenesis of myocarditis caused by CVB3 infection. - Highlights: • CVB3 replication induced autophagosome assembly in primary cardiac fibroblasts. • Both IL-6 and TNF-α in cardiac fibroblasts infected by CVB3 were increased. • IL-6 and TNF-α were reduced in cardiac fibroblasts when autophagy was inhibited. • Autophagosome assembly in cardiac fibroblasts of CVB-infected mice was increased.

  20. Echovirus plays major roles in the natural recombination of Coxsackievirus B3.

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    Shen, Hongxing; Liu, Tingjun; Luo, Yucheng; Shao, Shihe; Deng, Xintao; Wang, Hua

    2017-08-29

    Coxsakievirus B3 (CVB3) is a member of enterovirus B (EVB) group, which can cause serious heart diseases such as viral myocarditis. In order to analyze the evolution of CVB3, we performed a recombination analysis of all viral genomes of enterovirus B, and found that there were 19 putative recombination events that produced CVB3. A total of 11 serotypes were found to be involved in the generation of CVB3 progeny virus. These recombination events involved echovirus, EcoV (which includes EcoV6, EcoV9, EcoV14, EcoV15, EcoV17, EcoV21, EcoV24, and EcoV25), CVB4, CVB5, and EVB81, as major or minor parents. The most active, EcoV, which was involved in the 14 of 19 recombination events, acts as one of the parental viruses for CVB3 strains among molecular evolution and recombination events in circulating CVB3. Our study indicates that, EcoV plays major roles in CVB3 recombination, and is involved in the production of 11 new CVB3 recombinant strains. © 2017 Wiley Periodicals, Inc.

  1. AIM2 Co-immunization with VP1 Is Associated with Increased Memory CD8 T Cells and Mounts Long Lasting Protection against Coxsackievirus B3 Challenge

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    Liang Yin

    2017-06-01

    Full Text Available The recurrent Coxsackievirus B3 (CVB3 infection is the most important cause of intractable myocarditis which often leads to chronic myocarditis and even dilated cardiomyopathy. Therefore, enhanced DNA vaccines capable of memory CD8 T cells are essential for long-lasting immunological protection against CVB3 infection. In this study, absent in melanoma 2 (AIM2 was used as an adjuvant to enhance the induction of memory CD8 T cells elicited by VP1 (viral capsid protein 1 vaccine. Mice were intramuscularly injected with 50 μg AIM2 plasmid and equal amount of VP1 plasmid (pAIM2/pVP1 vaccine 4 times at 2 week-intervals. We observed that the protection of pAIM2/pVP1 vaccine against CVB3 challenge was evidenced by significantly improved cardiac function, reduced myocardial injuries, and increased survival rate when compared with immunization with pVP1. Co-immunization with pAIM2/pVP1 robustly augmented T lymphocytes proliferation and CVB3-specific cytotoxic T lymphocyte responses. Importantly, 16 weeks after the last immunization, pAIM2/pVP1 co-immunization significantly enhanced the expression of Bcl-6, SOCS3, and Sca-1 which are critical for memory CD8 T cells as compared with pVP1 immunization. Notably, CD8 T cells that are likely vaccine-induced memory T cells were responsible for the protective efficacy of pAIM2/pVP1 vaccine by abolition of a CD8 T cell immune response following a lethal dose of CVB3 infection. Our results indicate that AIM2-adjuvanted vaccine could be a potential and promising approach to promote a long-lasting protection against CVB3-induced myocarditis.

  2. Coxsackievirus infections in pregnant women with a parallel experimental model infection showing possible effects on coarse of pregnancy

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    Borsanyiova M.

    2011-04-01

    Full Text Available Aim of our work was firstly to determine the prevalence of anti-coxsackievirus antibodies during pregnancy. 217 serum samples were tested for antibodies by virus neutralization test against coxsackieviruses (CV B1–B6, A7 and A9. The second aim was to investigate experimental transmission of virus to the fetus during pregnancy. Methods. Virus Neutralization Test, RT-PCR. Results. In the serological study, paired blood serum samples from 217 pregnant women were studied for antibodies against coxsackievirus serotypes (CVB1–CVB6, CVA7 and CVA9 in sera of pregnant women from selected areas of the Slovak Republic. Coxsackievirus B4 (CVB4 infection was most prevalent, followed by CVB3, CVA7, CVA9, CVB5, CVB2, CVB1 while coxsackievirus B6 (CVB6 was scarce. In 30 out of 217 cases (13.82 % current infection was recorded. In the experimental murine study, in the second week of gravidity we observed presence of enteroviral RNA in the placenta and the intestine of the dead fetuses of the mice. Conclusions. Anti-CV antibodies were prevalent in the pregnant mothers indicating circulation of these viruses in the population. Current infection was shown in 13.82 % of studied cases. Presence of virus RNA in the organs of the unborn fetuses in the experimental infection indicates the possibility of transfer of the coxsackievirus B4-E2 infection from mother to child during antenatal development

  3. A new monoclonal antibody (Cox mAB 31A2) detects VP1 protein of coxsackievirus B3 with high sensitivity and specificity.

    Science.gov (United States)

    Ettischer-Schmid, Nicole; Normann, Andrea; Sauter, Martina; Kraft, Lisa; Kalbacher, Hubert; Kandolf, Reinhard; Flehmig, Bertram; Klingel, Karin

    2016-11-01

    Human enteroviruses, e.g. coxsackieviruses, induce a variety of severe acute and chronic forms of disease, including myocarditis, meningitis and diabetes mellitus type 1. To visualize enterovirus infection with a diagnostic intent, many studies have applied a commercially available antibody (anti-CVB5 VP1, clone 5-D8/1, Dako, Hamburg, Germany) that identifies VP1 of different enteroviral serotypes. Many antibodies, however, have been found to bind non-specifically to proteins of cardiomyocytes and in the interstitial space, resulting in non-specific staining in immunohistochemistry. In this paper we show that the anti-CVB5 VP1 antibody, recognizing VP1 of coxsackieviruses and widely used in diagnostics and research, shows strong cross-reactivity with cellular proteins in the heart (and pancreas) of humans and mice, which calls for a more specific antibody to be used for diagnostic purposes. We observed by Western blot analyses of lysates from human heart tissue samples and HeLa cells two cross-reactive bands when using clone 5-D8/1. Peptide mass fingerprinting (MALDI-TOF) identified these proteins as creatine kinase (B-type) and tubulin, confirming that this mAb detects cellular proteins in addition to viral VP1. In order to overcome the problems of false positive VP1 staining we generated a new highly specific and sensitive monoclonal antibody (Cox mAB 31A2) that recognizes VP1 from CVB3. The new antibody was characterized and was found to function well in immunohistochemistry, immunofluorescence staining, Western blotting, ELISA and FACS analyses.

  4. Involvement of Endoplasmic Reticulum Stress-Mediated C/EBP Homologous Protein Activation in Coxsackievirus B3-Induced Acute Viral Myocarditis.

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    Cai, Zhejun; Shen, Li; Ma, Hong; Yang, Jin; Yang, Du; Chen, Han; Wei, Jia; Lu, Qiulun; Wang, Dao Wen; Xiang, Meixiang; Wang, Jian'an

    2015-07-01

    This study tested the hypothesis whether endoplasmic reticulum (ER) stress/C/EBP homologous protein (CHOP) signaling is linked with coxsackievirus B3 (CVB3)-induced acute viral myocarditis (AVMC) in vivo. AVMC was induced by intraperitoneal injection of 1000 tissue culture infectious dose (TCID50) of CVB3 virus in mice. In AVMC mouse hearts (n=11), ER stress and CHOP were significantly activated, and were linked to the induction of proapoptotic signaling including reduction of Bcl-2, activation of Bax and caspase 3, compared with the controls (n=10), whereas these could be markedly blocked by ER stress inhibitor tauroursodeoxycholic acid administration (n=11). Moreover, chemical inhibition of ER stress significantly attenuated cardiomyocytes apoptosis, and prevented cardiac troponin I elevation, ameliorated cardiac dysfunction assessed by both hemodynamic and echocardiographic analysis, reduced viral replication, and increased survival rate after CVB3 inoculation. We further discovered that genetic ablation of CHOP (n=10) suppressed cardiac Bcl-2/Bax ratio reduction and caspase 3 activation, and prevented cardiomyotes apoptosis in vivo, compared with wild-type receiving CVB3 inoculation (n=10). Strikingly, CHOP deficiency exhibited dramatic protective effects on cardiac damage, cardiac dysfunction, viral replication, and promoted survival in CVB3-caused AVMC. Our data imply the involvement of ER stress/CHOP signaling in CVB3-induced AVMC via proapoptotic pathways, and provide a novel strategy for AVMC treatment. © 2015 American Heart Association, Inc.

  5. Persistence of viral RNA in the brain of experimentally infected mice with coxsackievirus B5

    OpenAIRE

    Sobotova Z.; Marosova L.; Badurova M.; Sojka M.; Borsanyiova M.; Stipalova D.; Bopegamage S.

    2011-01-01

    The aim of our study was to follow the persistence of viral RNA in selected organs of experimentally infected with coxsackievirus (CV) B5 strains from different sources such as a patient’s sample, an environmental sample and a prototype virus strain. Methods . CD-1 mice were infected with CVB5 strain Faulkner the prototype, CVB5 – isolate from treated sewage waste and isolate from patient’s stool sample both identified as CVB5. The viral RNA was detected by RT-PCR using enterovirus primers sp...

  6. Adult-onset Kawasaki disease (mucocutaneous lymph node syndrome and concurrent Coxsackievirus A4 infection: a case report

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    Ueda Y

    2015-09-01

    Full Text Available Yuki Ueda,1 Tsuneaki Kenzaka,1,2 Ayako Noda,1 Yu Yamamoto,1 Masami Matsumura1 1Division of General Internal Medicine, Jichi Medical University Hospital, Shimotsuke, 2Division of Community Medicine and Career Development, Kobe University Graduate School of Medicine, Japan Introduction: Kawasaki disease (KD most commonly develops in infants, although its specific cause is still unclear. We report here a rare case of adult-onset KD which revealed to be concurrently infected by Coxsackievirus A4. Case presentation: The patient was a 37-year-old Japanese man who presented with fever, exanthema, changes in the peripheral extremities, bilateral non-exudative conjunctival injection, and changes in the oropharynx, signs that meet the diagnostic criteria for KD defined by the Centers for Disease Control and Prevention. In this case, the patient had a significantly high antibody titer for Coxsackievirus A4, which led us to presume that the occurrence of KD was concurrent Coxsackievirus A4 infection. Conclusion: We reported a very rare case of KD which suggests that the disease can be concurrent Coxsackievirus A4 infection. Although KD is an acute childhood disease, with fever as one of the principal features, KD should also be considered in the differential diagnosis when adult patients present with a fever of unknown cause associated with a rash. Keywords: adult-onset, Coxsackievirus A4, Kawasaki disease, mucocutaneous lymph node syndrome, skin rash

  7. Persistence of viral RNA in the brain of experimentally infected mice with coxsackievirus B5

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    Sobotova Z.

    2011-04-01

    Full Text Available The aim of our study was to follow the persistence of viral RNA in selected organs of experimentally infected with coxsackievirus (CV B5 strains from different sources such as a patient’s sample, an environmental sample and a prototype virus strain. Methods . CD-1 mice were infected with CVB5 strain Faulkner the prototype, CVB5 – isolate from treated sewage waste and isolate from patient’s stool sample both identified as CVB5. The viral RNA was detected by RT-PCR using enterovirus primers specific for the non-coding 5' region. Results . We observed presence of RNA in the brain and heart of mice infected with isolate from patient’s stool at day 45 post infection (p. i.. Conclusion. We conclude that CVB5 persists in the brain and heart after oral infection of CD1 mice. The relevance of viral persistence maybe related viral origin and the genetics

  8. An RNA replication-center assay for high content image-based quantifications of human rhinovirus and coxsackievirus infections

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    Lötzerich Mark

    2010-10-01

    Full Text Available Abstract Background Picornaviruses are common human and animal pathogens, including polio and rhinoviruses of the enterovirus family, and hepatits A or food-and-mouth disease viruses. There are no effective countermeasures against the vast majority of picornaviruses, with the exception of polio and hepatitis A vaccines. Human rhinoviruses (HRV are the most prevalent picornaviruses comprising more than one hundred serotypes. The existing and also emerging HRVs pose severe health risks for patients with asthma or chronic obstructive pulmonary disease. Here, we developed a serotype-independent infection assay using a commercially available mouse monoclonal antibody (mabJ2 detecting double-strand RNA. Results Immunocytochemical staining for RNA replication centers using mabJ2 identified cells that were infected with either HRV1A, 2, 14, 16, 37 or coxsackievirus (CV B3, B4 or A21. MabJ2 labeled-cells were immunocytochemically positive for newly synthesized viral capsid proteins from HRV1A, 14, 16, 37 or CVB3, 4. We optimized the procedure for detection of virus replication in settings for high content screening with automated fluorescence microscopy and single cell analysis. Our data show that the infection signal was dependent on multiplicity, time and temperature of infection, and the mabJ2-positive cell numbers correlated with viral titres determined in single step growth curves. The mabJ2 infection assay was adapted to determine the efficacy of anti-viral compounds and small interfering RNAs (siRNAs blocking enterovirus infections. Conclusions We report a broadly applicable, rapid protocol to measure infection of cultured cells with enteroviruses at single cell resolution. This assay can be applied to a wide range of plus-sense RNA viruses, and hence allows comparative studies of viral infection biology without dedicated reagents or procedures. This protocol also allows to directly compare results from small compound or siRNA infection screens

  9. Role of Heparan Sulfate in Cellular Infection of Integrin-Binding Coxsackievirus A9 and Human Parechovirus 1 Isolates

    NARCIS (Netherlands)

    Merilahti, Pirjo; Karelehto, Eveliina; Susi, Petri

    2016-01-01

    Heparan sulfate/heparin class of proteoglycans (HSPG) have been shown to function in cellular attachment and infection of numerous viruses including picornaviruses. Coxsackievirus A9 (CV-A9) and human parechovirus 1 (HPeV-1) are integrin-binding members in the family Picornaviridae. CV-A9 Griggs and

  10. Recruitment of PI4KIIIβ to coxsackievirus B3 replication organelles is independent of ACBD3, GBF1, and Arf1

    NARCIS (Netherlands)

    Dorobantu, Cristina M; van der Schaar, Hilde M; Ford, Lauren A; Strating, Jeroen R P M; Ulferts, Rachel; Fang, Ying; Belov, George; van Kuppeveld, Frank J M

    2014-01-01

    Members of the Enterovirus (poliovirus [PV], coxsackieviruses, and human rhinoviruses) and Kobuvirus (Aichi virus) genera in the Picornaviridae family rely on PI4KIIIβ (phosphatidylinositol-4-kinase IIIβ) for efficient replication. The small membrane-anchored enteroviral protein 3A recruits PI4KIIIβ

  11. Prevalence of multiple enteroviruses associated with hand, foot, and mouth disease in Shijiazhuang City, Hebei province, China: outbreaks of coxsackieviruses a10 and b3.

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    Huifang Tian

    Full Text Available Hand, foot, and mouth disease (HFMD has been one of the most common infectious diseases in Shijiazhuang City, as is the situation in China overall. In the National HFMD surveillance system, the pathogen detection was focused on EV-A71 and CVA16, and therefore, information on the other EVs is very limited. In order to identify the circulating EV serotypes in the HFMD outbreaks in Shijiazhuang City during 2010-2012, 4045 patients presented with HFMD were recruited in the study, and clinical samples were investigated. Typing of EV serotypes was performed using the molecular typing methods, and phylogenetic analyses based on entire VP1 sequences of human enterovirus 71 (EV-A71, coxsackievirus A16 (CVA16, CVA10 and CVB3 was performed. The results revealed that EV-A71 and CVA16 were the 2 most important pathogens but the circulating trends of the 2 viruses showed a shift, the spread of EV-A71 became increasingly weak, whereas the spread of CVA16 became increasingly stronger. CVA10 and CVB3 were the third and fourth most prevalent pathogens, respectively. Co-infection of two viruses at the same time was not found in these samples. Based on entire VP1 region sequences, the phylogenetic analysis revealed that C4a subgenotype EV-A71, B1a and B1b subgenotype CVA16 continued to evolve. The CVA10 strains were assigned to 4 genotypes (A-D, whereas the CVB3 strains were assigned to 5 genotypes (A-E, with clear geographical and temporal-specific distributions. The Shijiazhuang CVA10 sequences belonged to 4 epidemic lineages within genotype C, whereas the Shijiazhuang CVB3 sequences belonged to 2 epidemic lineages within genotype E, which may have the same origins as the strains reported in other part of China. CVA10 and CVB3, 2 pathogens that were previously infrequently detected, were identified as pathogens causing the HFMD outbreaks. This study underscores the need for detailed laboratory-based surveillances of HFMD in mainland China.

  12. A murine model of coxsackievirus A16 infection for anti-viral evaluation.

    Science.gov (United States)

    Liu, Qingwei; Shi, Jinping; Huang, Xulin; Liu, Fei; Cai, Yicun; Lan, Ke; Huang, Zhong

    2014-05-01

    Coxsackievirus A16 (CA16) is one of the main causative agents of hand, foot and mouth disease (HFMD), which is a common infectious disease in children. CA16 infection may lead to severe nervous system damage and even death in humans. However, study of the pathogenesis of CA16 infection and development of vaccines and anti-viral agents are hindered partly by the lack of an appropriate small animal model. In the present study, we developed and characterized a murine model of CA16 infection. We show that neonatal mice are susceptible to CA16 infection via intraperitoneal inoculation. One-day-old mice infected with 2×10(6)TCID50 of CA16/SZ05 strain consistently exhibited clinical signs, including reduced mobility, and limb weakness and paralysis. About 57% of the mice died within 14days after infection. Significant damage in the brainstem, limb muscles and intestines of the infected mice in the moribund state was observed by histological examination, and the presence of CA16 in neurons of the brainstem was demonstrated by immunohistochemical staining with a CA16-specific polyclonal antibody, strongly suggesting the involvement of the central nervous system in CA16 infection. Analysis of virus titers in various organs/tissues collected at 3, 6 and 9days post-infection, showed that skeletal muscle was the major site of virus replication at the early stage of infection, while the virus mainly accumulated in the brain at the late stage. In addition, susceptibility of mice to CA16 infection was found to be age dependent. Moreover, different CA16 strains could exhibit varied virulence in vivo. Importantly, we demonstrated that post-exposure treatment with an anti-CA16 monoclonal antibody fully protected mice against lethal CA16 infection. Collectively, these results indicate the successful development of a CA16 infection mouse model for anti-viral evaluation. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Atypical hand-foot-and-mouth disease associated with coxsackievirus A6 infection.

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    Lott, Jason P; Liu, Kristina; Landry, Marie-Louise; Nix, W Allan; Oberste, M Steven; Bolognia, Jean; King, Brett

    2013-11-01

    Hand-foot-and-mouth disease (HFMD) is an acute viral illness commonly caused by coxsackievirus (CV)-A16 and enterovirus 71 infections. Recently, atypical HFMD has been reported in association with CV-A6, an uncommon enterovirus strain. We sought to describe the clinical features of atypical HFMD associated with CV-A6 infection and its diagnostic laboratory evaluation. Patients presenting to our institution with history and examination suggestive of atypical HFMD from January 2012 to July 2012 were identified. Morphology and distribution of mucocutaneous lesions were recorded. Enterovirus infection was assessed by reverse transcriptase polymerase chain reaction of biologic specimens. Enterovirus type was determined by viral capsid protein 1 gene sequencing. Two adults and 3 children with atypical HFMD were identified. Four of 5 patients exhibited widespread cutaneous lesions. In 2 patients with a history of atopic dermatitis, accentuation in areas of dermatitis was noted. Associated systemic symptoms prompted 4 of 5 patients to seek emergency care, and both adults were hospitalized for diagnostic evaluation. Infection with CV-A6 was confirmed in all patients. This study is a case series from a single institution. Consideration of the expanded range of cutaneous findings in atypical HFMD caused by CV-A6 infection may assist clinicians in diagnosis and management. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  14. Persistent infection of human pancreatic cells with Coxsackievirus B4 is cured by fluoxetine.

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    Alidjinou, Enagnon Kazali; Sané, Famara; Bertin, Antoine; Caloone, Delphine; Hober, Didier

    2015-04-01

    Group B Coxsackieviruses (CVB) are involved in various acute clinical features and they can play a role in the development of chronic diseases like type 1 diabetes. The persistence of CVB has been described in vitro and in vivo in various models. Fluoxetine was reported to inhibit the replication of CVB1-3, which prompted us to study the in vitro antiviral activity of fluoxetine against CVB4 in models of acute infection. In addition we took advantage of a chronically CVB4-infected Panc-1 cell line to evaluate the antiviral effect of fluoxetine in a model of persistent CVB4 infection. An inhibition of the CVB4 replication was obtained when fluoxetine was added at 5.48μM to Hep-2 cell cultures. No inhibitory effect was observed when CVB4 was mixed with fluoxetine for 2h and filtered to eliminate fluoxetine before inoculation to cells, or when cells were treated up to 96h and washed before viral inoculation. Fluoxetine (5.48μM) reduced viral replication by more than 50% in acutely infected Panc-1 cell cultures. A dramatic decrease of infectious particles levels in supernatants of Panc-1 cells chronically infected with CVB4 was obtained a few days after treatment with fluoxetine and no infectious viral particle was found as soon as day 21 of treatment, and intracellular enteroviral RNA was undetectable by RT-PCR after three weeks of treatment. These data display that fluoxetine can inhibit the replication of CVB4 and can cure Panc-1 cells chronically infected with CVB4. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. How does thymus infection by coxsackievirus contribute to the pathogenesis of type 1 diabetes?

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    Hélène eMichaux

    2015-06-01

    Full Text Available Through synthesis and presentation of neuroendocrine self-antigens by major histocompatibility complex (MHC proteins, thymic epithelial cells (TECs play a crucial role in programming central immune self-tolerance to neuroendocrine functions. Insulin-like growth factor-2 (IGF-2 is the dominant gene/polypeptide of the insulin family that is expressed in TECs from different animal species and humans. Igf2 transcription is defective in the thymus of diabetes-prone Bio-Breeding (BB rats, and tolerance to insulin is severely decreased in Igf2-/- mice. For more than 15 years now, our group is investigating the hypothesis that, besides a pancreotropic action, infection by coxsackievirus B4 (CV-B4 could implicate the thymus as well, and interfere with the intrathymic programming of central tolerance to the insulin family and secondarily to insulin-secreting islet β cells. In this perspective, we have demonstrated that a productive infection of the thymus occurs after oral CV-B4 inoculation of mice. Moreover, our most recent data have demonstrated that CV-B4 infection of a murine medullary (m TEC line induces a significant decrease in Igf2 expression and IGF-2 production. In these conditions, Igf1 expression was much less affected by CV-B4 infection, while Ins2 transcription was not detected in this cell line. Through the inhibition of Igf2 expression in TECs, CV-B4 infection could lead to a breakdown of central immune tolerance to the insulin family and promote an autoimmune response against insulin-secreting islet β cells. Our major research objective now is to understand the molecular mechanisms by which CV-B4 infection of TECs leads to a major decrease in Igf2 expression in these cells.

  16. A neonatal mouse model of coxsackievirus A10 infection for anti-viral evaluation.

    Science.gov (United States)

    Li, Shuxuan; Zhao, Huan; Yang, Lisheng; Hou, Wangheng; Xu, Longfa; Wu, Yangtao; Wang, Wei; Chen, Chunye; Wan, Junkai; Ye, Xiangzhong; Liang, Zhenglun; Mao, Qunying; Cheng, Tong; Xia, Ningshao

    2017-08-01

    Epidemiological data indicate that coxsackievirus A10 (CVA10) has become one of the main causative agents of hand, foot and mouth disease (HFMD) and in recent years has often been found to co-circulate with other enteroviruses, which poses a challenge for the prevention and control of HFMD. Although most CVA10-associated HFMD cases present mild symptoms, severe manifestations and even death can also occur. However, the study of the pathogenesis and the development of drugs and vaccines for CVA10 infection are still far from complete. In this study, we established a neonatal mouse model for anti-viral evaluation and characterized the pathology of CVA10 infection. To develop the mouse model, both inbred and outbred mouse strains were used to compare their sensitivity to CVA10 infection; then, one-day-old BALB/c mice were selected and inoculated intraperitoneally with a CVA10 clinical strain, CVA10-FJ-01. Clinical symptoms, such as wasting, hind-limb paralysis and even death were observed in the CVA10-infected mice. Moreover, pathological examination and immunohistochemistry staining showed that severe myonecrosis with inflammatory infiltration was observed in CVA10-infected mice, indicating that CVA10 exhibited strong tropism to muscle tissue. Using real-time PCR, we also found that the viral load in the blood and muscle was higher than that in other organs/tissues at different time points post-infection, suggesting that CVA10 had a strong tropism to mice muscle and that viremic spread may also contribute to the death of the CVA10-infected mice. Additionally, to evaluate the neonatal mouse model of CVA10 infection, female mice were immunized with formalin-inactivated CVA10 and then allowed to mate after the third immunization. The results showed that maternal antibodies could protect mice against CVA10 infection. In summary, the results demonstrated that the neonatal mice model was a useful tool for evaluating the protective effects of CVA10 vaccines and anti

  17. Distribution of viral RNA in mouse tissues during acute phase of coxsackievirus B5 infection.

    Science.gov (United States)

    Moon, Mi Sun; Joo, Chul Hyun; Hwang, In Seok; Ye, Jeong Sook; Jun, Eun Jung; Lee, Hui Sun; Kim, Donghou; Lee, Min-Jae; Lee, Heuiran; Kim, Yoo Kyum

    2005-01-01

    To investigate histopathological changes and distribution of coxsackievirus B5 (CVB5) RNA in mouse heart, liver, and pancreas during the acute phase of infection. C3H/HeJ male mice, aged 3-4 weeks, were inoculated intraperitoneally with 5 x 10(5) plaque-forming units of CVB5 and sacrificed at 1, 2, 3, 4, 7 and 10 days postinfection (p.i.). Inflammation of the heart, liver, and pancreatic tissue sections was evaluated by hematoxylin and eosin staining, and virus was detected using antibody to viral coat protein VP1. A quantitative real-time RT-PCR method, using primers and probe targeted to the highly conserved sequences in the 5'-untranslated region of the virus, was used to evaluate the kinetics of CVB5 RNA during the development of myocarditis or pancreatitis. Marginal inflammatory changes were observed in the heart tissues although viral RNA was constantly present between 1 and 10 days p.i., peaking at 4 days p.i. The pancreatic tissues displayed massive lymphocyte infiltration and loss of acinar cells at day 4 p.i. and viral RNA was detected between 1 and 10 days p.i., peaking at 2-3 days p.i. In the liver, viral RNA was detected between 1 and 7 days. No mortality was observed. CVB5 induced acute pancreatitis without subsequent development of myocarditis. Clearance of CVB5 RNA from the pancreas and heart was slower than clearance from the liver. Our real-time RT-PCR method, which is more sensitive than conventional plaque assay, may provide valuable insight into viral RNA kinetics during CVB5 infection. Copyright (c) 2005 S. Karger AG, Basel.

  18. Mutations in the 5' NTR and the Non-Structural Protein 3A of the Coxsackievirus B3 Selectively Attenuate Myocarditogenicity.

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    Chandirasegaran Massilamany

    Full Text Available The 5' non-translated region (NTR is an important molecular determinant that controls replication and virulence of coxsackievirus B (CVB3. Previous studies have reported many nucleotide (nt sequence differences in the Nancy strain of the virus, including changes in the 5' NTR with varying degrees of disease severity. In our studies of CVB3-induced myocarditis, we sought to generate an infectious clone of the virus for routine in vivo experimentation. By determining the viral nt sequence, we identified three new nt substitutions in the clone that differed from the parental virus strain: C97U in the 5' NTR; a silent mutation, A4327G, in non-structural protein 2C; and C5088U (resulting in P1449L amino acid change in non-structural protein 3A of the virus leading us to evaluate the role of these changes in the virulence properties of the virus. We noted that the disease-inducing ability of the infectious clone-derived virus in three mouse strains was restricted to pancreatitis alone, and the incidence and severity of myocarditis were significantly reduced. We then reversed the mutations by creating three new clones, representing 1 U97C; 2 G4327A and U5088C; and 3 their combination together in the third clone. The viral titers obtained from all the clones were comparable, but the virions derived from the third clone induced myocarditis comparable to that induced by wild type virus; however, the pancreatitis-inducing ability remained unaltered, suggesting that the mutations described above selectively influence myocarditogenicity. Because the accumulation of mutations during passages is a continuous process in RNA viruses, it is possible that CVB3 viruses containing such altered nts may evolve naturally, thus favoring their survival in the environment.

  19. Differential cell autonomous responses determine the outcome of coxsackievirus infections in murine pancreatic α and β cells.

    Science.gov (United States)

    Marroqui, Laura; Lopes, Miguel; dos Santos, Reinaldo S; Grieco, Fabio A; Roivainen, Merja; Richardson, Sarah J; Morgan, Noel G; Op de Beeck, Anne; Eizirik, Decio L

    2015-06-10

    Type 1 diabetes (T1D) is an autoimmune disease caused by loss of pancreatic β cells via apoptosis while neighboring α cells are preserved. Viral infections by coxsackieviruses (CVB) may contribute to trigger autoimmunity in T1D. Cellular permissiveness to viral infection is modulated by innate antiviral responses, which vary among different cell types. We presently describe that global gene expression is similar in cytokine-treated and virus-infected human islet cells, with up-regulation of gene networks involved in cell autonomous immune responses. Comparison between the responses of rat pancreatic α and β cells to infection by CVB5 and 4 indicate that α cells trigger a more efficient antiviral response than β cells, including higher basal and induced expression of STAT1-regulated genes, and are thus better able to clear viral infections than β cells. These differences may explain why pancreatic β cells, but not α cells, are targeted by an autoimmune response during T1D.

  20. Role of Heparan Sulfate in Cellular Infection of Integrin-Binding Coxsackievirus A9 and Human Parechovirus 1 Isolates.

    Science.gov (United States)

    Merilahti, Pirjo; Karelehto, Eveliina; Susi, Petri

    2016-01-01

    Heparan sulfate/heparin class of proteoglycans (HSPG) have been shown to function in cellular attachment and infection of numerous viruses including picornaviruses. Coxsackievirus A9 (CV-A9) and human parechovirus 1 (HPeV-1) are integrin-binding members in the family Picornaviridae. CV-A9 Griggs and HPeV-1 Harris (prototype) strains have been reported not to bind to heparin, but it was recently shown that some CV-A9 isolates interact with heparin in vitro via VP1 protein with a specific T132R/K mutation. We found that the infectivity of both CV-A9 Griggs and HPeV-1 Harris was reduced by sodium chlorate and heparinase suggestive of HSPG interactions. We analyzed the T132 site in fifty-four (54) CV-A9 clinical isolates and found that only one of them possessed T132/R mutation while the other nine (9) had T132K. We then treated CV-A9 Griggs and HPeV-1 Harris and eight CV-A9 and six HPeV-1 clinical isolates with heparin and protamine. Although infectivity of Griggs strain was slightly reduced (by 25%), heparin treatment did not affect the infectivity of the CV-A9 isolates that do not possess the T132R/K mutation, which is in line with the previous findings. Some of the HPeV-1 isolates were also affected by heparin treatment, which suggested that there may be a specific heparin binding site in HPeV-1. In contrast, protamine (a specific inhibitor of heparin) completely inhibited the infection of both prototypes and clinical CV-A9 and HPeV-1 isolates. We conclude that T132R/K mutation has a role in heparin binding of CV-A9, but we also show data, which suggest that there are other HSPG binding sites in CV-A9. In all, we suggest that HSPGs play a general role in both CV-A9 and HPeV-1 infections.

  1. Role of Heparan Sulfate in Cellular Infection of Integrin-Binding Coxsackievirus A9 and Human Parechovirus 1 Isolates.

    Directory of Open Access Journals (Sweden)

    Pirjo Merilahti

    Full Text Available Heparan sulfate/heparin class of proteoglycans (HSPG have been shown to function in cellular attachment and infection of numerous viruses including picornaviruses. Coxsackievirus A9 (CV-A9 and human parechovirus 1 (HPeV-1 are integrin-binding members in the family Picornaviridae. CV-A9 Griggs and HPeV-1 Harris (prototype strains have been reported not to bind to heparin, but it was recently shown that some CV-A9 isolates interact with heparin in vitro via VP1 protein with a specific T132R/K mutation. We found that the infectivity of both CV-A9 Griggs and HPeV-1 Harris was reduced by sodium chlorate and heparinase suggestive of HSPG interactions. We analyzed the T132 site in fifty-four (54 CV-A9 clinical isolates and found that only one of them possessed T132/R mutation while the other nine (9 had T132K. We then treated CV-A9 Griggs and HPeV-1 Harris and eight CV-A9 and six HPeV-1 clinical isolates with heparin and protamine. Although infectivity of Griggs strain was slightly reduced (by 25%, heparin treatment did not affect the infectivity of the CV-A9 isolates that do not possess the T132R/K mutation, which is in line with the previous findings. Some of the HPeV-1 isolates were also affected by heparin treatment, which suggested that there may be a specific heparin binding site in HPeV-1. In contrast, protamine (a specific inhibitor of heparin completely inhibited the infection of both prototypes and clinical CV-A9 and HPeV-1 isolates. We conclude that T132R/K mutation has a role in heparin binding of CV-A9, but we also show data, which suggest that there are other HSPG binding sites in CV-A9. In all, we suggest that HSPGs play a general role in both CV-A9 and HPeV-1 infections.

  2. Vitamin D receptor protects glioblastoma A172 cells against Coxsackievirus A16 infection induced cell death in the pathogenesis of hand, foot, and mouth disease.

    Science.gov (United States)

    Qu, Meiling; Di, Shunxiang; Zhang, Shuyun; Xia, Zhiqun; Quan, Guohong

    2017-11-18

    Hand, foot, and mouth disease (HFMD) was one of the most common children illnesses. Coxsackievirus A16 was one of the major pathogens that cause HFMD. However, the role of vitamin D underlying this common illness has not been elucidated. Our study examined that vitamin D levels was significantly lower in 33 HFMD patients, compared to 36 healthy children. Unexpectedly, both mRNA and protein expression of VDR were significantly decreased in CA16 infected glioblastoma A172 cells. And overexpression of VDR or vitamin D treatment in CA16 infected glioblastoma A172 cells could reverse the CA16 infection induced cell death, apoptosis or mitochondrial membrane rupture. Therefore, our study, for the first time, demonstrated that vitamin D and VDR could associate with the pathogenesis of HFMD. Thus might provide useful information for HFMD prevention and treatments. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. [Group enterovirus infection due to coxsackievirus A16 in Northwestern Russia].

    Science.gov (United States)

    Bichurina, M A; Romanenkova, N I; Novikova, N A; Golitsyna, L N; Rozaeva, N R; Kanaeva, O I; Ermakova, M V; Kamynina, L S; Madoian, A G; Valdaĭtseva, N V; Leonova, N P; Ivanova, T G

    2014-01-01

    Study features of epidemic process and etiology of oral cavity and limb enterovirus exanthema group diseases in a number of territories of Northwestern Russia. Isolation and identification of non-poliomyelitis enteroviruses from material of patients was carried out according to WHO recommendations. Phenotyping and phylogenetic analysis of enteroviruses was carried out. In 3 territories of Northwestern Russia oral cavity and limb enterovirus group diseases were registered. Children aged less than 14 years, predominately aged less than 3 years, were shown to be involved in the epidemic process. Coxsackie A16 enteroviruses from 27 samples of patients were isolated in cell cultures and identified by using specific sera. Coxsackie A16 enteroviruses from 16 samples were identified by using partial sequencing of VP1 genome area. Phylogenetic analysis has shown that the identified Coxsackie A16 viruses distributed among 2 phylogenetic groups. Coxsackie A16 enteroviruses that had never been detected in the region previously were established to be the etiologic factor of oral cavity and limb enterovirus exanthema group disease in the 3 territories of Northwestern Russia. The data obtained give evidence on the necessity of epidemiologic and virological control for enterovirus infection with the aim of obtaining novel information on the circulation of non-poliomyelitis enteroviruses in the population and the establishment of development patterns for epidemic process of this infection.

  4. Eczema Coxsackium Caused by Coxsackievirus A6

    DEFF Research Database (Denmark)

    Horsten, Hans-Henrik; Fisker, Niels; Bygum, Anette

    2016-01-01

    We present the first case of atypical hand, food, and mouth disease in our department with the distinct cutaneous morphology of eczema coxsackium. Clinicians should be aware of the possibility for more extensive cutaneous eruption related to coxsackievirus A6 infection and the diagnostic methods...

  5. Coxsackievirus B5 Infection Induces Dysregulation of microRNAs Predicted to Target Known Type 1 Diabetes Risk Genes in Human Pancreatic Islets.

    Science.gov (United States)

    Kim, Ki Wook; Ho, Andy; Alshabee-Akil, Ammira; Hardikar, Anandwardhan A; Kay, Thomas W H; Rawlinson, William D; Craig, Maria E

    2016-04-01

    Extensive research has identified enterovirus (EV) infections as key environmental triggers of type 1 diabetes. However, the underlying molecular mechanisms via which EVs contribute to the pathogenesis of type 1 diabetes remain unclear. Given that EVs dysregulate host microRNAs (miRNAs), which function as key regulators of β-cell biology, we investigated the impact of coxsackievirus B5 (CVB5) infection on the cellular expression of miRNAs within human islets. Using high-throughput quantitative PCR nanofluidics arrays, the expression of 754 miRNAs was examined in CVB5-infected human pancreatic islets. In total, 33 miRNAs were significantly dysregulated (≥ threefold difference) in the infected compared with control islets (P CVB5-infected human pancreatic islets. We propose that EVs disrupt the miRNA-directed suppression of proinflammatory factors within β-cells, thereby resulting in an exacerbated antiviral immune response that promotes β-cell destruction and eventual type 1 diabetes. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  6. Coxsackievirus A 16 infection does not interfere with the specific immune response induced by an enterovirus 71 inactivated vaccine in rhesus monkeys.

    Science.gov (United States)

    Wang, Jingjing; Qi, Sudong; Zhang, Xiaolong; Zhang, Ying; Liu, Longding; Che, Yanchun; He, Zhanlong; Zhao, Yuan; Lu, Shuaiyao; Yu, Wenhai; Li, Qihan

    2014-07-31

    Hand, foot and mouth disease is usually caused by enterovirus 71 (EV71) and coxsackievirus A 16 (CA16), which are members of the Picornaviridae family. In the present study, the characteristics of the immune response induced by an EV71 inactivated vaccine (made from human diploid cells) were explored in the presence of CA16 infection, based on the previously established neonatal rhesus monkey model. The typical clinical manifestations, including body temperature, viral viremia and virus shedding in the mouth, pharynx and feces, were characterized. A specific neutralizing antibody assay showed that the specific immune response induced by the EV71 inactivated vaccine was active against EV71 but not against CA16. No remarkable fluctuation in proinflammatory cytokine release was identified in the serum of immunized monkeys with EV71 vaccine and CA16 infections subsequently. The results showed that the specific immune response induced by the EV71 inactivated vaccine is effective against EV71 infection but is not affected by CA16 infection. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Ambulatory Pediatric Surveillance of Hand, Foot and Mouth Disease as Signal of an Outbreak of Coxsackievirus A6 Infections, France, 2014–2015

    Science.gov (United States)

    le Sage, François Vié; Pereira, Bruno; Cohen, Robert; Levy, Corinne; Archimbaud, Christine; Peigue-Lafeuille, Hélène; Bailly, Jean-Luc; Henquell, Cécile

    2016-01-01

    The clinical impact of enteroviruses associated with hand, foot and mouth disease (HFMD) is unknown outside Asia, and the prevalence of enterovirus A71 (EV-A71) in particular might be underestimated. To investigate the prevalence of enterovirus serotypes and the clinical presentations associated with HFMD in France, we conducted prospective ambulatory clinic–based surveillance of children during April 2014–March 2015. Throat or buccal swabs were collected from children with HFMD and tested for the enterovirus genome. Physical examinations were recorded on a standardized form. An enterovirus infection was detected in 523 (79.3%) of 659 children tested. Two epidemic waves occurred, dominated by coxsackievirus (CV) A6, which was detected in 53.9% of enterovirus-infected children. CV-A6 was more frequently related to atypical HFMD manifestations (eruptions extended to limbs and face). Early awareness and documentation of HFMD outbreaks can be achieved by syndromic surveillance of HFMD by ambulatory pediatricians and rapid enterovirus testing and genotyping. PMID:27767012

  8. Serum microRNA expression profile distinguishes enterovirus 71 and coxsackievirus 16 infections in patients with hand-foot-and-mouth disease.

    Directory of Open Access Journals (Sweden)

    Lunbiao Cui

    Full Text Available Altered circulating microRNA (miRNA profiles have been noted in patients with microbial infections. We compared host serum miRNA levels in patients with hand-foot-and-mouth disease (HFMD caused by enterovirus 71 (EV71 and coxsackievirus 16 (CVA16 as well as in other microbial infections and in healthy individuals. Among 664 different miRNAs analyzed using a miRNA array, 102 were up-regulated and 26 were down-regulated in sera of patients with enteroviral infections. Expression levels of ten candidate miRNAs were further evaluated by quantitative real-time PCR assays. A receiver operating characteristic (ROC curve analysis revealed that six miRNAs (miR-148a, miR-143, miR-324-3p, miR-628-3p, miR-140-5p, and miR-362-3p were able to discriminate patients with enterovirus infections from healthy controls with area under curve (AUC values ranged from 0.828 to 0.934. The combined six miRNA using multiple logistic regression analysis provided not only a sensitivity of 97.1% and a specificity of 92.7% but also a unique profile that differentiated enterovirial infections from other microbial infections. Expression levels of five miRNAs (miR-148a, miR-143, miR-324-3p, miR-545, and miR-140-5p were significantly increased in patients with CVA16 versus those with EV71 (p<0.05. Combination of miR-545, miR-324-3p, and miR-143 possessed a moderate ability to discrimination between CVA16 and EV71 with an AUC value of 0.761. These data indicate that sera from patients with different subtypes of enteroviral infection express unique miRNA profiles. Serum miRNA expression profiles may provide supplemental biomarkers for diagnosing and subtyping enteroviral HFMD infections.

  9. [Infection status of enterovirus 71 and coxsackievirus A16 among children receiving health examination for child care setting entrance in Beijing and their related medical care seeking practice].

    Science.gov (United States)

    Wang, Xiaoli; Lin, Changying; Zhang, Haiyan; Ma, Jianxin; Li, Chao; Li, Jie; Jia, Lei; Yang, Yang; Du, Yiwei; Liang, Zhichao; Wang, Quanyi; He, Xiong

    2015-07-01

    To understand the infection status of enterovirus 71 (EV71) and coxsackievirus A16 (Cox A16) among children receiving health examination for child care setting entrance in Beijing and their related medical care seeking practice and provide evidence for the estimation of disease burden caused by hand foot and mouth disease (HFMD). Serological survey was conducted in the local children receiving health examination for child care setting entrance. Enzyme-linked immunosorbent assay (ELISA) was conducted to detect anti-EV71 and anti-Cox A16 IgG and IgM. A total of 813 children were surveyed (mean age: 3.5 ± 1.0 year old). The seropositive rate was 61.9% and 4.4% for anti-Cox A16 IgG and IgM. The seropositive rate was 9.3% and 1.1% for anti-EV71 IgG and IgM. No significant difference was observed in sex specific seropositive rate (P > 0.05). However, significant differences were found in seropositive rate among different age groups (P < 0.05). Among the children who were anti-Cox A16 positive, 7.8% had ever had rashes on their hands and feet, mouth or buttocks (HFMD-like rashes). Among the children who were anti-EV71 positive, 10.7% had ever had HFMD-like rashes. For the children who were anti-Cox A16 or anti-EV71 positive, only 7.1% were brought to see doctors by their parents. However, among the seropositive children with rashes, 80.5% were brought to see doctors. In the healthy children at the age to go to child care setting in Beijing, most had ever infected with Cox A16. The anti-EV71 positive rate was much lower than the anti-Cox A16 positive rate. It was necessary to strengthen the prevention and control of EV71 infection in child cares settings.

  10. Coxsackievirus A6 and hand, foot, and mouth disease, Finland.

    Science.gov (United States)

    Osterback, Riikka; Vuorinen, Tytti; Linna, Mervi; Susi, Petri; Hyypiä, Timo; Waris, Matti

    2009-09-01

    During fall 2008, an outbreak of hand, foot, and mouth disease (HFMD) with onychomadesis (nail shedding) as a common feature occurred in Finland. We identified an unusual enterovirus type, coxsackievirus A6 (CVA6), as the causative agent. CVA6 infections may be emerging as a new and major cause of epidemic HFMD.

  11. Efficient replication of recombinant Enterovirus B types, carrying different P1 genes in the coxsackievirus B5 replicative backbone.

    Science.gov (United States)

    Jonsson, Nina; Sävneby, Anna; Gullberg, Maria; Evertsson, Kim; Klingel, Karin; Lindberg, A Michael

    2015-06-01

    Recombination is an important feature in the evolution of the Enterovirus genus. Phylogenetic studies of enteroviruses have revealed that the capsid genomic region (P1) is type specific, while the parts of the genome coding for the non-structural proteins (P2-P3) are species specific. Hence, the genome may be regarded as consisting of two modules that evolve independently. In this study, it was investigated whether the non-structural coding part of the genome in one type could support replication of a virus with a P1 region from another type of the same species. A cassette vector (pCas) containing a full-length cDNA copy of coxsackievirus B5 (CVB5) was used as a replicative backbone. The P1 region of pCas was replaced with the corresponding part from coxsackievirus B3 Nancy (CVB3N), coxsackievirus B6 Schmitt (CVB6S), and echovirus 7 Wallace (E7W), all members of the Enterovirus B species. The replication efficiency after transfection with clone-derived in vitro transcribed RNA was studied and compared with that of pCas. All the recombinant viruses replicated with similar efficiencies and showed threshold cycle (Ct) values, tissue culture infectivity dose 50 %, and plaque-forming unit titers comparable to viruses generated from the pCas construct. In addition to this, a clone without the P1 region was also constructed, and Western Blot and immunofluorescence staining analysis showed that the viral genome could be translated and replicated despite the lack of the structural protein-coding region. To conclude, the replicative backbone of the CVB5 cassette vector supports replication of intraspecies constructs with P1 regions derived from other members of the Enterovirus B species. In addition to this, the replicative backbone can be both translated and replicated without the presence of a P1 region.

  12. Seroprevalence of Enterovirus A71 and Coxsackievirus A16 in Healthy People in Shandong Province, China.

    Directory of Open Access Journals (Sweden)

    Jian-Xing Wang

    Full Text Available Hand, foot, and mouth disease has become very common in mainland of China in recent years, and enterovirus A71 and coxsackievirus A16 are its major etiologic factors. Here we investigated the seroprevalence of enterovirus A71 and coxsackievirus A16 based on a large group of healthy individuals in Shandong province, China.A total of 1378 healthy individuals were tested for serum neutralizing antibodies against enterovirus A71 and coxsackievirus A16 using a micro neutralization test.The overall seroprevalence of enterovirus A71 neutralizing antibodies was 74.75%. It increased significantly from 48.84% in children aged 0-1 years old to 88.64% in those aged 20-29 years (p 40 years old with a significant gender-specific difference (p 40 years without a gender-specific difference. Nearly 50% of the children <1 year were susceptible to enterovirus A71 infection versus 40% to coxsackievirus A16 infection. Sample collection time and place also played a role in the enterovirus A71 and coxsackievirus A16 positive rates. The overall rates in January were significantly lower than those in April and August (p < 0.01; enterovirus A71 positive rates in Jinan city (capital city of Shandong province were lower than those in Jining city and Zibo city (p < 0.05; and oxsackievirus A16 positive rates in Jining city were significantly higher than those in Jinan city and Zibo city (p < 0.01.There were significant differences among age groups, locations, and time points in the seroprevalence rates of enterovirus A71 and coxsackievirus A16 neutralizing antibodies in healthy people in Shandong province.

  13. Coxsackievirus cloverleaf RNA containing a 5' triphosphate triggers an antiviral response via RIG-I activation.

    Directory of Open Access Journals (Sweden)

    Qian Feng

    Full Text Available Upon viral infections, pattern recognition receptors (PRRs recognize pathogen-associated molecular patterns (PAMPs and stimulate an antiviral state associated with the production of type I interferons (IFNs and inflammatory markers. Type I IFNs play crucial roles in innate antiviral responses by inducing expression of interferon-stimulated genes and by activating components of the adaptive immune system. Although pegylated IFNs have been used to treat hepatitis B and C virus infections for decades, they exert substantial side effects that limit their use. Current efforts are directed toward the use of PRR agonists as an alternative approach to elicit host antiviral responses in a manner similar to that achieved in a natural infection. RIG-I is a cytosolic PRR that recognizes 5' triphosphate (5'ppp-containing RNA ligands. Due to its ubiquitous expression profile, induction of the RIG-I pathway provides a promising platform for the development of novel antiviral agents and vaccine adjuvants. In this study, we investigated whether structured RNA elements in the genome of coxsackievirus B3 (CVB3, a picornavirus that is recognized by MDA5 during infection, could activate RIG-I when supplied with 5'ppp. We show here that a 5'ppp-containing cloverleaf (CL RNA structure is a potent RIG-I inducer that elicits an extensive antiviral response that includes induction of classical interferon-stimulated genes, as well as type III IFNs and proinflammatory cytokines and chemokines. In addition, we show that prophylactic treatment with CVB3 CL provides protection against various viral infections including dengue virus, vesicular stomatitis virus and enterovirus 71, demonstrating the antiviral efficacy of this RNA ligand.

  14. Integrins are not essential for entry of coxsackievirus A9 into SW480 human colon adenocarcinoma cells

    NARCIS (Netherlands)

    Heikkilä, Outi; Merilahti, Pirjo; Hakanen, Marika; Karelehto, Eveliina; Alanko, Jonna; Sukki, Maria; Kiljunen, Saija; Susi, Petri

    2016-01-01

    Coxsackievirus A9 (CV-A9) is a pathogenic enterovirus type within the family Picornaviridae. CV-A9 infects A549 human epithelial lung carcinoma cells by attaching to the αVβ6 integrin receptor through a highly conserved Arg-Gly-Asp (RGD) motif, which is located at the exposed carboxy-terminus of the

  15. Coxsackievirus B exits the host cell in shed microvesicles displaying autophagosomal markers.

    Directory of Open Access Journals (Sweden)

    Scott M Robinson

    2014-04-01

    Full Text Available Coxsackievirus B3 (CVB3, a member of the picornavirus family and enterovirus genus, causes viral myocarditis, aseptic meningitis, and pancreatitis in humans. We genetically engineered a unique molecular marker, "fluorescent timer" protein, within our infectious CVB3 clone and isolated a high-titer recombinant viral stock (Timer-CVB3 following transfection in HeLa cells. "Fluorescent timer" protein undergoes slow conversion of fluorescence from green to red over time, and Timer-CVB3 can be utilized to track virus infection and dissemination in real time. Upon infection with Timer-CVB3, HeLa cells, neural progenitor and stem cells (NPSCs, and C2C12 myoblast cells slowly changed fluorescence from green to red over 72 hours as determined by fluorescence microscopy or flow cytometric analysis. The conversion of "fluorescent timer" protein in HeLa cells infected with Timer-CVB3 could be interrupted by fixation, suggesting that the fluorophore was stabilized by formaldehyde cross-linking reactions. Induction of a type I interferon response or ribavirin treatment reduced the progression of cell-to-cell virus spread in HeLa cells or NPSCs infected with Timer-CVB3. Time lapse photography of partially differentiated NPSCs infected with Timer-CVB3 revealed substantial intracellular membrane remodeling and the assembly of discrete virus replication organelles which changed fluorescence color in an asynchronous fashion within the cell. "Fluorescent timer" protein colocalized closely with viral 3A protein within virus replication organelles. Intriguingly, infection of partially differentiated NPSCs or C2C12 myoblast cells induced the release of abundant extracellular microvesicles (EMVs containing matured "fluorescent timer" protein and infectious virus representing a novel route of virus dissemination. CVB3 virions were readily observed within purified EMVs by transmission electron microscopy, and infectious virus was identified within low-density isopycnic

  16. Coxsackievirus B exits the host cell in shed microvesicles displaying autophagosomal markers.

    Science.gov (United States)

    Robinson, Scott M; Tsueng, Ginger; Sin, Jon; Mangale, Vrushali; Rahawi, Shahad; McIntyre, Laura L; Williams, Wesley; Kha, Nelson; Cruz, Casey; Hancock, Bryan M; Nguyen, David P; Sayen, M Richard; Hilton, Brett J; Doran, Kelly S; Segall, Anca M; Wolkowicz, Roland; Cornell, Christopher T; Whitton, J Lindsay; Gottlieb, Roberta A; Feuer, Ralph

    2014-04-01

    Coxsackievirus B3 (CVB3), a member of the picornavirus family and enterovirus genus, causes viral myocarditis, aseptic meningitis, and pancreatitis in humans. We genetically engineered a unique molecular marker, "fluorescent timer" protein, within our infectious CVB3 clone and isolated a high-titer recombinant viral stock (Timer-CVB3) following transfection in HeLa cells. "Fluorescent timer" protein undergoes slow conversion of fluorescence from green to red over time, and Timer-CVB3 can be utilized to track virus infection and dissemination in real time. Upon infection with Timer-CVB3, HeLa cells, neural progenitor and stem cells (NPSCs), and C2C12 myoblast cells slowly changed fluorescence from green to red over 72 hours as determined by fluorescence microscopy or flow cytometric analysis. The conversion of "fluorescent timer" protein in HeLa cells infected with Timer-CVB3 could be interrupted by fixation, suggesting that the fluorophore was stabilized by formaldehyde cross-linking reactions. Induction of a type I interferon response or ribavirin treatment reduced the progression of cell-to-cell virus spread in HeLa cells or NPSCs infected with Timer-CVB3. Time lapse photography of partially differentiated NPSCs infected with Timer-CVB3 revealed substantial intracellular membrane remodeling and the assembly of discrete virus replication organelles which changed fluorescence color in an asynchronous fashion within the cell. "Fluorescent timer" protein colocalized closely with viral 3A protein within virus replication organelles. Intriguingly, infection of partially differentiated NPSCs or C2C12 myoblast cells induced the release of abundant extracellular microvesicles (EMVs) containing matured "fluorescent timer" protein and infectious virus representing a novel route of virus dissemination. CVB3 virions were readily observed within purified EMVs by transmission electron microscopy, and infectious virus was identified within low-density isopycnic iodixanol

  17. Tissue-specific deletion of the coxsackievirus and adenovirus receptor (CAR) protects mice from virus-induced pancreatitis and myocarditis

    Science.gov (United States)

    Kallewaard, Nicole L.; Zhang, Lili; Chen, Jin-Wen; Guttenberg, Marta; Sanchez, Melissa D.; Bergelson, Jeffrey M.

    2009-01-01

    SUMMARY In cultured cells, infection by Group B coxsackieviruses (CVB) is mediated by the coxsackievirus and adenovirus receptor (CAR), but the importance of this molecule in CVB disease has not been determined. We used tissue-specific CAR gene deletion to generate mice that lacked CAR within each of two major CVB target organs, the pancreas and heart. Deletion of CAR from the pancreas resulted in a 1000-fold reduction in virus titers within the pancreas during infection, and a significant reduction in virus-induced tissue damage and inflammation. Similarly, cardiomyocyte-specific CAR deletion resulted in a 100-fold reduction in virus titer within the heart, and a marked reduction in cytokine production and histopathology. Although primary cardiomyocytes from control animals were susceptible to virus infection, CAR-deficient cardiomyocytes resisted infection in vitro. These results demonstrate a critical function for CAR in the pathogenesis of CVB infection in vivo, and in virus tropism for the heart and pancreas. PMID:19616768

  18. Tissue-specific deletion of the coxsackievirus and adenovirus receptor protects mice from virus-induced pancreatitis and myocarditis.

    Science.gov (United States)

    Kallewaard, Nicole L; Zhang, Lili; Chen, Jin-Wen; Guttenberg, Marta; Sanchez, Melissa D; Bergelson, Jeffrey M

    2009-07-23

    In cultured cells, infection by group B coxsackievirus (CVB) is mediated by the coxsackievirus and adenovirus receptor (CAR), but the importance of this molecule in CVB-induced disease has not been determined. We generated mice with tissue-specific ablation of CAR within each of two major CVB target organs, the pancreas and heart. In the pancreas, deletion of CAR resulted in a significant reduction in both virus titers and virus-induced tissue damage. Similarly, cardiomyocyte-specific CAR deletion resulted in a marked reduction in virus titer, infection-associated cytokine production, and histopathology within the heart. Consistent with the in vivo phenotype, CAR-deficient cardiomyocytes resisted infection in vitro. These results demonstrate a critical function for CAR in the pathogenesis of CVB infection in vivo and in virus tropism for the heart and pancreas.

  19. Recombination in human coxsackievirus B5 strains that caused an outbreak of viral encephalitis in Henan, China.

    Science.gov (United States)

    Ma, Hongxia; Huang, Xueyong; Kang, Kai; Li, Xingle; Tang, Xiaoyan; Ren, Yunhui; Wang, Youchun; Zhao, Guirang; Xu, Bianli

    2013-10-01

    In 2011, human coxsackievirus B5 (CVB5) caused an outbreak of viral encephalitis in Henan, China. Complete genome sequence analysis based on two isolates showed that the 5' half of the genome (nt 1-4540) had high similarity (>97 %) to that of CVB5 strain GU376747, and the 3' half (nt 4700-7402) showed high similarity (>96 %) to that of human coxsackievirus B3 (CVB3) strain GQ141875. These isolates had the highest similarity (97.7 %) to the Changchun strain, based on the complete genome, rather than to other CVB5 strains isolated from Henan in recent years. There were therefore at least two groups of CVB5 circulating in Henan Province, which evolved at different rates.

  20. Coxsackievirus B5 induced apoptosis of HeLa cells: effects on p53 and SUMO.

    OpenAIRE

    Gomes,Rogério; Guerra-Sá, Renata; ARRUDA, Eurico

    2010-01-01

    Coxsackievirus B5 (CVB5), a human enterovirus of the family Picornaviridae, is a frequent cause of acute and chronic human diseases. The pathogenesis of enteroviral infections is not completely understood, and the fate of the CVB5-infected cell has a pivotal role in this process. We have investigated the CVB5-induced apoptosis of HeLa cells and found that it happens by the intrinsic pathway by a mechanism dependent on the ubiquitin–proteasome system, associated with nuclear aggregation of ...

  1. Hand, foot and mouth disease caused by coxsackievirus A6, Beijing, 2013.

    Science.gov (United States)

    Hongyan, Gu; Chengjie, Ma; Qiaozhi, Yang; Wenhao, Hua; Juan, Li; Lin, Pang; Yanli, Xu; Hongshan, Wei; Xingwang, Li

    2014-12-01

    Specimens and clinical data were collected from 243 hand, foot and mouth disease patients in Beijing in 2013. In total, 130 stool specimens were genotyped for enterovirus. Hand, foot and mouth disease was mainly detected in suburban areas and at the edges of urban areas between May and August. Coxsackievirus (CV) A6 replaced enterovirus (EV) 71 and CVA16, becoming the main causative agent of hand, foot and mouth disease. CVA6 infection led to significantly reduced fever duration and glucose levels compared with EV71 infection.

  2. Acute localized exanthem due to Coxsackievirus A4.

    Science.gov (United States)

    Drago, Francesco; Ciccarese, Giulia; Gariazzo, Lodovica; Cioni, Margherita; Parodi, Aurora

    2017-09-01

    Enteroviruses are the leading cause of exanthems in children, especially during summer and autumn. Enterovirus infections may occur in epidemics or small outbreaks. A 30-year-old woman presented with a three-day history of an erythematous maculopapular skin rash with petechiae localized exclusively under the nipple of the right breast. The skin eruption was associated with an erythematous-petechial enanthem. The patient complained of low-grade fever, headache, asthenia, sore throat and arthromyalgias. IgM (1:128) and IgG (1:640) antibodies against Coxsackievirus A4 were detected by the virus neutralization test. Reverse transcriptase real time polymerase chain reaction (PCR) assay detected enterovirus RNA in the patient's plasma and faeces. Diagnosis of an acute localized exanthem due to Coxsachievirus A4 was performed. Skin lesions improved in seven days and completely cleared in two weeks without any systemic or topical treatment. Physicians should be aware of the possibility that enteroviruses may determine localized skin eruptions in addition to hand-foot-mouth disease and atypical exanthems. Viral infections should be considered in the differential diagnosis of localized dermatitis especially when the skin eruption is associated with enanthems and with systemic symptoms.

  3. CLINICAL EPIDEMIOLOGICAL PECULIARITIES OF ENTEROVIRUS COXSACKIEVIRUS A16 GROUP MORBIDITY IN CHILDREN

    Directory of Open Access Journals (Sweden)

    L. A. Lityaeva

    2013-01-01

    Full Text Available Federal Service on Customers' Rights Protection and Human Well-Being Surveillance in Orenburg Region, Orenburg The authors presented the results of the clinical and epidemiological analysis of enterovirus coxsackievirus A-16 group morbidity among kindergarten children in the Orenburg region occurring in the form of the syndrome of ≪hand-foot-mouth≫ with exantem. 20 children were involved in the epidemic process, 72,2% of the children are 1—2 years old, they became a source of infection to other groups of children. The disease had a mild course and did not require special treatment.

  4. Coxsackievirus A6 and Hand,Foot and Mouth Disease:Three Case Reports of FamilialChild-to-Immunocompetent Adult Transmission and a Literature Review

    Directory of Open Access Journals (Sweden)

    Karolina Kaminska

    2013-08-01

    Full Text Available Hand, foot and mouth disease (HFMD is a highly contagious viral infection characterized by typical maculopapular or vesicular eruptions on the hands and feet and in the oral cavity. It affects predominantly children and/or immunocompromised adults. It usually follows a benign and self-limiting course. However, HFMD cases with severe or lethal complications such as encephalitis, meningitis, pulmonary edema and myocarditis have also been reported, mostly in children, but also in adults. High infectivity of HFMD has contributed to several large outbreaks of this disease in recent decades in East and Southeast Asia, the United States and Finland. The most common pathogens were Coxsackievirus A16, Enterovirus 71 and, recently, also Coxsackieviruses A6 and A10. Differences in the course of HFMD have been observed, depending on the virus type. Recently, many cases of atypical HFMD have been described in the literature with unusual morphology and/or localization of skin lesions. Atypical HFMD manifestations including vesiculobullous exanthema, often on the trunk or extremities, and perioral zone involvement were often caused by Coxsackievirus A6 infections. We present 3 cases of familial transmission of HFMD caused by Coxsackievirus A6 with some atypical features, benign course and complete recovery among immunocompetent adults.

  5. Non-rhinovirus enteroviruses associated with respiratory infections in Peru (2005-2010).

    Science.gov (United States)

    Huaman, Jose L; Carrion, Gladys; Ampuero, Julia S; Gomez, Jorge; Ocaña, Victor; Paz, Irmia; Gomez, Elizabeth; Chavez, Edward; Sarmiento, Favio; Pozo, Edward; Laguna-Torres, V Alberto; Halsey, Eric S

    2014-09-22

    Enteroviruses (EVs) are a common cause of respiratory tract infections and are classified into seven species (EVA-D and rhinoviruses [RHVs] A-C) with more than 200 different serotypes. Little is known about the role of non-RHV EVs in respiratory infections in South America. The aim of this study was to describe the epidemiology of non-RHV EVs detected in patients with influenza-like illness enrolled in a passive surveillance network in Peru. Throat swabs and epidemiological data were collected from participants after obtaining verbal consent. Viral isolation was performed in cell culture and identified by immunofluorescence assay. Serotype identification of EV isolates was performed using commercial monoclonal antibodies. Identification of non-serotypeable isolations was carried out by reverse transcriptase-PCR, followed by sequencing. Between 2005 and 2010, 24,239 samples were analyzed, and 9,973 (41.1%) possessed at least one respiratory virus. EVs were found in 175 samples (0.7%). Our results revealed a clear predominance of EVB species, 90.9% (159/175). No EVDs were isolated. The mean and median ages of EV-positive subjects were 9.1 and 4.0 years, respectively, much younger than the population sampled, 17.6 and 12.0 years. Sixteen serotypes were identified, four EVA, 11 EVB, and one EVC species. The most common serotypes were coxsackievirus B1, coxsackievirus B2, coxsackievirus B5, and coxsackievirus B3. This study provides data about the serotypes of EVs circulating in Peru and sets the need for further studies.

  6. Synthesis and evaluation of halogenated 12N-sulfonyl matrinic butanes as potential anti-coxsackievirus agents.

    Science.gov (United States)

    Cheng, Xin-Yue; Li, Yu-Huan; Tang, Sheng; Zhang, Xin; Wang, Yan-Xiang; Wang, Sheng-Gang; Jiang, Jian-Dong; Li, Ying-Hong; Song, Dan-Qing

    2017-01-27

    Twenty-eight new 12N-benzenesulfonyl matrinic butane and halogenated 12N-sulfonyl matrinic butane/ethane derivatives were designed, synthesized and evaluated for their anti-coxsakievirus activities against CVB3 taking compound 1 as the lead. SAR analysis indicated the introduction of a fluoro atom on the 1'-position might be helpful for keeping potency. Among them, compound 8a exhibited potential activities against all CVBs with IC50 ranging from 0.69 to 5.14 μM, suggesting a broad-spectrum anti-coxsackievirus B feature. In addition, it also displayed an excellent PK and a good safety profile, indicating a highly druggable nature. Thus, we consider compound 8a to be a promising drug candidate in the treatment of not only viral myocarditis caused by CVB3 but also various diseases infected with coxsackieviruses B. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  7. Coxsackievirus B5 induced apoptosis of HeLa cells: effects on p53 and SUMO.

    Science.gov (United States)

    Gomes, Rogério; Guerra-Sá, Renata; Arruda, Eurico

    2010-01-20

    Coxsackievirus B5 (CVB5), a human enterovirus of the family Picornaviridae, is a frequent cause of acute and chronic human diseases. The pathogenesis of enteroviral infections is not completely understood, and the fate of the CVB5-infected cell has a pivotal role in this process. We have investigated the CVB5-induced apoptosis of HeLa cells and found that it happens by the intrinsic pathway by a mechanism dependent on the ubiquitin-proteasome system, associated with nuclear aggregation of p53. Striking redistribution of both SUMO and UBC9 was noted at 4 h post-infection, simultaneously with a reduction in the levels of the ubiquitin-ligase HDM2. Taken together, these results suggest that CVB5 infection of HeLa cells elicit the intrinsic pathway of apoptosis by MDM2 degradation and p53 activation, destabilizing protein sumoylation, by a mechanism that is dependent on a functional ubiquitin-proteasome system.

  8. Applications of coxsackievirus A21 in oncology

    Science.gov (United States)

    Bradley, Stephen; Jakes, Adam D; Harrington, Kevin; Pandha, Hardev; Melcher, Alan; Errington-Mais, Fiona

    2014-01-01

    The clinical management of cancer continues to be dominated by macroscopic surgical resection, radiotherapy, and cytotoxic drugs. The major challenge facing oncology is to achieve more selective, less toxic and effective methods of targeting disseminated tumors, a challenge oncolytic virotherapy may be well-placed to meet. Characterization of coxsackievirus A21 (CVA21) receptor-based mechanism of virus internalization and lysis in the last decade has suggested promise for CVA21 as a virotherapy against malignancies which overexpress those receptors. Preclinical studies have demonstrated proof of principle, and with the results of early clinical trials awaited, CVA21 may be one of the few viruses to demonstrate benefit for patients. This review outlines the potential of CVA21 as an oncolytic agent, describing the therapeutic development of CVA21 in preclinical studies and early stage clinical trials. Preclinical evidence supports the potential use of CVA21 across a range of malignancies. Malignant melanoma is the most intensively studied cancer, and may represent a “test case” for future development of the virus. Although there are theoretical barriers to the clinical utility of oncolytic viruses like CVA21, whether these will block the efficacy of the virus in clinical practice remains to be established, and is a question which can only be answered by appropriate trials. As these data become available, the rapid journey of CVA21 from animal studies to clinical trials may offer a model for the translation of other oncolytic virotherapies from laboratory to clinic. PMID:27512662

  9. Atypical hand, foot and mouth disease in adults associated with coxsackievirus A6: a clinico-pathologic study.

    Science.gov (United States)

    Laga, Alvaro C; Shroba, Suzanne M; Hanna, John

    2016-11-01

    Hand, foot, and mouth disease (HFMD) is a contagious illness most commonly occurring in children 5 years old or younger. The most common cause of HFMD in the United States is Coxsackievirus A16. HFMD is uncommon in adults, and may show other atypical features including a broader spectrum of cutaneous involvement and a greater degree of severity. We evaluated the clinical, histopathologic and molecular features of three cases of atypical HFMD occurring in adults. All three cases showed clinical features that were worrisome for erythema multiforme or a disseminated herpesvirus infection. The histopathologic findings were quite uniform, and showed intraepidermal vesiculation with a predominantly neutrophil-rich infiltrate. A characteristic feature was the specific involvement of the upper stratum spinosum and stratum granulosum, with relative sparing of the stratum corneum. In none of the cases was there evidence of herpesvirus. Molecular analysis performed on two of the cases showed involvement by Coxsackievirus A6, an uncommon serotype in HFMD. All three cases resolved spontaneously. Atypical HFMD associated with Coxsackievirus A6 represents an uncommon and potentially diagnostically challenging cutaneous eruption. Its recognition is critical to avoid unneeded therapy and to establish accurate prognostic expectations. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. The mechanism of chronic coxsackievirus B hepatitis in rabbits.

    Science.gov (United States)

    See, D M; Berger, M; Lina, B; Aymard, M; Tilles, J

    1999-01-01

    The pathophysiology of chronic hepatitis in rabbits infected with coxsackievirus B5 (CVB5), (strain Mitchell) was investigated. Three-week-old male New Zealand White rabbits were inoculated intraperitoneally with 1 x 10(5) plaque forming units of virus. Every 3 months for 15 months postinoculation (p.i.) groups of animals were sacrificed for the following tests: interleukin (IL)-6, tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-beta cytokine levels by enzyme-linked immunosorbent assay (ELISA); splenic natural killer (NK) cell function; sequence of a 154-bp section of the 5' noncoding region; antihepatocyte autoantibodies; histologic examination; in situ polymerase chain reaction (ISPCR) of the liver; neutralizing antibody response to CVB5; and viral cultures of liver, spleen, blood, brain, heart, skeletal muscle, and pancreas samples. Histologic evidence of hepatocyte necrosis was evident at each time point, although few inflammatory cells were seen. Liver samples were positive at each time by ISPCR, with viral nucleic acid localized to hepatocyte cytoplasm. Other cells in the liver did not stain. No hepatocyte autoantibodies were detected, and there was no elevation of intrahepatic cytokine levels compared to uninfected controls. There were no mutations in the virus over time. A vigorous neutralizing antibody response to CVB5, Mitchell was generated, but splenic natural killer (NK) function and numbers of splenic NK cells were significantly decreased. Virus culture was positive at 3 months, but negative at further time points. Cultures were negative at 3 months for the other tissues tested. Thus, CVB5, Mitchell causes a chronic hepatitis in rabbits, with virus limited to hepatocyte cytoplasm and no evidence of autoimmunity.

  11. Keratins provide virus-dependent protection or predisposition to injury in coxsackievirus-induced pancreatitis

    Directory of Open Access Journals (Sweden)

    DM Toivola, SE Ostrowski

    2009-08-01

    Full Text Available DM Toivola1, SE Ostrowski2, H Baribault3, TM Magin4, AI Ramsingh2, MB Omary51Åbo Akademi University, Dept. Biology, BioCity, Turku, Finland and Stanford University School of Medicine and Digestive Disease Center; 2New York State Department of Health, Albany, NY, USA; 3Amgen, South San Francisco, CA, USA; 4University of Bonn, Bonn, Germany; 5Department of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, Mi, USAAbstract: Keratins 8 and 18 (K8/K18 are the two major intermediate filament proteins in hepatocytes and pancreatic acinar cells. Acinar cell keratins are organized as cytoplasmic and apicolateral filaments. An important role of hepatocyte K8/K18 is to maintain cellular integrity, while this cytoprotective function of K8/K18 is not evident in the pancreas since keratin-deficient mice cope well with pancreatitis models. To further study the roles of keratins in the exocrine pancreas, we used coxsackievirus B4-models, CVB4-V and CVB4-P, to induce severe acute/chronic pancreatitis and acute pancreatitis, respectively, in K8-null (which lack acinar keratins and K18-null (which lack cytoplasmic keratins mice. Despite similar virus titers in all mice, CVB4-V resulted in 40% mortality of the K8-null mice 14 days post-infection compared to no lethality of WT and K18-null mice. In contrast, K8-null mice were far less susceptible to CVB4-P-induced damage as determined by histology and serology analysis, and they recover faster than WT and K18-null mice. After CVB4 virus infection, keratins aggregated during acinar degranulation, and K8/K18 site-specific phosphorylation was observed during degranulation and recovery. Hence, keratins significantly affect CVB4 virulence, positively or negatively, depending on the virus subtype and keratin makeup, in a virus replication-independent manner.Keywords: keratin, pancreatitis, coxsackievirus

  12. Characterization of a Putative Ancestor of Coxsackievirus B5 ▿

    OpenAIRE

    Gullberg, Maria; Tolf, Conny; Jonsson, Nina; Mulders, Mick N.; Savolainen-Kopra, Carita; Hovi, Tapani; Van Ranst, Marc; Lemey, Philippe; Hafenstein, Susan; Lindberg, A. Michael

    2010-01-01

    Like other RNA viruses, coxsackievirus B5 (CVB5) exists as circulating heterogeneous populations of genetic variants. In this study, we present the reconstruction and characterization of a probable ancestral virion of CVB5. Phylogenetic analyses based on capsid protein-encoding regions (the VP1 gene of 41 clinical isolates and the entire P1 region of eight clinical isolates) of CVB5 revealed two major cocirculating lineages. Ancestral capsid sequences were inferred from sequences of these con...

  13. Complete genome sequences of three strains of coxsackievirus a7.

    Science.gov (United States)

    Ylä-Pelto, Jani; Koskinen, Satu; Karelehto, Eveliina; Sittig, Eleonora; Roivainen, Merja; Hyypiä, Timo; Susi, Petri

    2013-04-11

    Genomes of three strains (Parker, USSR, and 275/58) of coxsackievirus A7 (CV-A7) were amplified by the long reverse transcription (RT)-PCR method and sequenced. While the sequences of Parker and USSR were identical, the similarities of 275/58 to the CV-A7 reference sequence, accession no. AY421765, were 82.6% and 96.2% for nucleotides and amino acids, respectively.

  14. Molecular analysis of the prototype coxsackievirus B5 genome.

    Science.gov (United States)

    Lindberg, A M; Polacek, C

    2000-01-01

    To facilitate studies of the phylogenetic relationship between enteroviruses, in particular the prototype strain (Faulkner) of coxsackievirus B5 (CVB5F) and other CVB5 isolates and to facilitate studies of the interactions between CVB5F and the target cell, the complete nucleotide sequence of the prototype has been determined. The complete sequence was collected from three overlapping reverse transcription polymerase chain reaction (RT-PCR) generated amplicons. Molecular analysis of the CVB5F genome verified that this strain is more related to other CVB5 isolates and to swine vesicular disease virus strains than to other enteroviruses. In addition, comparison of the amino acid sequence derived from the structural genes indicated a division of group B coxsackievirus into subgroups, where CVB1, CVB3 and CVB5 constitute one group, CVB2 and CVB4 from a second group and CVB6 prototype forms a branch of its own. This observation, supported by reports describing the interactions between CVB and the cell surface, may reflect that these subgroups of group B coxsackieviruses have evolved to use slightly different approaches to carry out the complete infectious cycle within the cell.

  15. Interspecies differences in virus uptake versus cardiac function of the coxsackievirus and adenovirus receptor.

    NARCIS (Netherlands)

    Freiberg, F.; Sauter, M.; Pinkert, S.; Govindarajan, T.; Kaldrack, J.; Thakkar, M.; Fechner, H.; Klingel, K.; Gotthardt, M.

    2014-01-01

    The coxsackievirus and adenovirus receptor (CAR) is a cell contact protein with an important role in virus uptake. Its extracellular immunoglobulin domains mediate the binding to coxsackievirus and adenovirus as well as homophilic and heterophilic interactions between cells. The cytoplasmic tail

  16. Active Coxsackieviral B infection is associated with disruption of dystrophin in endomyocardial tissue of patients who died suddenly of acute myocardial infarction.

    Science.gov (United States)

    Andréoletti, Laurent; Ventéo, Lydie; Douche-Aourik, Fatima; Canas, Frédéric; Lorin de la Grandmaison, Geoffroy; Jacques, Jérôme; Moret, Hélène; Jovenin, Nicolas; Mosnier, Jean-François; Matta, Mathieu; Duband, Sébastien; Pluot, Michel; Pozzetto, Bruno; Bourlet, Thomas

    2007-12-04

    In this study, we evaluated the potential direct role of enterovirus (EV) cardiac infections in the pathogenesis of myocardial infarction (MI). Enteroviruses (Picornaviridae) have been suspected to play a role in the development of acute MI. The presence of EV ribonucleic acid (RNA) sequences and capsid viral protein 1 (VP1) and the virus-mediated focal disruption of dystrophin were retrospectively investigated by reverse transcriptase-polymerase chain reaction and immunohistochemistry assays in endomyocardial tissues of patients who died suddenly of acute MI by comparison with similar samples of control patients matched for gender, residence area, and year of death. Enterovirus infection markers were detected in 20 (40%) of 50 patients who died suddenly of MI, 2 (4%) of 50 matched subjects without cardiac disease (p < 0.001), and 4 (8%) of 50 matched patients exhibiting a noncoronary chronic cardiopathy (p < 0.001). All of the EV RNA-positive patients exhibited VP1, which provided evidence of viral protein synthesis activity. The VP1 gene sequences amplified after cloning from myocardial or coronary samples of 8 of the MI patients and showed a strong homology with sequences of coxsackievirus B2 and B3 serotypes. Moreover, in the endomyocardial tissue of these 8 patients, immunohistochemical analyses demonstrated that there was disruption of the sarcolemmal localization of dystrophin in the same tissue areas that were infected by coxsackieviruses. Our findings demonstrate a significantly higher proportion of active coxsackievirus B cardiovascular infections in patients who suddenly died of MI compared with matched control subjects, suggesting that these EVs may significantly contribute to the pathogenesis of acute MI by a focal disruption of the dystrophin-glycoprotein complex.

  17. Inactivated coxsackievirus A10 experimental vaccines protect mice against lethal viral challenge.

    Science.gov (United States)

    Shen, Chaoyun; Liu, Qingwei; Zhou, Yu; Ku, Zhiqiang; Wang, Lili; Lan, Ke; Ye, Xiaohua; Huang, Zhong

    2016-09-22

    Coxsackievirus A10 (CVA10) has become one of the major causative agents of hand, foot and mouth disease (HFMD). It is now recognized that CVA10 should be targeted for vaccine development. We report here that β-propiolactone inactivated whole-virus based CVA10 vaccines can elicit protective immunity in mice. We prepared two inactivated CVA10 experimental vaccines derived from the prototype strain CVA10/Kowalik and from a clinical isolate CVA10/S0148b, respectively. Immunization with the experimental vaccines elicited CVA10-specific serum antibodies in mice. The antisera from vaccinated mice could potently neutralize in vitro infection with either homologous or heterologous CVA10 strains. Importantly, passive transfer of the anti-CVA10 sera protected recipient mice against CVA10/Kowalik or CVA10/S0148b infections. Moreover, active immunization with the inactivated vaccines also conferred protection against homologous and heterologous infections in mice. Collectively, our results demonstrate the proof-of-concept for inactivated whole-virus based CVA10 vaccines. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Nucleic acid sequences encoding D1 and D1/D2 domains of human coxsackievirus and adenovirus receptor (CAR)

    Science.gov (United States)

    Freimuth, Paul I.

    2010-04-06

    The invention provides recombinant human CAR (coxsackievirus and adenovirus receptor) polypeptides which bind adenovirus. Specifically, polypeptides corresponding to adenovirus binding domain D1 and the entire extracellular domain of human CAR protein comprising D1 and D2 are provided. In another aspect, the invention provides nucleic acid sequences encoding these domains and expression vectors for producing the domains and bacterial cells containing such vectors. The invention also includes an isolated fusion protein comprised of the D1 polypeptide fused to a polypeptide which facilitates folding of D1 when expressed in bacteria. The functional D1 domain finds application in a therapeutic method for treating a patient infected with a CAR D1-binding virus, and also in a method for identifying an antiviral compound which interferes with viral attachment. The invention also provides a method for specifically targeting a cell for infection by a virus which binds to D1.

  19. Integrin alphaVbeta6 is a high-affinity receptor for coxsackievirus A9.

    Science.gov (United States)

    Heikkilä, Outi; Susi, Petri; Stanway, Glyn; Hyypiä, Timo

    2009-01-01

    Coxsackievirus A9 (CAV9), a member of the genus Enterovirus in the family Picornaviridae, possesses an integrin-binding arginine-glycine-aspartic acid (RGD) motif in the C terminus of VP1 capsid protein. CAV9 has been shown to utilize integrins alphaVbeta3 and alphaVbeta6 as primary receptors for cell attachment. While CAV9 RGD-mutants (RGE and RGDdel) are capable of infecting rhabdomyosarcoma (RD) cell line, they grow very poorly in an epithelial lung carcinoma cell line (A549). In this study, the relationships between CAV9 infectivity in A549 and RD cells, receptor expression and integrin binding were analysed. A549 cells were shown to express both integrins alphaVbeta3 and alphaVbeta6, whereas alphaVbeta6 expression was not detected on the RD cells. Native CAV9 but not RGE and RGDdel mutants bound efficiently to immobilized alphaVbeta3 and alphaVbeta6. Adhesion of CAV9 but not RGE/RGDdel to A549 cells was also significantly higher than to RD cells. In contrast, no affinity or adhesion of bacterially produced VP1 proteins to the integrins or to the cells was detected. Function-blocking antibodies against alphaV-integrins blocked CAV9 but not CAV9-RGDdel infectivity, indicating that the viruses use different internalization routes; this may explain the differential infection kinetics of CAV9 and RGDdel. In an affinity assay, soluble alphaVbeta6, but not alphaVbeta3, bound to immobilized CAV9. Similarly, only soluble alphaVbeta6 blocked virus infectivity. These data suggest that CAV9 binding to alphaVbeta6 is a high-affinity interaction, which may indicate its importance in clinical infections; this remains to be determined.

  20. The role of Coxsackievirus A16 in a case of sudden unexplained death in an infant

    DEFF Research Database (Denmark)

    Astrup, B. S.; Johnsen, I. B. G.; Engsbro, Anne Line

    2016-01-01

    The Coxsackievirus A16 (CV-A16) is one of the main pathogens causing hand-foot-and-mouth disease in young children. It is a low-virulence virus rarely involved in serious illness. It is seen sporadically or in outbreaks all over the world. We report a case of sudden unexplained death in infancy......, SUDI, in a 3 and 1/2 months old infant, in which a thorough post mortem investigation pointed at a fatal infection with CV-A16 as the most likely cause of death. Only five cases of fatal CV-A16 infection have been published and none of these presented as sudden death. The fatal cases involved two...... infants, two young children and an elderly man. Post mortem, pre-autopsy CT-scan and C-reactive protein analysis allowed for an autopsy procedure targeted at a microbiological cause of death. The case illustrates the usefulness of supplementary testing during autopsy. © 2015 Elsevier Ireland Ltd....

  1. 32 CFR 806b.3 - Violation penalties.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 6 2010-07-01 2010-07-01 false Violation penalties. 806b.3 Section 806b.3 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE ADMINISTRATION PRIVACY ACT PROGRAM Overview of the Privacy Act Program § 806b.3 Violation penalties. An individual may file a civil...

  2. Oncolysis of malignant human melanoma tumors by Coxsackieviruses A13, A15 and A18

    Directory of Open Access Journals (Sweden)

    Barry Richard D

    2011-01-01

    Full Text Available Abstract Many RNA viruses are displaying great promise in the field of oncolytic virotherapy. Previously, we reported that the picornavirus Coxsackievirus A21 (CVA21 possessed potent oncolytic activity against cultured malignant melanoma cells and melanoma xenografts in mice. In the present study, we demonstrate that three additional Group A Coxsackieviruses; Coxsackievirus A13 (CVA13, Coxsackievirus A15 (CVA15 and Coxsackievirus A18 (CVA18, also have similar oncolytic activity against malignant melanoma. Each of the viruses grew quickly to high titers in cancer cells expressing ICAM-1 and intratumoral injection of preformed subcutaneous SK-Mel-28 xenografts in mice with CVA13, CVA15 and CVA18 resulted in significant tumor volume reduction. As preexisting immunity could potentially hinder oncolytic virotherapy, sera from stage IV melanoma patients and normal controls were tested for levels of protective antibody against the panel of oncolytic Coxsackieviruses. Serum neutralization assays revealed that 3 of 21 subjects possessed low levels of anti-CVA21 antibodies, while protective antibodies for CVA13, CVA15 and CVA18 were not detected in any sample. Serum from individuals who were seropositive for CVA21 failed to exhibit cross-neutralization of CVA13, CVA15 and CVA18. From these studies it can be concluded that the administration of CVA13, CVA15 or CVA18 could be employed as a potential multivalent oncolytic therapy against malignant melanoma.

  3. Clinical features and phylogenetic analysis of Coxsackievirus A9 in Northern Taiwan in 2011

    Directory of Open Access Journals (Sweden)

    Huang Yi-Chuan

    2013-01-01

    Full Text Available Abstract Background Coxsackievirus A9 (CA9 was one of the most prevalent serotype of enteroviral infections in Taiwan in 2011. After several patient series were reported in the 1960s and 1970s, few studies have focused on the clinical manifestations of CA9 infections. Our study explores and deepens the current understanding of CA9. Methods We analyzed the clinical presentations of 100 culture-proven CA9-infected patients in 2011 by reviewing their medical records and depicted the CA9 phylogenetic tree. Results Of the 100 patients with culture-proven CA9 infections, the mean (SD age was 4.6 (3.4 years and the male to female ratio was 1.9. For clinical manifestations, 96 patients (96% had fever and the mean (SD duration of fever was 5.9 (3.4 days. Sixty one patients (61% developed a skin rash, and the predominant pattern was a generalized non-itchy maculopapular rash without vesicular changes. While most patients showed injected throat, oral ulcers were found in only 19 cases (19%, among whom, 6 were diagnosed as herpangina. Complicated cases included: aseptic meningitis (n=8, bronchopneumonia (n=6, acute cerebellitis (n=1, and polio-like syndrome (n=1. Phylogenetic analysis for current CA9 strains is closest to the CA9 isolate 27-YN-2008 from the border area of mainland China and Myanmar. Conclusions The most common feature of CA9 during the 2011 epidemic in Taiwan is generalized febrile exanthema rather than herpangina or hand, foot, and mouth disease. Given that prolonged fever and some complications are possible, caution should be advised in assessing patients as well as in predicting the clinical course.

  4. Clinical features and phylogenetic analysis of Coxsackievirus A9 in Northern Taiwan in 2011

    Science.gov (United States)

    2013-01-01

    Background Coxsackievirus A9 (CA9) was one of the most prevalent serotype of enteroviral infections in Taiwan in 2011. After several patient series were reported in the 1960s and 1970s, few studies have focused on the clinical manifestations of CA9 infections. Our study explores and deepens the current understanding of CA9. Methods We analyzed the clinical presentations of 100 culture-proven CA9-infected patients in 2011 by reviewing their medical records and depicted the CA9 phylogenetic tree. Results Of the 100 patients with culture-proven CA9 infections, the mean (SD) age was 4.6 (3.4) years and the male to female ratio was 1.9. For clinical manifestations, 96 patients (96%) had fever and the mean (SD) duration of fever was 5.9 (3.4) days. Sixty one patients (61%) developed a skin rash, and the predominant pattern was a generalized non-itchy maculopapular rash without vesicular changes. While most patients showed injected throat, oral ulcers were found in only 19 cases (19%), among whom, 6 were diagnosed as herpangina. Complicated cases included: aseptic meningitis (n=8), bronchopneumonia (n=6), acute cerebellitis (n=1), and polio-like syndrome (n=1). Phylogenetic analysis for current CA9 strains is closest to the CA9 isolate 27-YN-2008 from the border area of mainland China and Myanmar. Conclusions The most common feature of CA9 during the 2011 epidemic in Taiwan is generalized febrile exanthema rather than herpangina or hand, foot, and mouth disease. Given that prolonged fever and some complications are possible, caution should be advised in assessing patients as well as in predicting the clinical course. PMID:23347781

  5. Pleurodynia among football players at a high school. An outbreak associated with coxsackievirus B1.

    Science.gov (United States)

    Ikeda, R M; Kondracki, S F; Drabkin, P D; Birkhead, G S; Morse, D L

    1993-11-10

    Enteroviral outbreaks involving athletic teams have been described, although the mode of transmission has been unclear. In September 1991, an outbreak of pleurodynia among high school football players provided an opportunity to identify possible modes of transmission. Retrospective cohort outbreak investigation. Public high school in upstate New York. Illness was reported by 17 (20%) of the football players. Behaviors involving contact with common water containers were associated with illness, including eating ice cubes from the team ice chest (relative risk [RR], 9.2; 95% confidence interval [CI], 1.3 to 65.5) and drinking water from the team cooler (RR, 6.3; 95% CI, 1.5 to 25.7). Coxsackievirus B1 was isolated in four (50%) of the eight stool specimens collected. Contamination of common water containers by an infected player may have contributed to or initiated the outbreak. In addition to discouraging direct oral contact with common drinking containers, use of individual water containers and ice packs for injuries was recommended.

  6. Coxsackievirus B4 and type 1 diabetes pathogenesis: contribution of animal models.

    Science.gov (United States)

    Jaïdane, H; Sané, F; Gharbi, J; Aouni, M; Romond, M B; Hober, D

    2009-10-01

    The role of enteroviruses, in particular type B coxsackieviruses (CV-B), in type 1 diabetes (T1D) pathogenesis is supported by epidemiological, clinical and experimental observations.The investigation of T1D pathogenesis benefits from the contribution of animal models called spontaneously diabetic. Among these animals the non-obese diabetic (NOD) mouse and the bio-breeding diabetes-prone (BBDP) rat present a genetic susceptibility manifested by the expression of an autoimmune diabetes similar to the pathology observed in human beings. Other models whose genetic predisposition is less known are of considerable contribution as well. Numerous major observations relative to several aspects of T1D pathogenesis in the context of CV-B infections, such as susceptibility, diabetogenicity, pancreatotropism, mechanisms of beta cells destruction and others, have been deduced thanks to investigations with animal models. Despite their limits, these models are necessary in improving our knowledge of the role of enteroviruses, like CV-B4, in the pathogenesis of T1D, and the recent advances ensuing from their contribution may have important therapeutic and preventive spin-offs. (c) 2009 John Wiley & Sons, Ltd.

  7. Antiviral Ability of Kalanchoe gracilis Leaf Extract against Enterovirus 71 and Coxsackievirus A16

    Directory of Open Access Journals (Sweden)

    Ching-Ying Wang

    2012-01-01

    Full Text Available Pandemic infection or reemergence of Enterovirus 71 (EV71 and coxsackievirus A16 (CVA16 occurs in tropical and subtropical regions, being associated with hand-foot-and-mouth disease, herpangina, aseptic meningitis, brain stem encephalitis, pulmonary edema, and paralysis. However, effective therapeutic drugs against EV71 and CVA16 are rare. Kalanchoe gracilis (L. DC is used for the treatment of injuries, pain, and inflammation. This study investigated antiviral effects of K. gracilis leaf extract on EV71 and CVA16 replications. HPLC analysis with a C-18 reverse phase column showed fingerprint profiles of K. gracilis leaf extract had 15 chromatographic peaks. UV/vis absorption spectra revealed peaks 5, 12, and 15 as ferulic acid, quercetin, and kaempferol, respectively. K. gracilis leaf extract showed little cytotoxicity, but exhibited concentration-dependent antiviral activities including cytopathic effect, plaque, and virus yield reductions. K. gracilis leaf extract was shown to be more potent in antiviral activity than ferulic acid, quercetin, and kaempferol, significantly inhibiting in vitro replication of EV71 (IC50=35.88 μg/mL and CVA16 (IC50=42.91 μg/mL. Moreover, K. gracilis leaf extract is a safe antienteroviral agent with the inactivation of viral 2A protease and reduction of IL-6 and RANTES expressions.

  8. Oral immunization with a live coxsackievirus/HIV recombinant induces gag p24-specific T cell responses.

    Directory of Open Access Journals (Sweden)

    Rui Gu

    Full Text Available BACKGROUND: The development of an HIV/AIDS vaccine has proven to be elusive. Because human vaccine trials have not yet demonstrated efficacy, new vaccine strategies are needed for the HIV vaccine pipeline. We have been developing a new HIV vaccine platform using a live enterovirus, coxsackievirus B4 (CVB4 vector. Enteroviruses are ideal candidates for development as a vaccine vector for oral delivery, because these viruses normally enter the body via the oral route and survive the acidic environment of the stomach. METHODOLOGY/PRINCIPAL FINDINGS: We constructed a live coxsackievirus B4 recombinant, CVB4/p24(73(3, that expresses seventy-three amino acids of the gag p24 sequence (HXB2 and assessed T cell responses after immunization of mice. The CVB4 recombinant was physically stable, replication-competent, and genetically stable. Oral or intraperitoneal immunization with the recombinant resulted in strong systemic gag p24-specific T cell responses as determined by the IFN-gamma ELISPOT assay and by multiparameter flow cytometry. Oral immunization with CVB4/p24(73(3 resulted in a short-lived, localized infection of the gut without systemic spread. Because coxsackieviruses are ubiquitous in the human population, we also evaluated whether the recombinant was able to induce gag p24-specific T cell responses in mice pre-immunized with the CVB4 vector. We showed that oral immunization with CVB4/p24(73(3 induced gag p24-specific immune responses in vector-immune mice. CONCLUSIONS/SIGNIFICANCE: The CVB4/p24(73(3 recombinant retained the physical and biological characteristics of the parental CVB4 vector. Oral immunization with the CVB4 recombinant was safe and resulted in the induction of systemic HIV-specific T cell responses. Furthermore, pre-existing vector immunity did not preclude the development of gag p24-specific T cell responses. As the search continues for new vaccine strategies, the present study suggests that live CVB4/HIV recombinants are

  9. Fitness and virulence of a coxsackievirus mutant that can circumnavigate the need for phosphatidylinositol 4-kinase class III beta

    NARCIS (Netherlands)

    Thibaut, Hendrik Jan; van der Schaar, Hilde M; Lanke, Kjerstin H W; Verbeken, Erik; Andrews, Martin; Leyssen, Pieter; Neyts, Johan; van Kuppeveld, Frank J M

    2014-01-01

    Coxsackieviruses require phosphatidylinositol-4-kinase IIIβ (PI4KIIIβ) for replication but can bypass this need by an H57Y mutation in protein 3A (3A-H57Y). We show that mutant coxsackievirus is not outcompeted by wild-type virus during 10 passages in vitro. In mice, the mutant virus proved as

  10. Picornavirus infection leading to immunosuppression

    OpenAIRE

    Cusick, Matthew F; Libbey, Jane E.; Fujinami, Robert S.

    2014-01-01

    Viruses, such as HIV, hepatitis A, poliovirus, coxsackievirus B3 and foot-and-mouth disease virus, use a variety of mechanisms to suppress the human immune system in order to evade clearance by the host. Therefore, investigating how a few changes in the viral genome of a nonlethal virus can lead to an alteration in disease, from survivable to immunosuppression and death, would provide valuable information into viral pathogenesis. In addition, we propose that gaining a better insight into how ...

  11. The IL-33/ST2 pathway controls coxsackievirus B5-induced experimental pancreatitis.

    Science.gov (United States)

    Sesti-Costa, Renata; Silva, Grace K; Proença-Módena, José L; Carlos, Daniela; Silva, Maria L; Alves-Filho, José C; Arruda, Eurico; Liew, Foo Y; Silva, João S

    2013-07-01

    Coxsackievirus B (CVB) is a common cause of acute and chronic infectious myocarditis and pancreatitis. Th1 cells producing IFN-γ and TNF-α are important for CVB clearance, but they are also associated with the pathogenesis of inflammatory lesions, suggesting that the modulation of Th1 and Th2 balance is likely important in controlling CVB-induced pancreatitis. We investigated the role of IL-33, which is an important recently discovered cytokine for induction of Th2-associated responses, in experimental CVB5 infection. We found that mice deficient in IL-33R, T1/ST2, significantly developed more severe pancreatitis, had greater weight loss, and contained higher viral load compared with wild-type (WT) mice when infected with CVB5. Conversely, WT mice treated with rIL-33 developed significantly lower viral titers, and pancreatitis was attenuated. Mechanistic studies demonstrated that IL-33 enhances the degranulation and production of IFN-γ and TNF-α by CD8(+) T and NK cells, which is associated with viral clearance. Furthermore, IL-33 triggers the production of IL-4 from mast cells, which results in enhanced differentiation of M2 macrophages and regulatory T cells, leading to the attenuation of inflammatory pancreatitis. Adoptively transferred mast cells or M2 macrophages reversed the heightened pancreatitis in the T1/ST2(-/-) mice. In contrast, inhibition of regulatory T cells exacerbated the disease in WT mice. Together, our findings reveal an unrecognized IL-33/ST2 functional pathway and a key mechanism for CVB5-induced pancreatitis. These data further suggest a novel approach in treating virus-induced pancreatitis, which is a major medical condition with unmet clinical needs.

  12. Primary neurons become less susceptible to coxsackievirus B5 following maturation: the correlation with the decreased level of CAR expression on cell surface.

    Science.gov (United States)

    Ahn, Jeonghyun; Jee, Youngmee; Seo, Ilseon; Yoon, Seung Yong; Kim, DongHou; Kim, Yoo Kyum; Lee, Heuiran

    2008-03-01

    Coxsackievirus B (CVB) is one of the major pathogens of aseptic meningitis and meningioencephalitis, particularly in newborn infants. To analyze the influence of neural maturation on susceptibility to CVB infection, we prepared immature and mature neurons from 16-day-old BALB/c embryonic cortex. In contrast to immature neurons, mature neurons were less susceptible to CVB5 infection, as indicated by the decrease of cytopathic features. In mature neurons, progeny virus production was significantly hindered, and virus capsid protein VP1 synthesis and virus genome amplification were concomitantly reduced. In addition, the expression of coxsackievirus and adenovirus receptor (CAR), the major receptor of CVB5, was down-regulated in mature neurons. The antibody treatment specific to CAR significantly attenuated CVB5 susceptibility of immature neurons. These findings demonstrate that mature neurons become less susceptible to CVB by the decrease of CAR level. Thus, the data strongly support the idea that the level of virus receptor in neurons is one of the crucial determinants in the age-dependency of CVB virulence in central nervous system.

  13. Pathogenesis of coxsackievirus-B5 acquired from intra-renal porcine islet cell xenografts in diabetic mice.

    Science.gov (United States)

    Myers, Suzanne E; LaRue, Rebecca; Shaw, Daniel P; Love, Brenda C; M, Kariuki Njenga; Njenga, Moses K

    2009-01-01

    We previously demonstrated the ability of a human isolate of coxsackievirus-B5 (CVB5) to infect productively adult porcine islet cells (PICs) in vitro. PICs infected with CVB5 remain viable, and upon transplantation reversed diabetes in C56BL/6 mice for up to 5 days. In the present work, we expanded this graft-to-host xenozoonosis model by examining the long-term functionality of CVB5-infected PIC xenografts in immunosuppressed mice. And, we characterized the pathogenesis of CVB5 infection in mice resulting from directional transmission of the virus from PIC xenografts to surrounding tissues in a mouse model for immunosuppressed human PIC xenograft recipients. Both acutely (12 h) and chronically (72 h) infected PIC xenografts functioned in vivo to reverse diabetes in mice. The efficacy of both infected and un-infected PICs was transient beyond 5 days post-inoculation and the long-term functionality of the grafts was compromised by host-to-graft rejection. CVB5-infected PIC xenografts transmitted infectious virus to immunosuppressed recipient mice resulting in extensive histopathologic changes. The virus replicated in the heart, liver, spleen, kidney, pancreas, brain and skeletal muscle in higher levels in severe-combined immunodeficient (SCID) mice that were directly inoculated with virus when compared to controls. In addition, infectious virus was recovered for up to 22 days after inoculation in SCID mice whereas it was only detected up to Day 4 PI in non-SCID mice. Immunosuppressed PIC xenograft recipients may be more susceptible to infection with CVB5 which could target the xenograft leading to disseminated infection in the host.

  14. Characterization of a putative ancestor of coxsackievirus B5.

    Science.gov (United States)

    Gullberg, Maria; Tolf, Conny; Jonsson, Nina; Mulders, Mick N; Savolainen-Kopra, Carita; Hovi, Tapani; Van Ranst, Marc; Lemey, Philippe; Hafenstein, Susan; Lindberg, A Michael

    2010-10-01

    Like other RNA viruses, coxsackievirus B5 (CVB5) exists as circulating heterogeneous populations of genetic variants. In this study, we present the reconstruction and characterization of a probable ancestral virion of CVB5. Phylogenetic analyses based on capsid protein-encoding regions (the VP1 gene of 41 clinical isolates and the entire P1 region of eight clinical isolates) of CVB5 revealed two major cocirculating lineages. Ancestral capsid sequences were inferred from sequences of these contemporary CVB5 isolates by using maximum likelihood methods. By using Bayesian phylodynamic analysis, the inferred VP1 ancestral sequence dated back to 1854 (1807 to 1898). In order to study the properties of the putative ancestral capsid, the entire ancestral P1 sequence was synthesized de novo and inserted into the replicative backbone of an infectious CVB5 cDNA clone. Characterization of the recombinant virus in cell culture showed that fully functional infectious virus particles were assembled and that these viruses displayed properties similar to those of modern isolates in terms of receptor preferences, plaque phenotypes, growth characteristics, and cell tropism. This is the first report describing the resurrection and characterization of a picornavirus with a putative ancestral capsid. Our approach, including a phylogenetics-based reconstruction of viral predecessors, could serve as a starting point for experimental studies of viral evolution and might also provide an alternative strategy for the development of vaccines.

  15. Characterization of a Putative Ancestor of Coxsackievirus B5 ▿

    Science.gov (United States)

    Gullberg, Maria; Tolf, Conny; Jonsson, Nina; Mulders, Mick N.; Savolainen-Kopra, Carita; Hovi, Tapani; Van Ranst, Marc; Lemey, Philippe; Hafenstein, Susan; Lindberg, A. Michael

    2010-01-01

    Like other RNA viruses, coxsackievirus B5 (CVB5) exists as circulating heterogeneous populations of genetic variants. In this study, we present the reconstruction and characterization of a probable ancestral virion of CVB5. Phylogenetic analyses based on capsid protein-encoding regions (the VP1 gene of 41 clinical isolates and the entire P1 region of eight clinical isolates) of CVB5 revealed two major cocirculating lineages. Ancestral capsid sequences were inferred from sequences of these contemporary CVB5 isolates by using maximum likelihood methods. By using Bayesian phylodynamic analysis, the inferred VP1 ancestral sequence dated back to 1854 (1807 to 1898). In order to study the properties of the putative ancestral capsid, the entire ancestral P1 sequence was synthesized de novo and inserted into the replicative backbone of an infectious CVB5 cDNA clone. Characterization of the recombinant virus in cell culture showed that fully functional infectious virus particles were assembled and that these viruses displayed properties similar to those of modern isolates in terms of receptor preferences, plaque phenotypes, growth characteristics, and cell tropism. This is the first report describing the resurrection and characterization of a picornavirus with a putative ancestral capsid. Our approach, including a phylogenetics-based reconstruction of viral predecessors, could serve as a starting point for experimental studies of viral evolution and might also provide an alternative strategy for the development of vaccines. PMID:20631132

  16. Exposure to the viral by-product dsRNA or Coxsackievirus B5 triggers pancreatic beta cell apoptosis via a Bim / Mcl-1 imbalance.

    Directory of Open Access Journals (Sweden)

    Maikel L Colli

    2011-09-01

    Full Text Available The rise in type 1 diabetes (T1D incidence in recent decades is probably related to modifications in environmental factors. Viruses are among the putative environmental triggers of T1D. The mechanisms regulating beta cell responses to viruses, however, remain to be defined. We have presently clarified the signaling pathways leading to beta cell apoptosis following exposure to the viral mimetic double-stranded RNA (dsRNA and a diabetogenic enterovirus (Coxsackievirus B5. Internal dsRNA induces cell death via the intrinsic mitochondrial pathway. In this process, activation of the dsRNA-dependent protein kinase (PKR promotes eIF2α phosphorylation and protein synthesis inhibition, leading to downregulation of the antiapoptotic Bcl-2 protein myeloid cell leukemia sequence 1 (Mcl-1. Mcl-1 decrease results in the release of the BH3-only protein Bim, which activates the mitochondrial pathway of apoptosis. Indeed, Bim knockdown prevented both dsRNA- and Coxsackievirus B5-induced beta cell death, and counteracted the proapoptotic effects of Mcl-1 silencing. These observations indicate that the balance between Mcl-1 and Bim is a key factor regulating beta cell survival during diabetogenic viral infections.

  17. Molecular phylogeny of Coxsackievirus A16 in Shenzhen, China, from 2005 to 2009.

    Science.gov (United States)

    Zong, Wenping; He, Yaqing; Yu, Shouyi; Yang, Hong; Xian, Huixia; Liao, Yuxue; Hu, Guifang

    2011-04-01

    Phylogenetic analysis of a Coxsackievirus A16 (CA16) sequence from Shenzhen, China, and other Chinese and international CA16 sequences revealed a pattern of endemic cocirculation of strains of clusters B2a and B2b within subtype B2 viruses. Amino acid evolution and nucleotide variation in the VP1 region were slight for 5 years.

  18. Genome Sequences of Coxsackievirus B5 Isolates from Two Children with Meningitis in Australia

    OpenAIRE

    Huang, Bixing; Harrower, Bruce; Burtonclay, Peter; Constantino, Tanya; Warrilow, David

    2017-01-01

    ABSTRACT Two coxsackievirus B5 (CVB5) strains were isolated from two children with aseptic meningitis in Australia. Their genomes were sequenced and found to be divergent from the previously reported CVB5 genome sequences, with both having 84% and 97% identities to the closest strains at the nucleotide and amino acid levels, respectively.

  19. Genome Sequences of Coxsackievirus B5 Isolates from Two Children with Meningitis in Australia.

    Science.gov (United States)

    Huang, Bixing; Harrower, Bruce; Burtonclay, Peter; Constantino, Tanya; Warrilow, David

    2017-10-12

    Two coxsackievirus B5 (CVB5) strains were isolated from two children with aseptic meningitis in Australia. Their genomes were sequenced and found to be divergent from the previously reported CVB5 genome sequences, with both having 84% and 97% identities to the closest strains at the nucleotide and amino acid levels, respectively. © Crown copyright 2017.

  20. Increased Efficiency of Group B Coxsackievirus Isolation from Clinical Specimens by Use of BGM Cells.

    Science.gov (United States)

    Menegus, M A; Hollick, G E

    1982-05-01

    A continuous African green monkey kidney cell line, designated BGM, was compared with primary cynomolgus monkey kidney cells and human embryonic lung cells for efficiency of enterovirus isolation. A selective enhanced sensitivity of BGM cells both in terms of isolation rate and speed of isolation was found for group B coxsackieviruses but could not be demonstrated for a number of other nonpolio enteroviruses.

  1. The role of Coxsackievirus A16 in a case of sudden unexplained death in an infant - A SUDI case.

    Science.gov (United States)

    Astrup, B S; Johnsen, I B G; Engsbro, A L

    2016-02-01

    The Coxsackievirus A16 (CV-A16) is one of the main pathogens causing hand-foot-and-mouth disease in young children. It is a low-virulence virus rarely involved in serious illness. It is seen sporadically or in outbreaks all over the world. We report a case of sudden unexplained death in infancy, SUDI, in a 3 and 1/2 months old infant, in which a thorough post mortem investigation pointed at a fatal infection with CV-A16 as the most likely cause of death. Only five cases of fatal CV-A16 infection have been published and none of these presented as sudden death. The fatal cases involved two infants, two young children and an elderly man. Post mortem, pre-autopsy CT-scan and C-reactive protein analysis allowed for an autopsy procedure targeted at a microbiological cause of death. The case illustrates the usefulness of supplementary testing during autopsy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. A novel inactivated enterovirus 71 vaccine can elicit cross-protective immunity against coxsackievirus A16 in mice.

    Science.gov (United States)

    Yang, Lisheng; Liu, Yajing; Li, Shuxuan; Zhao, Huan; Lin, Qiaona; Yu, Hai; Huang, Xiumin; Zheng, Qingbing; Cheng, Tong; Xia, Ningshao

    2016-11-21

    Hand, foot, and mouth disease (HFMD) is a highly contagious disease that mainly affects infants and children. Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) are the major pathogens of HFMD. Two EV71 vaccines were recently licensed in China and the administration of the EV71 vaccines is believed to significantly reduce the number of HFMD-related severe or fatal cases. However, a monovalent EV71 vaccine cannot cross-protect against CA16 infection, this may result in that it cannot effectively control the overall HFMD epidemic. In this study, a chimeric EV71, whose VP1/210-225 epitope was replaced by that of CA16, was constructed using a reverse genetics technique to produce a candidate EV71/CA16 bivalent vaccine strain. The chimeric EV71 was infectious and showed similar growth characteristics as its parental strain. The replacement of the VP1/210-225 epitope did not significantly affect the antigenicity and immunogenicity of EV71. More importantly, the chimeric EV71 could induce protective immunity against both EV71 and CA16, and protect neonatal mice against either EV71 or CA16 lethal infections, the chimeric EV71 constructed in this study was shown to be a feasible and promising candidate bivalent vaccine against both EV71 and CA16. The construction of a chimeric enterovirus also provides an alternative platform for broad-spectrum HFMD vaccines development. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Elicitation of T-cell responses by structural and non-structural proteins of coxsackievirus B4.

    Science.gov (United States)

    Bengs, Suvi; Marttila, Jane; Susi, Petri; Ilonen, Jorma

    2015-02-01

    Coxsackievirus B4 (CV-B4) belongs to the genus Enterovirus within the family Picornaviridae. To investigate target proteins recognized by T-cells in human enterovirus B infections, virus-encoded structural [VP0 (VP4 and VP2), VP1, VP3] and non-structural (2A, 2B, 2C, 3C and 3D) proteins were expressed and purified in Escherichia coli. Peripheral blood of 19 healthy adult donors was used to create enterovirus-specific T-cell lines by repeated stimulation with CV-B4 cell lysate antigen. T-cell lines responded in individual patterns, and responses to all purified proteins were observed. The most often recognized enteroviral protein was VP0, which is the fusion between the most conserved structural proteins, VP4 and VP2. T-cell responses to VP0 were detected in 15 of the 19 (79 %) donor lines. Non-structural 2C protein was recognized in 11 of the 19 (58 %) lines, and 11 of the 19 (58 %) lines also had a response to 3D protein. Furthermore, responses to other non-structural proteins (2A, 2B and 3C) were also detected. T-cell responses did not correlate clearly to the individual HLA-DR-DQ phenotype or the history of past coxsackie B virus infections of the donors. © 2015 The Authors.

  4. 216-B-3 expansion ponds closure plan

    Energy Technology Data Exchange (ETDEWEB)

    1994-10-01

    This document describes the activities for clean closure under the Resource Conservation and Recovery Act of 1976 (RCRA) of the 216-B-3 Expansion Ponds. The 216-B-3 Expansion Ponds are operated by the US Department of Energy, Richland Operations Office (DOE-RL) and co-operated by Westinghouse Hanford Company (Westinghouse Hanford). The 216-B-3 Expansion Ponds consists of a series of three earthen, unlined, interconnected ponds that receive waste water from various 200 East Area operating facilities. The 3A, 3B, and 3C ponds are referred to as Expansion Ponds because they expanded the capability of the B Pond System. Waste water (primarily cooling water, steam condensate, and sanitary water) from various 200 East Area facilities is discharged to the Bypass pipe (Project X-009). Water discharged to the Bypass pipe flows directly into the 216-B-3C Pond. The ponds were operated in a cascade mode, where the Main Pond overflowed into the 3A Pond and the 3A Pond overflowed into the 3C Pond. The 3B Pond has not received waste water since May 1985; however, when in operation, the 3B Pond received overflow from the 3A Pond. In the past, waste water discharges to the Expansion Ponds had the potential to have contained mixed waste (radioactive waste and dangerous waste). The radioactive portion of mixed waste has been interpreted by the US Department of Energy (DOE) to be regulated under the Atomic Energy Act of 1954; the dangerous waste portion of mixed waste is regulated under RCRA.

  5. Epizootic of vesicular disease in pigs caused by coxsackievirus B4 in the Soviet Union in 1975.

    Science.gov (United States)

    Lomakina, Natalia F; Shustova, Elena; Strizhakova, Olga M; Drexler, Felix; Lukashev, Alexander N

    2016-01-01

    Swine vesicular disease virus (SVDV) emerged around 1960 from a human enterovirus ancestor, coxsackievirus B5 (CVB5), and caused a series of epizootics in Europe and Asia. We characterized a coxsackievirus B4 strain that caused an epizootic involving 24 488 pigs in the Soviet Union in 1975. Phylogenetic evidence suggested that the swine virus emerged from a human ancestor between 1945 and 1975, almost simultaneously with the transfer of CVB5.

  6. Coxsackievirus A6-related hand foot and mouth disease: skin manifestations in a cluster of adult patients.

    Science.gov (United States)

    Ben-Chetrit, Eli; Wiener-Well, Yonit; Shulman, Lester M; Cohen, Matan J; Elinav, Hila; Sofer, Danit; Feldman, Itamar; Marva, Eytan; Wolf, Dana G

    2014-03-01

    Hand foot and mouth disease (HFMD) is a common childhood manifestation of enterovirus (EV) infection. It predominantly affects young children, and has been mainly associated with coxsackievirus (CV) A16 and EV 71. We report an unusual cluster of adult patients with HFMD. Throat swabs and vesicular fluid samples obtained from patients admitted to the emergency room (ER) with HFMD were tested for EV by reverse transcription (RT)-real time PCR, and further subjected to sequencing and phylogenetic analysis. CVA6 was identified as the causative agent of HFMD in five epidemiologically-unrelated adult patients (28-37 years old) admitted to the ER between December 2012 and February 2013. Phylogenetic analysis mapped the CVA6 strains into one cluster. All patients manifested with fever and a severe vasculitis-like rash, followed by spontaneous recovery. This cluster identifies CVA6 as an emerging cause of HFMD of unusual age distribution, seasonality, and clinical severity, underscoring the need for continued alertness and clinical-genotypic surveillance of EV HFMD. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Development of a Coxsackievirus A16 neutralization assay based on pseudoviruses for measurement of neutralizing antibody titer in human serum.

    Science.gov (United States)

    Jin, Jun; Ma, Hongxia; Xu, Lin; An, Dong; Sun, Shiyang; Huang, Xueyong; Kong, Wei; Jiang, Chunlai

    2013-02-01

    Serum neutralizing antibody titers are indicative of protective immunity against Coxsackievirus A16 (CV-A16) and Enterovirus 71 (EV71), the two main etiological agents of hand, foot and mouth disease (HFMD), and provide the basis for evaluating vaccine efficacy. The current CV-A16 neutralization assay based on inhibition of cytopathic effects requires manual microscopic examination, which is time-consuming and labor-intensive. In this study, a high-throughput neutralization assay was developed by employing CV-A16 pseudoviruses expressing luciferase for detecting infectivity in rhabdomyosarcoma (RD) cells and measuring serum viral neutralizing antibodies. Without the need to use infectious CV-A16 strains, the neutralizing antibody titer against CV-A16 could be determined within 15h by measuring luciferase signals by this assay. The pseudovirus CV-A16 neutralization assay (pCNA) was validated by comparison with a conventional CV-A16 neutralization assay (cCNA) in testing 174 human serum samples collected from children (age <5 years). The neutralizing antibody titers determined by these two assays were well correlated (R(2)=0.7689). These results suggest that the pCNA can serve as a rapid and objective procedure for the measurement of neutralizing antibodies against CV-A16. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. The efficacy of simulated solar disinfection (SODIS) against coxsackievirus, poliovirus and hepatitis A virus.

    Science.gov (United States)

    Heaselgrave, Wayne; Kilvington, Simon

    2012-12-01

    The antimicrobial activity of simulated solar disinfection (SODIS) against enteric waterborne viruses including coxsackievirus-B5, poliovirus-2 and hepatitis A virus was investigated in this study. Assays were conducted in transparent 12-well polystyrene microtitre plates containing the appropriate viral test suspension. Plates were exposed to simulated sunlight at an optical irradiance of 550 Wm(-2) (watts per square metre) delivered from a SUNTEST™ CPS+ solar simulator for 6 hours. Aliquots of the viral test suspensions were taken at set time points and the level of inactivation of the viruses was determined by either culture on a HeLa cell monolayer for coxsackievirus-B5 and poliovirus-2 or by utilising a chromogenic antibody-based approach for hepatitis A virus. With coxsackievirus-B5, poliovirus-2 and hepatitis A virus, exposure to SODIS at an optical irradiance of 550 Wm(-2) for 1-2 hours resulted in complete inactivation of each virus. The findings from this study suggest that under appropriate conditions SODIS may be an effective technique for the inactivation of enteric viruses in drinking water. However, further verification studies need to be performed using natural sunlight in the region where the SODIS technology is to be employed to validate our results.

  9. Efficacy of a Trivalent Hand, Foot, and Mouth Disease Vaccine against Enterovirus 71 and Coxsackieviruses A16 and A6 in Mice

    Directory of Open Access Journals (Sweden)

    Elizabeth A. Caine

    2015-11-01

    Full Text Available Hand, foot, and mouth disease (HFMD has recently emerged as a major public health concern across the Asian-Pacific region. Enterovirus 71 (EV71 and Coxsackievirus A16 (CVA16 are the primary causative agents of HFMD, but other members of the Enterovirus A species, including Coxsackievirus A6 (CVA6, can cause disease. The lack of small animal models for these viruses have hampered the development of a licensed HFMD vaccine or antivirals. We have previously reported on the development of a mouse model for EV71 and demonstrated the protective efficacy of an inactivated EV71 vaccine candidate. Here, mouse-adapted strains of CVA16 and CVA6 were produced by sequential passage of the viruses through mice deficient in interferon (IFN α/β (A129 and α/β and γ (AG129 receptors. Adapted viruses were capable of infecting 3 week-old A129 (CVA6 and 12 week-old AG129 (CVA16 mice. Accordingly, these models were used in active and passive immunization studies to test the efficacy of a trivalent vaccine candidate containing inactivated EV71, CVA16, and CVA6. Full protection from lethal challenge against EV71 and CVA16 was observed in trivalent vaccinated groups. In contrast, monovalent vaccinated groups with non-homologous challenges failed to cross protect. Protection from CVA6 challenge was accomplished through a passive transfer study involving serum raised against the trivalent vaccine. These animal models will be useful for future studies on HFMD related pathogenesis and the efficacy of vaccine candidates.

  10. The PDZ3 domain of the cellular scaffolding protein MAGI-1 interacts with the Coxsackievirus and adenovirus receptor (CAR).

    Science.gov (United States)

    Yan, Ran; Sharma, Priyanka; Kolawole, Abimbola O; Martin, Sterling C T; Readler, James M; Kotha, Poornima L N; Hostetler, Heather A; Excoffon, Katherine J D A

    2015-04-01

    The Coxsackievirus and adenovirus receptor (CAR) is an essential cellular protein that is involved in cell-cell adhesion, protein trafficking, and viral infection. The major isoform of CAR is selectively sorted to the basolateral membrane of polarized epithelial cells where it co-localizes with the cellular scaffolding protein membrane-associated guanylate kinase with inverted domain structure-1 (MAGI-1). Previously, we demonstrated CAR interacts with MAGI-1 through a PDZ-domain dependent interaction. Here, we show that the PDZ3 domain of MAGI-1 is exclusively responsible for the high affinity interaction between the seven exon isoform of CAR and MAGI-1 using yeast-two-hybrid analysis and confirming this interaction biochemically and in cellular lysates by in vitro pull down assay and co-immunoprecipitation. The high affinity interaction between the PDZ3 domain and CAR C-terminus was measured by fluorescence resonance energy transfer. Further, we investigated the biological relevance of this high affinity interaction between CAR and the PDZ3 domain of MAGI-1 and found that it does not alter CAR-mediated adenovirus infection. By contrast, interruption of this high affinity interaction altered the localization of MAGI-1 indicating that CAR is able to traffic MAGI-1 to cell junctions. These data deepen the molecular understanding of the interaction between CAR and MAGI-1 and indicate that although CAR plays a role in trafficking PDZ-based scaffolding proteins to cellular junctions, association with a high affinity intracellular binding partner does not significantly alter adenovirus binding and entry via CAR. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Characterization of genome sequences and clinical features of coxsackievirus A6 strains collected in Hyogo, Japan in 1999-2013.

    Science.gov (United States)

    Ogi, Miki; Yano, Yoshihiko; Chikahira, Masatsugu; Takai, Denshi; Oshibe, Tomohiro; Arashiro, Takeshi; Hanaoka, Nozomu; Fujimoto, Tsuguto; Hayashi, Yoshitake

    2017-08-01

    Coxsackievirus A6 (CV-A6) is an enterovirus, which is known to cause herpangina. However, since 2009 it has frequently been isolated from children with hand, foot, and mouth disease (HFMD). In Japan, CV-A6 has been linked to HFMD outbreaks in 2011 and 2013. In this study, the full-length genome sequencing of CV-A6 strains were analyzed to identify the association with clinical manifestations. Five thousand six hundred and twelve children with suspected enterovirus infection (0-17 years old) between 1999 and 2013 in Hyogo Prefecture, Japan, were enrolled. Enterovirus infection was confirmed with reverse transcriptase-PCR in 753 children (791 samples), 127 of whom (133 samples) were positive for CV-A6 based on the direct sequencing of the VP4 region. The complete genomes of CV-A6 from 22 positive patients with different clinical manifestations were investigated. A phylogenetic analysis divided these 22 strains into two clusters based on the VP1 region; cluster I contained strains collected in 1999-2009 and mostly related to herpangina, and cluster II contained strains collected in 2011-2013 and related to HFMD outbreak. Based on the full-length polyprotein analysis, the amino acid differences between the strains in cluster I and II were 97.7 ± 0.28%. Amino acid differences were detected in 17 positions within the polyprotein. Strains collected in 1999-2009 and those in 2011-2013 were separately clustered by phylogenetic analysis based on 5'UTR and 3Dpol region, as well as VP1 region. In conclusion, HFMD outbreaks by CV-A6 were recently frequent in Japan and the accumulation of genomic change might be associated with the clinical course. © 2017 Wiley Periodicals, Inc.

  12. EphrinB3 blocks EphB3 dependence receptor functions to prevent cell death following traumatic brain injury.

    Science.gov (United States)

    Theus, M H; Ricard, J; Glass, S J; Travieso, L G; Liebl, D J

    2014-05-08

    Eph receptor tyrosine kinases and their membrane-bound ligands, ephrins, have a variety of roles in the developing and adult central nervous system that require direct cell-cell interactions; including regulating axon path finding, cell proliferation, migration and synaptic plasticity. Recently, we identified a novel pro-survival role for ephrins in the adult subventricular zone, where ephrinB3 blocks Eph-mediated cell death during adult neurogenesis. Here, we examined whether EphB3 mediates cell death in the adult forebrain following traumatic brain injury and whether ephrinB3 infusion could limit this effect. We show that EphB3 co-labels with microtubule-associated protein 2-positive neurons in the adult cortex and is closely associated with ephrinB3 ligand, which is reduced following controlled cortical impact (CCI) injury. In the complete absence of EphB3 (EphB3(-/-)), we observed reduced terminal deoxynucleotidyl transferase-dUTP nick end labeling (TUNEL), and functional improvements in motor deficits after CCI injury as compared with wild-type and ephrinB3(-/-) mice. We also demonstrated that EphB3 exhibits dependence receptor characteristics as it is cleaved by caspases and induces cell death, which is not observed in the presence of ephrinB3. Following trauma, infusion of pre-clustered ephrinB3-Fc molecules (eB3-Fc) into the contralateral ventricle reduced cortical infarct volume and TUNEL staining in the cortex, dentate gyrus and CA3 hippocampus of wild-type and ephrinB3(-/-) mice, but not EphB3(-/-) mice. Similarly, application of eB3-Fc improved motor functions after CCI injury. We conclude that EphB3 mediates cell death in the adult cortex through a novel dependence receptor-mediated cell death mechanism in the injured adult cortex and is attenuated following ephrinB3 stimulation.

  13. Effects of Source Water Quality on Chlorine Inactivation of Adenovirus, Coxsackievirus, Echovirus, and Murine Norovirus ▿

    OpenAIRE

    Kahler, Amy M.; Cromeans, Theresa L.; Roberts, Jacquelin M.; Hill, Vincent R.

    2010-01-01

    More information is needed on the disinfection efficacy of chlorine for viruses in source water. In this study, chlorine disinfection efficacy was investigated for USEPA Contaminant Candidate List viruses coxsackievirus B5 (CVB5), echovirus 1 (E1), murine norovirus (MNV), and human adenovirus 2 (HAdV2) in one untreated groundwater source and two partially treated surface waters. Disinfection experiments using pH 7 and 8 source water were carried out in duplicate, using 0.2 and 1 mg/liter free...

  14. Multiple phenotypes in adult mice following inactivation of the Coxsackievirus and Adenovirus Receptor (Car gene.

    Directory of Open Access Journals (Sweden)

    Ahmad Pazirandeh

    Full Text Available To determine the normal function of the Coxsackievirus and Adenovirus Receptor (CAR, a protein found in tight junctions and other intercellular complexes, we constructed a mouse line in which the CAR gene could be disrupted at any chosen time point in a broad spectrum of cell types and tissues. All knockouts examined displayed a dilated intestinal tract and atrophy of the exocrine pancreas with appearance of tubular complexes characteristic of acinar-to-ductal metaplasia. The mice also exhibited a complete atrio-ventricular block and abnormal thymopoiesis. These results demonstrate that CAR exerts important functions in the physiology of several organs in vivo.

  15. Comparative pathogenicity of Coxsackievirus A16 circulating and noncirculating strains in vitro and in a neonatal mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Huang, L. [Institute of Virology and AIDS Research, The First Hospital of Jilin University, Changchun (China); The 208th Hospital of PLA, Changchun (China); Liu, X.; Li, J.L.; Chang, J.L.; Liu, G.C. [Institute of Virology and AIDS Research, The First Hospital of Jilin University, Changchun (China); Yu, X.F. [Institute of Virology and AIDS Research, The First Hospital of Jilin University, Changchun (China); Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (United States); Zhang, W.Y. [Institute of Virology and AIDS Research, The First Hospital of Jilin University, Changchun (China)

    2015-03-27

    An enterovirus 71 (EV71) vaccine for the prevention of hand, foot, and mouth disease (HMFD) is available, but it is not known whether the EV71 vaccine cross-protects against Coxsackievirus (CV) infection. Furthermore, although an inactivated circulating CVA16 Changchun 024 (CC024) strain vaccine candidate is effective in newborn mice, the CC024 strain causes severe lesions in muscle and lung tissues. Therefore, an effective CV vaccine with improved pathogenic safety is needed. The aim of this study was to evaluate the in vivo safety and in vitro replication capability of a noncirculating CVA16 SHZH05 strain. The replication capacity of circulating CVA16 strains CC024, CC045, CC090 and CC163 and the noncirculating SHZH05 strain was evaluated by cytopathic effect in different cell lines. The replication capacity and pathogenicity of the CC024 and SHZH05 strains were also evaluated in a neonatal mouse model. Histopathological and viral load analyses demonstrated that the SHZH05 strain had an in vitro replication capacity comparable to the four CC strains. The CC024, but not the SHZH05 strain, became distributed in a variety of tissues and caused severe lesions and mortality in neonatal mice. The differences in replication capacity and in vivo pathogenicity of the CC024 and SHZH05 strains may result from differences in the nucleotide and amino acid sequences of viral functional polyproteins P1, P2 and P3. Our findings suggest that the noncirculating SHZH05 strain may be a safer CV vaccine candidate than the CC024 strain.

  16. Divergent Requirement for a DNA Repair Enzyme during Enterovirus Infections

    Directory of Open Access Journals (Sweden)

    Sonia Maciejewski

    2015-12-01

    Full Text Available Viruses of the Enterovirus genus of picornaviruses, including poliovirus, coxsackievirus B3 (CVB3, and human rhinovirus, commandeer the functions of host cell proteins to aid in the replication of their small viral genomic RNAs during infection. One of these host proteins is a cellular DNA repair enzyme known as 5′ tyrosyl-DNA phosphodiesterase 2 (TDP2. TDP2 was previously demonstrated to mediate the cleavage of a unique covalent linkage between a viral protein (VPg and the 5′ end of picornavirus RNAs. Although VPg is absent from actively translating poliovirus mRNAs, the removal of VPg is not required for the in vitro translation and replication of the RNA. However, TDP2 appears to be excluded from replication and encapsidation sites during peak times of poliovirus infection of HeLa cells, suggesting a role for TDP2 during the viral replication cycle. Using a mouse embryonic fibroblast cell line lacking TDP2, we found that TDP2 is differentially required among enteroviruses. Our single-cycle viral growth analysis shows that CVB3 replication has a greater dependency on TDP2 than does poliovirus or human rhinovirus replication. During infection, CVB3 protein accumulation is undetectable (by Western blot analysis in the absence of TDP2, whereas poliovirus protein accumulation is reduced but still detectable. Using an infectious CVB3 RNA with a reporter, CVB3 RNA could still be replicated in the absence of TDP2 following transfection, albeit at reduced levels. Overall, these results indicate that TDP2 potentiates viral replication during enterovirus infections of cultured cells, making TDP2 a potential target for antiviral development for picornavirus infections.

  17. An atypical course of coxsackievirus A6 associated hand, foot and mouth disease in extremely low birth weight preterm twins

    NARCIS (Netherlands)

    Bruning, Andrea H. L.; van der Sanden, Sabine M. G.; ten Hoedt, Amber E.; Wolthers, Katja C.; van Kaam, Anton H.; Pajkrt, Dasja

    2015-01-01

    The incidence of coxsackievirus A6 (CV-A6) associated hand, foot and mouth disease (HFMD) has reportedly increased since 2008 with sometimes severe complications. We here describe an atypical course of CV-A6-associated HFMD in extremely low birth weight twins. The CV-A6-strains are genetically

  18. Genome Sequence of Coxsackievirus A6, Isolated during a Hand-Foot-and-Mouth Disease Outbreak in Finland in 2008.

    Science.gov (United States)

    Osterback, Riikka; Koskinen, Satu; Merilahti, Pirjo; Pursiheimo, Juha-Pekka; Blomqvist, Soile; Roivainen, Merja; Laiho, Asta; Susi, Petri; Waris, Matti

    2014-10-16

    Reports of hand-foot-and-mouth disease (HFMD) outbreaks caused by coxsackievirus A6 have increased worldwide after the report of the first outbreak in Finland in 2008. The complete genome of the first outbreak strain from a vesicle fluid specimen was determined. Copyright © 2014 Österback et al.

  19. The role of enterovirus 71 and coxsackievirus A strains in a large outbreak of hand, foot, and mouth disease in 2012 in Changsha, China

    Directory of Open Access Journals (Sweden)

    Jing-Fang Chen

    2014-11-01

    Conclusions: Our results demonstrate that EV-71 was the primary causative agent responsible for the HFMD outbreak in Changsha in 2012, and the co-circulation of other coxsackievirus A strains posed a potential risk to public health.

  20. Integrins are not essential for entry of coxsackievirus A9 into SW480 human colon adenocarcinoma cells.

    Science.gov (United States)

    Heikkilä, Outi; Merilahti, Pirjo; Hakanen, Marika; Karelehto, Eveliina; Alanko, Jonna; Sukki, Maria; Kiljunen, Saija; Susi, Petri

    2016-10-18

    Coxsackievirus A9 (CV-A9) is a pathogenic enterovirus type within the family Picornaviridae. CV-A9 infects A549 human epithelial lung carcinoma cells by attaching to the αVβ6 integrin receptor through a highly conserved Arg-Gly-Asp (RGD) motif, which is located at the exposed carboxy-terminus of the capsid protein VP1 detected in all studied clinical isolates. However, genetically-modified CV-A9 that lacks the RGD motif (CV-A9-RGDdel) has been shown to be infectious in some cell lines but not in A549, suggesting that RGD-mediated integrin binding is not always essential for efficient entry of CV-A9. Two cell lines, A549 and SW480, were used in the study. SW480 was the study object for the integrin-independent entry and A549 was used as the control for integrin-dependent entry. Receptor levels were quantitated by cell sorting and quantitative PCR. Antibody blocking assay and siRNA silencing of receptor-encoding genes were used to block virus infection. Peptide phage display library was used to identify peptide binders to CV-A9. Immunofluorescence and confocal microscopy were used to visualize the virus infection in the cells. We investigated the receptor use and early stages of CV-A9 internalization to SW480 human epithelial colon adenocarcinoma cells. Contrary to A549 infection, we showed that both CV-A9 and CV-A9-RGDdel internalized into SW480 cells and that function-blocking anti-αV integrin antibodies had no effect on the binding and entry of CV-A9. Whereas siRNA silencing of β6 integrin subunit had no influence on virus infection in SW480, silencing of β2-microglobulin (β2M) inhibited the virus infection in both cell lines. By using a peptide phage display screening, the virus-binding peptide identical to the N-terminal sequence of HSPA5 protein was identified and shown to block the virus infection in both A549 and SW480 cell lines. HSPA5 was also found to co-localize with CV-A9 at the SW480 cell periphery during the early stages of infection by confocal

  1. Saffold virus, a human Theiler's-like cardiovirus, is ubiquitous and causes infection early in life.

    NARCIS (Netherlands)

    Zoll, J.; Erkens Hulshof, S.; Lanke, K.H.W.; Verduyn Lunel, F.M.; Melchers, W.J.G.; Schoondermark-van de Ven, E.M.E.; Roivainen, M.; Galama, J.M.D.; Kuppeveld, F.J.M. van

    2009-01-01

    The family Picornaviridae contains well-known human pathogens (e.g., poliovirus, coxsackievirus, rhinovirus, and parechovirus). In addition, this family contains a number of viruses that infect animals, including members of the genus Cardiovirus such as Encephalomyocarditis virus (EMCV) and

  2. Circulation of Coxsackievirus A10 and A6 in hand-foot-mouth disease in China, 2009-2011.

    Directory of Open Access Journals (Sweden)

    Qing-Bin Lu

    Full Text Available Coxsackieviruses A10 (CV-A10 and A6 (CV-A6 have been associated with increasingly occurred sporadic hand-foot-mouth disease (HFMD cases and outbreak events globally. However, our understanding of epidemiological and genetic characteristics of these new agents remains far from complete. This study was to explore the circulation of CV-A10 and CV-A6 in HFMD and their genetic characteristics in China. A hospital based surveillance was performed in three heavily inflicted regions with HFMD from March 2009 to August 2011. Feces samples were collected from children with clinical diagnosis of HFMD. The detection and genotyping of enteroviruses was performed by real-time PCR and sequencing of 5'UTR/VP1 regions. Phylogenetic analysis and selection pressure were performed based on the VP1 sequences. Logistic regression model was used to identify the effect of predominant enterovirus serotypes in causing severe HFMD. The results showed 92.0% of 1748 feces samples were detected positive for enterovirus, with the most frequently presented serotypes as EV-71 (944, 54.0% and CV-A16 (451, 25.8%. CV-A10 and CV-A6 were detected as a sole pathogen in 82 (4.7% and 44 (2.5% cases, respectively. Infection with CV-A10 and EV-71 were independently associated with high risk of severe HFMD (OR = 2.66, 95% CI: 1.40-5.06; OR = 4.81, 95% CI: 3.07-7.53, when adjusted for age and sex. Phylogenetic analysis revealed that distinct geographic and temporal origins correlated with the gene clusters based on VP1 sequences. An overall ω value of the VP1 was 0.046 for CV-A10 and 0.047 for CV-A6, and no positively selected site was detected in VP1 of both CV-A10 and CV-A6, indicating that purifying selection shaped the evolution of CV-A10 and CV-A6. Our study demonstrates variety of enterovirus genotypes as viral pathogens in causing HFMD in China. CV-A10 and CV-A6 were co-circulating together with EV-71 and CV-A16 in recent years. CV-A10 infection might also be independently

  3. 17 CFR 270.8b-3 - Title of securities.

    Science.gov (United States)

    2010-04-01

    ... funded debt, the rate of interest; the date of maturity, or if the issue matures serially, a brief... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Title of securities. 270.8b-3 Section 270.8b-3 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) RULES...

  4. An outbreak of aseptic meningitis caused by a distinct lineage of coxsackievirus B5 in China.

    Science.gov (United States)

    Liu, Nan; Jia, Leili; Yin, Jiye; Wu, Zhihao; Wang, Zhongqiang; Li, Peng; Hao, Rongzhang; Wang, Ligui; Wang, Yong; Qiu, Shaofu; Song, Hongbin

    2014-06-01

    In 2009, an outbreak of aseptic meningitis caused by coxsackievirus B5 (CVB5) occurred in China. Epidemiological investigations of this outbreak revealed that the proportion of severe cases (14/43, 33%) was higher than in other outbreaks associated with CVB5 in China. Phylogenetic analysis of the entire VP1 sequences demonstrated that the CVB5 isolates from the severe cases form a distinct lineage belonging to genogroup E with the Shandong isolates of 2009. A substitution of serine (S) to asparagine (N) at amino acid 95 in the VP1 region may be a major virulence determinant for the virus. Our findings suggest that this new lineage of CVB5 is circulating in China. Further genetic studies are needed in order to gain a better insight into the genetic variability of CVB5 isolates and the relationship with pathogenicity. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. New coxsackievirus B4 genotype circulating in Inner Mongolia Autonomous Region, China.

    Directory of Open Access Journals (Sweden)

    Xiaoling Tian

    Full Text Available Hand, foot, and mouth disease (HFMD surveillance was initiated in the Inner Mongolia Autonomous Region of China in 2007, a crucial scrutiny for monitoring the prevalence of enterovirus serotypes associated with HFMD patients. However, this surveillance mostly focused on enterovirus 71 (EV-A71 and coxsackievirus A16; therefore, information on other enterovirus serotypes is limited. To identify the other circulating enterovirus serotypes in the HFMD outbreaks in Inner Mongolia in 2010, clinical samples from HFMD patients were investigated. Six coxsackievirus B4 (CVB4 strains were isolated and phylogenetic analyses of VP1 sequences were performed. Full-length genome sequences of two representative CVB4 isolates were acquired and similarity plot and bootscanning analyses were performed. The phylogenetic dendrogram indicated that all CVB4 strains could be divided into 5 genotypes (Genotypes I-V with high bootstrap support (90-100%. The CVB4 prototype strain (JVB was the sole member of genotype I. CVB4 strains belonging to genotype II, which were once common in Europe and the Americas, seemingly disappeared and gave way to genotype III and IV strains, which appear to be the dominant circulating strains in the world. All Chinese CVB4 strains belonged to Genotype V, a newly identified genotype supported by a high bootstrap value (100%, and are circulating only in mainland of China. Intertypic recombination occurred in the Chinese CVB4 strains with novel unknown serotype EV-B donor sequences. Two Chinese CVB4 strains had a virulent residue at position 129 of VP1, and one strain also had a virulent residue at position 16 of VP4. Increased surveillance is needed to monitor the emergence of new genetic lineages of enteroviruses in areas that are often associated with large-scale outbreaks. In addition, continued monitoring of enteroviruses by clinical surveillance and genetic characterization should be enhanced.

  6. Mycobacterium tuberculosis WhiB3 maintains redox homeostasis by regulating virulence lipid anabolism to modulate macrophage response.

    Science.gov (United States)

    Singh, Amit; Crossman, David K; Mai, Deborah; Guidry, Loni; Voskuil, Martin I; Renfrow, Matthew B; Steyn, Adrie J C

    2009-08-01

    The metabolic events associated with maintaining redox homeostasis in Mycobacterium tuberculosis (Mtb) during infection are poorly understood. Here, we discovered a novel redox switching mechanism by which Mtb WhiB3 under defined oxidizing and reducing conditions differentially modulates the assimilation of propionate into the complex virulence polyketides polyacyltrehaloses (PAT), sulfolipids (SL-1), phthiocerol dimycocerosates (PDIM), and the storage lipid triacylglycerol (TAG) that is under control of the DosR/S/T dormancy system. We developed an in vivo radio-labeling technique and demonstrated for the first time the lipid profile changes of Mtb residing in macrophages, and identified WhiB3 as a physiological regulator of virulence lipid anabolism. Importantly, MtbDeltawhiB3 shows enhanced growth on medium containing toxic levels of propionate, thereby implicating WhiB3 in detoxifying excess propionate. Strikingly, the accumulation of reducing equivalents in MtbDeltawhiB3 isolated from macrophages suggests that WhiB3 maintains intracellular redox homeostasis upon infection, and that intrabacterial lipid anabolism functions as a reductant sink. MtbDeltawhiB3 infected macrophages produce higher levels of pro- and anti-inflammatory cytokines, indicating that WhiB3-mediated regulation of lipids is required for controlling the innate immune response. Lastly, WhiB3 binds to pks2 and pks3 promoter DNA independent of the presence or redox state of its [4Fe-4S] cluster. Interestingly, reduction of the apo-WhiB3 Cys thiols abolished DNA binding, whereas oxidation stimulated DNA binding. These results confirmed that WhiB3 DNA binding is reversibly regulated by a thiol-disulfide redox switch. These results introduce a new paradigmatic mechanism that describes how WhiB3 facilitates metabolic switching to fatty acids by regulating Mtb lipid anabolism in response to oxido-reductive stress associated with infection, for maintaining redox balance. The link between the WhiB3

  7. Internalization of coxsackievirus A9 is mediated by {beta}2-microglobulin, dynamin, and Arf6 but not by caveolin-1 or clathrin.

    Science.gov (United States)

    Heikkilä, Outi; Susi, Petri; Tevaluoto, Tuire; Härmä, Heidi; Marjomäki, Varpu; Hyypiä, Timo; Kiljunen, Saija

    2010-04-01

    Coxsackievirus A9 (CAV9) is a member of the human enterovirus B species within the Enterovirus genus of the family Picornaviridae. It has been shown to utilize alphaV integrins, particularly alphaVbeta6, as its receptors. The endocytic pathway by which CAV9 enters human cells after the initial attachment to the cell surface has so far been unknown. Here, we present a systematic study concerning the internalization mechanism of CAV9 to A549 human lung carcinoma cells. The small interfering RNA (siRNA) silencing of integrin beta6 subunit inhibited virus proliferation, confirming that alphaVbeta6 mediates the CAV9 infection. However, siRNAs against integrin-linked signaling molecules, such as Src, Fyn, RhoA, phosphatidylinositol 3-kinase, and Akt1, did not reduce CAV9 proliferation, suggesting that the internalization of the virus does not involve integrin-linked signaling events. CAV9 endocytosis was independent of clathrin or caveolin-1 but was restrained by dynasore, an inhibitor of dynamin. The RNA interference silencing of beta2-microglobulin efficiently inhibited virus infection and caused CAV9 to accumulate on the cell surface. Furthermore, CAV9 infection was found to depend on Arf6 as both silencing of this molecule by siRNA and the expression of a dominant negative construct resulted in decreased virus infection. In conclusion, the internalization of CAV9 to A549 cells follows an endocytic pathway that is dependent on integrin alphaVbeta6, beta2-microglobulin, dynamin, and Arf6 but independent of clathrin and caveolin-1.

  8. Rare bile duct anomaly: B3 duct draining to gallbladder

    Directory of Open Access Journals (Sweden)

    Seung Eun Lee

    2016-01-01

    Full Text Available A 10-year-old girl presented with recurrent right upper abdominal pain and dyspepsia. Magnetic resonance cholangiopancreatography revealed a dilated common channel of intrahepatic bile duct of segment 3 (B3 and segment 4 (B4 drained into the gallbladder directly. The patient underwent laparoscopic cholecystectomy and Roux-en Y hepaticojejunostomy (B3-jejunostomy. Among the anatomical variability of the biliary system, the cholecystohepatic ducts are controversial in existence and incidence. We report a very rare variant of a cholecystohepatic duct in which the B3 duct drained into gallbladder directly and to the best of our knowledge this is the first report.

  9. Outbreak of variant hand-foot-and-mouth disease caused by coxsackievirus A6 in Auckland, New Zealand.

    Science.gov (United States)

    Hayman, Rebecca; Shepherd, Michael; Tarring, Claire; Best, Emma

    2014-10-01

    Hand-foot-and-mouth disease is a common, usually mild childhood illness caused by enteroviruses. Over the last five years, coxsackievirus A6 has been identified as a causative agent in outbreaks in Europe, South-East Asia and America. It has an atypical presentation compared with other enteroviruses, with more widespread rash, larger blisters and subsequent skin peeling and/or nail shedding. We give the first description of an outbreak of coxsackievirus A6 in New Zealand and how health-care communication networks enabled detection of and dissemination of information about this emergent strain. © 2014 The Authors. Journal of Paediatrics and Child Health © 2014 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

  10. Relative efficacy of egg albumin as blocking agent in dot immunobinding assay for detection of group B coxsackieviruses.

    Science.gov (United States)

    Pandya, G; Tuteja, U; Jana, A M

    1994-09-01

    Non specific binding (NSB) is an important factor affecting sensitivity and specificity in dot immunobinding assay (DIA). Several blocking agents e.g. egg albumin, casein, gelatin, milk powder and goat serum were evaluated for their relative efficacy vis-a-vis bovine serum albumin (BSA) for DIA system purported for detection of group B coxsackieviruses (CVB). The results suggest that egg albumin (5%) which is economical and readily available may act as an effective blocking agent in DIA system.

  11. Enterovirus infection in children attending two outpatient clinics in Zhejiang Province, China.

    Science.gov (United States)

    Cai, Jian; Lv, Huakun; Lin, Junfen; Chen, Zhiping; Fang, Chunfu; Han, Jiankang

    2014-09-01

    Enteroviruses are responsible for hand, foot, and mouth disease, and have caused many deaths in China during recent years. But the natural history of enterovirus infection in children, especially asymptomatic children, is not yet clear. From April 2011 to May 2012, 505 stool and throat swab samples of children attending outpatients clinics in two hospitals were collected weekly to test for Enterovirus 71, Coxsackievirus A16, and other enterovirus nucleic acids by real-time RT-PCR. Two hundred sixty-four patients were enterovirus positive, the positive rate was 52.3%, 27.5% (22/80) in children without a rash and 56.9% (242/425) in children with a rash. Coxsackievirus A16 positive rate of male (24%, 61/254) was higher than that of female (15.2%, 26/171) (χ(2)  = 4.87, P = 0.027). The highest positive rate of enterovirus infection was 63.5% in the 2-year-old age group. Comparing children with and without a rash, within the same age groups, no statistical difference was found (P > 0.05). The seasonal distribution of Enterovirus 71 had only one peak in May, but Coxsackievirus A16 had two peaks in April and October. In patients with a rash, the frequency of Enterovirus 71 was relatively high before July, and then that of Coxsackievirus A16 increased gradually. In the case of Enterovirus 71 and Coxsackievirus A16, stool specimens had a higher positive rate than throat swab specimens' (χ(2)  = 3.88, P = 0.05; χ(2)  = 15.13, P < 0.001). Enterovirus infection was more frequent in males 2-3 year-old children, with the implicated virus varying by season. Targeted prevention and control measures should be carried out. © 2014 Wiley Periodicals, Inc.

  12. Focal encephalitis with enterovirus infections.

    Science.gov (United States)

    Modlin, J F; Dagan, R; Berlin, L E; Virshup, D M; Yolken, R H; Menegus, M

    1991-10-01

    We report on four pediatric patients with Enterovirus infections who were admitted to the hospital with signs or symptoms of acute, focal encephalitis. All four experienced focal seizures. Each had a cerebrospinal fluid pleocytosis at the initial lumbar puncture. In all four patients the diagnosis of herpes simplex encephalitis was entertained. Each child improved spontaneously within a few days of admission to the hospital, and only one had residual neurologic abnormalities at the time of discharge. A brief review of these cases, and three additional cases from the literature, indicate that the enteroviruses, particularly the group A Coxsackieviruses, are rare causes of acute focal encephalitis in children and adolescents.

  13. Effects of hypervitaminosis of vitamin B3 on silkworm biology

    Indian Academy of Sciences (India)

    Unknown

    A high-dose of vitamin B3 in silkworm diet interrupts larval feeding and normal growth. High mortality of lar- vae occurs during molting and they cannot complete this process normally. Also the larvae exhibit nicotinamide hypervitaminosis symptoms such as immobility, dyspepsia, darkening of the skin, inability to excrete ...

  14. Effects of hypervitaminosis of vitamin B3 on silkworm biology

    Indian Academy of Sciences (India)

    A high-dose of vitamin B3 in silkworm diet interrupts larval feeding and normal growth. High mortality of larvae occurs during molting and they cannot complete this process normally. Also the larvae exhibit nicotinamide hypervitaminosis symptoms such as immobility, dyspepsia, darkening of the skin, inability to excrete ...

  15. 26 CFR 1.652(b)-3 - Allocation of deductions.

    Science.gov (United States)

    2010-04-01

    ....652(b)-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX.... Items of deduction of a trust that enter into the computation of distributable net income are to be...) included in computing distributable net income, but a portion must be allocated to nontaxable income...

  16. Co-circulation and genomic recombination of coxsackievirus A16 and enterovirus 71 during a large outbreak of hand, foot, and mouth disease in Central China.

    Directory of Open Access Journals (Sweden)

    Weiyong Liu

    Full Text Available A total of 1844 patients with hand, foot, and mouth disease (HFMD, most of them were children of age 1-3-year-old, in Central China were hospitalized from 2011 to 2012. Among them, 422 were infected with coxsackievirus A16 (CVA16, 334 were infected with enterovirus 71 (EV71, 38 were co-infected with EV71 and CVA16, and 35 were infected with other enteroviruses. Molecular epidemiology analysis revealed that EV71 and CVA16 were detected year-round, but EV71 circulated mainly in July and CVA16 circulated predominantly in November, and incidence of HFMD was reduced in January and February and increased in March. Clinical data showed that hyperglycemia and neurologic complications were significantly higher in EV71-infected patients, while upper respiratory tract infection and C-reactive protein were significantly higher in CVA16-associated patients. 124 EV71 and 80 CVA16 strains were isolated, among them 56 and 68 EV71 strains were C4a and C4b, while 25 and 55 CVA16 strains were B1a and B1b, respectively. Similarity plots and bootscan analyses based on entire genomic sequences revealed that the three C4a sub-genotype EV71 strains were recombinant with C4b sub-genotype EV71 in 2B-2C region, and the three CVA16 strains were recombinant with EV71 in 2A-2B region. Thus, CVA16 and EV71 were the major causative agents in a large HFMD outbreak in Central China. HFMD incidence was high for children among household contact and was detected year-round, but outbreak was seasonal dependent. CVA16 B1b and EV71 C4b reemerged and caused a large epidemic in China after a quiet period of many years. Moreover, EV71 and CVA16 were co-circulated during the outbreak, which may have contributed to the genomic recombination between the pathogens. It should gain more attention as there may be an upward trend in co-circulation of the two pathogens globally and the new role recombination plays in the emergence of new enterovirus variants.

  17. Nucleotide sequence of the 5'nontranslated and virion polypeptides regions of coxsackievirus B6.

    Science.gov (United States)

    Kato, S; Tsutsumi, R; Sato, S

    1999-01-01

    The nucleotide sequence of coxsackievirus B6 (CVB6) has been determined, and the nucleotides encoding the 5' nontranslated region (5' NTR) and virion polypeptides (VP4, 2, 3 and 1) were compared with other serotype CVBs. An Unweighted Pair-Group Method Analysis (UPGMA) of phylogenetic trees indicated that the 5' NTR of CVB6 locates on an independent branch from the other CVBs. The tree based on the amino acid sequences showed that CVB6 has close correlation with CVB4 in the VP4 and VP2 regions, with CVB1 and CVB5 in the VP3 region, and with CVB5 in the VP1 region. Amino acid sequences of variable regions within the VP2, VP3, and VP1 of CVB6 were unique among CVBs. Thus, by comparison of the nucleotide and amino acid sequences of these variable regions, CVB6 can be easily distinguished from other serotypes. In addition, serine, instead of glycine, was found to locate at the amino-terminus of the VP1 region of CVB6, indicating that CVB6 has a unique cleavage site (i.e., glutamine/serine instead of glutamine/glycine) for proteinase 3C of Picornaviridae.

  18. [Genome sequences of coxsackievirus B5 isolated from viral encephalitis patients in Henan province, 2011].

    Science.gov (United States)

    Ma, Hong-xia; Pan, Jing-jing; Kang, Kai; Xie, Zhi-qiang; Ru, Wei-ping; Chen, Hao-min; Huang, Xue-yong; Xu, Bian-li

    2013-12-01

    To analyze the complete genome sequences of two coxsackievirus B5 (CVB5) isolated in Henan province, 2011. Specimens were collected from viral encephalitis patients and followed by viral isolation on them. RNA were extracted from positive isolates and the amplified products were sequenced. The full-length genomes of them were acquired by assembling the fragments, using DNAStar 5.01 software while phylogenetic analysis were performed with Mega 5.05 and other software. The genomes RNA of 03001N and 17Y showed 7408 bp and 7404 bp long, and the 5'- and 3'-untranslated regions were 747 bp, 743 bp and 103 bp, 103 bp, respectively. BLAST analysis of these two isolates, based on the complete genome, showed 97% identity, with both of them having the highest similarity(98%, 99%)to the CVB5 strain isolated from Henan in 2010 rather than other CVB5 strains. Coding regions of both isolates were 6558 bp, code for a polyprotein of 2185 amino acids (aa) and both of them showed 99% amino acid identity. Phylogenetic tree in VP1 region showed that the two isolates belonged to the same clade with other strains isolated from all over the country in the past years, except for some CVB5 strains isolated from Henan and Shandong province in 2009 that formed the other cluster. It seemed that more than one group of CVB5 were circulating in Henan province and these two isolates appeared the main epidemic strains circulating in the past years.

  19. Molecular epidemiology of coxsackievirus A16: intratype and prevalent intertype recombination identified.

    Directory of Open Access Journals (Sweden)

    Xiangpeng Chen

    Full Text Available Coxsackievirus A16 (CVA16 is responsible for nearly 50% of all the confirmed hand, foot, and mouth disease (HFMD cases in mainland China, sometimes it could also cause severe complications, and even death. To clarify the genetic characteristics and the epidemic patterns of CVA16 in mainland China, comprehensive bioinfomatics analyses were performed by using 35 CVA16 whole genome sequences from 1998 to 2011, 593 complete CVA16 VP1 sequences from 1981 to 2011, and prototype strains of human enterovirus species A (EV-A. Analysis on complete VP1 sequences revealed that subgenotypes B1a and B1b were prevalent strains and have been co-circulating in many Asian countries since 2000, especially in mainland China for at least 13 years. While the prevalence of subgenotype B1c (totally 20 strains was much limited, only found in Malaysia from 2005 to 2007 and in France in 2010. Genotype B2 only caused epidemic in Japan and Malaysia from 1981 to 2000. Both subgenotypes B1a and B1b were potential recombinant viruses containing sequences from other EV-A donors in the 5'-untranslated region and P2, P3 non-structural protein encoding regions.

  20. Optimization and Characterization of Candidate Strain for Coxsackievirus A16 Inactivated Vaccine.

    Science.gov (United States)

    Li, Jingliang; Liu, Guanchen; Liu, Xin; Yang, Jiaxin; Chang, Junliang; Zhang, Wenyan; Yu, Xiao-Fang

    2015-07-17

    Coxsackievirus A16 (CA16) and enterovirus 71 (EV71), both of which can cause hand, foot and mouth disease (HFMD), are responsible for large epidemics in Asian and Pacific areas. Although inactivated EV71 vaccines have completed testing in phase III clinical trials in Mainland China, CA16 vaccines are still under development. A Vero cell-based inactivated CA16 vaccine was developed by our group. Screening identified a CA16 vaccine strain (CC024) isolated from HFMD patients, which had broad cross-protective abilities and satisfied all requirements for vaccine production. Identification of the biological characteristics showed that the CA16CC024 strain had the highest titer (107.5 CCID50/mL) in Vero cells, which would benefit the development of an EV71/CA16 divalent vaccine. A potential vaccine manufacturing process was established, including the selection of optimal time for virus harvesting, membrane for diafiltration and concentration, gel-filtration chromatography for the down-stream virus purification and virus inactivation method. Altogether, the analyses suggested that the CC-16, a limiting dilution clone of the CC024 strain, with good genetic stability, high titer and broad-spectrum immunogenicity, would be the best candidate strain for a CA16 inactivated vaccine. Therefore, our study provides valuable information for the development of a Vero cell-based CA16 or EV71-CA16 divalent inactivated vaccine.

  1. Optimization and Characterization of Candidate Strain for Coxsackievirus A16 Inactivated Vaccine

    Directory of Open Access Journals (Sweden)

    Jingliang Li

    2015-07-01

    Full Text Available Coxsackievirus A16 (CA16 and enterovirus 71 (EV71, both of which can cause hand, foot and mouth disease (HFMD, are responsible for large epidemics in Asian and Pacific areas. Although inactivated EV71 vaccines have completed testing in phase III clinical trials in Mainland China, CA16 vaccines are still under development. A Vero cell-based inactivated CA16 vaccine was developed by our group. Screening identified a CA16 vaccine strain (CC024 isolated from HFMD patients, which had broad cross-protective abilities and satisfied all requirements for vaccine production. Identification of the biological characteristics showed that the CA16CC024 strain had the highest titer (107.5 CCID50/mL in Vero cells, which would benefit the development of an EV71/CA16 divalent vaccine. A potential vaccine manufacturing process was established, including the selection of optimal time for virus harvesting, membrane for diafiltration and concentration, gel-filtration chromatography for the down-stream virus purification and virus inactivation method. Altogether, the analyses suggested that the CC-16, a limiting dilution clone of the CC024 strain, with good genetic stability, high titer and broad-spectrum immunogenicity, would be the best candidate strain for a CA16 inactivated vaccine. Therefore, our study provides valuable information for the development of a Vero cell-based CA16 or EV71-CA16 divalent inactivated vaccine.

  2. Detection, characterization and quantitation of coxsackievirus A16 using polyclonal antibodies against recombinant capsid subunit proteins.

    Science.gov (United States)

    Liu, Qingwei; Ku, Zhiqiang; Cai, Yicun; Sun, Bing; Leng, Qibin; Huang, Zhong

    2011-04-01

    Coxsackievirus A16 (CVA16), together with enterovirus type 71 (EV71), is responsible for most cases of hand, foot and mouth disease (HFMD) worldwide. Recent findings suggest that the recombination between CVA16 and EV71, and co-circulation of these two viruses may have contributed to the increase of HFMD cases in China over the past few years. Thus, for CVA16, further understanding of its virology, epidemiology and development of diagnostic tests and vaccines are of importance. The present study aimed to develop reagents and protocols for the detection, characterization and quantitation of CVA16. Recombinant CVA16 capsid subunit proteins VP0, VP3 and truncated VP1, were produced in Escherichia coli and used to immunize guinea pigs to generate polyclonal antibodies. The resultant three antisera detected specifically CVA16 propagated in Vero cells by immunostaining, ELISA and Western blotting. The antisera was used to show that CVA16 capsids were composed of correctly processed VP0, VP1 and VP3 subunits, and were present in the form of efficiently assembled particles. A method for the quantitation of the yield of CVA16 in Vero cells was established based on a Western blotting protocol using the recombinant VP0 as a reference standard and anti-VP0 as the detection antibody. This study shows the development and validation of reagents and methods, for qualitative and quantitative determination of CVA16, which are essential for the development of vaccines. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. Coxsackievirus A6 associated hand, foot and mouth disease in adults: clinical presentation and review of the literature.

    Science.gov (United States)

    Ramirez-Fort, Marigdalia K; Downing, Christopher; Doan, Hung Q; Benoist, Frances; Oberste, M Steven; Khan, Farhan; Tyring, Stephen K

    2014-08-01

    Hand, foot, and mouth disease (HFMD) is generally considered a rare illness in adults. Classically, HFMD has been strongly associated with coxsackievirus strain A16 and enterovirus 71. The coxsackievirus A6 (CVA6) strain has been linked to severe worldwide outbreaks since 2008. CVA6 is associated with a more severe and profound course of disease, affecting both children and adults. To present a series of five adult patients diagnosed with HFMD due to CVA6. We investigate method of diagnosis and compare clinical presentation of adult cases to those in children. Each patient underwent a full-body skin exam as well as inspection of the oral cavity. Rapid plasma reagin (RPR) and serologic assays by complement fixation against coxsackievirus B (1-6) and A (2,4,7,9,10,16) were performed as indicated. As standard serological testing does not detect CVA6, real-time reverse transcription-polymerase chain reaction (qRT-PCR) of serum, buccal swabs, and skin scrapings were performed by the Centers for Disease Control and Prevention (CDC). Each patient had clinical findings consistent with various stages of HFMD. One patient presented with delayed onychomadesis and desquamation of the palms and soles. RPR and serologic assays by complement fixation against CVB (1-6) and CVA (2,4,7,9,10,16) were mostly negative, although elevated in two patients due to cross-reactivity. qRT-PCR identified CVA6 genetic material in samples from all patients. This series demonstrates that there is a wide array of disease presentation of CVA6 associated HFMD in adults. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Potassium zinc borate, KZnB(3)O(6).

    Science.gov (United States)

    Wu, Yang; Yao, Ji-Yong; Zhang, Jian-Xiu; Fu, Pei-Zhen; Wu, Yi-Cheng

    2010-04-30

    The title compound, KZnB(3)O(6) contains a remarkable [B(6)O(12)](6-) group ( symmetry) formed by two rings linked by edge-sharing BO(4) tetra-hedra, a feature that has only been observed previously under high pressure conditions. These borate groups are connected through distorted ZnO(4) tetra-hedra in edge-shared pairs ( symmetry), forming a three-dimensional network whose cavities are filled by K(+) cations.

  5. Potassium zinc borate, KZnB3O6

    OpenAIRE

    Yang Wu; Ji-Yong Yao; Jian-Xiu Zhang; Pei-Zhen Fu; Yi-Cheng Wu

    2010-01-01

    The title compound, KZnB3O6 contains a remarkable [B6O12]6− group (overline{1} symmetry) formed by two rings linked by edge-sharing BO4 tetrahedra, a feature that has only been observed previously under high pressure conditions. These borate groups are connected through distorted ZnO4 tetrahedra in edge-shared pairs (overline{1} symmetry), forming a three-dimensional network whose cavities are filled by K+ cations.

  6. Potassium zinc borate, KZnB3O6

    Directory of Open Access Journals (Sweden)

    Yang Wu

    2010-05-01

    Full Text Available The title compound, KZnB3O6 contains a remarkable [B6O12]6− group (overline{1} symmetry formed by two rings linked by edge-sharing BO4 tetrahedra, a feature that has only been observed previously under high pressure conditions. These borate groups are connected through distorted ZnO4 tetrahedra in edge-shared pairs (overline{1} symmetry, forming a three-dimensional network whose cavities are filled by K+ cations.

  7. Eupafolin and Ethyl Acetate Fraction of Kalanchoe gracilis Stem Extract Show Potent Antiviral Activities against Enterovirus 71 and Coxsackievirus A16

    Directory of Open Access Journals (Sweden)

    Ching-Ying Wang

    2013-01-01

    Full Text Available Enterovirus 71 (EV71 and coxsackievirus A16 (CoxA16 are main pathogens of hand-foot-and-mouth disease, occasionally causing aseptic meningitis and encephalitis in tropical and subtropical regions. Kalanchoe gracilis, Da-Huan-Hun, is a Chinese folk medicine for treating pain and inflammation, exhibiting antioxidant and anti-inflammatory activities. Our prior report (2012 cited K. gracilis leaf extract as moderately active against EV71 and CoxA16. This study further rates antienteroviral potential of K. gracilis stem (KGS extract to identify potent antiviral fractions and components. The extract moderately inhibits viral cytopathicity and virus yield, as well as in vitro replication of EV71 (IC50 = 75.18 μg/mL and CoxA16 (IC50 = 81.41 μg/mL. Ethyl acetate (EA fraction of KGS extract showed greater antiviral activity than that of n-butanol or aqueous fraction: IC50 values of 4.21 μg/mL against EV71 and 9.08 μg/mL against CoxA16. HPLC analysis, UV-Vis absorption spectroscopy, and plaque reduction assay indicate that eupafolin is a vital component of EA fraction showing potent activity against EV71 (IC50 = 1.39 μM and CoxA16 (IC50 = 5.24 μM. Eupafolin specifically lessened virus-induced upregulation of IL-6 and RANTES by inhibiting virus-induced ERK1/2, AP-1, and STAT3 signals. Anti-enteroviral potency of KGS EA fraction and eupafolin shows the clinical potential against EV71 and CoxA16 infection.

  8. [Genomic characteristics of coxsackievirus B5 A210/KM/09 strain isolated in Yunnan, China].

    Science.gov (United States)

    Liu, Jiansheng; Shao, Congwen; Zhao, Weizhong; Zhang, Yunkun; Ji, Ma; Zhu, Yanju; Ma, Zhongfei; Ma, Shaohui

    2014-03-01

    To characterize the complete genome sequence of coxsackievirus B5 (CVB5)A210/KM/09 strain which was isolated from Yunnan, China, 2009. Eight overlapping clones covering the whole viral genome (excluding the poly-A tail)were obtained by RT-PCR and sequenced, with their nucleotide and amino acid sequences compared with other known CVB5 strains. The genome of the CVB5 A210/KM/09 strain had 7 372 nucleotides in length, and containing a 742-nt non-translated region (NTR) at the 5' end and a 98-nt NTR at the 3' end. The entire open reading frame contained 6 555 nt, encoding a 2 185-aa polyprotein. In the coding region, there appeared no nucleotide deletion or insertion, but some changes of amino acid seemed unique. Based on the complete genome sequence alignments, CVB5 isolate A210/KM/09 strain showed the highest nucleotide (92.5%) and amino acid (97.3%) identities to the CVB5/CC10/10. It also shared nucleotide (80.1%-92.5%) and amino acid (95.0%-97.3%) homology with other CVB5 strains: 17Y, 19CSF, 20CSF, 1954/85/US, 2000/CSF/KOR, 03001N, CoxB5/Henan/2010, VB5/SD/09 and Faulkner. Blast between genome fragments, A210/KM/09 showed similarity on nucleotide (80.1%-92.5%) and amino acid (95.0%-97.3%) identities with other CVB5 strains. The phylogenetic tree, constructed on the complete VP1 regions, indicated that CVB5 could be divided into genotype A, B, C and D. while Genotype C and D could be further divided into C1-C4 and D1-D4 subgenotypes. A210/KM/09 and other CVB5 predominant strains isolated in China belonged to CVB5 subgenotype C4.

  9. Effects of source water quality on chlorine inactivation of adenovirus, coxsackievirus, echovirus, and murine norovirus.

    Science.gov (United States)

    Kahler, Amy M; Cromeans, Theresa L; Roberts, Jacquelin M; Hill, Vincent R

    2010-08-01

    More information is needed on the disinfection efficacy of chlorine for viruses in source water. In this study, chlorine disinfection efficacy was investigated for USEPA Contaminant Candidate List viruses coxsackievirus B5 (CVB5), echovirus 1 (E1), murine norovirus (MNV), and human adenovirus 2 (HAdV2) in one untreated groundwater source and two partially treated surface waters. Disinfection experiments using pH 7 and 8 source water were carried out in duplicate, using 0.2 and 1 mg/liter free chlorine at 5 and 15 degrees C. The efficiency factor Hom (EFH) model was used to calculate disinfectant concentration x contact time (CT) values (mg x min/liter) required to achieve 2-, 3-, and 4-log(10) reductions in viral titers. In all water types, chlorine disinfection was most effective for MNV, with 3-log(10) CT values at 5 degrees C ranging from CVB5 in all water types, with 3-log(10) CT values at 5 degrees C ranging from 2.3 to 7.9. Overall, disinfection proceeded faster at 15 degrees C and pH 7 for all water types. Inactivation of the study viruses was significantly different between water types, but no single source water had consistently different inactivation rates than another. CT values for CVB5 in one type of source water exceeded the recommended CT values set forth by USEPA's Guidance Manual for Compliance with the Filtration and Disinfection Requirements for Public Water Systems using Surface Water Sources. The results of this study demonstrate that water quality plays a substantial role in the inactivation of viruses and should be considered when developing chlorination plans.

  10. Source water quality effects on monochloramine inactivation of adenovirus, coxsackievirus, echovirus, and murine norovirus.

    Science.gov (United States)

    Kahler, Amy M; Cromeans, Theresa L; Roberts, Jacquelin M; Hill, Vincent R

    2011-02-01

    There is a need for more information regarding monochloramine disinfection efficacy for viruses in water. In this study, monochloramine disinfection efficacy was investigated for coxsackievirus B5 (CVB5), echovirus 11 (E11), murine norovirus (MNV), and human adenovirus 2 (HAdV2) in one untreated ground water and two partially treated surface waters. Duplicate disinfection experiments were completed at pH 7 and 8 in source water at concentrations of 1 and 3 mg/L monochloramine at 5 and 15 °C. The Efficiency Factor Hom (EFH) model was used to calculate CT values (mg-min/L) required to achieve 2-, 3-, and 4-log(10) reductions in viral titers. In all water types, monochloramine disinfection was most effective for MNV, with 3-log(10) CT values at 5 °C ranging from 27 to 110. Monochloramine disinfection was least effective for HAdV2 and E11, depending on water type, with 3-log(10) CT values at 5 °C ranging from 1200 to 3300 and 810 to 2300, respectively. Overall, disinfection proceeded faster at 15 °C and pH 7 for all water types. Inactivation of the study viruses was significantly different between water types, but there was no indication that overall disinfection efficacy was enhanced or inhibited in any one water type. CT values for HAdV2 in two types of source water exceeded federal CT value recommendations in the US. The results of this study demonstrate that water quality impacts the inactivation of viruses and should be considered when developing chloramination plans. Published by Elsevier Ltd.

  11. Effects of Source Water Quality on Chlorine Inactivation of Adenovirus, Coxsackievirus, Echovirus, and Murine Norovirus ▿

    Science.gov (United States)

    Kahler, Amy M.; Cromeans, Theresa L.; Roberts, Jacquelin M.; Hill, Vincent R.

    2010-01-01

    More information is needed on the disinfection efficacy of chlorine for viruses in source water. In this study, chlorine disinfection efficacy was investigated for USEPA Contaminant Candidate List viruses coxsackievirus B5 (CVB5), echovirus 1 (E1), murine norovirus (MNV), and human adenovirus 2 (HAdV2) in one untreated groundwater source and two partially treated surface waters. Disinfection experiments using pH 7 and 8 source water were carried out in duplicate, using 0.2 and 1 mg/liter free chlorine at 5 and 15°C. The efficiency factor Hom (EFH) model was used to calculate disinfectant concentration × contact time (CT) values (mg·min/liter) required to achieve 2-, 3-, and 4-log10 reductions in viral titers. In all water types, chlorine disinfection was most effective for MNV, with 3-log10 CT values at 5°C ranging from ≤0.020 to 0.034. Chlorine disinfection was least effective for CVB5 in all water types, with 3-log10 CT values at 5°C ranging from 2.3 to 7.9. Overall, disinfection proceeded faster at 15°C and pH 7 for all water types. Inactivation of the study viruses was significantly different between water types, but no single source water had consistently different inactivation rates than another. CT values for CVB5 in one type of source water exceeded the recommended CT values set forth by USEPA's Guidance Manual for Compliance with the Filtration and Disinfection Requirements for Public Water Systems using Surface Water Sources. The results of this study demonstrate that water quality plays a substantial role in the inactivation of viruses and should be considered when developing chlorination plans. PMID:20562285

  12. Characterizing Enterovirus 71 and Coxsackievirus A16 virus-like particles production in insect cells.

    Science.gov (United States)

    Somasundaram, Balaji; Chang, Cindy; Fan, Yuan Y; Lim, Pei-Yin; Cardosa, Jane; Lua, Linda

    2016-02-15

    Enterovirus 71 (EV71) and Coxsackievirus A16 (CVA16) are two viruses commonly responsible for hand, foot and mouth disease (HFMD) in children. The lack of prophylactic or therapeutic measures against HFMD is a major public health concern. Insect cell-based EV71 and CVA16 virus-like particles (VLPs) are promising vaccine candidates against HFMD and are currently under development. In this paper, the influence of insect cell line, incubation temperature, and serial passaging effect and stability of budded virus (BV) stocks on EV71 and CVA16 VLP production was investigated. Enhanced EV71 and CVA16 VLP production was observed in Sf9 cells compared to High Five™ cells. Lowering the incubation temperature from the standard 27°C to 21°C increased the production of both VLPs in Sf9 cells. Serial passaging of CVA16 BV stocks in cell culture had a detrimental effect on the productivity of the structural proteins and the effect was observed with only 5 passages of BV stocks. A 2.7× higher production yield was achieved with EV71 compared to CVA16. High-resolution asymmetric flow field-flow fractionation couple with multi-angle light scattering (AF4-MALS) was used for the first time to characterize EV71 and CVA16 VLPs, displaying an average root mean square radius of 15±1nm and 15.3±5.8 nm respectively. This study highlights the need for different approaches in the design of production process to develop a bivalent EV71 and CVA16 vaccine. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Preocular Tear Film Tests in Acute Hemorrhagic Conjunctivitis Caused by Coxsackievirus A24 Variant

    Directory of Open Access Journals (Sweden)

    Gökhan Pekel

    2012-05-01

    Full Text Available Pur po se: Our aim was to evaluate the preocular tear film in patients who had acute hemorrhagic conjunctivitis (AHC caused by coxsackievirus A24 variant (CVA24v. Ma te ri als and Met hod: Seventy-six patients having AHC caused by CVA24v were enrolled in this study. An AHC outbreak was seen in Istanbul during August and September 2010 and lasted for four weeks. All the patients were seen at the first days of their disease period and none of them had received any treatment before. Conjunctival swab specimens were taken from the patients at their first visit. Tear film tests including Schirmer test, tear meniscus height measurement and tear break-up time (TBUT were done in all patients. Re sults: The mean age of the patients was 27.8 years (range: 7-68 years. Forty patients were male (53% and 36 patients were female (47%. In bilateral conjunctivitis cases, the mean Schirmer test result was 23.7±4.7 mm, mean TBUT was 15.1±2.4 seconds and the mean tear meniscus height was 0.37±0.06 mm. In unilateral conjunctivitis cases, the mean Schirmer test result was 24.4±3.6 mm, mean TBUT was 15.1±2.3 seconds and the mean tear meniscus height was 0.38±0.07 mm in the diseased eyes. Dis cus si on: The results of the routine preocular tear film tests did not differ in AHC caused by CVA24v when compared with healthy eyes. (Turk J Ophthalmol 2012; 42: 186-9

  14. Structural analysis of coxsackievirus A7 reveals conformational changes associated with uncoating.

    Science.gov (United States)

    Seitsonen, Jani J T; Shakeel, Shabih; Susi, Petri; Pandurangan, Arun P; Sinkovits, Robert S; Hyvönen, Heini; Laurinmäki, Pasi; Ylä-Pelto, Jani; Topf, Maya; Hyypiä, Timo; Butcher, Sarah J

    2012-07-01

    Coxsackievirus A7 (CAV7) is a rarely detected and poorly characterized serotype of the Enterovirus species Human enterovirus A (HEV-A) within the Picornaviridae family. The CAV7-USSR strain has caused polio-like epidemics and was originally thought to represent the fourth poliovirus type, but later evidence linked this strain to the CAV7-Parker prototype. Another isolate, CAV7-275/58, was also serologically similar to Parker but was noninfectious in a mouse model. Sequencing of the genomic region encoding the capsid proteins of the USSR and 275/58 strains and subsequent comparison with the corresponding amino acid sequences of the Parker strain revealed that the Parker and USSR strains are nearly identical, while the 275/58 strain is more distant. Using electron cryomicroscopy and three-dimensional image reconstruction, the structures of the CAV7-USSR virion and empty capsid were resolved to 8.2-Å and 6.1-Å resolutions, respectively. This is one of the first detailed structural analyses of the HEV-A species. Using homology modeling, reconstruction segmentation, and flexible fitting, we constructed a pseudoatomic T = 1 (pseudo T = 3) model incorporating the three major capsid proteins (VP1 to VP3), addressed the conformational changes of the capsid and its constituent viral proteins occurring during RNA release, and mapped the capsid proteins' variable regions to the structure. During uncoating, VP4 and RNA are released analogously to poliovirus 1, the interfaces of VP2 and VP3 are rearranged, and VP1 rotates. Variable regions in the capsid proteins were predicted to map mainly to the surface of VP1 and are thus likely to affect the tropism and pathogenicity of CAV7.

  15. Structures of coxsackievirus, rhinovirus, and poliovirus polymerase elongation complexes solved by engineering RNA mediated crystal contacts.

    Directory of Open Access Journals (Sweden)

    Peng Gong

    Full Text Available RNA-dependent RNA polymerases play a vital role in the growth of RNA viruses where they are responsible for genome replication, but do so with rather low fidelity that allows for the rapid adaptation to different host cell environments. These polymerases are also a target for antiviral drug development. However, both drug discovery efforts and our understanding of fidelity determinants have been hampered by a lack of detailed structural information about functional polymerase-RNA complexes and the structural changes that take place during the elongation cycle. Many of the molecular details associated with nucleotide selection and catalysis were revealed in our recent structure of the poliovirus polymerase-RNA complex solved by first purifying and then crystallizing stalled elongation complexes. In the work presented here we extend that basic methodology to determine nine new structures of poliovirus, coxsackievirus, and rhinovirus elongation complexes at 2.2-2.9 Å resolution. The structures highlight conserved features of picornaviral polymerases and the interactions they make with the template and product RNA strands, including a tight grip on eight basepairs of the nascent duplex, a fully pre-positioned templating nucleotide, and a conserved binding pocket for the +2 position template strand base. At the active site we see a pre-bound magnesium ion and there is conservation of a non-standard backbone conformation of the template strand in an interaction that may aid in triggering RNA translocation via contact with the conserved polymerase motif B. Moreover, by engineering plasticity into RNA-RNA contacts, we obtain crystal forms that are capable of multiple rounds of in-crystal catalysis and RNA translocation. Together, the data demonstrate that engineering flexible RNA contacts to promote crystal lattice formation is a versatile platform that can be used to solve the structures of viral RdRP elongation complexes and their catalytic cycle

  16. Whole genome and transcriptome sequencing of a B3 thymoma.

    Directory of Open Access Journals (Sweden)

    Iacopo Petrini

    Full Text Available Molecular pathology of thymomas is poorly understood. Genomic aberrations are frequently identified in tumors but no extensive sequencing has been reported in thymomas. Here we present the first comprehensive view of a B3 thymoma at whole genome and transcriptome levels. A 55-year-old Caucasian female underwent complete resection of a stage IVA B3 thymoma. RNA and DNA were extracted from a snap frozen tumor sample with a fraction of cancer cells over 80%. We performed array comparative genomic hybridization using Agilent platform, transcriptome sequencing using HiSeq 2000 (Illumina and whole genome sequencing using Complete Genomics Inc platform. Whole genome sequencing determined, in tumor and normal, the sequence of both alleles in more than 95% of the reference genome (NCBI Build 37. Copy number (CN aberrations were comparable with those previously described for B3 thymomas, with CN gain of chromosome 1q, 5, 7 and X and CN loss of 3p, 6, 11q42.2-qter and q13. One translocation t(11;X was identified by whole genome sequencing and confirmed by PCR and Sanger sequencing. Ten single nucleotide variations (SNVs and 2 insertion/deletions (INDELs were identified; these mutations resulted in non-synonymous amino acid changes or affected splicing sites. The lack of common cancer-associated mutations in this patient suggests that thymomas may evolve through mechanisms distinctive from other tumor types, and supports the rationale for additional high-throughput sequencing screens to better understand the somatic genetic architecture of thymoma.

  17. Classical and quantum electrodynamics and the B(3) field

    CERN Document Server

    Evans, Myron W

    2001-01-01

    It is well known that classical electrodynamics is riddled with internal inconsistencies springing from the fact that it is a linear, Abelian theory in which the potentials are unphysical. This volume offers a self-consistent hypothesis which removes some of these problems, as well as builds a framework on which linear and nonlinear optics are treated as a non-Abelian gauge field theory based on the emergence of the fundamental magnetizing field of radiation, the B(3) field. Contents: Interaction of Electromagnetic Radiation with One Fermion; The Field Equations of Classical O (3) b Electrodyn

  18. Data of evolutionary structure change: 1B3JA-1TVBD [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B3JA-1TVBD 1B3J 1TVB A D EPHSLRYNLTVLSWDGSVQSGFLTEVHLDGQPFLRCDRQ----KCRAKPQ---GQW...LAMNVR------NFLKEDAMADCLQELRRYLKSGVVL-RRTVPPMVNVTRSEASEGNITVTCRASGFYPWNITLSWRQDGVSLSHDTQQWGDVLPDGNGT...WIEQEGPEYW------DGETRKVKAHSQTHRVDLGTLRGYYNQSEAGSHTVQRMYGCDVGSDWRFLRGYHQYAYDGKDYIALKEDLRSWTA-ADMAAQTT... 1TVB D 1TVBD 1B3JA SGVVL-RRTVP -

  19. Data of evolutionary structure change: 1B3JA-1TVHA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B3JA-1TVHA 1B3J 1TVH A A EPHSLRYNLTVLSWDGSVQSGFLTEVHLDGQPFLRCDRQ----KCRAKPQ---GQW...LAMNVR------NFLKEDAMADCLQELRRYLKSGVVL-RRTVPPMVNVTRSEASEGNITVTCRASGFYPWNITLSWRQDGVSLSHDTQQWGDVLPDGNGT...WIEQEGPEYW------DGETRKVKAHSQTHRVDLGTLRGYYNQSEAGSHTVQRMYGCDVGSDWRFLRGYHQYAYDGKDYIALKEDLRSWTAAD-MAAQTT... 1TVH A 1TVHA 1B3JA SGVVL-RRTVP -

  20. Radiative decay of HeLi+(b3∑+)

    Science.gov (United States)

    Zámečníková, Martina; Soldán, Pavel

    2018-01-01

    Radiative lifetimes of the ro-vibrational bound states of HeLi+ (b3∑+) are calculated quantum-mechanically when both bound-bound and bound-free processes are taken into account. The calculations are restricted to the initial states with low rotational quantum numbers. For the rotationless molecular ion, the shortest lifetime is 1.30 ×10-6 s of the ground vibrational state. With increasing vibration excitations the radiative lifetimes slightly increase, but keep below 10-5 s for the next 17 vibrational states, then they start to increase more rapidly up to 2.41 ×10-2 s for the highest vibrational state. The radiative lifetimes also tend to slightly prolong with increasing rotational excitations but stay on the same magnitude for the low rotational quantum numbers.

  1. Infection

    Science.gov (United States)

    2010-09-01

    whether BMPs maintain their osteoinductive capability in infected human wounds. The authors are aware of only one series describing the use of BMP in an...et al. Osteogenic protein-1 induces bone formation in the presence of bacterial infection in a rat intramuscular osteoinduction model. J Orthop Trauma

  2. B3GNT3 Expression Is a Novel Marker Correlated with Pelvic Lymph Node Metastasis and Poor Clinical Outcome in Early-Stage Cervical Cancer

    Science.gov (United States)

    Niu, Chunhao; Song, Libing; Zhang, Yanna

    2015-01-01

    Background The β1,3-N-acetylglucosaminyltransferase-3 gene (B3GNT3) encodes a member of the B3GNT family that functions as the backbone structure of dimeric sialyl-Lewis A and is involved in L-selectin ligand biosynthesis, lymphocyte homing and lymphocyte trafficking. B3GNT3 has been implicated as an important element in the development of certain cancers. However, the characteristics of B3GNT3 in the development and progression of cancer remain largely unknown. Thus, our study aimed to investigate the expression pattern and the prognostic value of B3GNT3 in patients with early-stage cervical cancer. Methods The mRNA and protein levels of B3GNT3 expression were examined in eight cervical cancer cell lines and ten paired cervical cancer tumors, using real-time PCR and western blotting, respectively. Immunohistochemistry (IHC) was used to analyze B3GNT3 protein expression in paraffin-embedded tissues from 196 early-stage cervical cancer patients. Statistical analyses were applied to evaluate the association between B3GNT3 expression scores and clinical parameters, as well as patient survival. Results B3GNT3 expression was significantly upregulated in cervical cancer cell lines and lesions compared with normal cells and adjacent noncancerous cervical tissues. In the 196 cases of tested early-stage cervical cancer samples, the B3GNT3 protein level was positively correlated with high risk TYPES of human papillomavirus (HPV) infection (P = 0.026), FIGO stage (P cervical cancer patients. Conclusions Our study demonstrated that elevated B3GNT3 expression is associated with pelvic lymph node metastasis and poor outcome in early-stage cervical cancer patients. B3GNT3 may be a novel prognostic marker and therapeutic target for the treatment of cervical cancer. PMID:26709519

  3. 16 CFR Appendix B3 to Part 305 - Chest Freezers and All Other Freezers

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Chest Freezers and All Other Freezers B3 Appendix B3 to Part 305 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER SPECIFIC ACTS OF...) Pt. 305, App. B3 Appendix B3 to Part 305—Chest Freezers and All Other Freezers Range Information...

  4. Vaginal Lactobacillus gasseri CMUL57 can inhibit herpes simplex type 2 but not Coxsackievirus B4E2.

    Science.gov (United States)

    Kassaa, Imad Al; Hober, Didier; Hamze, Monzer; Caloone, Delphine; Dewilde, Anny; Chihib, Nour-Eddine; Drider, Djamel

    2015-06-01

    This study aimed at demonstrating the antiviral activity of Lactobacillus gasseri CMUL57 (L. gasseri CMUL57), L. acidophilus CMUL67 and L. plantarum CMUL140 against herpes simplex type 2 (HSV-2) and Coxsackievirus B4E2 (CVB4E2), which are enveloped and naked viruses, respectively. These lactobacilli were non-cytotoxic and were able to reduce the cytopathic effect induced by HSV-2 in Vero cell monolayers. However, lactobacilli were not active against CVB4E2. Tested lactobacilli displayed anti-HSV-2 activity when they were co-incubated with the virus prior to inoculating the mixture to Vero cell monolayers. The detection of HSV-2 DNA by PCR in pellets of bacteria/virus mixtures let us to hypothesize that anti-HSV-2 activity of lactobacilli resulted from the viruses' entrapment. This study showed the capabilities of vaginal lactobacilli to inhibit enveloped viruses such as HSV-2.

  5. Structural and functional analysis of coxsackievirus A9 integrin αvβ6 binding and uncoating.

    Science.gov (United States)

    Shakeel, Shabih; Seitsonen, Jani J T; Kajander, Tommi; Laurinmäki, Pasi; Hyypiä, Timo; Susi, Petri; Butcher, Sarah J

    2013-04-01

    Coxsackievirus A9 (CVA9) is an important pathogen of the Picornaviridae family. It utilizes cellular receptors from the integrin αv family for binding to its host cells prior to entry and genome release. Among the integrins tested, it has the highest affinity for αvβ6, which recognizes the arginine-glycine-aspartic acid (RGD) loop present on the C terminus of viral capsid protein, VP1. As the atomic model of CVA9 lacks the RGD loop, we used surface plasmon resonance, electron cryo-microscopy, and image reconstruction to characterize the capsid-integrin interactions and the conformational changes on genome release. We show that the integrin binds to the capsid with nanomolar affinity and that the binding of integrin to the virion does not induce uncoating, thereby implying that further steps are required for release of the genome. Electron cryo-tomography and single-particle image reconstruction revealed variation in the number and conformation of the integrins bound to the capsid, with the integrin footprint mapping close to the predicted site for the exposed RGD loop on VP1. Comparison of empty and RNA-filled capsid reconstructions showed that the capsid undergoes conformational changes when the genome is released, so that the RNA-capsid interactions in the N termini of VP1 and VP4 are lost, VP4 is removed, and the capsid becomes more porous, as has been reported for poliovirus 1, human rhinovirus 2, enterovirus 71, and coxsackievirus A7. These results are important for understanding the structural basis of integrin binding to CVA9 and the molecular events leading to CVA9 cell entry and uncoating.

  6. MicroRNA-19b-3p Modulates Japanese Encephalitis Virus-Mediated Inflammation via Targeting RNF11.

    Science.gov (United States)

    Ashraf, Usama; Zhu, Bibo; Ye, Jing; Wan, Shengfeng; Nie, Yanru; Chen, Zheng; Cui, Min; Wang, Chong; Duan, Xiaodong; Zhang, Hao; Chen, Huanchun; Cao, Shengbo

    2016-05-01

    Japanese encephalitis virus (JEV) can invade the central nervous system and consequently induce neuroinflammation, which is characterized by profound neuronal cell damage accompanied by astrogliosis and microgliosis. Albeit microRNAs (miRNAs) have emerged as major regulatory noncoding RNAs with profound effects on inflammatory response, it is unknown how astrocytic miRNAs regulate JEV-induced inflammation. Here, we found the involvement of miR-19b-3p in regulating the JEV-induced inflammatory responsein vitroandin vivo The data demonstrated that miR-19b-3p is upregulated in cultured cells and mouse brain tissues during JEV infection. Overexpression of miR-19b-3p led to increased production of inflammatory cytokines, including tumor necrosis factor alpha, interleukin-6, interleukin-1β, and chemokine (C-C motif) ligand 5, after JEV infection, whereas knockdown of miR-19b-3p had completely opposite effects. Mechanistically, miR-19b-3p modulated the JEV-induced inflammatory response via targeting ring finger protein 11, a negative regulator of nuclear factor kappa B signaling. We also found that inhibition of ring finger protein 11 by miR-19b-3p resulted in accumulation of nuclear factor kappa B in the nucleus, which in turn led to higher production of inflammatory cytokines.In vivosilencing of miR-19b-3p by a specific antagomir reinvigorates the expression level of RNF11, which in turn reduces the production of inflammatory cytokines, abrogates gliosis and neuronal cell death, and eventually improves the survival rate in the mouse model. Collectively, our results demonstrate that miR-19b-3p positively regulates the JEV-induced inflammatory response. Thus, miR-19b-3p targeting may constitute a thought-provoking approach to rein in JEV-induced inflammation. Japanese encephalitis virus (JEV) is one of the major causes of acute encephalitis in humans worldwide. The pathological features of JEV-induced encephalitis are inflammatory reactions and neurological diseases

  7. Comparing Enterovirus 71 with Coxsackievirus A16 by analyzing nucleotide sequences and antigenicity of recombinant proteins of VP1s and VP4s

    Directory of Open Access Journals (Sweden)

    Sun Yu

    2011-11-01

    Full Text Available Abstract Background Enterovirus 71 (EV71 and Coxsackievirus A16 (CA16 are two major etiological agents of Hand, Foot and Mouth Disease (HFMD. EV71 is associated with severe cases but not CA16. The mechanisms contributed to the different pathogenesis of these two viruses are unknown. VP1 and VP4 are two major structural proteins of these viruses, and should be paid close attention to. Results The sequences of vp1s from 14 EV71 and 14 CA16, and vp4s from 10 EV71 and 1 CA16 isolated in this study during 2007 to 2009 HFMD seasons were analyzed together with the corresponding sequences available in GenBank using DNAStar and MEGA 4.0. Phylogenetic analysis of complete vp1s or vp4s showed that EV71 isolated in Beijing belonged to C4 and CA16 belonged to lineage B2 (lineage C. VP1s and VP4s from 4 strains of viruses expressed in E. coli BL21 cells were used to detect IgM and IgG in human sera by Western Blot. The detection of IgM against VP1s of EV71 and CA16 showed consistent results with current infection, while none of the sera were positive against VP4s of EV71 and CA16. There was significant difference in the positive rates between EV71 VP1 and CA16 VP1 (χ2 = 5.02, P 2 = 15.30, P 2 = 26.47, P 2 = 16.78, P Conclusions EV71 and CA16 were highly diverse in the nucleotide sequences of vp1s and vp4s. The sera positive rates of VP1 and VP4 of EV71 were lower than those of CA16 respectively, which suggested a less exposure rate to EV71 than CA16 in Beijing population. Human serum antibodies detected by Western blot using VP1s and VP4s as antigen indicated that the immunological reaction to VP1 and VP4 of both EV71 and CA16 was different.

  8. Infection

    African Journals Online (AJOL)

    from the neonatal period to school age.' In Saudi Arabia, the rate of 5.3 per cent was reported' while in Nigeria,. Okafor et a1,7 found the prevalence rate .... the multiplication of the organisms in the urine, resulting in lalse diagnosis of urinary tract infection. This over-diagnosis ofl ITI may account for the high prevalence rate ...

  9. Infection,

    Science.gov (United States)

    1980-10-16

    lost by diuresis in early convalescence (1). Severe retention of body water, especially during central nervous system infection, has now been widely...adrenocortical production of glucocorticoid and ketosteroid hormones often declines into a subnormal range. The labile pool of body nitrogen is...may not become apparent until early convalescence when postfebrile diuresis causes excessive fluid to be excreted. (3) Protein requirements ’- Despite

  10. Data of evolutionary structure change: 1B3IA-2AANA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B3IA-2AANA 1B3I 2AAN A A ASVQIKMGTDKYAPLYEPKALSISAGDTVE--FVMN-KVGPHNVIFDKVPAGESAP...GPVTIEIGSKGEELAFDKTELTVSAGQTVTIRFKNNSAVQQHNWILV-KGGEAEAANIANAGLSAGPAANYLPADKSNIIAESPLANGNETVEVTFTAPAAGTYLYICTV...2AAN A 2AANA VEVTFTAPAAGTYL...2AAN A 2AANA NWILV-KGGEA

  11. Data of evolutionary structure change: 1B3JA-1TVHD [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B3JA-1TVHD 1B3J 1TVH A D EPHSLRYNLTVLSWDGSVQSGFLTEVHLDGQPFLRCDRQ----KCRAKPQ---GQW...LAMNVR------NFLKEDAMADCLQELRRYLKS-GVVLRRTVPPMVNVTRSEASEGNITVTCRASGFYPWNITLSWRQDGVSLSHDTQQWGDVLPDGNGT...WIEQEGPEYW------DGETRKVKAHSQTHRVDLGTLRGYYNQSEAGSHTVQRMYGCDVGSDWRFLRGYHQYAYDGKDYIALKEDLRSWTA-ADMAAQTT... 1TVH D 1TVHD 1TVH D 1TVHD

  12. Data of evolutionary structure change: 1B3JA-1TVBA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B3JA-1TVBA 1B3J 1TVB A A EPHSLRYNLTVLSWDGSVQSGFLTEVHLDGQPFLRCDRQ----KCRAK--------...LAMNVR------NFLKEDAMADCLQELRRYLKS-GVVLRRTVPPMVNVTRSEASEGNITVTCRASGFYPWNITLSWRQDGVSLSHDTQQWGDVLPDGNGT...GPEYW-----------DGETRKVKAHSQTHRVDLGTLRGYYNQSEAGSHTVQRMYGCDVGSDWRFLRGYHQYAYDGKDYIALKEDLRSWTAAD-MAAQTT... 1TVB A 1TVBA 1TVB A 1TVBA

  13. Up-regulated ephrinB3/EphB3 expression in intractable temporal lobe epilepsy patients and pilocarpine induced experimental epilepsy rat model.

    Science.gov (United States)

    Huang, Hao; Li, Ruohan; Yuan, Jinxian; Zhou, Xin; Liu, Xi; Ou, Shu; Xu, Tao; Chen, Yangmei

    2016-05-15

    EphB family receptor tyrosine kinases, in cooperation with cell surface-bound ephrinB ligands, play a critical role in maintenance of dendritic spine morphogenesis, axons guidance, synaptogenesis, synaptic reorganization and plasticity in the central nervous system (CNS). However, the expression pattern of ephrinB/EphB in intractable temporal lobe epilepsy (TLE) and the underlying molecular mechanisms during epileptogenesis remain poorly understood. Here we investigated the expression pattern and cellular distribution of ephrinB/EphB in intractable TLE patients and lithium chloride-pilocarpine induced TLE rats using real-time quantitative polymerase chain reaction (RT-qPCR), immunohistochemistry, double-labeled immunofluorescence and Western blot analysis. Compared to control groups, ephrinB3 and EphB3 mRNA expression were significantly up-regulated in intractable TLE patients and TLE rats, while the mRNA expression trend of ephrinB1/2 and EphB1/2/4/6 in intractable TLE patients and TLE rats were inconsistent. Western blot analysis and semi-quantitative immunohistochemistry confirmed that ephrinB3 and EphB3 protein level were up-regulated in intractable TLE patients and TLE rats. At the same time, double-labeled immunofluorescence indicate that ephrinB3 was expressed mainly in the cytoplasm and protrusions of glia and neurons, while EphB3 was expressed mainly in the cytoplasm of neurons. Taken together, up-regulated expression of ephrinB3/EphB3 in intractable TLE patients and experimental TLE rats suggested that ephrinB3/EphB3 might be involved in the pathogenesis of TLE. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. 22 CFR 9b.3 - Press correspondents employed by foreign media organizations.

    Science.gov (United States)

    2010-04-01

    ...) Social Security or passport number; (8) Marital status; (9) Spouse name; (10) Office address and... organizations. 9b.3 Section 9b.3 Foreign Relations DEPARTMENT OF STATE GENERAL REGULATIONS GOVERNING DEPARTMENT OF STATE PRESS BUILDING PASSES § 9b.3 Press correspondents employed by foreign media organizations...

  15. Data of evolutionary structure change: 1BS7B-3CMDB [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1BS7B-3CMDB 1BS7 3CMD B B SVLQ---VLHIPDERLRKVAKPVE-EVNAEIQRIVDDMF...ine> GLU CA 210 3CMD B 3CMD...ne>GLY CA 251 ILE CA 245 3CMD... B 3CMDB ILSHSVQDACL... 296 LEU CA 264 VAL CA 310 3CMD

  16. Data of evolutionary structure change: 1BS5B-3CMDB [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1BS5B-3CMDB 1BS5 3CMD B B SVLQ---VLHIPDERLRKVAKPVE-EVNAEIQRIVDDMF...ne> GLU CA 209 3CMD B 3CMD...e>GLY CA 253 ILE CA 241 3CMD... B 3CMDB ILSHSVQDACL ...> ARG CA 309 ALA CA 299 LEU CA 263 3CMD

  17. Atypical Hand, Foot, and Mouth Disease Caused by Coxsackievirus A6 in Denmark

    DEFF Research Database (Denmark)

    Horsten, Hans-Henrik; Kemp, Michael; Fischer, Thea K

    2018-01-01

    , vasculitis, syphilis, dermatophytid, erythema multiforme and Stevens-Johnson syndrome. Three adults and 3 children required hospitalization due to extensive skin involvement and fever. All reported patients had laboratory confirmed enterovirus infection. This study demonstrated an upsurge in atypical HFMD...

  18. The Epidemiological Study of Coxsackievirus A6 revealing Hand, Foot and Mouth Disease Epidemic patterns in Guangdong, China.

    Science.gov (United States)

    Zeng, Hanri; Lu, Jing; Zheng, Huanying; Yi, Lina; Guo, Xue; Liu, Leng; Rutherford, Shannon; Sun, Limei; Tan, Xiaohua; Li, Hui; Ke, Changwen; Lin, Jinyan

    2015-05-21

    Enterovirus A71 (EVA71) and Coxsackievirus A16 (CVA16) are regarded as the two major causative pathogens in hand, foot and mouth disease (HFMD) epidemics. However, CVA6, previously largely ignored, became the predominant pathogen in China in 2013. In this study, we describe the epidemiological trends of CVA6 during the annual HFMD outbreaks from 2008 to 2013 in Guangdong, China. The study results show that CVA6 has been one of three major causative agents of HFMD epidemics since 2009. The periodic rotation and dominance of the three pathogens, EVA71, CVA16 and CVA6, may have contributed to the continuously increasing HFMD epidemics. Moreover, phylogenetic analysis of the VP1 gene shows that major circulating CVA6 strains collected from 2009 to 2013 are distinct from the earlier strains collected before 2009. In conclusion, the discovery from this research investigating epidemiological trends of CVA6 from 2008 to 2013 explains the possible pattern of the continuous HFMD epidemic in China. The etiological change pattern also highlights the need for improvement for pathogen surveillance and vaccine strategies for HFMD control in China.

  19. Two Genotypes of Coxsackievirus A2 Associated with Hand, Foot, and Mouth Disease Circulating in China since 2008.

    Science.gov (United States)

    Yang, Qian; Zhang, Yong; Yan, Dongmei; Zhu, Shuangli; Wang, Dongyan; Ji, Tianjiao; Li, Xiaolei; Song, Yang; Gu, Xinrui; Xu, Wenbo

    2016-01-01

    Coxsackievirus A2 (CV-A2) has been frequently detected and commonly associated with hand, foot, and mouth disease (HFMD) in China since 2008. However, limited sequences of CV-A2 are currently available. As a result, we have been focusing on the genetic characteristics of CV-A2 in the mainland of China during 2008-2015 based on national HFMD surveillance. In this study, 20 CV-A2 strains were isolated and phylogenetic analyses of the VP1 sequences were performed. Full-length genome sequences of two representative CV-A2 isolates were acquired and similarity plot and bootscanning analyses were performed. The phylogenetic dendrogram indicated that all CV-A2 strains could be divided into four genotypes (Genotypes A-D). The CV-A2 prototype strain (Fleetwood) was the sole member of genotype A. From 2008 to 2015, the CV-A2 strains isolated in China dispersed into two different genotypes (B and D). And the genotype D became the dominant circulating strains in China. Strains isolated in Russia and India from 2005 to 2011 converged into genotype C. Intertypic recombination occurred between the Chinese CV-A2 strains and other enterovirus-A donor sequences. This result reconfirmed that recombination is a common phenomenon among enteroviruses. This study helps expand the numbers of whole virus genome sequence and entire VP1 sequence of CV-A2 in the GenBank database for further researcher.

  20. Etiology of acute conjunctivitis due to coxsackievirus A24 variant, human adenovirus, herpes simplex virus, and Chlamydia in Beijing, China.

    Science.gov (United States)

    Li, Jie; Yang, Yongsheng; Lin, Changying; Li, Weihong; Yang, Yang; Zhang, Yong; Jia, Lei; Li, Xitai; Chen, Lijuan; Wang, Quanyi

    2014-01-01

    Acute conjunctivitis is a common disease associated with high morbidity and economic burden. To clarify the etiological characteristics of acute conjunctivitis in Beijing, surveillance of acute conjunctivitis was conducted from July to October during 2007-2012 by collecting eye swabs from patients treated at surveillance hospitals affiliated with a surveillance program of 18 districts Center for Disease Prevention and Control in Beijing. Coxsackievirus A24 variant (CA24v), enterovirus 70 (EV70), human adenovirus (HAdV), herpes simplex virus (HSV), and chlamydia were identified by PCR. Phylogenetic analysis of the VP1 region of CA24v was conducted. Comparisons of proportions and statistical significance were performed using the chi-square test. HAdV was found to be the most prevalent pathogen, followed by CA24v, chlamydia, and HSV. Significant differences in the symptoms of ocular pain, photophobia, and epiphora were identified among the 4 agents. The prevalence of HAdV- and CA24v-mediated conjunctivitis peaked in July or August and September or October, respectively. Nucleotide sequences of the VP1 regions among the isolated CA24v strains shared 92.8%-100% homology. In conclusion, HAdV followed by CA24v, chlamydia, and HSV were the most common causative agents of acute conjunctivitis in Beijing. Comprehensive, continuous surveillance and advanced laboratory techniques are needed for further studies.

  1. Infezioni del Sistema Nervoso centrale da Coxsackievirus ed Echovirus - Risultati di 5 anni di osservazione nel territorio Piemontese

    Directory of Open Access Journals (Sweden)

    Pietro Giorgio Pistono

    2006-06-01

    Full Text Available The report is an overview of enterovirus epidemiology in Piemonte during a 5-year period from 2000 to 2004 with an investigative protocol recording epidemiologic, clinical, and laboratory data. A total of 1232 clinical cerebrospinal fluid (CSF were collected from patients having clinical manifestations of aseptic meningitis (AAM or encephalitis. Enterovirus detection was performed by isolation on cell culture (MRC5, BGM, Hep 2 e VERO according to World Health Organization recommended protocols, and molecular methods based on reverse transcription (RT-PCR. Isolates were identificated by indirect immunofluorescence staining with commercially available monoclonal antibodies and serotype identification was performed by seroneutralization (Lim and Benyesh-Melnick of the cytopathic effect using pools of specific antisera. Twenty-six patients (2.1%, 15 males and 21 females, were found positive for Enterovirus with at least one of the test used.The average age was 23 (6-43.A total of 26 Non-Polio Enterovirus (NPEV strains were isolated (11 Echovirus, 5 Coxsackievirus, 10 not identified; the dominant strain of the outbreak was identified as a human Echovirus 6 (4 cases followed by Echo 31 (3, Coxsackie B5 (3, Echo 17 (2 Echo 9, 11, (1 and Coxsackie A16 (1. The yearly distribution of positive cases was homogeneous; a seasonal variation was noted with a predominance in summer-autumn; the higher transmission period starts in May and peaks in June-July; sporadic cases were also observed in winter and spring.

  2. Impact of Coxsackievirus A6 emergence on hand, foot, and mouth disease epidemic in Osaka City, Japan.

    Science.gov (United States)

    Kanbayashi, Daiki; Kaida, Atsushi; Yamamoto, Seiji P; Hirai, Yuki; Kubo, Hideyuki; Fujimori, Ryoko; Hakui, Noritaka; Hirokawa, Hidetetsu; Iritani, Nobuhiro

    2017-12-01

    Hand, foot, and mouth disease (HFMD) is an acute febrile illness characterized by fever; sore throat; and vesicular eruptions on the hands, feet, and oral mucosa. Until 2010, HFMD was predominantly associated with enterovirus (EV) A71 and coxsackievirus (CV) A16 in Japan. In 2011, CV-A6 emerged as a primary causative agent, causing the largest HFMD epidemic in Japan since 1981. Since then, CV-A6 has caused large HFMD epidemics every 2 years. The phylogenetic analysis of complete Viral Protein 1 (VP1) sequences revealed that most CV-A6 strains detected from 2011 to 2015 in Osaka City were classified into a different clade compared with CV-A6 strains detected from 1999 until 2009. The majority of CV-A6 strains detected in 2011 and most CV-A6 strains detected from 2013 to 2015 were mainly divided into two distinct genetic groups. Each epidemic strain carried unique amino acid substitutions in the presumed DE, EF, and GH loops of the VP1 protein that is exposed on the surface of the virion. There is a possibility that the appearance of substitutions on the surface of the virion and an accumulation of a susceptible population are significant factors in recent HFMD epidemics. © 2017 Wiley Periodicals, Inc.

  3. Activation of macrophages by an exopolysaccharide isolated from Antarctic Psychrobacter sp. B-3

    Science.gov (United States)

    Yu, Leiye; Sun, Guojie; Wei, Jingfang; Wang, Yingze; Du, Chao; Li, Jiang

    2016-09-01

    An exopolysaccharide (EPS) was isolated and purified from an Antarctic psychrophilic bacterium B-3, identified as Psychrobacter sp., and the activation of RAW264.7 cells by B-3 EPS was investigated. The results show that B-3 EPS, over a certain concentration range, promoted cell viability, nitric oxide production, tumor necrosis factor (TNF)α secretion, and phagocytic ability. Furthermore, TAK-242, an inhibitor of the toll-like receptor 4 (TLR4) significantly reduced nitric oxide production by these cells after stimulation with B-3 EPS. Moreover, B-3 EPS induced p65 phosphorylation and IκBα degradation in these cells. In conclusion, B-3 EPS might have activated RAW264.7 cells by combining with TLR4 on cell surface and triggering activation of NF-κB signaling pathways, implying that this EPS could activate macrophages and regulate initial immune response.

  4. Singleton reactors in the diagnosis of swine vesicular disease: the role of coxsackievirus B5.

    Science.gov (United States)

    Moonen, P; Van Poelwijk, F; Moormann, R; Dekker, A

    2000-10-01

    Swine vesicular disease virus (SVDV) and Coxsackie B5 virus (CVB5) are closely related viruses that can infect swine and man and give rise to cross-reacting serum antibodies. It is, therefore, possible that SVD antibodies found in serologic screenings of pigs are induced by CVB5. Single positive animals found in screening programmes are generally referred to as singleton reactors (SR). To determine whether SR in SVDV screenings are induced by CVB5 infection, virus neutralisation tests (VNTs) and radioimmunoprecipitation assays (RIPA) were carried out on sera of SR, sera of pigs experimentally infected with SVDV, and sera from pigs vaccinated with CVB5 isolates. The SR sera reacted repeatedly positive in the SVDV UKG/27/72 VNT, but reacted differently in three other VNTs (SVDV NET/1/92, CVB5A, and CVB5B). The VNT titres obtained with the SR sera revealed a correlation between both SVDV strains, and also between both CVB5 stains, but no correlation was found between SVD and CVB5 VNT titres. Sera of experimentally infected (SVDV) or vaccinated (CVB5) pigs showed titres in all four neutralisation tests. In the RIPA, the reaction patterns of the SR sera varied considerably with all four antigens used, in contrast to sera from pigs experimentally infected with SVDV that reacted with all antigens used, and sera from pigs vaccinated with CVB5 that reacted only with CVB5 antigens. The results presented in this paper show that neither CVB5 nor SVDV infections are the only cause of the SR phenomenon. Testing for CVB5 specific antibodies can reduce the number of SR sera in the serodiagnosis of SVDV.

  5. Tapered fluted titanium stems in the management of Vancouver B2 and B3 periprosthetic femoral fractures.

    Science.gov (United States)

    Munro, Jacob T; Garbuz, Donald S; Masri, Bassam A; Duncan, Clive P

    2014-02-01

    Surgeons have several implant choices when managing Vancouver B2 and B3 periprosthetic fractures about the hip. Few long-term studies have reported outcomes for tapered fluted titanium stems. We determined (1) survival, with femoral revision as the end point, of distal taper stems in the treatment of Vancouver B2 and B3 periprosthetic fractures at our institution, (2) radiographic outcomes, and (3) quality of life and hip function after revision. Of the 200 patients with Vancouver B2 or B3 periprosthetic fractures treated with femoral revision between February 2000 and February 2010, 55 (38 B2, 17 B3) were treated with modular tapered titanium stems. Of the surviving 47 patients, one was lost to followup, leaving 46 (30 B2, 16 B3) available for review at a mean of 54 months (range, 24-143 months). Initial indications for using these implants were treatment of periprosthetic fractures where less than 4 cm of diaphyseal fit was available, but this evolved during the study period to all fractures unless no diaphysis remained, in which case complex revision techniques were used. Radiographs were assessed to establish fracture healing, stem subsidence, and bone stock restoration. Quality of life and hip function were assessed using WOMAC, Oxford, SF-12, UCLA activity level, and satisfaction scores. Two femoral stems were revised: one subsided and was revised at 12 months; the other had deep infection and underwent two-stage revision at 49 months. Radiographic review showed one nonunion, with maintenance or improvement of bone stock in 89% of patients. Subsidence occurred in 24%. Mean Oxford score was 76 of 100, WOMAC function and pain scores were 75 and 82 of 100, satisfaction score was 91 of 100, and SF-12 mental and physical scores were 53 and 40 of 100. We report encouraging short-term results in terms of survival of distal taper stems in the treatment of B2 and B3 periprosthetic fractures. Although subsidence was frequent, most migrated less than 3 mm without

  6. Coxsackievirus cloverleaf RNA containing a 5' triphosphate triggers an antiviral response via RIG-I activation

    NARCIS (Netherlands)

    Feng, Qian; Langereis, Martijn A; Olagnier, David; Chiang, Cindy; van de Winkel, Roel; van Essen, Peter; Zoll, Jan; Hiscott, John; van Kuppeveld, Frank J M

    2014-01-01

    Upon viral infections, pattern recognition receptors (PRRs) recognize pathogen-associated molecular patterns (PAMPs) and stimulate an antiviral state associated with the production of type I interferons (IFNs) and inflammatory markers. Type I IFNs play crucial roles in innate antiviral responses by

  7. Complete Genome Sequence of a Recombinant Coxsackievirus B4 from a Patient with a Fatal Case of Hand, Foot, and Mouth Disease in Guangxi, China

    OpenAIRE

    Hu, Y. F.; Du, J.; Zhao, R.; Xue, Y.; Yang, Fan; Jin, Qi

    2012-01-01

    The coxsackievirus B4 (CVB4) belongs to human enterovirus B species within the family Picornaviridae. Here we report a novel complete genome sequence of a recombinant CVB4 strain, CVB4/GX/10, which was isolated from a patient with a fatal case of hand, foot, and mouth disease in China. The complete genome consists of 7,293 nucleotides, excluding the 3′ poly(A) tail, and has an open reading frame that maps between nucleotide positions 742 and 7293 and encodes a 2,183-amino-acid polyprotein. Ph...

  8. Full Genome Sequence of a Novel Coxsackievirus B5 Strain Isolated from Neurological Hand, Foot, and Mouth Disease Patients in China

    OpenAIRE

    Hu, Y. F.; Zhao, R.; Xue, Y.; Yang, Fan; Q. Jin

    2012-01-01

    Coxsackievirus B5 (CVB5) belongs to the human enterovirus B species within the family Picornaviridae. We report the complete genome sequence of a novel CVB5 strain, CVB5/SD/09, that is associated with neurological hand, foot, and mouth disease in China. The complete genome consists of 7,399 nucleotides, excluding the 3′ poly(A) tail, and has an open reading frame that maps between nucleotide positions 744 and 7301 and encodes a 2,185-amino-acid polyprotein. Phylogenetic analysis based on diff...

  9. Coxsackievirus B4 as a Causative Agent of Diabetes Mellitus Type 1: Is There a Role of Inefficiently Treated Drinking Water and Sewage in Virus Spreading?

    Science.gov (United States)

    El-Senousy, Waled M; Abdel-Moneim, Adel; Abdel-Latif, Mahmoud; El-Hefnawy, Mohamed H; Khalil, Rehab G

    2018-03-01

    This study proposed to detect the enterovirus (EV) infection in children with type 1 diabetes mellitus (T1D) and to assess the role of insufficiently treated water and sewage as sources of viral spreading. Three hundred and eighty-two serum specimens of children with T1D, one hundred serum specimens of children who did not suffer from T1D as control, and forty-eight water and sewage samples were screened for EV RNA using nested RT-PCR. The number of genome copies and infectious units of EVs in raw and treated sewage and water samples were investigated using real-time (RT)-PCR and plaque assay, respectively. T1D markers [Fasting blood glucose (FBG), HbA1c, and C-peptide], in addition to anti-Coxsackie A & B viruses (CVs A & B) IgG, were measured in control, T1D-negative EV (T1D-EV - ), and T1D-positive EV (T1D-EV + ) children specimens. The prevalence of EV genome was significantly higher in diabetic children (26.2%, 100 out of 382) than the control children (0%, 0 out of 100). FBG and HbA1c in T1D-EV - and T1D-EV + children specimens were significantly higher than those in the control group, while c-peptide in T1D-EV - and T1D-EV + children specimens was significantly lower than that in the control (n = 100; p water and treated sewage samples was 25 and 33.3%, respectively. The prevalence of EV infectious units in drinking water and treated sewage samples was 8.5 and 25%, respectively. Quantification assays were performed to assess the capabilities of both wastewater treatment plants (WWTPs) and water treatment plants (WTPs) to remove EV. The reduction of EV genome in Zenin WWTP ranged from 2 to 4 log 10 , while the reduction of EV infectious units ranged from 1 to 4 log 10 . The reduction of EV genome in El-Giza WTP ranged from 1 to 3 log 10 , while the reduction of EV infectious units ranged from 1 to 2 log 10 . This capability of reduction did not prevent the appearance of infectious EV in treated sewage and drinking water. Plaque purification was performed

  10. 26 CFR 48.6416(b)(3)-2 - Further manufacture included.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 16 2010-04-01 2010-04-01 true Further manufacture included. 48.6416(b)(3)-2... of Special Application to Retailers and Manufacturers Taxes § 48.6416(b)(3)-2 Further manufacture... overpayment by reason of any use in further manufacture, or sale as part of a second manufactured article...

  11. Band-Gap Engineering of Graphene Heterostructures via Substitutional Doping with B3N3.

    Science.gov (United States)

    Sawahata, Hisaki; Maruyama, Mina; Omachi, Haruka; Shinohara, Hisanori; Cuong, Nguyen Thanh; Okada, Susumu

    2017-10-11

    We investigated the energetics and electronic structures of B3N3-doped graphene using the density functional theory with the generalized gradient approximation. Our calculations showed that all of the B3N3-doped graphene structures were semiconductors, irrespective of the periodicity of the B3N3 embedded into the graphene network, in contrast to graphene nanomeshes which are either semiconductors or metals depending on the mesh arrangement. The B3N3-doped graphene has small effective masses for both electron and hole. The band gap in the B3N3-doped graphene networks was inversely proportional to the B3N3 spacing. The total energy of the B3N3-doped graphene was also inversely proportional to the B3N3 spacing. The band gap and total energy further depended on whether the graphene region possessed a Clar structure or not. In particular, the sheets with a Clar structure had a wider band gap and a slightly lower total energy than those without a Clar structure. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Interaction of vitamins B3 and C and their radicals with (5, 0) single ...

    Indian Academy of Sciences (India)

    Electronic properties of the covalent and noncovalent adsorption of single-walled boron nitride nanotube with vitamins B3 and C and their radicals are investigated through the density functional theory. Results show that noncovalent and covalent adsorption of vitamin B3 on BNNT could make these systems of interest for ...

  13. ErbB3 drives mammary epithelial survival and differentiation during pregnancy and lactation.

    Science.gov (United States)

    Williams, Michelle M; Vaught, David B; Joly, Meghan Morrison; Hicks, Donna J; Sanchez, Violeta; Owens, Philip; Rahman, Bushra; Elion, David L; Balko, Justin M; Cook, Rebecca S

    2017-09-08

    During pregnancy, as the mammary gland prepares for synthesis and delivery of milk to newborns, a luminal mammary epithelial cell (MEC) subpopulation proliferates rapidly in response to systemic hormonal cues that activate STAT5A. While the receptor tyrosine kinase ErbB4 is required for STAT5A activation in MECs during pregnancy, it is unclear how ErbB3, a heterodimeric partner of ErbB4 and activator of phosphatidyl inositol-3 kinase (PI3K) signaling, contributes to lactogenic expansion of the mammary gland. We assessed mRNA expression levels by expression microarray of mouse mammary glands harvested throughout pregnancy and lactation. To study the role of ErbB3 in mammary gland lactogenesis, we used transgenic mice expressing WAP-driven Cre recombinase to generate a mouse model in which conditional ErbB3 ablation occurred specifically in alveolar mammary epithelial cells (aMECs). Profiling of RNA from mouse MECs isolated throughout pregnancy revealed robust Erbb3 induction during mid-to-late pregnancy, a time point when aMECs proliferate rapidly and undergo differentiation to support milk production. Litters nursed by ErbB3 KO dams weighed significantly less when compared to litters nursed by ErbB3 WT dams. Further analysis revealed substantially reduced epithelial content, decreased aMEC proliferation, and increased aMEC cell death during late pregnancy. Consistent with the potent ability of ErbB3 to activate cell survival through the PI3K/Akt pathway, we found impaired Akt phosphorylation in ErbB3 KO samples, as well as impaired expression of STAT5A, a master regulator of lactogenesis. Constitutively active Akt rescued cell survival in ErbB3-depleted aMECs, but failed to restore STAT5A expression or activity. Interestingly, defects in growth and survival of ErbB3 KO aMECs as well as Akt phosphorylation, STAT5A activity, and expression of milk-encoding genes observed in ErbB3 KO MECs progressively improved between late pregnancy and lactation day 5. We found a

  14. Detection of human enterovirus 71 and coxsackievirus A16 in children with hand, foot and mouth disease in China.

    Science.gov (United States)

    Chen, Ling; Mou, Xiaozhou; Zhang, Qiong; Li, Yifei; Lin, Jian; Liu, Fanlong; Yuan, Li; Tang, Yiming; Xiang, Charlie

    2012-04-01

    The aims of the present study were to investigate the genetic characteristics of enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) strains in China and to evaluate the relationship between the genotypes of CVA16 and EV71 and their geographical distribution. A total of 399 stool specimens were collected from children with symptoms of hand, foot and mouth disease (HFMD) in Zhejiang Province. The presence of enteroviruses was determined using reverse transcription-semi-nested PCR targeted to the VP1 gene of all human enteroviruses and DNA sequencing. EV71 and CVA16, the major etiological agents of HFMD, were detected in 38.4% (38/99) and 35.4% (35/99) of HEV-A species-positive cases, respectively. Based on the phylogenetic analysis of the VP1 gene, EV71 strains identified in this study belong to subgenotype C4, and CVA16 strains herein were classified into clusters B2a and B2b within the genotype B2. Taking into consideration other published data, we conclude that the genetic characteristics of enteroviruses in China reflect the pattern of the endemic circulation of the subgenotype C4 to EV71 and clusters B2a and B2b within genotype B2 to CVA16, which have been continuously circulating in China since 1997. This observation indicates that the genetic characteristics of enteroviruses in China seem to depend on their special geographical and climatical features allowing them to be sustained with little external effect.

  15. [Identification and phylogenic analysis of Coxsackie-virus B5 during an outbreak of aseptic meningitis in Shandong].

    Science.gov (United States)

    Wang, Hai-yan; Li, Yan; Xu, Ai-qiang; Zhang, Yong; Tao, Ze-xin; Liu, Gui-fang; Liu, Yao; Song, Li-zhi; Zhang, Li; Yan, Bing-yu; Ji, Feng; Xu, Wen-bo

    2010-01-01

    To identify the pathogen that caused an outbreak of aseptic meningitis in Shandong province in 2005. Phylogenic analysis was carried out on Coxsackie-virus B5 (CVB5) which was isolated during this outbreak. 78 stool and 58 cerebrospinal fluids (CSF) specimens were collected from some inpatients during this outbreak. Virus isolation and reverse transcription-polymerase chain reaction (RT-PCR) was then performed. Phylo-genetic trees based on entire and partial VP1 sequences were constructed among CVB5 isolates and others published in GenBank. The isolation rates of stool and CSF specimens were 38.5% (30/78) and 48.3% (28/58) respectively. Among the results of serotype identification and molecular typing of 58 positive isolates, 54 were identified as CVB5, 2 as ECHO24, 1 as CVB3 and 1 as CVA9. Results from viral investigation showed that CVB5 was the main pathogen causing this outbreak. Data from homological comparisons indicated that Shandong strains had the highest nucleotide acid identity with the Zhejiang/12/02 strain (97.5% - 97.8%), and lower identity (78.3% - 78.6%) with the prototype strain (Faulkner strain). Phylogenic tree in VP1 region showed that CVB5 could be separated into four genotypes. Isolates of this outbreak belonged to genotype D. CVB5 was the major etiological agent correlated with this outbreak. The shift of predominant genotype might serve as one of the causes that associated with the outbreaks of aseptic meningitis.

  16. Marine microbial biodiversity, bioinformatics and biotechnology (M2B3) data reporting and service standards.

    Science.gov (United States)

    Ten Hoopen, Petra; Pesant, Stéphane; Kottmann, Renzo; Kopf, Anna; Bicak, Mesude; Claus, Simon; Deneudt, Klaas; Borremans, Catherine; Thijsse, Peter; Dekeyzer, Stefanie; Schaap, Dick Ma; Bowler, Chris; Glöckner, Frank Oliver; Cochrane, Guy

    2015-01-01

    Contextual data collected concurrently with molecular samples are critical to the use of metagenomics in the fields of marine biodiversity, bioinformatics and biotechnology. We present here Marine Microbial Biodiversity, Bioinformatics and Biotechnology (M2B3) standards for "Reporting" and "Serving" data. The M2B3 Reporting Standard (1) describes minimal mandatory and recommended contextual information for a marine microbial sample obtained in the epipelagic zone, (2) includes meaningful information for researchers in the oceanographic, biodiversity and molecular disciplines, and (3) can easily be adopted by any marine laboratory with minimum sampling resources. The M2B3 Service Standard defines a software interface through which these data can be discovered and explored in data repositories. The M2B3 Standards were developed by the European project Micro B3, funded under 7(th) Framework Programme "Ocean of Tomorrow", and were first used with the Ocean Sampling Day initiative. We believe that these standards have value in broader marine science.

  17. Application of the Quantum Cluster Equilibrium (QCE) model for the liquid phase of primary alcohols using B3LYP and B3LYP-D DFT methods.

    Science.gov (United States)

    Matisz, Gergely; Kelterer, Anne-Marie; Fabian, Walter M F; Kunsági-Máté, Sándor

    2011-04-14

    The Quantum Cluster Equilibrium (QCE) model was applied to the liquid phase for the first few members of the homologous series of unbranched aliphatic primary alcohols, methanol, ethanol, propan-1-ol, and butan-1-ol. Cluster structures and energies were calculated by density functional theory [B3LYP/6-311++G(2d,2p)]. For butan-1-ol the dispersion interaction was also considered with the B3LYP-D method. In agreement with previous findings, cyclic cluster structures are the most probable ones. In addition, weak C-H...O interactions as well as dispersion interactions between the longer alkyl chains were found to be important in the cluster formation. The reliability of the model was assessed by the calculated constant pressure heat capacity (C(p)) values. Larger deviations between theory and experiment were found for higher homologes (propan-1-ol, butan-1-ol) with the B3LYP method. When the B3LYP-D method was applied for butan-1-ol, adequate agreement was found between experimental and calculated C(p) values.

  18. Performance of Diesel Engine Using Diesel B3 Mixed with Crude Palm Oil

    Science.gov (United States)

    Namliwan, Nattapong; Wongwuttanasatian, Tanakorn

    2014-01-01

    The objective of this study was to test the performance of diesel engine using diesel B3 mixed with crude palm oil in ratios of 95 : 5, 90 : 10, and 85 : 15, respectively, and to compare the results with diesel B3. According to the tests, they showed that the physical properties of the mixed fuel in the ratio of 95 : 5 were closest to those of diesel B3. The performance of the diesel engine that used mixed fuels had 5–17% lower torque and power than that of diesel B3. The specific fuel consumption of mixed fuels was 7–33% higher than using diesel B3. The components of gas emissions by using mixed fuel had 1.6–52% fewer amount of carbon monoxide (CO), carbon dioxide (CO2), sulfur dioxide (SO2), and oxygen (O2) than those of diesel B3. On the other hand, nitric oxide (NO) and nitrogen oxides (NOX) emissions when using mixed fuels were 10–39% higher than diesel B3. By comparing the physical properties, the performance of the engine, and the amount of gas emissions of mixed fuel, we found out that the 95 : 5 ratio by volume was a suitable ratio for agricultural diesel engine (low-speed diesel engine). PMID:24688402

  19. Performance of diesel engine using diesel B3 mixed with crude palm oil.

    Science.gov (United States)

    Namliwan, Nattapong; Wongwuttanasatian, Tanakorn

    2014-01-01

    The objective of this study was to test the performance of diesel engine using diesel B3 mixed with crude palm oil in ratios of 95 : 5, 90 : 10, and 85 : 15, respectively, and to compare the results with diesel B3. According to the tests, they showed that the physical properties of the mixed fuel in the ratio of 95 : 5 were closest to those of diesel B3. The performance of the diesel engine that used mixed fuels had 5-17% lower torque and power than that of diesel B3. The specific fuel consumption of mixed fuels was 7-33% higher than using diesel B3. The components of gas emissions by using mixed fuel had 1.6-52% fewer amount of carbon monoxide (CO), carbon dioxide (CO2), sulfur dioxide (SO2), and oxygen (O2) than those of diesel B3. On the other hand, nitric oxide (NO) and nitrogen oxides (NO X ) emissions when using mixed fuels were 10-39% higher than diesel B3. By comparing the physical properties, the performance of the engine, and the amount of gas emissions of mixed fuel, we found out that the 95 : 5 ratio by volume was a suitable ratio for agricultural diesel engine (low-speed diesel engine).

  20. Evolution of the B3 DNA binding superfamily: new insights into REM family gene diversification.

    Directory of Open Access Journals (Sweden)

    Elisson A C Romanel

    Full Text Available BACKGROUND: The B3 DNA binding domain includes five families: auxin response factor (ARF, abscisic acid-insensitive3 (ABI3, high level expression of sugar inducible (HSI, related to ABI3/VP1 (RAV and reproductive meristem (REM. The release of the complete genomes of the angiosperm eudicots Arabidopsis thaliana and Populus trichocarpa, the monocot Orysa sativa, the bryophyte Physcomitrella patens,the green algae Chlamydomonas reinhardtii and Volvox carteri and the red algae Cyanidioschyzon melorae provided an exceptional opportunity to study the evolution of this superfamily. METHODOLOGY: In order to better understand the origin and the diversification of B3 domains in plants, we combined comparative phylogenetic analysis with exon/intron structure and duplication events. In addition, we investigated the conservation and divergence of the B3 domain during the origin and evolution of each family. CONCLUSIONS: Our data indicate that showed that the B3 containing genes have undergone extensive duplication events, and that the REM family B3 domain has a highly diverged DNA binding. Our results also indicate that the founding member of the B3 gene family is likely to be similar to the ABI3/HSI genes found in C. reinhardtii and V. carteri. Among the B3 families, ABI3, HSI, RAV and ARF are most structurally conserved, whereas the REM family has experienced a rapid divergence. These results are discussed in light of their functional and evolutionary roles in plant development.

  1. Antibody-mediated neutralization of myelin-associated EphrinB3 accelerates CNS remyelination.

    Science.gov (United States)

    Syed, Yasir A; Zhao, Chao; Mahad, Don; Möbius, Wiebke; Altmann, Friedrich; Foss, Franziska; González, G A; Sentürk, Aycan; Acker-Palmer, Amparo; Lubec, Gert; Lilley, Kathryn; Franklin, Robin J M; Nave, Klaus-A; Kotter, Mark R N

    2016-02-01

    Remyelination in multiple sclerosis (MS) lesions often remains incomplete despite the presence of oligodendrocyte progenitor cells (OPCs). Amongst other factors, successful remyelination depends on the phagocytic clearance of myelin debris. However, the proteins in myelin debris that act as potent and selective inhibitors on OPC differentiation and inhibit CNS remyelination remain unknown. Here, we identify the transmembrane signalling protein EphrinB3 as important mediator of this inhibition, using a protein analytical approach in combination with a primary rodent OPC assay. In the presence of EphrinB3, OPCs fail to differentiate. In a rat model of remyelination, infusion of EphrinB3 inhibits remyelination. In contrast, masking EphrinB3 epitopes using antibodies promotes remyelination. Finally, we identify EphrinB3 in MS lesions and demonstrate that MS lesion extracts inhibit OPC differentiation while antibody-mediated masking of EphrinB3 epitopes promotes it. Our findings suggest that EphrinB3 could be a target for therapies aiming at promoting remyelination in demyelinating disease.

  2. 17 CFR 275.203(b)(3)-2 - Methods for counting clients in certain private funds.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Methods for counting clients....203(b)(3)-2 Methods for counting clients in certain private funds. (a) For purposes of section 203(b)(3) of the Act (15 U.S.C. 80b-3(b)(3)), you must count as clients the shareholders, limited partners...

  3. Data of evolutionary structure change: 1AO5B-3BSQC [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1AO5B-3BSQC 1AO5 3BSQ B C VVGGFNCEKNSQPWQVAVYYQKEHICGGVLLDRNWVLTA...AHCYVDQYEVWLGKNKLFQEEPSAQHRLVSKSFPHPGFNMSLLMLQTIPPGADFSDDLMLLRLSKPADITDVVKPIALPTKEPKPGSKCLASGWGSITPT-WQKPDDLQC...bChain>C 3BSQC TTTSPDVTFPS 3BSQ C 3BSQC DT

  4. 17 CFR 275.203(b)(3)-1 - Definition of “client” of an investment adviser.

    Science.gov (United States)

    2010-04-01

    ... Definition of “client” of an investment adviser. Preliminary Note to § 275.203(b)(3)-1. This section is a... single client for purposes of section 203(b)(3) of the Act. Under paragraph (b)(6) of this section, the... be a single client for purposes of section 203(b)(3) of the Act (15 U.S.C. 80b-3(b)(3)): (1) A...

  5. ErbB3 mRNA leukocyte levels as a biomarker for major depressive disorder

    Directory of Open Access Journals (Sweden)

    Milanesi Elena

    2012-09-01

    Full Text Available Abstract Background In recent years, the identification of peripheral biomarkers that are associated with psychiatric diseases, such as Major Depressive Disorder (MDD, has become relevant because these biomarkers may improve the efficiency of the differential diagnosis process and indicate targets for new antidepressant drugs. Two recent candidate genes, ErbB3 and Fgfr1, are growth factors whose mRNA levels have been found to be altered in the leukocytes of patients that are affected by bipolar disorder in a depressive state. On this basis, the aim of the study was to determine if ErbB3 and Fgfr1 mRNA levels could be a biomarkers of MDD. Methods We measured by Real Time PCR ErbB3 and Fgfr1 mRNA expression levels in leukocytes of MDD patients compared with controls. Successively, to assess whether ErbB3 mRNA levels were influenced by previous antidepressant treatment we stratified our patients sample in two cohorts, comparing drug-naive versus drug-free patients. Moreover, we evaluated the levels of the transcript in MDD patients after 12 weeks of antidepressant treatment, and in prefrontal cortex of rats stressed and treated with an antidepressant drug of the same class. Results These results showed that ErbB3 but not Fgfr1 mRNA levels were reduced in leukocytes of MDD patients compared to healthy subjects. Furthermore, ErbB3 levels were not affected by antidepressant treatment in either human or animal models Conclusions Our data suggest that ErbB3 might be considered as a biomarker for MDD and that its deficit may underlie the pathopsysiology of the disease and is not a consequence of treatment. Moreover the study supports the usefulness of leukocytes as a peripheral system for identifying biomarkers in psychiatric diseases.

  6. Full genome sequence of a novel coxsackievirus B5 strain isolated from neurological hand, foot, and mouth disease patients in China.

    Science.gov (United States)

    Hu, Y F; Zhao, R; Xue, Y; Yang, Fan; Jin, Q

    2012-10-01

    Coxsackievirus B5 (CVB5) belongs to the human enterovirus B species within the family Picornaviridae. We report the complete genome sequence of a novel CVB5 strain, CVB5/SD/09, that is associated with neurological hand, foot, and mouth disease in China. The complete genome consists of 7,399 nucleotides, excluding the 3' poly(A) tail, and has an open reading frame that maps between nucleotide positions 744 and 7301 and encodes a 2,185-amino-acid polyprotein. Phylogenetic analysis based on different genome region regions reveals that CVB5/SD/09 belongs to a novel CVB5 lineage, and similarity plotting and bootscanning analysis based on the whole genome of CVB5 in the present study and those available in GenBank indicate that the genome of CVB5/SD/09 has a mosaic-like structure, suggesting that recombination between different CVB5 strains may occur.

  7. Characterization of VP1 gene of coxsackievirus A16 prevalent among hand foot mouth disease suffered children in Taizhou, P. R. China, between 2010 and 2013.

    Science.gov (United States)

    Ma, Zhilong; Zha, Jie

    2016-02-01

    A total of 453 strains of Coxsackievirus A16 (CV-A16) were screened out of 1,509 hand-foot-mouth disease (HFMD) samples collected in Taizhou during the period from 2010 to 2013. And between first quarter of 2011 and first quarter of 2013, an outbreak of CV-A16 was found among the HFMD sufferers in Taizhou. Phylogenic analysis of VP1 sequences indicated a major CV-A16 sub-group in Taizhou, whose change pattern of effective population sizes was found to be similar to the pattern of the actual percentage changes of CV-A16 during the outbreak over the same period. More importantly, the sub-group all displayed a Leu (L) to Met (M) mutation at site-23 of capsid VP1 which might be correlated with the outbreak of CV-A16 in Taizhou. © 2015 Wiley Periodicals, Inc.

  8. Molecular identification and phylogenetic study of coxsackievirus A24 variant isolated from an outbreak of acute hemorrhagic conjunctivitis in India in 2010.

    Science.gov (United States)

    Shukla, Deepti; Kumar, Arvind; Srivastava, Shalini; Dhole, Tapan N

    2013-03-01

    An outbreak of acute hemorrhagic conjunctivitis (AHC) occured in India between August and October 2010. Molecular typing by RT-PCR and sequencing of a partial VP1 region identified coxsackievirus A24 variant (CV A24v) as the serotype involved in this outbreak. Phylogenetic analysis based on the VP1 and 3C genes revealed that CV A24v strains associated with the 2010 AHC outbreak in India were genetically similar to strains from Central and South America that caused outbreaks of AHC in Cuba between 2008 and 2009 and Brazil in 2009. The result shows that the Indian strain of CV A24v may be responsible for the recent AHC outbreak in Marseille, France, in 2012.

  9. NONPOLIO ENTEROVIRUSES WHICH CAUSED THE RISE OF ENTEROVIRUS INFECTION ON SOME TERRITORIES OF RUSSIA IN 2016

    Directory of Open Access Journals (Sweden)

    N. I. Romanenkova

    2017-01-01

    Full Text Available Aim: Characteristics of the peculiarities and the etiological factor of enterovirus infection on some territories of Russia in 2016. Materials and methods: We investigated 2138 samples from the patients with enterovirus infection. The isolation and identification of enteroviruses were conducted by the virological method and by partial sequencing of the genome region VP1. Phylogenic trees were constructed according to the method of Bayesian Monte Carlo Markov Chain. Results: Epidemic peaks of enterovirus infection were fixed on some territories of Russia. In Saratov region the morbidity index of enterovirus infection in 2016 was twice as high as the median morbidity index over previous years. The morbidity level of enterovirus meningitis – 3, 21 for 100000 of the population (77% from all the cases of enterovirus infection was higher than on the other territories. In Kostroma region the morbidity index of enterovirus infection in 2016 was 11 times higher than the index of the previous year. On both territories the rise of morbidity depends on the active circulation of enterovirus ЕСНО30. Enteroviruses ECHO30 from Saratov region belonged to two phylogenic groups of genotype h. To one of them belonged viruses ECHO30 from Kostroma region. In Murmansk and Leningrad regions in 2016 most cases of enterovirus infection were represented by hand, foot and mouth disease (HFMD. The grouped foci of infection were registered in some preschool institutions. The etiological factor of this clinical form was Coxsackieviruses A6 belonging to different genetic variants. Conclusion: Epidemic peaks of enterovirus infection with the prevalence of different clinical forms of the disease were provoked by different etiological factors. On territories where enterovirus meningitis prevailed strains of enterovirus ECHO30 belonging to different variants of genotype h were detected. In patients with clinical picture of HFMD from territories where this form was leading

  10. Fasciola gigantica: production and characterization of a monoclonal antibody against recombinant cathepsin B3.

    Science.gov (United States)

    Anuracpreeda, Panat; Songkoomkrong, Sineenart; Sethadavit, Manussabhorn; Chotwiwatthanakun, Charoonroj; Tinikul, Yotsawan; Sobhon, Prasert

    2011-02-01

    A number of monoclonal antibodies (MoAbs) against a recombinant cathepsin B3 (rCatB3) of Fasciola gigantica were produced in BALB/c mice. Reactivity and specificity of these MoAbs were assessed by indirect ELISA and immunoblotting techniques. Six stable clones, namely 1C4, 1E9, 2E5, 2F9, 5B4, 5D7 were obtained. All MoAbs reacted with rCatB3 at molecular weight (MW) 37 kDa as well as the glycosylated peptide at 55-75 kDa and with the native CatB3 at MW 37 kDa in WB extracts of metacercariae (Met) and newly excysted juveniles (NEJ). It was found to be IgG(1) and λ light chain isotypes. Immunolocalization of CatB3 in metacercariae, NEJ, 4-week-old juvenile and adult F. gigantica performed by immunoperoxidase technique by using these MoAbs as probes indicated that CatB3 was present in high concentration in the caecal epithelium and caecal lumen of the Met and NEJ, but not in the 4-week-old juvenile and adult fluke. The MoAbs show no cross-reactions with antigens of other parasites including Gigantocotyl explanatum, Eurytrema pancreaticum, Paramphistomum cervi, Schistosoma spindale, S. mansoni, Haemonchus placei and Setaria labiato-papillosa. Thus, it is possible that these MoAbs could be a good candidate for immunodiagnosis of fasciolosis. Copyright © 2010 Elsevier Inc. All rights reserved.

  11. MOLECULAR DYNAMICS STUDY OF INTERACTIONS OF POLYMYXIN B3 AND ITS ALA-MUTANTS WITH LIPOPOLYSACCHARIDE

    Directory of Open Access Journals (Sweden)

    Lisnyak Yu. V.

    2015-12-01

    Full Text Available Introduction. Emergence of nosocomial bacterial pathogens (especially Gram-negative bacteria with multiple resistance against almost all available antibiotics is a growing medical problem. No novel drugs targeting multidrug-resistant Gram-negative bacteria have been developed in recent years. In this context, there has been greatly renewed interest to cyclic lipodecapeptides polymyxins. Polymyxins exhibit rapid bactericidal activity, they are specific and highly potent against Gramnegative bacteria, but have potential nephrotoxic side effects. So polymyxins are attractive lead compounds to develop analogues with improved microbiological, pharmacological and toxicological properties. A detailed knowledge of the molecular mechanisms of polymyxin interactions with its cell targets is a prerequisite for the purposeful improvement of its therapeutic properties. The primary cell target of a polymyxin is a lipopolysaccharide (LPS in the outer membrane of Gram-negative bacteria. The binding site of polymyxin on LPS has been supposed to be Kdo2-lipid A fragment. Methods. For all molecular modeling and molecular dynamics simulation experiments the YASARA suite of programs was used. Complex of antimicrobial peptide polymyxin В3 (PmB3 with Kdo2-lipid A portion of E. coli lipopolysaccharide was constructed by rigid docking with flexible side chains of the peptide. By alanine scanning of polymyxin В3 bound to LPS followed by simulated annealing minimization of the complexes in explicit water environment, the molecular aspects of PmB3-LPS binding have been studied by 20 ns molecular dynamics simulations at 298 K and pH 7.0. The AMBER03 force field was used with a 1.05 nm force cutoff. To treat long range electrostatic interactions the Particle Mesh Ewald algorithm was used. Results. Ala-mutations of polymyxin’s residues Dab1, Dab3, Dab5, Dab8 and Dab9 in the PmB3-LPS complex caused sustained structural changes resulting in the notable loss in stability of

  12. Short syntheses of enantiopure calystegine B-2, B-3, and B-4

    DEFF Research Database (Denmark)

    Skaanderup, Philip Robert; Madsen, Robert

    2001-01-01

    Calystegine B-2 B-3, and B-4 have been prepared in 5 steps from the benzyl protected methyl 6-iodoglycopyranosides of glucose, galactose and mannose, respectively, by using a zinc-mediated domino reaction followed by ring-closing olefin metathesis as the key steps.......Calystegine B-2 B-3, and B-4 have been prepared in 5 steps from the benzyl protected methyl 6-iodoglycopyranosides of glucose, galactose and mannose, respectively, by using a zinc-mediated domino reaction followed by ring-closing olefin metathesis as the key steps....

  13. Fracturas del radio distal tipo B3. Tratamiento quirúrgico.

    OpenAIRE

    Arenas Planelles, Antonio; Ortega Arruti, J.A.; Corchuelo Maíllo, C.; Arenas Miquélez, A.; Ortega Sáez, M. (Marta)

    2007-01-01

    Se presentan 67 casos de fractura de radio distal tipo B3 tratadas en nuestro Servicio. Se utilizó como método de osteosíntesis una placa palmar en 30 casos, agujas de Kirschner en 19 casos, fijadores externos en 17 y fijador externo + agujas en 1 caso. Los mejores resultados se obtuvieron en el grupo de casos tratados con placa palmar (90 % de resultados satisfactorios). A total of 67 cases of B3 type fracture of the distal radius treated in our Department are presented. A volar plate ...

  14. Methionine sulfoxide reductase B3 deficiency stimulates heme oxygenase-1 expression via ROS-dependent and Nrf2 activation pathways

    Energy Technology Data Exchange (ETDEWEB)

    Kwak, Geun-Hee; Kim, Ki Young; Kim, Hwa-Young, E-mail: hykim@ynu.ac.kr

    2016-05-13

    Methionine sulfoxide reductase B3 (MsrB3), which is primarily found in the endoplasmic reticulum (ER), is an important protein repair enzyme that stereospecifically reduces methionine-R-sulfoxide residues. We previously found that MsrB3 deficiency arrests the cell cycle at the G{sub 1}/S stage through up-regulation of p21 and p27. In this study, we report a critical role of MsrB3 in gene expression of heme oxygenase-1 (HO-1), which has an anti-proliferative effect associated with p21 up-regulation. Depletion of MsrB3 elevated HO-1 expression in mammalian cells, whereas MsrB3 overexpression had no effect. MsrB3 deficiency increased cellular reactive oxygen species (ROS), particularly in the mitochondria. ER stress, which is associated with up-regulation of HO-1, was also induced by depletion of MsrB3. Treatment with N-acetylcysteine as an ROS scavenger reduced augmented HO-1 levels in MsrB3-depleted cells. MsrB3 deficiency activated Nrf2 transcription factor by enhancing its expression and nuclear import. The activation of Nrf2 induced by MsrB3 depletion was confirmed by increased expression levels of its other target genes, such as γ-glutamylcysteine ligase. Taken together, these data suggest that MsrB3 attenuates HO-1 induction by inhibiting ROS production, ER stress, and Nrf2 activation. -- Highlights: •MsrB3 depletion induces HO-1 expression. •MsrB3 deficiency increases cellular ROS and ER stress. •MsrB3 deficiency activates Nrf2 by increasing its expression and nuclear import. •MsrB3 attenuates HO-1 induction by inhibiting ROS production and Nrf2 activation.

  15. 75 FR 63052 - Airworthiness Directives; Eurocopter France (ECF) Model AS350B3 and EC130 B4 Helicopters

    Science.gov (United States)

    2010-10-14

    ... (ECF) Model AS350B3 and EC130 B4 Helicopters AGENCY: Federal Aviation Administration (FAA), DOT. ACTION... Model AS350B3 and EC130 B4 helicopters. This amendment is prompted by a mandatory continuing... amend 14 CFR part 39 to include an AD that would apply to ECF Model AS350B3 and EC130 B4 helicopters on...

  16. Determining the frequencies of B1, B2, B3 and E alleles of the ...

    African Journals Online (AJOL)

    Ada

    2016-06-04

    Jun 4, 2016 ... gene and their effects on milk yield and composition in the Saanen goat breed. ... the potential for improving milk composition by selecting for B3 and E allele may be significant in Saanen goats. ... bp of intronic regions with a total similarity with the corresponding bovine sequence of about 57% (Ramunno.

  17. The AFL subfamily of B3 transcription factors: evolution and function in angiosperm seeds.

    Science.gov (United States)

    Carbonero, Pilar; Iglesias-Fernández, Raquel; Vicente-Carbajosa, Jesús

    2017-02-01

    Seed development follows zygotic embryogenesis; during the maturation phase reserves accumulate and desiccation tolerance is acquired. This is tightly regulated at the transcriptional level and the AFL (ABI3/FUS3/LEC2) subfamily of B3 transcription factors (TFs) play a central role. They alter hormone biosynthesis, mainly in regards to abscisic acid and gibberellins, and also regulate the expression of other TFs and/or modulate their downstream activity via protein-protein interactions. This review deals with the origin of AFL TFs, which can be traced back to non-vascular plants such as Physcomitrella patens and achieves foremost expansion in the angiosperms. In green algae, like the unicellular Chlamydomonas reinhardtii or the pluricellular Klebsormidium flaccidum, a single B3 gene and four B3 paralogous genes are annotated, respectively. However, none of them present with the structural features of the AFL subfamily, with the exception of the B3 DNA-binding domain. Phylogenetic analysis groups the AFL TFs into four Major Clusters of Ortologous Genes (MCOGs). The origin and function of these genes is discussed in view of their expression patterns and in the context of major regulatory interactions in seeds of monocotyledonous and dicotyledonous species. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  18. Data of evolutionary structure change: 3EK2B-3FNFC [Confc[Archive

    Lifescience Database Archive (English)

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  19. 17 CFR 270.24b-3 - Sales literature deemed filed.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Sales literature deemed filed... (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.24b-3 Sales literature deemed filed. Any advertisement, pamphlet, circular, form letter or other sales literature addressed to or intended...

  20. Identical Genotype B3 Sequences from Measles Patients in 4 Countries, 2005

    Science.gov (United States)

    Lowe, Luis; Rota, Paul; Bellini, William; Redd, Susan; Dayan, Gustavo; van Binnendijk, Rob; Hahné, Susan; Tipples, Graham; Macey, Jeannette; Espinoza, Rita; Posey, Drew; Plummer, Andrew; Bateman, John; Gudiño, José; Cruz-Ramirez, Edith; Lopez-Martinez, Irma; Anaya-Lopez, Luis; Akwar, Teneg Holy; Giffin, Scott; Carrión, Verónica; Bispo de Filippis, Ana Maria; Vicari, Andrea; Tan, Christina; Wolf, Bruce; Wytovich, Katherine; Borus, Peter; Mbugua, Francis; Chege, Paul; Kombich, Janeth; Akoua-Koffi, Chantal; Smit, Sheilagh; Bukenya, Henry; Bwogi, Josephine; Baliraine, Frederick Ndhoga; Kremer, Jacques; Muller, Claude; Santibanez, Sabine

    2006-01-01

    Surveillance of measles virus detected an epidemiologic link between a refugee from Kenya and a Dutch tourist in New Jersey, USA. Identical genotype B3 sequences from patients with contemporaneous cases in the United States, Canada, and Mexico in November and December 2005 indicate that Kenya was likely to have been the common source of virus. PMID:17283637

  1. Determining the frequencies of B1, B2, B3 and E alleles of the ...

    African Journals Online (AJOL)

    The aim of the study was to determine the frequencies of B1, B2, B3 and E alleles of the CSN1S1 gene and their effects on milk yield and composition in the Saanen goat breed. Milk samples were collected to identify milk composition with Fourier transform ınfrared (FTIR) spectroscopy. The polymerase chain ...

  2. Energy transfer phenomena in lanthanide metaborates (LnB3O6)

    NARCIS (Netherlands)

    Zhiran, Hao; Blasse, G.

    1984-01-01

    It is shown that GdB3O6 is an excellent host lattice to obtain efficient photoluminescent materials. For this purpose we need a sensitizer (S) of the Gd3+ sublattice and an activator (A). Energy transport from S to A occurs via the Gd3+ sublattice. We studied S = Sb3+, Bi3+, Ce3+ and A = Eu3+, Tb3+.

  3. Niacin (Vitamin B-3) Supplementation in Patients with Serotonin-Producing Neuroendocrine Tumor

    NARCIS (Netherlands)

    Bouma, Grietje; van Faassen, Martijn; Kats-Ugurlu, Gursah; Vries, de Elisabeth G. E.; Kema, Ido P.; Walenkamp, Annemiek M. E.

    2016-01-01

    BACKGROUND/AIMS: Tryptophan is the precursor of serotonin and niacin (vitamin B3). The latter is critical for normal cellular metabolism. Tryptophan and niacin can be deficient in patients with serotonin producing neuroendocrine tumors (NETs). Niacin deficiency can lead to severe symptoms including

  4. 2-Bromohydroquinone: structures, vibrational assignments and RHF, B- and B3-based density functional calculations.

    Science.gov (United States)

    Ramoji, Anuradha; Yenagi, Jayashree; Tonannavar, J

    2008-03-01

    Vibrational spectral measurements, namely, infrared (4000-400 cm(-1)) and Raman (3500-50 cm(-1)) spectra have been made for 2-Bromohydroquinone. Optimized geometrical structures, harmonic vibrational frequencies and intensities have been computed by the ab initio (RHF), B-based (BLYP, BP86) and B3-based (B3P86, B3LYP, B3PW91) density functional methods using 6-31G(d) basis set. A complete assignment of the observed spectra has been proposed. Coupling of vibrations has been determined by calculating potential energy distributions (PEDs) at BP86/6-31G(d) level of theory. In the computed equilibrium geometries by all the levels, the bond lengths and bond angles show changes in the neighborhood of Bromine. Similarly, the vibrational spectra exhibit some marked spectral features unlike in hydroquinone and phenol. On the other hand, the infrared spectrum shows a clear evidence of O-H...O bonding near 3200 cm(-1) as in hydroquinone. Evaluation of the theoretical methods demonstrates that all the levels but the RHF have reproduced frequencies fairly accurately in the 2000-500 cm(-1); below 500 cm(-1) the RHF has performed reasonably well.

  5. Probable transmission of coxsackie B3 virus from human to chimpanzee, Denmark

    DEFF Research Database (Denmark)

    Nielsen, Sandra Cathrine Abel; Mourier, Tobias; Baandrup, Ulrik

    2012-01-01

    In 2010, a chimpanzee died at Copenhagen Zoo following an outbreak of respiratory disease among chimpanzees in the zoo. Identification of coxsackie B3 virus, a common human pathogen, as the causative agent, and its severe manifestation, raise questions about pathogenicity and transmissibility among...

  6. Quark structure of the X(3872) and χb(3P) resonances

    Science.gov (United States)

    Ferretti, J.; Galatà, G.; Santopinto, E.

    2014-09-01

    We discuss the nature of the χb(3P) and X(3872) mesons. Are the χb(3P)'s standard bb¯ mesons or bb¯ states with a significative continuum component? Is the X(3872) a cc¯ state with continuum coupling effects or a meson-meson molecule? To do that, we compare quark model and unquenched quark model results for the mass barycenter and splittings of the χb(3P) multiplet. Future and more precise experimental results will discriminate between the two interpretations. In the case of the X(3872), we interpret it as a cc¯ core plus higher Fock components due to the coupling to the meson-meson continuum, and thus we think that it is compatible with the meson χc1(2P), with JPC=1++. The JPC=1++ quantum numbers are in agreement with the experimental results found by the LHCb collaboration. In our view, the X(3872)'s mass is lower than the quark model's predictions because of self-energy shifts. We also provide an estimation of the open charm/bottom strong decay modes of the X(3872) and χb(3P) mesons, such as X(3872)→DD¯* and χb2(3P)→BB¯, and radiative transitions.

  7. Data of evolutionary structure change: 1DR8B-3ICDA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1DR8B-3ICDA 1DR8 3ICD B A ------------------------MKVAVLPGDGIGPEV...LA CA 264 3ICD ...A 3ICDA AVEKAYKGERKIS HHHH...e>PHE CA 404 PRO CA 327 GLU CA 244 3ICD... A 3ICDA TQVYGQDVWLPA

  8. The promise of anti-ErbB3 monoclonals as new cancer therapeutics

    Science.gov (United States)

    Roscilli, Giuseppe; Mancini, Rita; Ciliberto, Gennaro

    2012-01-01

    In the last 3-5 years strong evidence has been gathered demonstrating ErbB3 as a key node for the progression of several cancer types. From the mechanistic standpoint the intracellular region of this receptor is rich of tyrosine residues that, upon phosphorylation, become high affinity binding sites for PI3K and other proteins involved in signal transduction. The involvement of ErbB3 occurs at different levels, most likely as a consequence of its promiscuity in the interaction with other RTKs of the same or other families. Several efforts are therefore being put in the development of antibodies that target this receptor either singly or in combination with other synergizing receptors. Some of these compounds have already entered clinical development. Although clinical proof-of-concept has not yet been achieved, this is likely to occur soon and will further accelerate the inclusion of anti-ErbB3 monoclonals in the repertoire of anticancer agents for more effective combination therapy. In this paper we review the wealth of anti-ErbB3 antibodies under development and compare their properties and potential to become marketed drugs. PMID:22889873

  9. 17 CFR 240.16b-3 - Transactions between an issuer and its officers or directors.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Transactions between an issuer... Rules and Regulations Under the Securities Exchange Act of 1934 Exemption of Certain Transactions from Section 16(b) § 240.16b-3 Transactions between an issuer and its officers or directors. (a) General. A...

  10. Effects of partial La filling and Sb vacancy defects on CoS b3 skutterudites

    Science.gov (United States)

    Hu, Chongze; Zeng, Xiaoyu; Liu, Yufei; Zhou, Menghan; Zhao, Huijuan; Tritt, Terry M.; He, Jian; Jakowski, Jacek; Kent, Paul R. C.; Huang, Jingsong; Sumpter, Bobby G.

    2017-04-01

    Over the past decade, the open frame ("cagey") structure of CoS b3 skutterudite has invited intensive filling studies with various rare-earth elements for delivering state-of-the-art midtemperature thermoelectric performance. To rationalize previously reported experimental results and provide new insight into the underexplored roles of La fillers and Sb vacancies, ab initio density functional theory studies, along with semiclassical Boltzmann transport theory calculations, are performed for pristine CoS b3 of different lattice settings and La-filled CoS b3 with and without Sb's mono- and divacancy defects. The effects of spin-orbit coupling (SOC), partial La filling, Sb vacancy defects, and spin polarization on the electronic and thermoelectric properties are systematically examined. The SOC shows minor effects on the electronic and thermoelectric properties of CoS b3 . The peculiar quasi-Dirac band in the pristine CoS b3 largely survives La filling but not Sb vacancies, which instead introduce dispersive bands in the band gap region. The non-spin-polarized and spin-polarized solutions of La-filled CoS b3 are nearly degenerate. Importantly, the band structure, density of states, and Fermi surface of the latter are significantly spin polarized, giving rise to spin-dependent thermoelectric properties. Seebeck coefficients directly calculated as a function of chemical potential are interpreted in connection with the electronic structures. Temperature-dependent Seebeck coefficients derived for the experimentally studied materials agree well with available experimental data. Seebeck coefficients obtained as a function of charge carrier concentration corroborate the thermoelectrically favorable role at high filling fractions played by the Fermi electron pockets associated with the degenerate valleys in the conduction bands, and also point toward a similar role of the Fermi hole pockets associated with the degenerate hills in the valence bands. These results serve to

  11. Evaluasi Fungsi Insinerator Dalam Memusnahkan Limbah B3 Di Rumah Sakit NI Dr.Ramelan Surabaya

    Directory of Open Access Journals (Sweden)

    Jahn Leonard Saragih

    2013-09-01

    Full Text Available Pengelolaan limbah padat B3 di Rumah Sakit TNI Angkatan Laut Dr. Ramelan sangat penting diperhatikan karena dapat berdampak buruk apabila tidak dikelola dengan baik. Oleh sebab itu diperlukan adanya penelitian untuk mengidentifikasi jumlah timbulan dan penanganan limbah padat B3, mengevaluasi manajemen, penyimpanan sementara serta mengevaluasi proses insinerasi. Evaluasi fungsi incinerator di Rumah Sakit TNI Angkatan Laut Dr. Ramelan dilakukan dengan meneliti jumlah timbulan limbah B3, kapasitas pembakaran insinerator, suhu pembakaran insinerator, densitas limbah dan abu pembakaran, dan tes TCLP residu pembakaran incinerator Rumah Sakit TNI Angkatan Laut Dr. Ramelan. Dalam penelitian ini, Rumkital Dr. Ramelan memusnahkan limbah dengan incinerator. Limbah B3 yang dihasilkan Rumkital Dr. Ramelan dimusnakan dengan satu incinerator dengan type KAMINE TYPE BDR-INC 10. Limbah yang dimusnahkan di Rumkital Dr. Ramelan berasal dari Rumkital Dr. Ramelan dan Lantamal Perak. Setelah dilakukan penelitian langsung selama 14 hari berturut-turut, didapatkan bahwa rata-rata timbulan limbah B3 di Rumkital Dr. Ramelan adalah 89.98 Kg/hari dan dengan densitas rata-rata limbah ialah 166,67 kg/m3. Tinggat removal dari pembakaran limbah dengan incinerator di Rumah Sakit TNI Angkatan Laut Dr. Ramelan ialah 82,63%. Pengelolaan abu sisa incinerator Rumkital Dr. Ramelan belum sesuai dengan peraturan yang berlaku dan dari penelitian yang dilakukan yaitu pengujian kandungan abu incinerator, solidifikasi abu incinerator dengan perbandingan semen:abu adalah 1:3 dan uji TCLP, didapatkan bahwa limbah abu sisa insinerator Rumah Sakit TNI Angkatan Laut Dr. Ramelan Surabaya, dapat ditimbun pada landfill kategori I sesuai dengan Keputusan Kepala Bapedal No.4 Tahun 1995.

  12. Revision hip arthroplasty as a treatment of Vancouver B3 periprosthetic femoral fractures without bone grafting.

    Science.gov (United States)

    Wang, Jia-Qi; Gao, You-Shui; Mei, Jiong; Rao, Zhi-Tao; Wang, Shu-Qing

    2013-09-01

    It is conventionally considered that bone grafting is mandatory for Vancouver B3 periprosthetic femoral fractures (PFF) although few clinical studies have challenged the concept previously. The aim of the current study was to investigate the radiographic and functional results of Vancouver B3 PFF treated by revision total hip or hemiarthroplasty (HA) in combination with appropriate internal fixation without bone grafting. 12 patients with Vancouver B3 PFF were treated by revision THA/HA without bone grafting between March 2004 and May 2008. There were nine females and three males, with an average age of 76 years. PFFs were following primary THA/HA in nine patients and following revision THA/HA in three. Postoperative followup was 5.5 years on average (range, 3.5-6.5 years). At the final followup, radiographic results were evaluated with Beals and Tower's criteria and functional outcomes were evaluated using the Merle d'Aubigné scoring system. All fractures healed within an average of 20 weeks (range, 12-28 weeks). There was no significant deformity and shortening of the affected limb and the implant was stable. The average Merle d'Aubigné score was 15.8. Walking ability was regained in 10 patients without additional assistance, while 2 patients had to use crutches. There were 2 patients with numbness of lateral thigh, possibly due to injury to the lateral femoral cutaneous nerve. There were no implant failures, dislocation and refractures. Revision THA/HA in combination with appropriate internal fixation without bone grafting is a good option for treatment of Vancouver B3 periprosthetic femoral fractures in the elderly.

  13. NQRS Data for B3LiO5 (Subst. No. 0180)

    Science.gov (United States)

    Chihara, H.; Nakamura, N.

    This document is part of Subvolume A `Substances Containing Ag … C10H15' of Volume 48 `Nuclear Quadrupole Resonance Spectroscopy Data' of Landolt-Börnstein - Group III `Condensed Matter'. It contains an extract of Section `3.2 Data tables' of the Chapter `3 Nuclear quadrupole resonance data' providing the NQRS data for B3LiO5 (Subst. No. 0180)

  14. Polygonumnolides A1-B3, minor dianthrone derivatives from the roots of Polygonum multiflorum Thunb.

    Science.gov (United States)

    Yang, Jianbo; Yan, Zheng; Ren, Jin; Dai, Zhong; Ma, Shuangcheng; Wang, Aiguo; Su, Yalun

    2017-07-05

    Seven new dianthrone glycosides, named polygonumnolides A1-B3 (1-7), were isolated from the 70 % EtOH extract of the dried roots of Polygonum multiflorum Thunb. using column chromatography and preparative high-performance liquid chromatography. Their structures were determined by 1D and 2D NMR and mass spectroscopy. The isolated compounds were evaluated for their cytotoxic effects against KB tumor cell lines and compounds 1-4 showed moderate cytotoxicity.

  15. [Distribution characteristics of ApoB3'VNTR and hyperlipemia correlation factors in civil aircrew].

    Science.gov (United States)

    Zhu, Feng; Chen, Wei-ru; Chen, Xiao-fei; Liang, Li-quan; Feng, Ying-jin; Zhang, Tao; Yang, Jian; Zhao, Rong-pu; Chen, Liang; Zhu, Hong-hai; Wu, Yu-kun

    2010-03-01

    To study the frequency distribution in polymorphism of the apoprotein B 3' variable number tandem repeat (ApoB3'VNTR) and influence factors on hyperlipemia in civil aircrew. ApoB genotypes were determined by PCR technology and agarose gel electrophoresis. The blood lipids were measured by routine kits. Personal information of flight personnel was collected by questionnaire. Prevalence of the total dyslipidemia (49.5%) and overweight (55.6%) of flight personnel were much higher than that of domestic general population (29.2% and 49.1%) respectively (P abroad (21.50%). The frequency of the big allele (VNTR > or =39) in hyperlipemia groups were higher than that of normal groups. By analysis of co-variance, the body mass index (BMI), low density lipoprotein (LDL) and the total cholesterol(TC) increased with the cumulate flight hours (P independent variable(X), and the BMI as dependent variable(Y), the linearity equations was: Y = 2.730X + 13.584 (R2 = 0.159, P < 0.01). There are perhaps special genetic characteristics in the polymorphism of the ApoB3'VNTR in the aircrew. The big allele is correlated with the hyperlipemia. The flight burden not only directly affects the BMI and blood lipids levels, but also it can indirectly affect the lipids levels by BMI.

  16. B3GALNT2 is a gene associated with congenital muscular dystrophy with brain malformations.

    Science.gov (United States)

    Hedberg, Carola; Oldfors, Anders; Darin, Niklas

    2014-05-01

    Congenital muscular dystrophies associated with brain malformations are a group of disorders frequently associated with aberrant glycosylation of α-dystroglycan. They include disease entities such a Walker-Warburg syndrome, muscle-eye-brain disease and various other clinical phenotypes. Different genes involved in glycosylation of α-dystroglycan are associated with these dystroglycanopathies. We describe a 5-year-old girl with psychomotor retardation, ataxia, spasticity, muscle weakness and increased serum creatine kinase levels. Immunhistochemistry of skeletal muscle revealed reduced glycosylated α-dystroglycan. Magnetic resonance imaging of the brain at 3.5 years of age showed increased T2 signal from supratentorial and infratentorial white matter, a hypoplastic pons and subcortical cerebellar cysts. By whole exome sequencing, the patient was identified to be compound heterozygous for a one-base duplication and a missense mutation in the gene B3GALNT2 (β-1,3-N-acetylgalactosaminyltransferase 2; B3GalNAc-T2). This patient showed a milder phenotype than previously described patients with mutations in the B3GALNT2 gene.

  17. Distinct and Overlapping Requirements for Cyclins A, B, and B3 in Drosophila Female Meiosis

    Directory of Open Access Journals (Sweden)

    Mohammed Bourouh

    2016-11-01

    Full Text Available Meiosis, like mitosis, depends on the activity of the cyclin dependent kinase Cdk1 and its cyclin partners. Here, we examine the specific requirements for the three mitotic cyclins, A, B, and B3 in meiosis of Drosophila melanogaster. We find that all three cyclins contribute redundantly to nuclear envelope breakdown, though cyclin A appears to make the most important individual contribution. Cyclin A is also required for biorientation of homologs in meiosis I. Cyclin B3, as previously reported, is required for anaphase progression in meiosis I and in meiosis II. We find that it also plays a redundant role, with cyclin A, in preventing DNA replication during meiosis. Cyclin B is required for maintenance of the metaphase I arrest in mature oocytes, for spindle organization, and for timely progression through the second meiotic division. It is also essential for polar body formation at the completion of meiosis. With the exception of its redundant role in meiotic maturation, cyclin B appears to function independently of cyclins A and B3 through most of meiosis. We conclude that the three mitotic cyclin-Cdk complexes have distinct and overlapping functions in Drosophila female meiosis.

  18. Proliferation of colorectal cancer is promoted by two signaling transduction expression patterns: ErbB2/ErbB3/AKT and MET/ErbB3/MAPK.

    Directory of Open Access Journals (Sweden)

    Yong-Liang Yao

    Full Text Available One of the recent breakthroughs in cancer research is the identification of activating mutations in various receptor tyrosine kinase(RTK pathways in many cancers including colorectal cancer(CRC. We hypothesize that, alternative to mutations, overexpression of various oncogenic RTKs may also underpin CRC pathogenesis, and different RTK may couple with distinct downstream signaling pathways in different subtypes of human CRC. By immunohistochemistry, we show here that RTK members ErbB2, ErbB3 and c-Met were in deed differentially overexpressed in colorectal cancer patient samples leading to constitutive activation of RTK signaling pathways. Using ErbB2 specific inhibitor Lapatinib and c-Met specific inhibitor PHA-665752, we further demonstrated that this constitutive activation of RTK signaling is necessary for the survival of colorectal cancer cells. Furthermore, we show that RTK overexpression pattern dictates the use of downstream AKT and/or MAPK pathways. Our data are important additions to current oncogenic mutation models, and further explain the clinical variation in therapeutic responses of colorectal cancer. Our findings advocate for more personalized therapy tailored to individual patients based on their type of RTK expression in addition to their mutation status.

  19. A systematic review of Vancouver B2 and B3 periprosthetic femoral fractures.

    Science.gov (United States)

    Khan, T; Grindlay, D; Ollivere, B J; Scammell, B E; Manktelow, A R J; Pearson, R G

    2017-04-01

    The aim of this study was to investigate the outcomes of Vancouver type B2 and B3 fractures by performing a systematic review of the methods of surgical treatment which have been reported. A systematic search was performed in Ovid MEDLINE, Embase and the Cochrane Central Register of Controlled Trials. For inclusion, studies required a minimum of ten patients with a Vancouver type B2 and/or ten patients with a Vancouver type B3 fracture, a minimum mean follow-up of two years and outcomes which were matched to the type of fracture. Studies were also required to report the rate of re-operation as an outcome measure. The protocol was registered in the PROSPERO database. A total of 22 studies were included based on the eligibility criteria, including 343 B2 fractures and 167 B3 fractures. The mean follow-up ranged from 32 months to 74 months. Of 343 Vancouver B2 fractures, the treatment in 298 (86.8%) involved revision arthroplasty and 45 (12.6%) were treated with internal fixation alone. A total of 37 patients (12.4%) treated with revision arthroplasty and six (13.3%) treated by internal fixation only underwent further re-operation. Of 167 Vancouver B3 fractures, the treatment in 160 (95.8%) involved revision arthroplasty and eight (4.8%) were treated with internal fixation without revision. A total of 23 patients (14.4%) treated with revision arthroplasty and two (28.6%) treated only with internal fixation required re-operation. A significant proportion, particularly of B2 fractures, were treated without revision of the stem. These were associated with a higher rate of re-operation. The treatment of B3 fractures without revision of the stem resulted in a high rate of re-operation. This demonstrates the importance of careful evaluation and accurate characterisation of the fracture at the time of presentation to ensure the correct management. There is a need for improvement in the reporting of data in case series recording the outcome of the surgical treatment of

  20. Vancouver type B2 and B3 periprosthetic fractures treated with revision total hip arthroplasty.

    Science.gov (United States)

    Amenabar, Tomas; Rahman, Wael A; Avhad, Vineet V; Vera, Ramiro; Gross, Allan E; Kuzyk, Paul R

    2015-10-01

    Periprosthetic fractures are the fourth most common cause for hip revision and a devastating complication. Our purpose is to report results and quality of life following revision THA for Vancouver B2 and B3 fractures. This was a retrospective review from January 2000 to November 2012 to identify all revision THA performed for Vancouver types B2 and B3 that had a minimum follow-up of two years. Routine post-operative and radiographic evaluation to assess patient survival, implant failure, complications and quality of life was involved. Statistical analysis was made with the Kaplan-Meier survival curve with 95 % confidence interval and the log rank (Mantel-Cox) test. A total of 76 fractures were included, with an average follow-up 74.4 months. Mean age at the revision surgery was 75.7 years (range, 41-97 years; SD, 12.4). Sixty-six cases were classified as Vancouver B2 and treated with distal fixation stem. Ten cases were Vancouver B3 and a proximal femoral allograft technique was used. The overall five-year Kaplan-Meier survival rate for the patients was 77.9 % (95 % CI, 67.4-88.4), and the ten-year rate was 65.1 % (95 % CI, 51.4-78.8). Five-year Kaplan-Meier survival rate for the implants was 89.6 % (95 % CI, 82.2-97); we presented seven failures. The mean SF-12 mental was 55.1 (range, 31-68; SD, 8.1) and the physical was 37.4 (range, 16-55; SD, 9.4). Mortality rate after periprosthetic fractures is high as compared to other hip surgeries; our Kaplan-Meier analysis showed that it tends to plateau after five years. In our series the failure rate was low and occurred early in the post-operative period.

  1. Association of group B coxsackie viruses with cases of pericarditis, myocarditis, or pleurodynia by demonstration of immunoglobulin M antibody.

    Science.gov (United States)

    Schmidt, N J; Magoffin, R L; Lennette, E H

    1973-09-01

    Tests for immunoglobulin M (IgM) antibody to group B coxsackieviruses were performed on sera from 259 patients with a clinical diagnosis of pericarditis, myocarditis, or pleurodynia on whom there were no definitive serological or virus isolation findings to establish a viral etiology, and on 259 "control" patients with clinical diagnoses of viral or mycoplasmal pneumonia or pneumonitis. IgM antibodies to coxsackievirus types B1, B3, B4, B5, and B6 were detected by a micro-immunodiffusion technique, and antibodies to virus type B2 were detected by reduction of neutralizing antibodies with ethanethiol. Of the patients with pericarditis, myocarditis, or pleurodynia, 27% (70) had IgM antibody to group B coxsackieviruses, as compared with 8% in the control group. On retrospective review of the clinical diagnosis, some of the patients in the control group with IgM antibody were found to have had additional clinical findings which could be attributed to a coxsackievirus infection. Coxsackievirus IgM antibody was demonstrable in 30% of 113 patients in the study group for whom virus isolation had been attempted with negative results. The presence of coxsackievirus IgM is discussed in relation to the time of serum collection, age of the patients, and month of onset of illness.

  2. Phylogenetic patterns of human coxsackievirus B5 arise from population dynamics between two genogroups and reveal evolutionary factors of molecular adaptation and transmission.

    Science.gov (United States)

    Henquell, Cécile; Mirand, Audrey; Richter, Jan; Schuffenecker, Isabelle; Böttiger, Blenda; Diedrich, Sabine; Terletskaia-Ladwig, Elena; Christodoulou, Christina; Peigue-Lafeuille, Hélène; Bailly, Jean-Luc

    2013-11-01

    The aim of this study was to gain insights into the tempo and mode of the evolutionary processes that sustain genetic diversity in coxsackievirus B5 (CVB5) and into the interplay with virus transmission. We estimated phylodynamic patterns with a large sample of virus strains collected in Europe by Bayesian statistical methods, reconstructed the ancestral states of genealogical nodes, and tested for selection. The genealogies estimated with the structural one-dimensional gene encoding the VP1 protein and nonstructural 3CD locus allowed the precise description of lineages over time and cocirculating virus populations within the two CVB5 clades, genogroups A and B. Strong negative selection shaped the evolution of both loci, but compelling phylogenetic data suggested that immune selection pressure resulted in the emergence of the two genogroups with opposed evolutionary pathways. The genogroups also differed in the temporal occurrence of the amino acid changes. The virus strains of genogroup A were characterized by sequential acquisition of nonsynonymous changes in residues exposed at the virus 5-fold axis. The genogroup B viruses were marked by selection of three changes in a different domain (VP1 C terminus) during its early emergence. These external changes resulted in a selective sweep, which was followed by an evolutionary stasis that is still ongoing after 50 years. The inferred population history of CVB5 showed an alternation of the prevailing genogroup during meningitis epidemics across Europe and is interpreted to be a consequence of partial cross-immunity.

  3. Complete genome sequence of a recombinant coxsackievirus B4 from a patient with a fatal case of hand, foot, and mouth disease in Guangxi, China.

    Science.gov (United States)

    Hu, Y F; Du, J; Zhao, R; Xue, Y; Yang, Fan; Jin, Qi

    2012-10-01

    The coxsackievirus B4 (CVB4) belongs to human enterovirus B species within the family Picornaviridae. Here we report a novel complete genome sequence of a recombinant CVB4 strain, CVB4/GX/10, which was isolated from a patient with a fatal case of hand, foot, and mouth disease in China. The complete genome consists of 7,293 nucleotides, excluding the 3' poly(A) tail, and has an open reading frame that maps between nucleotide positions 742 and 7293 and encodes a 2,183-amino-acid polyprotein. Phylogenetic analysis based on different genome regions reveals that CVB4/GX/10 is closest to a CVB4 strain, EPIHFMD-CLOSE CONTACT-16, in the 5' half (VP4∼2B) of the genome, although it is closer to a Chinese CVB5 strain, CVB5/Henan/2010, in the 3' half (2C∼3D) of the genome. Furthermore, similar bootscan analysis based on the whole genomes demonstrates that recombination has possibly occurred within the 2C domain and that CVB4/GX/10 is a possible progeny of intertypic recombination of the CVB4 strain EPIHFMD-CLOSE CONTACT-16 and CVB5/Henan/2010 that occurred during their cocirculation and evolution, which is a relatively common phenomenon in enteroviruses.

  4. Rapid and visual detection of human enterovirus coxsackievirus A16 by reverse transcription loop-mediated isothermal amplification combined with lateral flow device.

    Science.gov (United States)

    Yan, G; Jun, L; Kangchen, Z; Yiyue, G; Yang, Y; Xiaoyu, Z; Zhiyang, S; Lunbiao, C

    2015-12-01

    In this study, a reverse transcription loop-mediated isothermal amplification (RT-LAMP) combined with lateral flow device (LFD) technology to rapidly detect CVA16 was developed and evaluated. RT-LAMP assay was optimized to amplify VP1 gene of CVA16. Amplified products were analysed by LFD and capillary electrophoresis. The RT-LAMP-LFD assay showed 100% specificity in detecting CVA16, and showed analytical sensitivity of 0·55 TCID50 per reaction mixture. Comparison of the RT-LAMP-LFD assay with real-time RT-PCR developed previously in clinical specimens showed 93·3% agreement. The RT-LAMP-LFD assay is more sensitive in detecting CVA16 RNA. The RT-LAMP-LFD assay presented here might offer a rapid and simple alternative in clinical diagnosis of CVA16. Coxsackievirus A16 (CVA16) is one of the major causative agents of hand, foot and mouth disease (HFMD). Rapid and reliable detection and typing of it can limit the spread. We developed a reverse transcription loop-mediated isothermal amplification (RT-LAMP) combined with lateral flow device (LFD) technology to rapidly detect CVA16. The high sensitivity and specificity and its ease of use make this assay ideal for use in resource-limited settings such as primary care facilities and clinical laboratories in developing countries. © 2015 The Society for Applied Microbiology.

  5. Host cell recognition by the henipaviruses: Crystal structures of the Nipah G attachment glycoprotein and its complex with ephrin-B3

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Kai; Rajashankar, Kanagalaghatta R.; Chan, Yee-Peng; Himanen, Juha P.; Broder, Christopher C.; Nikolov, Dimitar B. (USUHS); (Cornell); (MSKCC)

    2008-07-28

    Nipah virus (NiV) and Hendra virus are the type species of the highly pathogenic paramyxovirus genus Henipavirus, which can cause severe respiratory disease and fatal encephalitis infections in humans, with case fatality rates approaching 75%. NiV contains two envelope glycoproteins, the receptor-binding G glycoprotein (NiV-G) that facilitates attachment to host cells and the fusion (F) glycoprotein that mediates membrane merger. The henipavirus G glycoproteins lack both hemagglutinating and neuraminidase activities and, instead, engage the highly conserved ephrin-B2 and ephrin-B3 cell surface proteins as their entry receptors. Here, we report the crystal structures of the NiV-G both in its receptor-unbound state and in complex with ephrin-B3, providing, to our knowledge, the first view of a paramyxovirus attachment complex in which a cellular protein is used as the virus receptor. Complex formation generates an extensive protein-protein interface around a protruding ephrin loop, which is inserted in the central cavity of the NiV-G {beta}-propeller. Analysis of the structural data reveals the molecular basis for the highly specific interactions of the henipavirus G glycoproteins with only two members (ephrin-B2 and ephrin-B3) of the very large ephrin family and suggests how they mediate in a unique fashion both cell attachment and the initiation of membrane fusion during the virus infection processes. The structures further suggest that the NiV-G/ephrin interactions can be effectively targeted to disrupt viral entry and provide the foundation for structure-based antiviral drug design.

  6. 7 CFR Exhibit B-3 to Subpart B of... - Letter for Notifying Applicants, Lender, Holders and Borrowers of Adverse Decisions Where the...

    Science.gov (United States)

    2010-01-01

    ... Farmer Program Primary Loan Servicing Actions) B Exhibit B-3 to Subpart B of Part 1900 Agriculture... GENERAL Adverse Decisions and Administrative Appeals Pt. 1900, Subpt. B, Exh. B-3 Exhibit B-3 to Subpart B...

  7. Influence of carbohydrates on the interaction of procyanidin B3 with trypsin.

    Science.gov (United States)

    Gonçalves, Rui; Mateus, Nuno; De Freitas, Victor

    2011-11-09

    The biological properties of procyanidins, in particular their inhibition of digestive enzymes, have received much attention in the past few years. Dietary carbohydrates are an environmental factor that is known to affect the interaction of procyanidins with proteins. This work aimed at understanding the effect of ionic food carbohydrates (polygalacturonic acid, arabic gum, pectin, and xanthan gum) on the interaction between procyanidins and trypsin. Physical-chemical techniques such as saturation transfer difference-NMR (STD-NMR) spectroscopy, fluorescence quenching, and nephelometry were used to evaluate the interaction process. Using STD-NMR, it was possible to identify the binding of procyanidin B3 to trypsin. The tested carbohydrates prevented the association of procyanidin B3 and trypsin by a competition mechanism in which the ionic character of carbohydrates and their ability to encapsulate procyanidins seem crucial leading to a reduction in STD signal and light scattering and to a recovery of the proteins intrinsic fluorescence. On the basis of these results, it was possible to grade the carbohydrates in their aggregation inhibition ability: XG > PA > AG ≫ PC. These effects may be relevant since the coingestion of procyanidins and ionic carbohydrates are frequent and furthermore since these might negatively affect the antinutritional properties ascribed to procyanidins in the past.

  8. 26 CFR 48.4216(b)-3 - Constructive sale price; special rule for arm's-length sales.

    Science.gov (United States)

    2010-04-01

    ... not maintain a sales force to resell the article whose constructive sale price was established under... 26 Internal Revenue 16 2010-04-01 2010-04-01 true Constructive sale price; special rule for arm's-length sales. 48.4216(b)-3 Section 48.4216(b)-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF...

  9. Inhibition of PTEN gene expression by oncogenic miR-23b-3p in renal cancer.

    Directory of Open Access Journals (Sweden)

    Mohd Saif Zaman

    Full Text Available BACKGROUND: miR-23b is located on chromosome number 9 and plays different roles in different organs especially with regards to cancer development. However, the functional significance of miR-23b-3p in renal cell carcinoma (RCC has not been reported. METHODS AND RESULTS: We measured miR-23b-3p levels in 29 pairs of renal cell carcinoma and their normal matched tissues using real-time PCR. The expression level of miR-23b-3p was correlated with the 5 year survival rate of renal cancer patients. In 15 cases (52%, miR-23b-3p expression was found to be high. All patients with moderate to low miR-23b-3p expression survived 5 years, while those with high miR-23b-3p expression, only 50% survived. After knocking down miRNA-23b-3p expression in RCC cell lines, there was an induction of apoptosis and reduced invasive capabilities. MiR-23b-3p was shown to directly target PTEN gene through 3'UTR reporter assays. Inhibition of miR-23b-3p induces PTEN gene expression with a concomitant reduction in PI3-kinase, total Akt and IL-32. Immunohistochemistry showed the lack of PTEN protein expression in cancerous regions of tissue samples where the expression of miR-23b-3p was high. We studied the in vitro effects of the dietary chemo preventive agent genistein on miR-23b-3p expression and found that it inhibited expression of miR-23b-3p in RCC cell lines. CONCLUSIONS: The current study shows that miR-23b-3p is an oncogenic miRNA and inhibits PTEN tumor suppressor gene in RCC. Therefore, inhibition of miR-23b-3p may be a useful therapeutic target for the treatment of renal cell carcinoma.

  10. Mutation of SH2B3 (LNK), a GWAS candidate for hypertension, attenuates Dahl SS hypertension via inflammatory modulation

    Science.gov (United States)

    Rudemiller, Nathan P.; Lund, Hayley; Priestley, Jessica R. C.; Endres, Bradley T.; Prokop, Jeremy W.; Jacob, Howard J.; Geurts, Aron M.; Cohen, Eric P.; Mattson, David L.

    2015-01-01

    Human genome wide association studies (GWAS) have linked SH2B3 (LNK) to hypertension and renal disease, though little experimental investigation has been done to verify a role for SH2B3 in these pathologies. SH2B3, a member of the SH2B adaptor protein family, is an intracellular adaptor protein that functions as a negative regulator in many signaling pathways, including inflammatory signaling processes. To explore a mechanistic link between SH2B3 and hypertension, we targeted the SH2B3 gene for mutation on the Dahl salt-sensitive (SS) rat genetic background with zinc-finger nucleases (ZFN). The resulting mutation was a 6 base-pair, in-frame deletion within a highly-conserved region of the Src Homology 2 (SH2) domain of SH2B3. This mutation significantly attenuated Dahl salt-sensitive (SS) hypertension and renal disease. Also, infiltration of leukocytes into the kidneys, a key mediator of Dahl SS pathology, was significantly blunted in the Sh2b3em1Mcwi mutant rats. To determine if this was due to differences in immune signaling, bone marrow transplant studies were performed in which Dahl SS and Sh2b3em1Mcwi mutants underwent total body irradiation and were then transplanted with Dahl SS or Sh2b3em1Mcwi mutant bone marrow. Rats that received Sh2b3em1Mcwi mutant bone marrow had a significant reduction in mean arterial pressure and kidney injury when placed on a high salt diet (4% NaCl). These data further support a role for the immune system as a modulator of disease severity in the pathogenesis of hypertension and provide insight into inflammatory mechanisms at play in human hypertension and renal disease. PMID:25776069

  11. Homomultimerization of the coxsackievirus 2B protein in living cells visualized by fluorescence resonance energy transfer microscopy.

    NARCIS (Netherlands)

    Kuppeveld, F.J.M. van; Melchers, W.J.G.; Willems, P.H.G.M.; Gadella, T.W.

    2002-01-01

    The 2B protein of enteroviruses is the viral membrane-active protein that is responsible for the modifications in host cell membrane permeability that take place in enterovirus-infected cells. The 2B protein shows structural similarities to the group of lytic polypeptides, polypeptides that permeate

  12. Vibrational thermodynamics of Fe90Zr7B3 nanocrystalline alloy from nuclear inelastic scattering

    DEFF Research Database (Denmark)

    Stankov, S.; Miglierini, M.; Chumakov, A. I.

    2010-01-01

    Recently we determined the iron-partial density of vibrational states (DOS) of nanocrystalline Fe(90)Zr(7)B(3) (Nanoperm), synthesized by crystallization of an amorphous precursor, for various stages of nanocrystallization separating the DOS of the nanograins from that of the interfaces [S. Stankov......, Y. Z. Yue, M. Miglierini, B. Sepiol, I. Sergueev, A. I. Chumakov, L. Hu, P. Svec, and R. Ruffer, Phys. Rev. Lett. 100, 235503 (2008)]. Here we present quantitative analysis of the evolution of various thermoelastic properties calculated from DOS such as mean-force constant, mean atomic displacement......, vibrational entropy, and lattice specific heat as the material transforms from amorphous, through nanocrystalline, to fully crystallized state. The reported results shed new light on the previously observed anomalies in the vibrational thermodynamics of nanocrystalline materials....

  13. B3 and B9 huts at the Bronze Age settlement of Mursia (Pantelleria

    Directory of Open Access Journals (Sweden)

    Matteo Cantisani

    2015-12-01

    Full Text Available The hut B3 and B9, located on the southwestern edge of Sector B of the prehistoric settlement of Mursia, identify frequent structural changes inside the residential unit. The huts are characterized by architectural components and floor plans typical of the early phase of this part of the settlement and show clear traces of continuous occupation in spite of the architectural rearrangement. The reconstruction of the stratigraphic sequence, the analysis of the formation processes of the material culture, the study on the use of the space associated with specific patterns of spatial distribution of objects showed a process of formation of the archaeological record dynamic and never interrupted by clear elements of discontinuity.

  14. Negative linear compressibility in a crystal of α-BiB3O6

    Science.gov (United States)

    Kang, Lei; Jiang, Xingxing; Luo, Siyang; Gong, Pifu; Li, Wei; Wu, Xiang; Li, Yanchun; Li, Xiaodong; Chen, Chuangtian; Lin, Zheshuai

    2015-01-01

    Negative linear compressibility (NLC), a rare and important mechanical effect with many application potentials, in a crystal of α-BiB3O6 (BIBO) is comprehensively investigated using first-principles calculations and high-pressure synchrotron X-ray diffraction experiments. The results indicate that the BIBO crystal exhibits the second largest NLC among all known inorganic materials over a broad pressure range. This unusual NLC behaviour is due to the rotation and displacement of the rigid [BO3] and [BO4] building units that result in hinge motion in an umbrella-like topology. More importantly, the parallel-polar lone-pair electrons on the Bi3+ cations act as “umbrella stands” to withstand the B-O hinges, thus significantly enhancing the NLC effect. BIBO presents a unique example of a “collapsible umbrella” mechanism for achieving NLC, which could be applied to other framework materials with lone-pair electrons. PMID:26305262

  15. Ginseng, the natural effectual antiviral: Protective effects of Korean Red Ginseng against viral infection

    Directory of Open Access Journals (Sweden)

    Kyungtaek Im

    2016-10-01

    Full Text Available Korean Red Ginseng (KRG is a heat-processed ginseng developed by the repeated steaming and air-drying of fresh ginseng. Compared with fresh ginseng, KRG has been shown to possess greater pharmacological activities and stability because of changes that occur in its chemical constituents during the steaming process. In addition to anticancer, anti-inflammatory, and immune-modulatory activities, KRG and its purified components have also been shown to possess protective effects against microbial infections. Here, we summarize the current knowledge on the properties of KRG and its components on infections with human pathogenic viruses such as respiratory syncytial virus, rhinovirus, influenza virus, human immunodeficiency virus, human herpes virus, hepatitis virus, norovirus, rotavirus, enterovirus, and coxsackievirus. Additionally, the therapeutic potential of KRG as an antiviral and vaccine adjuvant is discussed.

  16. Treatment with vitamin B3 improves functional recovery and reduces GFAP expression following traumatic brain injury in rats.

    Science.gov (United States)

    Hoane, Michael R; Akstulewicz, Stacy L; Toppen, James

    2003-11-01

    Previous studies have shown that administration of vitamin B(3) (B(3)) in animal models of ischemia significantly reduced the size of infarction and improved functional recovery. The present study evaluated the effect of administration of B(3) on recovery of function following traumatic brain injury (TBI), incorporating the bilateral medial frontal cortex contusion injury model. Groups of rats were assigned to B(3) (500 mg/kg) or saline (1.0 ml/kg) treatment conditions and received contusion injuries or sham surgeries. Drug treatment was administered 15 min and 24 h following injury. Rats were examined on a variety of tests to measure sensorimotor performance (bilateral tactile adhesive removal), skilled forelimb use (staircase test), and cognitive ability (reference and working memory) in the Morris Water Maze. Administration of B(3) following injury significantly reduced the behavioral impairments observed on the bilateral tactile removal test, but not on skilled forelimb use. The acquisition of reference and working memory tests were also significantly improved compared to saline-treated rats. Examination of the brains revealed that administration of B(3) significantly reduced the size of the lesion compared to treatment with saline. In addition, examination of glial fibrillary acidic protein (GFAP) expression around the lesion revealed that B(3) significantly reduced the number of GFAP(+) astrocytes. These results indicate that B(3) administration significantly improved behavioral outcome following injury, reduced the size of the lesion, and reduced the expression of GFAP. The current findings suggest that B(3) may have therapeutic potential for the treatment of TBI.

  17. ErbB3 ablation impairs phosphatidylinositol 3-kinase (PI3K)/AKT-dependent mammary tumorigenesis

    Science.gov (United States)

    Cook, Rebecca S.; Garrett, Joan T.; Sánchez, Violeta; Stanford, Jamie C.; Young, Christian; Chakravarty, Anindita; Rinehart, Cammie; Zhang, Yixian; Wu, Yaming; Greenberger, Lee; Horak, Ivan D.; Arteaga, Carlos L.

    2011-01-01

    Summary The ErbB receptor family member ErbB3 has been implicated in breast cancer growth but it has yet to be determined whether its disruption is therapeutically valuable. In a mouse model of mammary carcinoma driven by the polyomavirus middle T (PyVmT) oncogene, the ErbB2 tyrosine kinase inhibitor lapatinib reduced the activation of ErbB3 and Akt along with tumor cell growth. In this phosphatidylinositol-3 kinase (PI3K)-dependent tumor model, ErbB2 is part of a complex containing PyVmT, p85 (PI3K), ErbB3, and Src, that is disrupted by treatment with lapatinib. Thus, full engagement of PI3K/Akt by ErbB2 in this oncogene-induced mouse tumor model may involve its ability to dimerize with and phosphorylate ErbB3, which itself directly binds PI3K. Here we report that ErbB3 is critical for PI3K/AKT-driven tumor formation triggered by the PyVmT oncogene. Tissue-specific, Cre-mediated deletion of ErbB3 reduced Akt phosphorylation, primary tumor growth and pulmonary metastasis. Further EZN-3920, a chemically stabilized antisense oligonucleotide that targets the ErbB3 mRNA in vivo, produced similar effects while causing no mouse toxicity. Our findings offer further preclinical evidence that ErbB3 ablation may be therapeutically effective in tumors where ErbB3 engages PI3K/Akt signaling. PMID:21482676

  18. The adaptor protein SH2B3 (Lnk negatively regulates neurite outgrowth of PC12 cells and cortical neurons.

    Directory of Open Access Journals (Sweden)

    Tien-Cheng Wang

    Full Text Available SH2B adaptor protein family members (SH2B1-3 regulate various physiological responses through affecting signaling, gene expression, and cell adhesion. SH2B1 and SH2B2 were reported to enhance nerve growth factor (NGF-induced neuronal differentiation in PC12 cells, a well-established neuronal model system. In contrast, SH2B3 was reported to inhibit cell proliferation during the development of immune system. No study so far addresses the role of SH2B3 in the nervous system. In this study, we provide evidence suggesting that SH2B3 is expressed in the cortex of embryonic rat brain. Overexpression of SH2B3 not only inhibits NGF-induced differentiation of PC12 cells but also reduces neurite outgrowth of primary cortical neurons. SH2B3 does so by repressing NGF-induced activation of PLCγ, MEK-ERK1/2 and PI3K-AKT pathways and the expression of Egr-1. SH2B3 is capable of binding to phosphorylated NGF receptor, TrkA, as well as SH2B1β. Our data further demonstrate that overexpression of SH2B3 reduces the interaction between SH2B1β and TrkA. Consistent with this finding, overexpressing the SH2 domain of SH2B3 is sufficient to inhibit NGF-induced neurite outgrowth. Together, our data demonstrate that SH2B3, unlike the other two family members, inhibits neuronal differentiation of PC12 cells and primary cortical neurons. Its inhibitory mechanism is likely through the competition of TrkA binding with the positive-acting SH2B1 and SH2B2.

  19. The Lc3-synthase gene B3gnt5 is essential to pre-implantation development of the murine embryo

    Directory of Open Access Journals (Sweden)

    Cinelli Paolo

    2008-11-01

    Full Text Available Abstract Background Glycosphingolipids (GSL are integral components of mammalian cell membranes that are involved in cell adhesion and cell signaling processes. GSL are subdivided into structural series, like ganglio-, lacto/neolacto-, globo- and isoglo-series, which are defined by distinct trisaccharide cores. The β1,3 N-acetylglucosaminyltransferase-V (B3gnt5 enzyme catalyzes the formation of the Lc3 structure, which is the core of lactoseries derived GSL. Results The biological significance of the glycoconjugates produced by the B3gnt5 enzyme was investigated by inactivating the B3gnt5 gene in the mouse germline. The disruption of the B3gnt5 protein-coding region in mouse embryonic stem cells resulted in reduced Lc3-synthase activity, supporting its specific contribution to lactoseries derived GSL synthesis. Breeding of heterozygous mutant mice failed to produce any viable progeny homozygous for the B3gnt5-null allele. The genotypic examination of embryos from heterozygous crosses showed that the disruption of the B3gnt5 gene leads to pre-implantation lethality. This finding was compatible with the expression pattern of the B3gnt5 gene in the pre-implantation embryo as shown by in situ hybridization. The analysis of GSL profiles in embryonic stem cells heterozygous for the B3gnt5-null allele confirmed the reduced levels of lactoseries derived GSL levels and of other GSL species. Conclusion The disruption of the B3gnt5 gene in mice affected the expression of lactoseries derived GLS and possibly of protein-bound β3GlcNAc-linked glycans, thereby demonstrating an essential contribution of these glycoconjugates in early embryonic development, and supporting the importance of these glycoconjugates in cell differentiation and adhesion processes.

  20. Two key residues in ephrinB3 are critical for its use as an alternative receptor for Nipah virus.

    Directory of Open Access Journals (Sweden)

    Oscar A Negrete

    2006-02-01

    Full Text Available EphrinB2 was recently discovered as a functional receptor for Nipah virus (NiV, a lethal emerging paramyxovirus. Ephrins constitute a class of homologous ligands for the Eph class of receptor tyrosine kinases and exhibit overlapping expression patterns. Thus, we examined whether other ephrins might serve as alternative receptors for NiV. Here, we show that of all known ephrins (ephrinA1-A5 and ephrinB1-B3, only the soluble Fc-fusion proteins of ephrinB3, in addition to ephrinB2, bound to soluble NiV attachment protein G (NiV-G. Soluble NiV-G bound to cell surface ephrinB3 and B2 with subnanomolar affinities (Kd = 0.58 nM and 0.06 nM for ephrinB3 and B2, respectively. Surface plasmon resonance analysis indicated that the relatively lower affinity of NiV-G for ephrinB3 was largely due to a faster off-rate (K(off = 1.94 x 10(-3 s(-1 versus 1.06 x 10(-4 s(-1 for ephrinB3 and B2, respectively. EphrinB3 was sufficient to allow for viral entry of both pseudotype and live NiV. Soluble ephrinB2 and B3 were able to compete for NiV-envelope-mediated viral entry on both ephrinB2- and B3-expressing cells, suggesting that NiV-G interacts with both ephrinB2 and B3 via an overlapping site. Mutational analysis indicated that the Leu-Trp residues in the solvent exposed G-H loop of ephrinB2 and B3 were critical determinants of NiV binding and entry. Indeed, replacement of the Tyr-Met residues in the homologous positions in ephrinB1 with Leu-Trp conferred NiV receptor activity to ephrinB1. Thus, ephrinB3 is a bona fide alternate receptor for NiV entry, and two residues in the G-H loop of the ephrin B-class ligands are critical determinants of NiV receptor activity.

  1. Epidemiological and etiological characteristics of hand, foot, and mouth disease in Wuhan, China from 2012 to 2013: outbreaks of coxsackieviruses A10.

    Science.gov (United States)

    Yang, Qin; Ding, Jinya; Cao, Junhao; Huang, Qianchuan; Hong, Chun; Yang, Bin

    2015-06-01

    Hand-foot-mouth disease (HFMD) is a common infectious disease which often occurs in young children. It is caused by enteroviruses, most commonly enterovirus71 (EV71) and Coxsackievirus A16 (CVA16). The present study focuses on the molecular epidemiology of the pathogen of HFMD in the Wuhan region of China during the period 2012 to 2013. A total of 463 viruses were isolated from throat swab of 3,208 HFMD patients and analyzed by quantitative RT-PCR with all sets of specific primers for EV71, CVA16, and pan-enterovirus. Of the 463 viruses, 111 (21.2%) were EV71, 52 (9.6%) were CVA16, and 300 (69.2%) were pan-enterovirus. In pan-enterovirus isolations 190 (52.8%) were CVA10, 50 (13.9%) were CVA4, 30 were CB2, 17 were CB3, 13 were CB5 identified by VP4 gene sequencing. Eleven EV71 isolates were complete genome sequenced and phylogenetic analysis revealed that the EV71 strains that circulated in Wuhan belonged to the C4 subgenotype. Among the 190 CVA10 isolations, 187 CVA10 strains have the same nucleotide sequence, the other three CVA10 strains belongs to another type of nucleotide sequence. Phylogenetic analysis based on 19 CVA10 isolations suggested that they belonged to the clade of Chinese strains, but form different clusters isolated from Japan, Europe. This study showed that EVA71 and CVA16 were detected as the predominant viruses (>60%) in 2012 and the total reported HFMD cases attained a peak in June and July. In contrast, CVA10 was also detected during April 2012 and replaced EVA71 and CVA16 as the major HFMD-associated pathogen from May 2013. © 2015 Wiley Periodicals, Inc.

  2. Groundwater Monitoring Plan for the Hanford Site 216-B-3 Pond RCRA Facility

    Energy Technology Data Exchange (ETDEWEB)

    Barnett, D BRENT.; Smith, Ronald M.; Chou, Charissa J.; McDonald, John P.

    2005-11-01

    The 216-B-3 Pond system was a series of ponds used for disposal of liquid effluent from past Hanford production facilities. In operation from 1945 to 1997, the B Pond System has been a Resource Conservation and Recovery Act (RCRA) facility since 1986, with RCRA interim-status groundwater monitoring in place since 1988. In 1994 the expansion ponds of the facility were clean closed, leaving only the main pond and a portion of the 216-B-3-3 ditch as the currently regulated facility. In 2001, the Washington State Department of Ecology (Ecology) issued a letter providing guidance for a two-year, trial evaluation of an alternate, intrawell statistical approach to contaminant detection monitoring at the B Pond system. This temporary variance was allowed because the standard indicator-parameters evaluation (pH, specific conductance, total organic carbon, and total organic halides) and accompanying interim status statistical approach is ineffective for detecting potential B-Pond-derived contaminants in groundwater, primarily because this method fails to account for variability in the background data and because B Pond leachate is not expected to affect the indicator parameters. In July 2003, the final samples were collected for the two-year variance period. An evaluation of the results of the alternate statistical approach is currently in progress. While Ecology evaluates the efficacy of the alternate approach (and/or until B Pond is incorporated into the Hanford Facility RCRA Permit), the B Pond system will return to contamination-indicator detection monitoring. Total organic carbon and total organic halides were added to the constituent list beginning with the January 2004 samples. Under this plan, the following wells will be monitored for B Pond: 699-42-42B, 699-43-44, 699-43-45, and 699-44-39B. The wells will be sampled semi-annually for the contamination indicator parameters (pH, specific conductance, total organic carbon, and total organic halides) and annually for

  3. SiB3 Modeled Global 1-degree Hourly Biosphere-Atmosphere Carbon Flux, 1998-2006

    Data.gov (United States)

    National Aeronautics and Space Administration — ABSTRACT: The Simple Biosphere Model, Version 3 (SiB3) was used to produce a global data set of hourly carbon fluxes between the atmosphere and the terrestrial...

  4. SiB3 Modeled Global 1-degree Hourly Biosphere-Atmosphere Carbon Flux, 1998-2006

    Data.gov (United States)

    National Aeronautics and Space Administration — The Simple Biosphere Model, Version 3 (SiB3) was used to produce a global data set of hourly carbon fluxes between the atmosphere and the terrestrial biosphere for...

  5. A Study of A B3R Converter Based PCU, to Confirm the Flexibility and Performance of the Converter Topology

    Directory of Open Access Journals (Sweden)

    Mache Erik

    2017-01-01

    - Conclude the study by comparing the achieved performances (including efficiency and mass versus current solutions implemented on a satellite PCU. Summary of the pros and cons of the use of the B3R concept.

  6. EphrinB1/EphB3b Coordinate Bidirectional Epithelial-Mesenchymal Interactions Controlling Liver Morphogenesis and Laterality

    DEFF Research Database (Denmark)

    Cayuso, Jordi; Dzementsei, Aliaksandr; Fischer, Johanna C

    2016-01-01

    and adjacent lateral plate mesoderm (LPM), resulting in asymmetric positioning of the zebrafish liver. EphrinB1 in hepatoblasts regulates directional migration and mediates interactions with the LPM, where EphB3b controls polarity and movement of the LPM. EphB3b in the LPM concomitantly repels hepatoblasts...... to move leftward into the liver bud. Cellular protrusions controlled by Eph/Ephrin signaling mediate hepatoblast motility and long-distance cell-cell contacts with the LPM beyond immediate tissue interfaces. Mechanistically, intracellular EphrinB1 domains mediate EphB3b-independent hepatoblast extension...... formation, while EpB3b interactions cause their destabilization. We propose that bidirectional short- and long-distance cell interactions between epithelial and mesenchyme-like tissues coordinate liver bud formation and laterality via cell repulsion....

  7. A Study of A B3R Converter Based PCU, to Confirm the Flexibility and Performance of the Converter Topology

    OpenAIRE

    Mache Erik; Koch Michael

    2017-01-01

    The main objective of this activity was to study the B3R converter [1] and to confirm its flexibility and performance (mainly efficiency and mass reduction) versus solutions that is implemented in a satellite PCU. For details see [2] ESTEC SOW. An architecture with centralised regulated bus, single battery and centralised solar array was selected for this study. Project Plan: - Study, design and development of an evaluation prototype, based on the B3R topology (including protections ...

  8. Respiratory viral infections among pediatric inpatients and outpatients in Taiwan from 1997 to 1999.

    Science.gov (United States)

    Tsai, H P; Kuo, P H; Liu, C C; Wang, J R

    2001-01-01

    The present study examined the association of specific virus infections with acute respiratory tract conditions among hospitalized and outpatient children in a subtropical country. A total of 2,295 virus infections were detected in 6,986 patients between 1997 and 1999, including infections caused by respiratory syncytial virus (RSV) (1.7%), parainfluenza virus (2.0%), influenza B virus (2.6%), adenovirus (4.0%), herpes simplex virus type 1 (4. 4%), influenza A virus (5.5%), and enterovirus (12.7%). There were 61 mixed infections, and no consistent seasonal variation was found. One or more viruses were detected among 24.8% of hospitalized patients and 35.0% of outpatients. The frequencies and profiles of detection of various viruses among in- and outpatients were different. The occurrence of enterovirus infections exceeded that of other viral infections detected in 1998 and 1999 due to outbreaks of enterovirus 71 and coxsackievirus A10. RSV was the most prevalent virus detected among hospitalized children, whereas influenza virus was the most frequently isolated virus in the outpatient group. Most respiratory viral infections (39.3%) occurred in children between 1 and 3 years old. RSV (P tonsilitis (45.5%). These data expand our understanding of the etiology of acute respiratory tract viral infections among in- and outpatients in a subtropical country and may contribute to the prevention and control of viral respiratory tract infections.

  9. State Environmental Policy Act (SEPA) Environmental Checklist Form 216-B-3 Expansion Ponds Closure Plan. Revision 1

    Energy Technology Data Exchange (ETDEWEB)

    1993-12-01

    The 216-B-3 Expansion Ponds Closure Plan (Revision 1) consists of a Part A Dangerous Waste Permit Application and a Resource Conservation and Recovery Act Closure Plan. An explanation of the Part A submitted with this document is provided at the beginning of the Part A Section. The closure plan consists of nine chapters and five appendices. The 216-B-3 Pond System consists of a series of four earthen, unlined, interconnected ponds and the 216-B-3-3 Ditch that receive waste water from various 200 East Area operating facilities. These four ponds, collectively. Waste water (primarily cooling water, steam condensate, and sanitary water) from various 200 East Area facilities is discharged to the 216-B-3-3 Ditch. Water discharged to the 216-8-3-3 Ditch flows directly into the 216-B-3 Pond. In the past, waste water discharges to B Pond and the 216-B-3-3 Ditch contained mixed waste (radioactive waste and dangerous waste). The radioactive portion of mixed waste has been interpreted by the US Department of Energy (DOE) to be regulated under the Atomic Energy Act of 1954; the nonradioactive dangerous portion of mixed waste is regulated under RCRA. Mixed waste also may be considered a hazardous substance under the Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA) when considering remediation of waste sites.

  10. Modified creep and shrinkage prediction model B3 for serviceability limit state analysis of composite slabs

    Science.gov (United States)

    Gholamhoseini, Alireza

    2016-03-01

    Relatively little research has been reported on the time-dependent in-service behavior of composite concrete slabs with profiled steel decking as permanent formwork and little guidance is available for calculating long-term deflections. The drying shrinkage profile through the thickness of a composite slab is greatly affected by the impermeable steel deck at the slab soffit, and this has only recently been quantified. This paper presents the results of long-term laboratory tests on composite slabs subjected to both drying shrinkage and sustained loads. Based on laboratory measurements, a design model for the shrinkage strain profile through the thickness of a slab is proposed. The design model is based on some modifications to an existing creep and shrinkage prediction model B3. In addition, an analytical model is developed to calculate the time-dependent deflection of composite slabs taking into account the time-dependent effects of creep and shrinkage. The calculated deflections are shown to be in good agreement with the experimental measurements.

  11. Safety assessment of nicotinamide riboside, a form of vitamin B3.

    Science.gov (United States)

    Conze, D B; Crespo-Barreto, J; Kruger, C L

    2016-01-20

    Nicotinamide riboside (NR) is a naturally occurring form of vitamin B 3 present in trace amounts in some foods. Like niacin, it has been shown to be a precursor in the biosynthesis of nicotinamide adenine dinucleotide (NAD+). The safety of Niagen™, a synthetic form of NR, was determined using a bacterial reverse mutagenesis assay (Ames), an in vitro chromosome aberration assay, an in vivo micronucleus assay, and acute, 14-day and 90-day rat toxicology studies. NR was not genotoxic. There was no mortality at an oral dose of 5000 mg/kg. Based on the results of a 14-day study, a 90-day study was performed comparing NR at 300, 1000, and 3000 mg/kg/day to an equimolar dose of nicotinamide at 1260 mg/kg/day as a positive control. Results from the study show that NR had a similar toxicity profile to nicotinamide at the highest dose tested. Target organs of toxicity were liver, kidney, ovaries, and testes. The lowest observed adverse effect level for NR was 1000 mg/kg/day, and the no observed adverse effect level was 300 mg/kg/day. © The Author(s) 2016.

  12. Nicotinamide riboside, a form of vitamin B3, protects against excitotoxicity-induced axonal degeneration.

    Science.gov (United States)

    Vaur, Pauline; Brugg, Bernard; Mericskay, Mathias; Li, Zhenlin; Schmidt, Mark S; Vivien, Denis; Orset, Cyrille; Jacotot, Etienne; Brenner, Charles; Duplus, Eric

    2017-12-01

    NAD + depletion is a common phenomenon in neurodegenerative pathologies. Excitotoxicity occurs in multiple neurologic disorders and NAD + was shown to prevent neuronal degeneration in this process through mechanisms that remained to be determined. The activity of nicotinamide riboside (NR) in neuroprotective models and the recent description of extracellular conversion of NAD + to NR prompted us to probe the effects of NAD + and NR in protection against excitotoxicity. Here, we show that intracortical administration of NR but not NAD + reduces brain damage induced by NMDA injection. Using cortical neurons, we found that provision of extracellular NR delays NMDA-induced axonal degeneration (AxD) much more strongly than extracellular NAD + Moreover, the stronger effect of NR compared to NAD + depends of axonal stress since in AxD induced by pharmacological inhibition of nicotinamide salvage, both NAD + and NR prevent neuronal death and AxD in a manner that depends on internalization of NR. Taken together, our findings demonstrate that NR is a better neuroprotective agent than NAD + in excitotoxicity-induced AxD and that axonal protection involves defending intracellular NAD + homeostasis.-Vaur, P., Brugg, B., Mericskay, M., Li, Z., Schmidt, M. S., Vivien, D., Orset, C., Jacotot, E., Brenner, C., Duplus, E. Nicotinamide riboside, a form of vitamin B 3 , protects against excitotoxicity-induced axonal degeneration. © FASEB.

  13. Effective treatment of mitochondrial myopathy by nicotinamide riboside, a vitamin B3.

    Science.gov (United States)

    Khan, Nahid A; Auranen, Mari; Paetau, Ilse; Pirinen, Eija; Euro, Liliya; Forsström, Saara; Pasila, Lotta; Velagapudi, Vidya; Carroll, Christopher J; Auwerx, Johan; Suomalainen, Anu

    2014-06-01

    Nutrient availability is the major regulator of life and reproduction, and a complex cellular signaling network has evolved to adapt organisms to fasting. These sensor pathways monitor cellular energy metabolism, especially mitochondrial ATP production and NAD(+)/NADH ratio, as major signals for nutritional state. We hypothesized that these signals would be modified by mitochondrial respiratory chain disease, because of inefficient NADH utilization and ATP production. Oral administration of nicotinamide riboside (NR), a vitamin B3 and NAD(+) precursor, was previously shown to boost NAD(+) levels in mice and to induce mitochondrial biogenesis. Here, we treated mitochondrial myopathy mice with NR. This vitamin effectively delayed early- and late-stage disease progression, by robustly inducing mitochondrial biogenesis in skeletal muscle and brown adipose tissue, preventing mitochondrial ultrastructure abnormalities and mtDNA deletion formation. NR further stimulated mitochondrial unfolded protein response, suggesting its protective role in mitochondrial disease. These results indicate that NR and strategies boosting NAD(+) levels are a promising treatment strategy for mitochondrial myopathy. © 2014 The Authors. Published under the terms of the CC BY license.

  14. Characterization and functional analysis of a B3 domain factor from Zea mays.

    Science.gov (United States)

    Liu, Yinghui; Yuan, Jincheng; Ma, Halian; Song, Jinhui; Wang, Lingyun; Weng, Qiaoyun

    2015-11-01

    In this study, we isolated a full-length cDNA and named ZmBDF from zea mays. ZmBDF encoded a protein of 356 amino acids and phylogenetic analysis showed that it belongs to a closely related subgroup with B3 domain factors in plants. The transcript level of ZmBDF could be induced by ABA, MeJA, salt or drought treatments. To further investigated the function of ZmBDF, ZmBDF over-expression transgenic lines were got by transforming it into Arabidopsis thaliana. ZmBDF over-expression transgenic plants in Arabidopsis could increase drought and salt tolerant in germination assay. Under drought condition, net photosynthetic rates (PN), stomatal conductance (gs), and internal leaf CO2 concentration (Ci) were less affected in transgenic plants compared with wild type. Besides, the chlorophyll a and chlorophyll b (chl a/chl b) ratio decreased in WT plants than the transgenic plants and total carotenoid content show opposite trends. Moreover, transgenic plants could also reduce the stomatal density and changed the stomatal shape. Taken together, our data suggested that ZmBDF could improve stress tolerance to drought and salt in maize.

  15. On the formation of niacin (vitamin B3) and pyridine carboxylic acids in interstellar model ices

    Science.gov (United States)

    McMurtry, Brandon M.; Turner, Andrew M.; Saito, Sean E. J.; Kaiser, Ralf I.

    2016-06-01

    The formation of pyridine carboxylic acids in interstellar ice grains was simulated by electron exposures of binary pyridine (C5H5N)-carbon dioxide (CO2) ice mixtures at 10 K under contamination-free ultrahigh vacuum conditions. Chemical processing of the pristine ice and subsequent warm-up phase was monitored on line and in situ via Fourier transform infrared spectroscopy to probe for the formation of new radiation induced species. In the infrared spectra of the irradiated ice, bands assigned to nicotinic acid (niacin; vitamin B3; m-C5H4NCOOH) along with 2,3-, 2,5-, 3,4-, and 3,5-pyridine dicarboxylic acid (C5H3N(COOH)2) were unambiguously identified along with the hydroxycarbonyl (HOCO) radical. Our study suggests that the reactive pathway responsible for pyridine carboxylic acids formation involves a HOCO intermediate, which forms through the reaction of suprathermal hydrogen ejected from pyridine with carbon dioxide. The newly formed pyridinyl radical may then undergo radical-radical recombination with a hydroxycarbonyl radical to form a pyridine carboxylic acid.

  16. On the formation of niacin (vitamin B3) and pyridine carboxylic acids in interstellar model ices

    Energy Technology Data Exchange (ETDEWEB)

    McMurtry, Brandon M.; Turner, Andrew M.; Saito, Sean E.J.; Kaiser, Ralf I. [W. M. Keck Research Laboratory in Astrochemistry, University of Hawaii at Manoa, Honolulu, Hawaii, HI 96822 (United States); Department of Chemistry, University of Hawaii at Manoa, Honolulu, Hawaii, HI 96822 (United States)

    2016-06-15

    The formation of pyridine carboxylic acids in interstellar ice grains was simulated by electron exposures of binary pyridine (C{sub 5}H{sub 5}N)-carbon dioxide (CO{sub 2}) ice mixtures at 10 K under contamination-free ultrahigh vacuum conditions. Chemical processing of the pristine ice and subsequent warm-up phase was monitored on line and in situ via Fourier transform infrared spectroscopy to probe for the formation of new radiation induced species. In the infrared spectra of the irradiated ice, bands assigned to nicotinic acid (niacin; vitamin B3; m-C{sub 5}H{sub 4}NCOOH) along with 2,3-, 2,5-, 3,4-, and 3,5-pyridine dicarboxylic acid (C{sub 5}H{sub 3}N(COOH){sub 2}) were unambiguously identified along with the hydroxycarbonyl (HOCO) radical. Our study suggests that the reactive pathway responsible for pyridine carboxylic acids formation involves a HOCO intermediate, which forms through the reaction of suprathermal hydrogen ejected from pyridine with carbon dioxide. The newly formed pyridinyl radical may then undergo radical–radical recombination with a hydroxycarbonyl radical to form a pyridine carboxylic acid.

  17. Seroprevalence of human enterovirus 71 and coxsackievirus A16 in Guangdong, China, in pre- and post-2010 HFMD epidemic period.

    Directory of Open Access Journals (Sweden)

    Wei Li

    Full Text Available BACKGROUND: Human Enterovirus 71 and Coxsackie A16 have caused many outbreaks in the last decade in mainland China, resulting in thousands of fatal cases. Seroepidemiology which provides important information to document population immunity is rare in China. METHODOLOGY/PRINCIPAL FINDINGS: A cross sectional study of Enterovirus 71 (EV71 and Coxsackie A16 (CA16 seroprevalence was carried out in Guangdong, China, pre- and post- the 2010 hand, foot and mouth disease (HFMD epidemic period. The levels of EV71 and CA16 specific antibodies were evaluated by a microneutralization test and the geometric mean titer (GMT was calculated and compared. Our results indicated frequent infection by EV71 and CA16 in Guangdong before the 2010 epidemic. Only EV71 neutralizing antibody but not CA16 seroprevalence was significantly increased after the 2010 HFMD epidemic. Children less than 3 years old especially those aged 2 years showed the lowest positive rates for EV71 and CA16 NA before epidemic and the most significantly increased EV71 seroprevalence after epidemic. CA16 GMT values declined after the 2010 epidemic. CONCLUSIONS: These results indicate EV71 was the major pathogen of HFMD in Guangdong during the 2010 epidemic. The infection occurs largely in children less than 3 years, who should have first priority to receive an EV71 vaccine.

  18. Evaluation of FlaB1, FlaB2, FlaB3, and Tp0463 of Treponema pallidum for serodiagnosis of syphilis.

    Science.gov (United States)

    Jiang, Chuanhao; Xiao, Jinhong; Xie, Yafeng; Xiao, Yongjian; Wang, Chuan; Kuang, Xingxing; Xu, Man; Li, Ranhui; Zeng, Tiebing; Liu, Shuanquan; Yu, Jian; Zhao, Feijun; Wu, Yimou

    2016-02-01

    Syphilis is a multistage disease caused by the invasive spirochete Treponema pallidum subsp. pallidum, and accurate diagnosis is important for the prevention and treatment of syphilis. Here, to identify appropriate diagnostic antigens for serodiagnosis of syphilis, 6 recombinant proteins were expressed in Escherichia coli and purified, including flagellins (FlaB1 [Tp0868], FlaB2 [Tp0792], and FlaB3 [Tp0870]), Tp0463, Tp0751, and Tp1038. The sensitivities were determined by screening sera from individuals with primary (n=82), secondary (n=115), latent (n=105), and congenital (n=65) syphilis. The specificities were determined by screening sera from uninfected controls (n=30) and potentially cross-reactive infections including Lyme disease (n=30), leptospirosis (n=5), and hepatitis B (n=30). Our data showed that FlaB1, FlaB2, FlaB3, Tp0463, and Tp1038 exhibited higher overall sensitivities and specificities for detecting IgG antibody, with 95.4% and 98.9%, 92.6% and 95.8%, 95.1% and 95.8%, 92.6% and 97.9%, and 95.9% and 98.9%, respectively. In contrast, Tp0751 demonstrated only an overall sensitivity of 39.2%. For comparison, the sensitivity and specificity of Architect Syphilis TP were determined to be 98.1% and 93.7%, respectively. In addition, FlaB1, FlaB2, FlaB3, and Tp0463 demonstrated excellent performance for detecting IgM antibody in primary and congenital syphilis, with sensitivities of 76.8% and 83.1%, 72.0% and 87.7%, 74.4% and 89.2%, and 64.6% and 75.3%, respectively. These results indicate that FlaB1, FlaB2, FlaB3, and Tp0463 could be as novel diagnostic candidates for serodiagnosis of syphilis. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Type B3 Thymoma in a Twelve-Year-Old Girl

    Directory of Open Access Journals (Sweden)

    Nilgun Selçuk Duru

    2013-12-01

    Full Text Available Timik epitelyal tümörler; timomalar, timik karsinoidler ve timik karsinomaları kapsamaktadır. Hemen hemen tamamı 20 yaş üstü olan olguların %70’i 40 yaş üstüdür. Mediastinal tümorler içinde erişkinlerdeki %30’luk oran ile karşılaştırıldığında çocuklarda %1 oranındaki görülme sıklığı tanı koymayı güçleştirir. Biz burada öksürük, ateş ve göğüs ağrısı gibi pnömoni bulguları ile gelen 12 yaşında bir kız çocuğunu sunduk. Akciğer grafisinde mediastinal genişleme ve sağda opasite görülen hastanın bilgisayarlı tomografisinde kitle saptandı. Cerrahi olarak çıkarılan kitlenin histolojik ve immünohistokimyasal incelemeleri B3 timoma olduğunu gösterdi. Olgu çocuklarda timomanın nadir görülmesi nedeni ile sunulmuştur. (The Medical Bulletin of Haseki 2013;51:200-02

  20. Luteolin Inhibits Ischemia/Reperfusion-Induced Myocardial Injury in Rats via Downregulation of microRNA-208b-3p.

    Directory of Open Access Journals (Sweden)

    Chen Bian

    Full Text Available Luteolin (LUT, a kind of flavonoid which is extracted from a variety of diets, has been reported to convey protective effects of various diseases. Recent researches have suggested that LUT can carry out cardioprotective effects during ischemia/reperfusion (I/R. However, there have no reports on whether LUT can exert protective effects against myocardial I/R injury through the actions of specific microRNAs (miRs. The purpose of this study was to determine which miRs and target genes LUT exerted such function through.Expression of various miRs in perfused rat hearts was detected using a gene chip. Target genes were predicted with TargetScan, MiRDB and MiRanda. Anoxia/reoxygenation was used to simulate I/R. Cells were transfected by miR-208b-3p mimic, inhibitor and small interfering RNA of Ets1 (avian erythroblastosis virus E26 (v ets oncogene homolog 1. MiR-208b-3p and Ets1 mRNA were quantified by real-time quantitative polymerase chain reaction. The percentage of apoptotic cells was detected by annexin V-fluorescein isothiocyanate/propidium iodide dyeing and flow cytometry. The protein expression levels of cleaved caspase-3, Bcl-2, Bax, and Ets1 were examined by western blot analysis. A luciferase reporter assay was used to verify the combination between miR-208b-3p and the 3'-untranslated region of Ets1.LUT pretreatment reduced miR-208b-3p expression in myocardial tissue, as compared to the I/R group. And LUT decreased miR-208b-3p expression and apoptosis caused by I/R. However, overexpression of miR-208b-3p further aggravated the changes caused by I/R and blocked all the effects of LUT. Knockdown of miR-208b-3p expression also attenuated apoptosis, while knockdown of Ets1 promoted apoptosis. Further, the luciferase reporter assay showed that miR-208b-3p could inhibit Ets1 expression.LUT pretreatment conveys anti-apoptotic effects after myocardial I/R injury by decreasing miR-208b-3p and increasing Ets1 expression levels.

  1. Approximate first-principles anharmonic calculations of polyatomic spectra using MP2 and B3LYP potentials: comparisons with experiment.

    Science.gov (United States)

    Roy, Tapta Kanchan; Carrington, Tucker; Gerber, R Benny

    2014-08-21

    Anharmonic vibrational spectroscopy calculations using MP2 and B3LYP computed potential surfaces are carried out for a series of molecules, and frequencies and intensities are compared with those from experiment. The vibrational self-consistent field with second-order perturbation correction (VSCF-PT2) is used in computing the spectra. The test calculations have been performed for the molecules HNO3, C2H4, C2H4O, H2SO4, CH3COOH, glycine, and alanine. Both MP2 and B3LYP give results in good accord with experimental frequencies, though, on the whole, MP2 gives very slightly better agreement. A statistical analysis of deviations in frequencies from experiment is carried out that gives interesting insights. The most probable percentage deviation from experimental frequencies is about -2% (to the red of the experiment) for B3LYP and +2% (to the blue of the experiment) for MP2. There is a higher probability for relatively large percentage deviations when B3LYP is used. The calculated intensities are also found to be in good accord with experiment, but the percentage deviations are much larger than those for frequencies. The results show that both MP2 and B3LYP potentials, used in VSCF-PT2 calculations, account well for anharmonic effects in the spectroscopy of molecules of the types considered.

  2. Cryo-electron microscopy study of insect cell-expressed enterovirus 71 and coxsackievirus a16 virus-like particles provides a structural basis for vaccine development.

    Science.gov (United States)

    Gong, Minqing; Zhu, Hongtao; Zhou, Jun; Yang, Chunting; Feng, Jing; Huang, Xiaojun; Ji, Gang; Xu, Honglin; Zhu, Ping

    2014-06-01

    Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) are the two most common etiological agents responsible for the epidemics of hand, foot, and mouth disease (HFMD), a childhood illness with occasional severe neurological complications. A number of vaccine candidates against EV71 or CA16 have been reported; however, no vaccine is currently available for clinical use. Here, we generated a secreted version of EV71 and CA16 virus-like particles (VLPs) using a baculovirus-insect cell expression system and reconstructed the three-dimensional (3D) structures of both VLPs by cryo-electron microscopy (cryo-EM) single-particle analysis at 5.2-Å and 5.5-Å resolutions, respectively. The reconstruction results showed that the cryo-EM structures of EV71 and CA16 VLPs highly resemble the recently published crystal structures for EV71 natural empty particles and CA16 135S-like expanded particles, respectively. Our cryo-EM analysis also revealed that the majority of previously identified linear neutralizing epitopes are well preserved on the surface of EV71 and CA16 VLPs. In addition, both VLPs were able to induce efficiently neutralizing antibodies against various strains of EV71 and CA16 viruses in mouse immunization. These studies provide a structural basis for the development of insect cell-expressed VLP vaccines and for a potential bivalent VLP vaccine against both EV71- and CA16-associated HFMD. The recent outbreaks of hand, foot, and mouth disease (HFMD) in the Asia Pacific region spurred the search for effective vaccines against EV71 and CA16 viruses, the two most common etiological agents responsible for HFMD. In this paper, we show that secreted versions of EV71 and CA16 VLPs generated in the baculovirus-insect cell expression system highly resemble the crystal structures of their viral conterparts and that the majority of previously identified linear neutralizing epitopes are well preserved on the VLP surfaces. In addition, the generated VLPs can efficiently induce

  3. DFT study on the isomerization and tautomerism in vitamins B3 (niacin), B5 (pantothenic acid) and B7 (biotin)

    Science.gov (United States)

    Valadbeigi, Younes; Farrokhpour, Hossein; Tabrizchi, Mahmoud

    2014-05-01

    Isomerization and tautomerism of the three water soluble vitamins including B3, B5 and B7 were studied applying density functional theory using B3LYP method in gas and aqueous phases. Activation energies (Ea), Gibbs free energies of activation (ΔG#), and imaginary frequencies of the transition state structures were calculated for all the isomerization and tautomerism reactions. Activation energies of the neutral → zwitterion (amine-enamine) tautomerism in vitamin B3 were 310-360 kJ/mol where these values for the keto-enol tautomerism were 100-130 kJ/mol. It was found that water molecule catalyzes the tautomerism and decreases the activation energies about 90-160 kJ/mol.

  4. Interaction between the ADH1B*3 allele and drinking motives on alcohol use among Black college students.

    Science.gov (United States)

    Zaso, Michelle J; Desalu, Jessica M; Kim, Jueun; Suryadevara, Kavita; Belote, John M; Park, Aesoon

    2017-06-29

    Black young adults have lower rates of alcohol use than other racial groups. Genetic factors may protect against drinking. Specifically, the ADH1B*3 allele is present almost exclusively in Black populations and has been protective against alcohol use and alcohol use disorder. The protective effects of the ADH1B*3 allele, however, may differ as a function of alcohol-promoting cognitions. The current study examined whether ADH1B*3 moderated relations of drinking motives with alcohol consumption among Black college drinkers. Participants were 241 undergraduate students of self-identified Black race (mean age = 20 years; 66% female) who reported consuming alcohol at least once in the past 30 days. ADH1B*3 was not significantly associated with drinking motives or drinking behaviors. However, significant, albeit small, interaction effects of ADH1B*3 with drinking motives on drinking behavior were found; the presence of an ADH1B*3 allele protected against greater drinking quantity among students with high social motives (incidence rate ratio [IRR] = 0.95, 95% CI [0.92, 0.99]) and against frequent drinking among students with low coping motives (IRR = 1.06, 95% CI [1.01, 1.11]). These findings represent a novel demonstration of genetic modulation of alcohol-related cognitions within Black college drinkers, although replication is needed. Results represent an initial step toward better characterizing individual differences in associations of drinking motives with drinking behavior, with potential implications for interventions aimed at motivational processes in alcohol use.

  5. Remaining Sites Verification Package for the 128-B-3 Burn Pit Site, Waste Site Reclassification Form 2006-058

    Energy Technology Data Exchange (ETDEWEB)

    L. M. Dittmer

    2006-11-17

    The 128-B-3 waste site is a former burn and disposal site for the 100-B/C Area, located adjacent to the Columbia River. The 128-B-3 waste site has been remediated to meet the remedial action objectives specified in the Remaining Sites ROD. The results of verification sampling demonstrated that residual contaminant concentrations do not preclude any future uses and allow for unrestricted use of shallow zone soils. The results of sampling at upland areas of the site also showed that residual contaminant concentrations are protective of groundwater and the Columbia River.

  6. Serial prenatal and postnatal MRI of dystroglycanopathy in a patient with familial B3GALNT2 mutation

    Energy Technology Data Exchange (ETDEWEB)

    Ho, Mai-Lan [Mayo Clinic, Department of Radiology, Rochester, MN (United States); Glenn, Orit A. [University of California, Department of Radiology, San Francisco, CA (United States); Sherr, Eliott H. [University of California, Department of Neurology, San Francisco, CA (United States); University of California, Department of Pediatrics, San Francisco, CA (United States); Strober, Jonathan B. [University of California, Department of Neurology, San Francisco, CA (United States)

    2017-06-15

    The dystroglycanopathies are a heterogeneous group of conditions, with mutations in B3GALNT2 described in association with congenital muscular dystrophy. The serial prenatal MRI findings in this disorder have not been well described. We present sequential prenatal and postnatal MRI findings in a boy with compound heterozygous mutations in B3GALNT2, as well as the MRI findings of his two siblings with similar mutations. These findings provide new insight into the molecular pathogenesis and neurodevelopment of congenital muscular dystrophy. (orig.)

  7. A Three-Dimensional Cell Culture Model To Study Enterovirus Infection of Polarized Intestinal Epithelial Cells.

    Science.gov (United States)

    Drummond, Coyne G; Nickerson, Cheryl A; Coyne, Carolyn B

    2016-01-01

    Despite serving as the primary entry portal for coxsackievirus B (CVB), little is known about CVB infection of the intestinal epithelium, owing at least in part to the lack of suitable in vivo models and the inability of cultured cells to recapitulate the complexity and structure associated with the gastrointestinal (GI) tract. Here, we report on the development of a three-dimensional (3-D) organotypic cell culture model of Caco-2 cells to model CVB infection of the gastrointestinal epithelium. We show that Caco-2 cells grown in 3-D using the rotating wall vessel (RWV) bioreactor recapitulate many of the properties of the intestinal epithelium, including the formation of well-developed tight junctions, apical-basolateral polarity, brush borders, and multicellular complexity. In addition, transcriptome analyses using transcriptome sequencing (RNA-Seq) revealed the induction of a number of genes associated with intestinal epithelial differentiation and/or intestinal processes in vivo when Caco-2 cells were cultured in 3-D. Applying this model to CVB infection, we found that although the levels of intracellular virus production were similar in two-dimensional (2-D) and 3-D Caco-2 cell cultures, the release of infectious CVB was enhanced in 3-D cultures at early stages of infection. Unlike CVB, the replication of poliovirus (PV) was significantly reduced in 3-D Caco-2 cell cultures. Collectively, our studies show that Caco-2 cells grown in 3-D using the RWV bioreactor provide a cell culture model that structurally and transcriptionally represents key aspects of cells in the human GI tract and can thus be used to expand our understanding of enterovirus-host interactions in intestinal epithelial cells. IMPORTANCE Coxsackievirus B (CVB), a member of the enterovirus family of RNA viruses, is associated with meningitis, pericarditis, diabetes, dilated cardiomyopathy, and myocarditis, among other pathologies. CVB is transmitted via the fecal-oral route and encounters the

  8. Misbalance in type III collagen formation/degradation as a novel serological biomarker for penetrating (Montreal B3) Crohn's disease

    NARCIS (Netherlands)

    van Haaften, W. T.; Mortensen, J. H.; Karsdal, M. A.; Bay-Jensen, A. C.; Dijkstra, G.; Olinga, P.

    Background: Misbalances in extracellular matrix turnover are key factors in the development of stricturing (Montreal B2) and penetrating (Montreal B3) Crohn's disease. Aim: To determine whether serological markers for collagen formation and degradation could serve as biomarkers for complications of

  9. 75 FR 48615 - Airworthiness Directives; Eurocopter France (ECF) Model AS350B3 and EC130 B4 Helicopters

    Science.gov (United States)

    2010-08-11

    ... Directives; Eurocopter France (ECF) Model AS350B3 and EC130 B4 Helicopters AGENCY: Federal Aviation... 073254 and modification of the Model EC130 B4 by MOD 073773. Failure of a contactor can prevent switching... No. 05A009, for the Model EC130 B4 helicopters. Both ASB's are dated November 16, 2009. Both ASBs...

  10. Evaluation of dispersion-corrected density functional theory (B3LYP-DCP) for compounds of biochemical interest.

    Science.gov (United States)

    Lill, Sten O Nilsson

    2010-09-01

    An evaluation of a dispersion-corrected density functional theory method (B3LYP-DCP) [I.D. Mackie, G.A. DiLabio, Interactions in large, polyaromatic hydrocarbon dimers: application of density functional theory with dispersion corrections, J. Phys. Chem. A 112 (2008) 10968-10976] for three systems of biochemical interest is presented. Firstly, structures and energies of isomers of the tripeptide Phe-Gly-Phe have been compared with CCSD(T)/CBS//RI-MP2/cc-pVTZ literature values. In the system aromatic interactions compete with XH-pi (X=C, N) interactions and hydrogen bonds which makes it a reliable model for proteins. The resulting mean absolute deviation between B3LYP-DCP and CCSD(T)/CBS relative energies is found to be 0.50 kcal mol(-1). Secondly, a phenylalanine derivative featuring a CH-pi interaction has been investigated. A comparison between the optimized geometry and X-ray crystal data shows that B3LYP-DCP accurately predicts the interaction between the two aromatic rings. Thirdly, the dipeptide Ac-Phe-Phe-NH(2) which contains an edge-to-face interaction between two aromatic rings has been studied. The study demonstrates the general applicability of the B3LYP-DCP method on systems which features interactions typically present in biochemical compounds. (c) 2010 Elsevier Inc. All rights reserved.

  11. An EAV-HP insertion in 5' Flanking region of SLCO1B3 causes blue eggshell in the chicken.

    Directory of Open Access Journals (Sweden)

    Zhepeng Wang

    Full Text Available The genetic determination of eggshell coloration has not been determined in birds. Here we report that the blue eggshell is caused by an EAV-HP insertion that promotes the expression of SLCO1B3 gene in the uterus (shell gland of the oviduct in chicken. In this study, the genetic map location of the blue eggshell gene was refined by linkage analysis in an F(2 chicken population, and four candidate genes within the refined interval were subsequently tested for their expression levels in the shell gland of the uterus from blue-shelled and non-blue-shelled hens. SLCO1B3 gene was found to be the only one expressed in the uterus of blue-shelled hens but not in that of non-blue-shelled hens. Results from a pyrosequencing analysis showed that only the allele of SLCO1B3 from blue-shelled chickens was expressed in the uterus of heterozygous hens (O*LC/O*N. SLCO1B3 gene belongs to the organic anion transporting polypeptide (OATP family; and the OATPs, functioning as membrane transporters, have been reported for the transportation of amphipathic organic compounds, including bile salt in mammals. We subsequently resequenced the whole genomic region of SLCO1B3 and discovered an EAV-HP insertion in the 5' flanking region of SLCO1B3. The EAV-HP insertion was found closely associated with blue eggshell phenotype following complete Mendelian segregation. In situ hybridization also demonstrated that the blue eggshell is associated with ectopic expression of SLCO1B3 in shell glands of uterus. Our finding strongly suggests that the EAV-HP insertion is the causative mutation for the blue eggshell phenotype. The insertion was also found in another Chinese blue-shelled breed and an American blue-shelled breed. In addition, we found that the insertion site in the blue-shelled chickens from Araucana is different from that in Chinese breeds, which implied independent integration events in the blue-shelled chickens from the two continents, providing a parallel evolutionary

  12. Synthesis and characterization of the octahydrotriborate complexes Cp*V(B3H8)2 and Cp*Cr(B3H8)2 and the unusual cobaltaborane cluster Cp*2Co2(B6H14).

    Science.gov (United States)

    Kim, Do Young; Girolami, Gregory S

    2006-08-23

    The new compounds CpV(B(3)H(8))(2), CpCr(B(3)H(8))(2), and Cp(2)Co(2)(B(6)H(14)) have been synthesized by treating the pentamethylcyclopentadienyl complexes [CpVCl(2)](3), [CpCrCl(2)](2), and [CpCoCl](2) with NaB(3)H(8). X-ray crystallography shows that CpV(B(3)H(8))(2) and CpCr(B(3)H(8))(2) have the same ligand sets but different molecular structures: the vanadium compound contains two bidentate B(3)H(8) ligands (i.e., bound to the metal center via two vicinal hydrogen atoms), whereas the chromium compound has one bidentate B(3)H(8) ligand and one B(3)H(8) ligand bound in an unprecedented fashion via two geminal hydrogen atoms. The "gem-bound" B(3)H(8) group itself has an atypical structure consisting of a BH(2)-BH(2)-BH(3) triangle with one additional hydrogen atom bridging the unique BH(2)-BH(2) edge. The B-B distances are nearly identical within experimental error at 1.790(5), 1.792(5), and 1.786(6) Angstrom. The relationship between the electronic and molecular structures of the V and Cr compounds is briefly discussed. The structure of Cp(2)Co(2)(B(6)H(14)) can be viewed in two different ways: as a dicobalt complex in which two CpCo units are each bound to four adjacent boron atoms of an S-shaped B(6)H(14) ligand, or as an eight-vertex hypho cluster compound. In the former case, the B(6)H(14) ligand is best regarded as a dianionic bi-borallyl group H(3)B(mu-H)BH(mu-H)BHBH(mu-H)BH(mu-H)BH(3) in which one hydrogen at each end of the chain is involved in an agostic interaction. From a cluster point of view, the structure of Cp(2)Co(2)(B(6)H(14)) can be generated by removing three adjacent high-connectivity vertices from the eleven-vertex closo polyhedron. The Co-B distances vary from 2.008(5) to 2.183(4) Angstrom, and the B-B distances within in the S-shaped chain range from 1.734(8) to 1.889(6) Angstrom. Finally, a new synthesis of the known molybdenum compound Cp(2)Mo(2)(B(5)H(9)) is described; its structure as established by X-ray crystallography closely

  13. Linking organic anion transporting polypeptide 1B1 and 1B3 (OATP1B1 and OATP1B3) interaction profiles to hepatotoxicity - The hyperbilirubinemia use case.

    Science.gov (United States)

    Kotsampasakou, Eleni; Escher, Sylvia E; Ecker, Gerhard F

    2017-03-30

    Hyperbilirubinemia is a pathological condition of excessive accumulation of conjugated or unconjugated bilirubin in blood. It has been associated with neurotoxicity and non-neural organ dysfunctions, while it can also be a warning of liver side effects. Hyperbilirubinemia can either be a result of overproduction of bilirubin due to hemolysis or dyserythropoiesis, or the outcome of impaired bilirubin elimination due to liver transporter malfunction or inhibition. There are several reports in literature that inhibition of organic anion transporting polypeptides 1B1 and 1B3 (OATP1B1 and OATP1B3) might lead to hyperbilirubinemia. In this study we created a set of classification models for hyperbilirubinemia, which, besides physicochemical descriptors, also include the output of classification models of human OATP1B1 and 1B3 inhibition. Models were based on either human data derived from public toxicity reports or animal data extracted from the eTOX database VITIC. The generated models showed satisfactory accuracy (68%) and area under the curve (AUC) for human data and 71% accuracy and 70% AUC for animal data. However, our results did not indicate strong association between OATP inhibition and hyperbilirubinemia, neither for humans nor for animals. Copyright © 2017. Published by Elsevier B.V.

  14. Diets derived from maize monoculture cause maternal infanticides in the endangered European hamster due to a vitamin B3 deficiency.

    Science.gov (United States)

    Tissier, Mathilde L; Handrich, Yves; Dallongeville, Odeline; Robin, Jean-Patrice; Habold, Caroline

    2017-01-25

    From 1735 to 1940, maize-based diets led to the death of hundreds of thousands of people from pellagra, a complex disease caused by tryptophan and vitamin B3 deficiencies. The current cereal monoculture trend restricts farmland animals to similarly monotonous diets. However, few studies have distinguished the effects of crop nutritional properties on the reproduction of these species from those of other detrimental factors such as pesticide toxicity or agricultural ploughing. This study shows that maize-based diets cause high rates of maternal infanticides in the European hamster, a farmland species on the verge of extinction in Western Europe. Vitamin B3 supplementation is shown to effectively restore reproductive success in maize-fed females. This study pinpoints how nutritional deficiencies caused by maize monoculture could affect farmland animal reproduction and hence their fitness. © 2017 The Author(s).

  15. Organic anion transporter 3- and organic anion transporting polypeptides 1B1- and 1B3-mediated transport of catalposide

    Directory of Open Access Journals (Sweden)

    Jeong HU

    2015-01-01

    Full Text Available Hyeon-Uk Jeong,1 Mihwa Kwon,2 Yongnam Lee,3 Ji Seok Yoo,3 Dae Hee Shin,3 Im-Sook Song,2 Hye Suk Lee1 1College of Pharmacy, The Catholic University of Korea, Bucheon 420-743, Korea; 2College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Korea; 3Central R&D Institute, Yungjin Pharm Co., Ltd., Suwon 443-270, Korea Abstract: We investigated the in vitro transport characteristics of catalposide in HEK293 cells overexpressing organic anion transporter 1 (OAT1, OAT3, organic anion transporting polypeptide 1B1 (OATP1B1, OATP1B3, organic cation transporter 1 (OCT1, OCT2, P-glycoprotein (P-gp, and breast cancer resistance protein (BCRP. The transport mechanism of catalposide was investigated in HEK293 and LLC-PK1 cells overexpressing the relevant transporters. The uptake of catalposide was 319-, 13.6-, and 9.3-fold greater in HEK293 cells overexpressing OAT3, OATP1B1, and OATP1B3 transporters, respectively, than in HEK293 control cells. The increased uptake of catalposide via the OAT3, OATP1B1, and OATP1B3 transporters was decreased to basal levels in the presence of representative inhibitors such as probenecid, furosemide, and cimetidine (for OAT3 and cyclosporin A, gemfibrozil, and rifampin (for OATP1B1 and OATP1B3. The concentration-dependent OAT3-mediated uptake of catalposide revealed the following kinetic parameters: Michaelis constant (Km =41.5 µM, maximum uptake rate (Vmax =46.2 pmol/minute, and intrinsic clearance (CLint =1.11 µL/minute. OATP1B1- and OATP1B3-mediated catalposide uptake also showed concentration dependency, with low CLint values of 0.035 and 0.034 µL/minute, respectively. However, the OCT1, OCT2, OAT1, P-gp, and BCRP transporters were apparently not involved in the uptake of catalposide into cells. In addition, catalposide inhibited the transport activities of OAT3, OATP1B1, and OATP1B3 with half-maximal inhibitory concentration values of 83, 200, and 235 µ

  16. ErbB3 binding protein-1 (Ebp1) controls proliferation and myogenic differentiation of muscle stem cells.

    Science.gov (United States)

    Figeac, Nicolas; Serralbo, Olivier; Marcelle, Christophe; Zammit, Peter S

    2014-02-01

    Satellite cells are resident stem cells of skeletal muscle, supplying myoblasts for post-natal muscle growth, hypertrophy and repair. Many regulatory networks control satellite cell function, which includes EGF signalling via the ErbB family of receptors. Here we investigated the role of ErbB3 binding protein-1 (Ebp1) in regulation of myogenic stem cell proliferation and differentiation. Ebp1 is a well-conserved DNA/RNA binding protein that is implicated in cell growth, apoptosis and differentiation in many cell types. Of the two main Ebp1 isoforms, only p48 was expressed in satellite cells and C2C12 myoblasts. Although not present in quiescent satellite cells, p48 was strongly induced during activation, remaining at high levels during proliferation and differentiation. While retroviral-mediated over-expression of Ebp1 had only minor effects, siRNA-mediated Ebp1 knockdown inhibited both proliferation and differentiation of satellite cells and C2C12 myoblasts, with a clear failure of myotube formation. Ebp1-knockdown significantly reduced ErbB3 receptor levels, yet over-expression of ErbB3 in Ebp1 knockdown cells did not rescue differentiation. Ebp1 was also expressed by muscle cells during developmental myogenesis in mouse. Since Ebp1 is well-conserved between mouse and chick, we switched to chick to examine its role in muscle formation. In chick embryo, Ebp1 was expressed in the dermomyotome, and myogenic differentiation of muscle progenitors was inhibited by specific Ebp1 down-regulation using shRNA electroporation. These observations demonstrate a conserved function of Ebp1 in the regulation of embryonic muscle progenitors and adult muscle stem cells, which likely operates independently of ErbB3 signaling. © 2013 Published by Elsevier Inc.

  17. Fermi LAT detection of increasing gamma-ray activity from NGC 1275 and B3 0908+416B

    Science.gov (United States)

    Pivato, G.; Buson, S.

    2015-10-01

    The Large Area Telescope (LAT), one of the two instruments on the Fermi Gamma-ray Space Telescope, has observed increasing gamma-ray flux from sources positionally consistent with the flat spectrum radio quasar B3 0908+416B (also known as 3FGL J0912.2+4126, Acero et al. 2015 ApJS, 218, 23) and the radio galaxy NGC 1275 (also known as Perseus A and 3FGL J0319.8+4130).

  18. Theoretical insight into hydrogen adsorption onto graphene: a first-principles B3LYP-D3 study.

    Science.gov (United States)

    Darvish Ganji, M; Hosseini-Khah, S M; Amini-Tabar, Z

    2015-01-28

    This work investigates hydrogen adsorption onto various graphene flakes such as coronene and coronene-like as suitable models of graphene within the framework of the DFT-B3LYP method. The non-local van der Waals (vdW) density functional (B3LYP-D3) method is used for both structural geometry optimization and total energy estimations. Calculations were carried out for a hydrogen molecule above a coronene surface with both conventional and vdW corrected DFT to investigate how these approaches perform in the case of hydrogen adsorption on a graphene surface. Our first-principles results within the B3LYP-D3/def2-TZVPP model show that hydrogen physisorbs on a coronene surface with an adsorption energy of -5.013 (kJ mol(-1)) which is in good agreement with the experimental value. The influence of the basis set and graphene flake size were also evaluated and the results indicate that these slightly affect the adsorption properties. We found also that it is crucial to use non-local dispersion interactions to get accurate results for hydrogen adsorption on a graphene surface. Furthermore, the co-adsorption of H2 molecules onto the graphene surface was investigated. The results obtained at the B3LYP-D3/def2-TZVP level show that H2 molecules can be physisorbed on both sides of the graphene layer with adsorption properties similar to those for a single surface. Finally, we showed that H2 molecules might be bound to the graphene surface via a bilayer adsorption scheme with weak adsorption energy. Charge population and electron density analysis confirm the weak binding nature of the system under consideration.

  19. Enhanced radical scavenging activity of a procyanidin B3 analogue comprised of a dimer of planar catechin.

    Science.gov (United States)

    Mizuno, Mirei; Nakanishi, Ikuo; Matsumoto, Ken-Ichiro; Fukuhara, Kiyoshi

    2017-11-15

    Proanthocyanidins are oligomers of catechins that exhibit potent antioxidative activity and inhibit binding of oxidized low-density lipoprotein (OxLDL) to the lectin-like oxidized LDL receptor (LOX-1), which is involved in the onset and development of arteriosclerosis. Previous attempts aimed at developing proanthocyanidin derivatives with more potent antioxidative activity and stronger inhibition for LOX-1 demonstrated the synthesis of a novel proanthocyanidin derivative (1), in which the geometry of one catechin molecule in procyanidin B3 was constrained to a planar orientation. The radical scavenging activity of 1 was 1.9-fold higher than that of procyanidin B3. Herein, we synthesized another procyanidin B3 analogue (2), in which the geometries of both catechin molecules in the dimer were constrained to planar orientations. The radical scavenging activity of 2 was 1.5-fold higher than that of 1, suggesting that 2 may be a more effective candidate than 1 as a therapeutic agent to reduce oxidative stress induced in arteriosclerosis or related cerebrovascular disease. Copyright © 2017. Published by Elsevier Ltd.

  20. Nicotinamide riboside, a trace nutrient in foods, is a vitamin B3 with effects on energy metabolism and neuroprotection.

    Science.gov (United States)

    Chi, Yuling; Sauve, Anthony A

    2013-11-01

    This review focuses upon the biology and metabolism of a trace component in foods called nicotinamide riboside. Nicotinamide riboside is a precursor of nicotinamide adenine dinucleotide (NAD), and is a source of Vitamin B3. Evidence indicates that nicotinamide riboside has unique properties as a Vitamin B3. We review knowledge of the metabolism of this substance, as well as recent work suggesting novel health benefits that might be associated with nicotinamide riboside taken in larger quantities than is found naturally in foods. Recent work investigating the effects of nicotinamide riboside in yeast and mammals established that it is metabolized by at least two types of metabolic pathways. The first of these is degradative and produces nicotinamide. The second pathway involves kinases called nicotinamide riboside kinases (Nrk1 and Nrk2, in humans). The likely involvement of the kinase pathway is implicated in the unique effects of nicotinamide riboside in raising tissue NAD concentrations in rodents and for potent effects in eliciting insulin sensitivity, mitochondrial biogenesis, and enhancement of sirtuin functions. Additional studies with nicotinamide riboside in models of Alzheimer's disease indicate bioavailability to brain and protective effects, likely by stimulation of brain NAD synthesis. Initial studies have clarified the potential for a lesser-known Vitamin B3 called nicotinamide riboside that is available in selected foods, and possibly available to humans by supplements. It has properties that are insulin sensitizing, enhancing to exercise, resisting to negative effects of high-fat diet, and neuroprotecting.

  1. Experimental evidence of the B2 and B3 dependent circular birefringence of chiral molecules in high magnetic fields

    Science.gov (United States)

    Surma, M.

    The rotation of the plane of polarization of light passing through chiral media in the Faraday geometry of a magnetic field B and light propagation vector k have been measured in high magnetic fields of induction up to 30 T and a laser beam wavelength = 488 nm. The optically active enantiomers of neat alpha-methylbenzylamine and solutions in water of tartaric, malic and lactic acids, leucine and threonine exhibit dependence of the induced rotation of the light polarization plane on B 2 and B 3. The effect is reported of the magnetic field B 2 induced circular birefringence of laevorotatory and dextrorotatory enantiomers. Also differences are found in the effective rotation of the plane of polarization in the parallel (alpha ) and antiparallel (alpha ) configurations of B and k acting on a chiral medium. The first quantitative determination is made of the nonlinear ( B 3) Faraday effect in chiral media. The linear in B circular birefringence makes the largest contribution to the B 2 and B 3 dependent rotation.

  2. Novel mutations of HSD17B3 in three Chinese patients with 46,XY Disorders of Sex Development.

    Science.gov (United States)

    Yu, Bingqing; Liu, Zhaoxiang; Mao, Jiangfeng; Wang, Xi; Zheng, Junjie; Xiong, Shuyu; Cui, Mingxuan; Ma, Wanlu; Huang, Qibin; Xu, Hongli; Huang, Bingkun; Nie, Min; Wu, Xueyan

    2017-10-01

    17β-Hydroxysteroid dehydrogenase type 3 (17β-HSD3) converts the inactive Δ4-androstenedione (A) to testosterone (T). Its deficiency is the most common testosterone biosynthesis defect that results in 46,XY Disorders Of Sex Development (DSD). However, the disease is difficult to distinguish from other 46,XY DSD for similar clinical phenotypes. Therefore, genetic testing provides good criteria for the diagnosis of the disease. In this study, HSD17B3 gene was examined in 3 unrelated Chinese patients with 46,XY DSD. Direct sequencing and quantitative PCR of HSD17B3 gene revealed the presence of a compound heterozygous mutation (p.I60T/exon1 deletion) in Patient 1, a homozygous (p.I60T) mutation in Patient 2 and a frameshift mutation (p.V25Efs∗54) and an exon1 deletion in Patient 3. All of the mutations have not been reported previously. These novel mutations may expand the mutation database of HSD17B3 gene and provide us new insights into the molecular mechanism of 17β-HSD3 deficiency. It is noteworthy that when direct sequence analysis showed a rare homozygous mutation in patients with non-consanguineous parents, "apparent homozygosity" should be taken into an account and the intragenic deletion should be screened. In addition, when single mutation was found in patients with disease in recessive heredity mode, the intragenic deletion should also be screened. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Danger lurking in the "unknowns": structure-to-function studies of hypothetical protein Bleg1_2437 from Bacillus lehensis G1 alkaliphile revealed an evolutionary divergent B3 metallo-beta-lactamase.

    Science.gov (United States)

    Tan, Soo Huei; Normi, Yahaya M; Leow, Adam Thean Chor; Salleh, Abu Bakar; Murad, Abdul Munir Abdul; Mahadi, Nor Muhammad; Rahman, Mohd Basyaruddin Abdul

    2017-02-01

    The effectiveness of β-lactam antibiotics as chemotherapeutic agents to treat bacterial infections is gradually threatened with the emergence of antibiotic resistance mechanism among pathogenic bacteria through the production metallo-β-lactamase (MBL). In this study, we discovered a novel hypothetical protein (HP) termed Bleg1_2437 from the genome of alkaliphilic Bacillus lehensis G1 which exhibited MBL-like properties of B3 subclass; but evolutionary divergent from other circulating B3 MBLs. Domain and sequence analysis of HP Bleg1_2437 revealed that it contains highly conserved Zn2+-binding residues such as H54, H56, D58, H59, H131 and H191, important for catalysis, similar with the subclass B3 of MBL. Built 3-D Bleg1_2437 structure exhibited an αββα sandwich layer similar to the well-conserved global topology of MBL superfamily. Other features include a ceiling and floor in the model which are important for accommodation and orientation of β-lactam antibiotics docked to the protein model showed interactions at varying degrees with residues in the binding pocket of Bleg1_2437. Hydrolysis activity towards several β-lactam antibiotics was proven through an in vitro assay using purified recombinant Bleg1_2437 protein. These findings highlight the presence of a clinically important and evolutionary divergent antibiotics-degrading enzyme within the pools of uncharacterized HPs.

  4. Tratamiento de las fracturas periprotésicas de fémur Vancouver B2 y B3. [Treatment of Vancouver B2 and B3 perisprosthetic fractures of the femur

    Directory of Open Access Journals (Sweden)

    German Garabano

    2013-03-01

    Full Text Available Introducción Las fracturas periprotésicas femorales luego de un reemplazo total de cadera son cada vez más prevalentes. Cuando estas asientan sobre un tallo flojo (B2 o con déficit de capital óseo (B3, según la clasificación de Vancouver, el tratamiento es la revisión del tallo femoral. Material y métodos Se analizó retrospectivamente a 22 pacientes, 9 fracturas tipo B2 y 13 tipo B3 de la clasificación de Vancouver. El promedio del seguimiento fue de 48 meses. Se utilizaron tallos largos cementados junto con aloinjerto óseo impactado, tablas corticales, tallos largos no cementados de fijación distal y endoprótesis no convencionales, según el caso. Resultados Se observó la curación y la remodelación de la fractura en todos los pacientes. Las complicaciones fueron 2 (9% luxaciones, 1 (4,5% infección, 1 (4,5% fractura de calcar, 1 (4,5% aflojamiento de cotilo y 2 (9% decesos. Conclusiones Las fracturas posoperatorias periprotésicas de fémur tipo B2 y B3 requieren recambio del tallo femoral, si bien existe una tendencia actual a utilizar tallos no cementados, en esta serie, dada la superposición de tratamientos, según cada subtipo de fractura, no obtuvimos diferencias entre el uso de tallos cementados junto con injerto y tallos no cementados. En casos de grave déficit de capital óseo, las endoprótesis no convencionales ofrecen una opción terapéutica para pacientes con baja demanda funcional. La clasificación de Vancouver es un instrumento útil para evaluar y decidir el tratamiento.

  5. Efficient 1 kHz femtosecond optical parametric amplification in BiB(3)O(6) pumped at 800 nm.

    Science.gov (United States)

    Ghotbi, Masood; Ebrahim-Zadeh, Majid; Petrov, Valentin; Tzankov, Pancho; Noack, Frank

    2006-10-30

    We demonstrate efficient operation of a tunable femtosecond optical parametric amplifier based on BiB(3)O(6) pumped at 800 nm by a 1 kHz Ti:sapphire regenerative amplifier. The idler wavelength coverage extends to beyond 3 mum and the pulse duration at this wavelength is of the order of 110 fs. This new nonlinear borate crystal offers exceptionally high nonlinearity, making it a very promising candidate for power scaling of such frequency converters in the near-IR.

  6. Fracturas del cuello quirúrgico del húmero (B2-B3). Tratamiento quirúrgico.

    OpenAIRE

    Arenas Planelles, Antonio; D'Arrigo, A.; Arenas Miquélez, A.; Garbayo Marturet, Antonio Jesús

    2013-01-01

    Se presentan 36 casos de fractura de húmero proximal tipos B2 y B3 tratados quirúrgicamente mediante osteosíntesis con clavo proximal (4 casos) o placa bloqueada (29 casos) o utilizando una hemiartroplastia de hombro (3 casos). Los resultados fueron buenos en la mayor parte de los pacientes, con un dolor medio de 11,97/15 en la cotación cifrada de Constant, una fuerza de 13,42/25 puntos y una movilidad de 24,33/40 puntos. Las complicaciones más importantes fueron el conflicto subacromial (10 ...

  7. Staphylococcal Infections

    Science.gov (United States)

    Staph is short for Staphylococcus, a type of bacteria. There are over 30 types, but Staphylococcus aureus causes most staph infections (pronounced "staff infections"), including Skin infections Pneumonia ...

  8. NS2B-3 proteinase-mediated processing in the yellow fever virus structural region: in vitro and in vivo studies.

    Science.gov (United States)

    Amberg, S M; Nestorowicz, A; McCourt, D W; Rice, C M

    1994-06-01

    Several of the cleavages required to generate the mature nonstructural proteins from the flaviviral polyprotein are known to be mediated by a complex consisting of NS2B and a serine proteinase domain located in the N-terminal one-third of NS3. These cleavages typically occur after two basic residues followed by a short side chain residue. Cleavage at a similar dibasic site in the structural region is believed to produce the C terminus of the virion capsid protein. To study this cleavage, we developed a cell-free trans cleavage assay for yellow fever virus (YF)-specific proteolytic activity by using a substrate spanning the C protein dibasic site. Cleavage at the predicted site was observed when the substrate was incubated with detergent-solubilized lysates from YF-infected BHK cells. NS2B and the NS3 proteinase domain were the only YF-specific proteins required for this cleavage. Cell fractionation studies demonstrated that the YF-specific proteolytic activity was membrane associated and that activity could be detected only after detergent solubilization. Previous cell-free studies led to a hypothesis that processing in the C-prM region involves (i) translation of C followed by translocation and core glycosylation of prM by using an internal signal sequence, (ii) signalase cleavage to produce a membrane-anchored form of the C protein (anchC) and the N terminus of prM, and (iii) NS2B-3-mediated cleavage at the anchC dibasic site to produce the C terminus of the virion C protein. However, the results of in vivo transient-expression studies do not support this temporal cleavage order. Rather, expression of a YF polyprotein extending from C through the N-terminal one-third of NS3 revealed that C-prM processing, but not translocation, was dependent on an active NS2B-3 proteinase. This suggests that signalase-mediated cleavage in the lumen of the endoplasmic reticulum may be dependent on prior cleavage at the anchC dibasic site. Possible pathways for processing in the C

  9. Perfluorooctanoic acid affects endocytosis involving clathrin light chain A and microRNA-133b-3p in mouse testes.

    Science.gov (United States)

    Lu, Yin; Wang, Jianshe; Guo, Xuejiang; Yan, Shengmin; Dai, Jiayin

    2017-03-01

    Perfluorooctanoic acid (PFOA) is an abundant perfluoroalkyl substance widely applied in industrial and consumer products. Among its potential health hazards, testicular toxicity is of major concern. To explore the potential effect of miRNA on post-translational regulation after PFOA exposure, changes in miRNAs were detected via miRNA array. Seventeen miRNAs were differentially expressed (eight upregulated, nine downregulated) in male mouse testes after exposure to 5mg/kg/d of PFOA for 28d (>1.5-fold and Pendocytosis and blood-testis barrier (BTB) processes. These changes were further verified by immunohistochemical and Western blot analyses. Endocytosis-related genes were selected for qPCR analysis, with many found to be significantly changed after PFOA treatment, including epidermal growth factor receptor pathway substrate 8 (Eps8), Eps15, cortactin, cofilin, espin, vinculin, and zyxin. We further predicted the potential interaction between changed miRNAs and proteins, which indicated that miRNAs might play a role in the post-translational regulation of gene expression after PFOA treatment in mouse testes. Among them, miR-133b-3p/clathrin light chain A (CLTA) was selected and verified in vitro by transfection and luciferase activity assay. Results showed that PFOA exposure affects endocytosis in mouse testes and that CLTA is a potential target of miR-133b-3p. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. 26 CFR 48.6416(b)(3)-3 - Supporting evidence required in case of tax-paid articles used for further manufacture.

    Science.gov (United States)

    2010-04-01

    ... articles used for further manufacture. 48.6416(b)(3)-3 Section 48.6416(b)(3)-3 Internal Revenue INTERNAL... manufacture. (a) Evidence to be submitted by claimant. No claim for credit or refund of an overpayment, within... of payment, (5) Indicating that the article was used by the claimant as material in the manufacture...

  11. 26 CFR 31.3406(b)(3)-2 - Reportable barter exchanges and gross proceeds of sales of securities or commodities by brokers.

    Science.gov (United States)

    2010-04-01

    ... of sales of securities or commodities by brokers. 31.3406(b)(3)-2 Section 31.3406(b)(3)-2 Internal... or commodities by brokers. (a) Transactions subject to backup withholding. A payment of a kind, and to a payee, that any broker (as defined in section 6045(c) and § 1.6045-1(a)(1) of this chapter) or...

  12. Human papillomavirus 16 E2 interacts with neuregulin receptor degradation protein 1 affecting ErbB-3 expression in vitro and in clinical samples of cervical lesions.

    Science.gov (United States)

    Paolini, Francesca; Curzio, Gianfranca; Melucci, Elisa; Terrenato, Irene; Antoniani, Barbara; Carosi, Mariantonia; Mottolese, Marcella; Vici, Patrizia; Mariani, Luciano; Venuti, Aldo

    2016-05-01

    The ErbB tyrosine kinase receptors play a key role in regulating many cellular functions and human papillomaviruses (HPVs) may interact with transductional pathway of different growth factor receptors. Here, these interactions were analysed in W12 cell line carrying HPV 16 genome and in clinical samples. W12 cells, in which HPV16 becomes integrated during passages, were utilised to detect viral and ErbB family expression at early (W12E) and late passages (W12G). Interestingly, a strong reduction of ErbB-3 expression was observed in W12G. Loss of the E2 and E5 viral genes occurs in W12G and this may affect ErbB-3 receptor expression. E2 and E5 rescue experiments demonstrated that only E2 gene was able to restore ErbB-3 expression. E2 is a transcriptional factor but the expression levels of ErbB3 were unaffected and ErbB-3 promoter did not show any consensus sequence for E2, thus E2 may interact in another way with ErbB3. Indeed, HPV 16 E2 can modulate ErbB-3 by interacting with the ubiquitin ligase neuregulin receptor degradation protein 1 (Nrdp-1) that is involved in the regulation of this receptor, via ubiquitination and degradation. E2 co-immunoprecipitated in a complex with Nrdp-1 leading to hypothesise an involvement of this interaction in ErbB-3 regulation. In addition, 90% of the clinical samples with integrated virus and E2 loss showed no or low ErbB-3 positivity, confirming in vitro results. In conclusion, the new discovered interaction of HPV-16 E2 with Nrdp-1 may affect ErbB-3 expression. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Mutation of SH2B3 (LNK), a genome-wide association study candidate for hypertension, attenuates Dahl salt-sensitive hypertension via inflammatory modulation.

    Science.gov (United States)

    Rudemiller, Nathan P; Lund, Hayley; Priestley, Jessica R C; Endres, Bradley T; Prokop, Jeremy W; Jacob, Howard J; Geurts, Aron M; Cohen, Eric P; Mattson, David L

    2015-05-01

    Human genome-wide association studies have linked SH2B adaptor protein 3 (SH2B3, LNK) to hypertension and renal disease, although little experimental investigation has been performed to verify a role for SH2B3 in these pathologies. SH2B3, a member of the SH2B adaptor protein family, is an intracellular adaptor protein that functions as a negative regulator in many signaling pathways, including inflammatory signaling processes. To explore a mechanistic link between SH2B3 and hypertension, we targeted the SH2B3 gene for mutation on the Dahl salt-sensitive (SS) rat genetic background with zinc-finger nucleases. The resulting mutation was a 6-bp, in-frame deletion within a highly conserved region of the Src homology 2 (SH2) domain of SH2B3. This mutation significantly attenuated Dahl SS hypertension and renal disease. Also, infiltration of leukocytes into the kidneys, a key mediator of Dahl SS pathology, was significantly blunted in the Sh2b3(em1Mcwi) mutant rats. To determine whether this was because of differences in immune signaling, bone marrow transplant studies were performed in which Dahl SS and Sh2b3(em1Mcwi) mutants underwent total body irradiation and were then transplanted with Dahl SS or Sh2b3(em1Mcwi) mutant bone marrow. Rats that received Sh2b3(em1Mcwi) mutant bone marrow had a significant reduction in mean arterial pressure and kidney injury when placed on a high salt diet (4% NaCl). These data further support a role for the immune system as a modulator of disease severity in the pathogenesis of hypertension and provide insight into inflammatory mechanisms at play in human hypertension and renal disease. © 2015 American Heart Association, Inc.

  14. The simultaneous expression of both ephrin B3 receptor and E-cadherin in Barrett`s adenocarcinoma is associated with favorable clinical staging

    Directory of Open Access Journals (Sweden)

    Schauer Matthias C

    2012-05-01

    Full Text Available Abstract Background In intestinal epithelium, tyrosine kinase receptor Ephrin B3 (Eph B3 maintains the architecture of the crypt-villus axis by repulsive interaction with its ligand ephrin-B1. While loss of Eph B3 is linked to colorectal cancer initiation, overexpression of Eph B3 in cancer cell lines inhibits growth and induces functional changes with decreased mesenchymal and increased epithelial markers. In order to study this tumor suppressor activity of Eph B3 in esophageal adenocarcinoma we analyzed the simultaneous expression of Eph B3 and E-cadherin in both the healthy esophagus and in Barrett’s carcinoma. Methods Simultaneous expression of Eph B3 and E-cadherin was investigated in samples from 141 patients with Barrett’s carcinoma and from 20 healthy esophagi using immunhistology and quantitative PCR. Results from healthy squamous epithelium, Barrett’s metaplasia and staging-specific esophageal adenocarcinoma were correlated. Results A significantly reduced E-cadherin mRNA expression could be detected in adenocarcinoma compared to dysplasia. The immunhistological activity of E-cadherin and Eph B3 was reduced in adenocarcinoma compared to dysplasia or healthy esophageal mucosa. The intracellular E-cadherin distribution changed significantly from the cytoplasm to the membrane, when the Eph receptor was simultaneously expressed. Simultaneous expression of E-cadherin and Eph B3 showed a significant inverse correlation to tumor stage. Conclusions We present novel evidence of the tumor suppressor activity of Eph B3 in esophageal adenocarcinoma possibly due to the impact on redistribution of cellular E-cadherin to the membrane. Our results suggest that this effect might play a role in the dysplasia-adenocarcinoma sequence, the infiltrative growth pattern and the development of lymph node metastases.

  15. Preference of Conjugated Bile Acids over Unconjugated Bile Acids as Substrates for OATP1B1 and OATP1B3.

    Science.gov (United States)

    Suga, Takahiro; Yamaguchi, Hiroaki; Sato, Toshihiro; Maekawa, Masamitsu; Goto, Junichi; Mano, Nariyasu

    2017-01-01

    Bile acids, the metabolites of cholesterol, are signaling molecules that play critical role in many physiological functions. They undergo enterohepatic circulation through various transporters expressed in intestine and liver. Human organic anion-transporting polypeptides (OATP) 1B1 and OATP1B3 contribute to hepatic uptake of bile acids such as taurocholic acid. However, the transport properties of individual bile acids are not well understood. Therefore, we selected HEK293 cells overexpressing OATP1B1 and OATP1B3 to evaluate the transport of five major human bile acids (cholic acid, chenodeoxycholic acid, deoxycholic acid, ursodeoxycholic acid, lithocholic acid) together withtheir glycine and taurine conjugates via OATP1B1 and OATP1B3. The bile acids were quantified by liquid chromatography-tandem mass spectrometry. The present study revealed that cholic acid, chenodeoxyxcholic acid, and deoxycholic acid were transported by OATP1B1 and OATP1B3, while ursodeoxycholic acid and lithocholic acid were not significantly transported by OATPs. However, all the conjugated bile acids were taken up rapidly by OATP1B1 and OATP1B3. Kinetic analyses revealed the involvement of saturable OATP1B1- and OATP1B3-mediated transport of bile acids. The apparent Km values for OATP1B1 and OATP1B3 of the conjugated bile acids were similar (0.74-14.7 μM for OATP1B1 and 0.47-15.3 μM for OATP1B3). They exhibited higher affinity than cholic acid (47.1 μM for OATP1B1 and 42.2 μM for OATP1B3). Our results suggest that conjugated bile acids (glycine and taurine) are preferred to unconjugated bile acids as substrates for OATP1B1 and OATP1B3.

  16. Collisional excitation of metastable oxygen O(1D) atoms through the B3Sigma(-) sub u channel of O2

    Science.gov (United States)

    Jamieson, M. J.; Finch, M.; Friedman, R. S.; Dalgarno, A.

    1992-12-01

    Spectroscopic data on the shifts and widths of the energy levels of molecular oxygen have been used in the empirical construction of a diabatic potential matrix that characterizes the interactions of the B3Sigma(-) sub u state with the 5Pi sub u, 2 3Sigma(+) sub u, 3Pi sub u, and 1Pi sub u states. The diabatic potential matrix is used here in a scattering theory formulation to calculate the cross-sections for the excitation of O(1D) atoms in collisions of two O(3P) atoms. Total cross-sections are obtained by adding the excitation from the 3Pi sub g channel. The rate coefficient for quenching of O(1D) by O(3P) is evaluated as a function of temperature. The values conflict with a recent analysis of the emission of the oxygen red line in the upper atmosphere.

  17. Demonstration of an ultraviolet stimulated Brillouin scattering pulse compressed hundred picosecond laser in LiB3O5 crystals

    Science.gov (United States)

    Bai, Zhenxu; Wang, Yulei; Lu, Zhiwei; Jiang, Li; Yuan, Hang; Liu, Zhaohong

    2017-08-01

    A hundred picosecond ultraviolet (UV) laser is demonstrated with a pulse duration of less than 200 ps and peak power of 0.6 GW. With a hundred picosecond stimulated Brillouin scattering compressed pulse as the fundamental light, the UV output at 355 nm is obtained by extra-cavity sum-frequency-mixing in two LiB3O5 crystals. Maximum UV energy was 100 mJ when the incident energy was 280 mJ, yielding an optical-to-optical efficiency of 35.7%. This result is of interest for the generation of high energy sub-nanosecond UV lasers which finds applications in shock ignition and industrial processing.

  18. Vibrational assignments for 7-methyl-4-bromomethylcoumarin, as aided by RHF and B3LYP/6-31G* calculations.

    Science.gov (United States)

    Sortur, Veenasangeeta; Yenagi, Jayashree; Tonannavar, J; Jadhav, V B; Kulkarni, M V

    2008-11-15

    Infrared (4000-400 cm(-1)) and Raman (3500-50 cm(-1)) spectral measurements have been made for the solid sample of 7-methyl-4-bromomethylcoumarin. Electronic structure calculations at RHF/6-31G* and B3LYP/6-31G* levels of theory have been performed, giving equilibrium geometries, harmonic vibrational spectra and normal modes. Different orientations of bromomethyl group have yielded only two conformers, of which the most stable one lying lower from the other conformer by approximately 7.99 kJ/mol, is non-planar with no symmetry. A complete assignment of the vibrational modes, aided by the calculations, has been proposed. Coupled vibrations are manifest in many modes. Some spectral features, compared to 6-methyl-4-bromomethylcoumarin, show changes across both IR and Raman spectra, involving mainly skeletal vibrations, and to a lesser degree, methyl and bromomethyl vibrations. Low-frequency vibrations below 150 cm(-1) are assigned to lattice modes.

  19. Liquid chromatographic determination of fumonisins B1, B2, and B3 in corn: AOAC-IUPAC Collaborative Study.

    Science.gov (United States)

    Sydenham, E W; Shephard, G S; Thiel, P G; Stockenström, S; Snijman, P W; Van Schalkwyk, D J

    1996-01-01

    A liquid chromatographic (LC) method for simultaneous determination of fumonisins B1 (FB1), B2 (FB2), and B3 (FB3) in corn was subjected to a collaborative study involving 12 participants from 10 countries, in which the accuracy and reproducibility characteristics of the method were established. Mean analyte recoveries from corn ranged from 81.1 to 84.2% for FB1 (at a spiking range of 500 to 8000 ng/g), from 75.9 to 81.9% for FB2 (at a spiking range of 200 to 3200 ng/g), and from 75.8 to 86.8% for FB3 (at a spiking range of 100 to 1600 ng/g). The valid data were statistically evaluated after exclusion of outliers. Relative standard deviations for within-laboratory repeatability ranged from 5.8 to 13.2% for FB1, from 7.2 to 17.5% for FB2, and from 8.0 to 17.2% for FB3. Relative standard deviations for between-laboratory reproducibility varied from 13.9 to 22.2% for FB1, from 15.8 to 26.7% for FB2, and from 19.5 to 24.9% for FB3. HORRAT ratios, calculated for the individual toxin analogues, ranged from 0.75 to 1.73. The LC method for determination of fumonisins B1, B2, and B3 in corn (at concentrations of 800-12800 ng total fumonisins/g) has been adopted by AOAC INTERNATIONAL.

  20. Inhibition of Horseradish Peroxidase Activity by Boroxine Derivative, Dipotassium-trioxohydroxytetrafluorotriborate K2[B3O3F4OH

    Directory of Open Access Journals (Sweden)

    Jelena Ostojic

    2017-01-01

    Full Text Available Recently research shows that horseradish peroxidase, HRP, when combined with other compounds, is highly reactive toward different human tumour cells and that better understanding of catalytic mechanism and inhibition HPR could lead to a new targeted cancer therapy. Thus, the inhibition of HRP activity by dipotassium-trioxohydroxytetrafluorotriborate K2[B3O3F4OH] was investigated for possible explanation of previously observed antitumour activities of this promising drug. HRP activity was studied under steady-state kinetic conditions by a spectrophotometric method. In the absence of the inhibitor values of Km = 0.47 mM and Vmax = 0.34 mM min−1, respectively, were determined. The hydrogen peroxide H2O2 kinetic measurements show a competitive inhibition with the inhibition constant KI = 2.56 mM. The activation energy Ea values were found to be very similar for both reactions; in the absence of inhibitor activation energy was 17.7 kJ mol−1 and in the presence of inhibitor activation energy was 16.3 kJ mol−1. The values of Arrhenius constants were found to be different; A = 4.635 s−1 was measured in the absence of inhibitor while in the presence of inhibitor Arrhenius constant was 1.745 s−1 showing that K2[B3O3F4OH] initiates conformational change in the structure of the HRP and subsequently reduces its activity.

  1. Pharmacokinetics, Brain Delivery, and Efficacy in Brain Tumor-Bearing Mice of Glutathione Pegylated Liposomal Doxorubicin (2B3-101)

    Science.gov (United States)

    Gaillard, Pieter J.; Appeldoorn, Chantal C. M.; Dorland, Rick; van Kregten, Joan; Manca, Francesca; Vugts, Danielle J.; Windhorst, Bert; van Dongen, Guus A. M. S.; de Vries, Helga E.; Maussang, David; van Tellingen, Olaf

    2014-01-01

    Brain cancer is a devastating disease affecting many people worldwide. Effective treatment with chemotherapeutics is limited due to the presence of the blood-brain barrier (BBB) that tightly regulates the diffusion of endogenous molecules but also xenobiotics. Glutathione pegylated liposomal doxorubicin (2B3-101) is being developed as a new treatment option for patients with brain cancer. It is based on already marketed pegylated liposomal doxorubicin (Doxil®/Caelyx®), with an additional glutathione coating that safely enhances drug delivery across the BBB. Uptake of 2B3-101 by human brain capillary endothelial cells in vitro was time-, concentration- and temperature-dependent, while pegylated liposomal doxorubicin mainly remained bound to the cells. In vivo, 2B3-101 and pegylated liposomal doxorubicin had a comparable plasma exposure in mice, yet brain retention 4 days after administration was higher for 2B3-101. 2B3-101 was overall well tolerated by athymic FVB mice with experimental human glioblastoma (luciferase transfected U87MG). In 2 independent experiments a strong inhibition of brain tumor growth was observed for 2B3-101 as measured by bioluminescence intensity. The effect of weekly administration of 5 mg/kg 2B3-101 was more pronounced compared to pegylated liposomal doxorubicin (pbrain tumor growth (pbrain tumors and could become a promising new therapeutic option for the treatment of brain malignancies. PMID:24416140

  2. FY 1995 Report on the data processing for the geothermal development promotion investigation. No.B-3 Kumaishi Area (Phase 1); 1995 nendo chinetsu kaihatsu sokushin chosa data shori hokokusho. 1. No.B-3 Kumaishi chiiki

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-01-01

    Described herein are the FY 1995 results of the No.B-3 Kumaishi Area investigation, conducted as part of the geothermal development promotion investigation project. The project covers the geological structure, geochemical, gravitational, electromagnetic, environmental impact and supplementary investigations. The following findings are obtained by the comprehensive analysis of the data. The Kumaishi Area is based on the sedimentary rocks and granite formed in the Pre-Ternary, which are unconformably covered by the strata belonging to Upper Oligocene of Ternary to Lower Pleistocene of Quaternary. The presence of NW-SE to E-W to NE-SW systems is suggested as the main fracture systems. It is estimated by the K-Ar method that the intrusion was formed in the 2.06 to 2.28Ma. The geochemical temperature suggests the presence of the fluid of 200 degrees C or higher as the deep hot water temperature. The resistivity structure generally indicates the NW-SE direction. Each stratum is confirmed by the test drilling for the structural investigation. The fluid motion model suggests possibility of hot water of high salt content, similar to that confirmed deep in the Yagumo Area, distributed deep in the Kumaishi Area. (NEDO)

  3. Pneumococcal Infections

    Science.gov (United States)

    ... for many cases of Brain and spinal cord infection (meningitis) Lung infection (pneumonia) Infection of the bloodstream (bacteremia) Joint infection ( ... other illnesses or health conditions such as HIV infection, certain cancers (eg, leukemia, ... or kidney disease. Last Updated 11/21/2015 ...

  4. The National Shipbuilding Research Program, 1990 Ship Production Symposium, Paper No. 4B-3: The Development of CO2 Blasting Technology in Naval Shipyards

    Science.gov (United States)

    1990-08-01

    seaweed , and algae , can restrict the openings of piping, increase the weight of buoys or other navigational equipment, constrict moving parts such as...1990 Ship Production Symposium Paper No. 4B-3: The Development of CO2 Blasting Technology in Naval Shipyards U.S. DEPARTMENT OF THE NAVY CARDEROCK...Program, 1990 Ship Production Symposium, Paper No. 4B-3: The Development of CO2 Blasting Technology in Naval Shipyards 5a. CONTRACT NUMBER 5b. GRANT

  5. 18 CFR Appendix I to Subpart F of... - Procedures for Compliance With the Endangered Species Act of 1973 Under § 157.206(b)(3)(i)

    Science.gov (United States)

    2010-04-01

    ... Compliance With the Endangered Species Act of 1973 Under § 157.206(b)(3)(i) I Appendix I to Subpart F of... Transactions and Abandonment Pt. 157, Subpt. F, App. I Appendix I to Subpart F of Part 157—Procedures for Compliance With the Endangered Species Act of 1973 Under § 157.206(b)(3)(i) The following procedures apply to...

  6. 76 FR 28637 - Airworthiness Directives; Eurocopter France Model AS350B, B1, B2, B3, BA, and EC130 B4 Helicopters

    Science.gov (United States)

    2011-05-18

    ... Model AS350B, B1, B2, B3, BA, and EC130 B4 Helicopters AGENCY: Federal Aviation Administration (FAA..., 2009, for the Model EC130 B4 helicopters. The Model AS350 BB helicopter is not type certificated in the...) None. Applicability (c) This AD applies to Model AS350B, B1, B2, B3, BA, and EC130 B4 helicopters with...

  7. 75 FR 79988 - Airworthiness Directives; Eurocopter France Model AS350B, B1, B2, B3, BA, and EC130 B4 Helicopters

    Science.gov (United States)

    2010-12-21

    ... France Model AS350B, B1, B2, B3, BA, and EC130 B4 Helicopters AGENCY: Federal Aviation Administration..., Revision 1, dated February 6, 2009, for the Model EC130 B4 helicopter (80A003). The Model AS350 BB... Model AS350B, B1, B2, B3, BA, and EC130 B4 helicopters with ARRIEL engines with Aircraft Parts...

  8. Hookworm infection

    Science.gov (United States)

    Hookworm disease; Ground itch; Ancylostoma duodenale infection; Necator americanus infection; Parasitic infection - hookworm ... with any of the following roundworms: Necator americanus Ancylostoma ... Ancylostoma ceylanicum Ancylostoma braziliense The first 2 ...

  9. Why the standard B3LYP/6-31G* model chemistry should not be used in DFT calculations of molecular thermochemistry: understanding and correcting the problem.

    Science.gov (United States)

    Kruse, Holger; Goerigk, Lars; Grimme, Stefan

    2012-12-07

    We analyze the error compensations that are responsible for the relatively good performance of the popular B3LYP/6-31G* model chemistry for molecular thermochemistry. We present the B3LYP-gCP-D3/6-31G* scheme, which corrects for missing London dispersion and basis set superposition error (BSSE) in a physically sound manner. Benchmark results for the general main group thermochemistry, kinetics, and noncovalent interactions set (GMTKN30) are presented. A detailed look is cast on organic reactions of several arenes with C(60), Diels-Alder reactions, and barriers to [4 + 3] cycloadditions. We demonstrate the practical advantages of the new B3LYP-gCP-D3/6-31G* scheme and show its higher robustness over standard B3LYP/6-31G*. B3LYP-gCP-D3/6-31G* is meant to fully substitute standard B3LYP/6-31G* calculations in the same black-box sense at essentially no increase in computational cost. The energy corrections are made available by a Web service ( http://www.thch.uni-bonn.de/tc/gcpd3 ) and by freely available software.

  10. The fosfomycin resistance gene fosB3 is located on a transferable, extrachromosomal circular intermediate in clinical Enterococcus faecium isolates.

    Directory of Open Access Journals (Sweden)

    Xiaogang Xu

    Full Text Available Some VanM-type vancomycin-resistant Enterococcus faecium isolates from China are also resistant to fosfomycin. To investigate the mechanism of fosfomycin resistance in these clinical isolates, antimicrobial susceptibility testing, filter-mating, Illumina/Solexa sequencing, inverse PCR and fosfomycin resistance gene cloning were performed. Three E. faecium clinical isolates were highly resistant to fosfomycin and vancomycin with minimal inhibitory concentrations (MICs >1024 µg/ml and >256 µg/ml, respectively. The fosfomycin and vancomycin resistance of these strains could be co-transferred by conjugation. They carried a fosfomycin resistance gene fosB encoding a protein differing by one or two amino acids from FosB, which is encoded on staphylococcal plasmids. Accordingly, the gene was designated fosB3. The fosB3 gene was cloned into pMD19-T, and transformed into E. coli DH5α. The fosfomycin MIC for transformants with fosB3 was 750-fold higher than transformants without fosB3. The fosB3 gene could be transferred by an extrachromosomal circular intermediate. The results indicate that the fosB3 gene is transferable, can mediate high level fosfomycin resistance in both Gram-positive and Gram-negative bacteria, and can be located on a circular intermediate.

  11. Probing the specificity of the subclass B3 FEZ-1 metallo-beta-lactamase by site-directed mutagenesis.

    Science.gov (United States)

    Mercuri, Paola Sandra; García-Sáez, Isabel; De Vriendt, Kris; Thamm, Iris; Devreese, Bart; Van Beeumen, Jozef; Dideberg, Otto; Rossolini, Gian Maria; Frère, Jean-Marie; Galleni, Moreno

    2004-08-06

    The subclass B3 FEZ-1 beta-lactamase produced by Fluoribacter (Legionella) gormanii is a Zn(II)-containing enzyme that hydrolyzes the beta-lactam bond in penicillins, cephalosporins, and carbapenems. FEZ-1 has been extensively studied using kinetic, computational modeling and x-ray crystallography. In an effort to probe residues potentially involved in substrate binding and zinc binding, five site-directed mutants of FEZ-1 (H121A, Y156A, S221A, N225A, and Y228A) were prepared and characterized using metal analyses and steady state kinetics. The activity of H121A is dependent on zinc ion concentration. The H121A monozinc form is less active than the dizinc form, which exhibits an activity similar to that of the wild type enzyme. Tyr156 is not essential for binding and hydrolysis of the substrate. Substitution of residues Ser221 and Asn225 modifies the substrate profile by selectively decreasing the activity against carbapenems. The Y228A mutant is inhibited by the product formed upon hydrolysis of cephalosporins. A covalent bond between the side chain of Cys200 and the hydrolyzed cephalosporins leads to the formation of an inactive and stable complex.

  12. The SH2B3 and KCNK5 loci may be implicated in regulation of platelet count, volume, and maturity

    DEFF Research Database (Denmark)

    Christiansen, Morten K; Larsen, Sanne B; Nyegaard, Mette

    2017-01-01

    variants and five thrombopoiesis-related indices: platelet count (PC), mean platelet volume (MPV), immature platelet count (IPC), immature platelet fraction (IPF), and serum thrombopoietin (TPO). METHODS: We genotyped 45 genome-wide significant CAD/MI-markers in 879 stable CAD patients. A genetic risk...... geometric mean was 2% higher for MPV (95% confidence interval: 1-2%, p=0.002), 6% for IPC (0-12%, p=0.033), and 9% for IPF (3-16%, p=0.004) per CAD risk allele. Moreover, an 11% lower TPO (3-19%, p=0.010) was observed. Rs3184504 (SH2B3) was associated with a higher adjusted geometric mean of 3% (1-6%, p=0.......003) per CAD risk allele for PC, and an 11% (5-17%, pIPC was 5% (0-9%, p=0.037) lower per CAD risk allele for PC, whereas IPF levels did not vary across genotypes. CONCLUSION: As a novel finding, our study suggests a role for KCNK5 in the regulation of platelet...

  13. NLO and NBO Analysis of Sarcosine-Maleic Acid by Using HF and B3LYP Calculations

    Directory of Open Access Journals (Sweden)

    N. Günay

    2013-01-01

    Full Text Available We report a theoretical study on molecular structure, vibrational spectra, nonlinear optical (NLO, and natural bond orbital (NBO analysis of sarcosine-maleic acid (C7H11NO6 in the ground state calculated by using the Hartree-Fock (HF and density functional method (DFT/B3LYP with 6–31++G(d,p basis set. We repeat NBO calculations with 6–31G(d,p basis set so as to see the diffuse function impact on NBO analysis. Stability of the molecule arising from hyper conjugative interactions and charge delocalization has been analyzed using NBO analysis. NBO analysis shows that there is a O–H⋯O and N–H⋯O hydrogen bond in the title compound, which is consistent with the conclusion obtained by the analysis of molecular structure. The calculated HOMO and LUMO energies show that charge transfer occurs within the molecule. Also, these results are supported by the NLO parameters. Finally, the calculated results were applied to simulate infrared and Raman spectra of the title compound which showed good agreement with experimental ones.

  14. Transfection of CTGF siRNA inhibits transdifferentiation in human lens epithelium cell line B3 in vitro

    Directory of Open Access Journals (Sweden)

    Hua Zhuang

    2017-08-01

    Full Text Available AIM: To investigate the expression of connective tissue growth factor(CTGFand α-SMA in human lens epithelium cell(HLECline B3 after transfection by liposome-coated siRNA targeting CTGF. METHODS: HLECs were transfected with small interfering RNA(siRNAtargeting CTGF, labeled with 5'- fluorescein isothiocyanate(5'-FITCand coated with lipofectamine. The transfection ratio was evaluated via fluorescence intensity. Cell counting kit-8(CCK-8assay was performed to assess cytoviability of both non-transfected and transfected HLECs. Quantitative RT- PCR, cell immunochemistry and Western blot analysis were conducted to detect the expression changes of CTGF and α-SMA after transfection. RESULTS: A highly effective transfection ratio was observed in siRNA co-transfected with lipofectamine. The transfection ratio reached 95% at 24h. The proliferation of HLECs was inhibited by siRNA after 72h transfection. The expression of CTGF and α-SMA significantly decreased in HLECs after transfected by CTGF siRNA for 24h. This effect was not found in negative control siRNA. CONCLUSIONS: SiRNA targeting CTGF decreased CTGF and α-SMA expression in HLECs, which is a potential therapeutic strategy for posterior capsular opacification.

  15. Alterations in cell growth and signaling in ErbB3 binding protein-1 (Ebp1 deficient mice

    Directory of Open Access Journals (Sweden)

    Lee Myounghee

    2008-12-01

    Full Text Available Abstract Background The ErbB3 binding protein-1 (Ebp1 belongs to a family of DNA/RNA binding proteins implicated in cell growth, apoptosis and differentiation. However, the physiological role of Ebp1 in the whole organism is not known. Therefore, we generated Ebp1-deficient mice carrying a gene trap insertion in intron 2 of the Ebp1 (pa2g4 gene. Results Ebp1-/- mice were on average 30% smaller than wild type and heterozygous sex matched littermates. Growth retardation was apparent from Day 10 until Day 30. IGF-1 production and IGBP-3 and 4 protein levels were reduced in both embryo fibroblasts and adult knock-out mice. The proliferation of fibroblasts derived from Day 12.5 knock out embryos was also decreased as compared to that of wild type cells. Microarray expression analysis revealed changes in genes important in cell growth including members of the MAPK signal transduction pathway. In addition, the expression or activation of proliferation related genes such as AKT and the androgen receptor, previously demonstrated to be affected by Ebp1 expression in vitro, was altered in adult tissues. Conclusion These results indicate that Ebp1 can affect growth in an animal model, but that the expression of proliferation related genes is cell and context specific. The Ebp1-/- mouse line represents a new in vivo model to investigate Ebp1 function in the whole organism.

  16. Sidestream smoke exposure increases the susceptibility of airway epithelia to adenoviral infection.

    Directory of Open Access Journals (Sweden)

    Priyanka Sharma

    Full Text Available Although significant epidemiological evidence indicates that cigarette smoke exposure increases the incidence and severity of viral infection, the molecular mechanisms behind the increased susceptibility of the respiratory tract to viral pathogens are unclear. Adenoviruses are non-enveloped DNA viruses and important causative agents of acute respiratory disease. The Coxsackievirus and adenovirus receptor (CAR is the primary receptor for many adenoviruses. We hypothesized that cigarette smoke exposure increases epithelial susceptibility to adenovirus infection by increasing the abundance of apical CAR.Cultured human airway epithelial cells (CaLu-3 were used as a model to investigate the effect of sidestream cigarette smoke (SSS, mainstream cigarette smoke (MSS, or control air exposure on the susceptibility of polarized respiratory epithelia to adenoviral infection. Using a Cultex air-liquid interface exposure system, we have discovered novel differences in epithelial susceptibility between SSS and MSS exposures. SSS exposure upregulates an eight-exon isoform of CAR and increases adenoviral entry from the apical surface whilst MSS exposure is similar to control air exposure. Additionally, the level of cellular glycogen synthase kinase 3β (GSK3β is downregulated by SSS exposure and treatment with a specific GSK3β inhibitor recapitulates the effects of SSS exposure on CAR expression and viral infection.This is the first time that SSS exposure has been shown to directly enhance the susceptibility of a polarized epithelium to infection by a common respiratory viral pathogen. This work provides a novel understanding of the impact of SSS on the burden of respiratory viral infections and may lead to new strategies to alter viral infections. Moreover, since GSK3β inhibitors are under intense clinical investigation as therapeutics for a diverse range of diseases, studies such as these might provide insight to extend the use of clinically relevant

  17. Sidestream smoke exposure increases the susceptibility of airway epithelia to adenoviral infection.

    Science.gov (United States)

    Sharma, Priyanka; Kolawole, Abimbola O; Core, Susan B; Kajon, Adriana E; Excoffon, Katherine J D A

    2012-01-01

    Although significant epidemiological evidence indicates that cigarette smoke exposure increases the incidence and severity of viral infection, the molecular mechanisms behind the increased susceptibility of the respiratory tract to viral pathogens are unclear. Adenoviruses are non-enveloped DNA viruses and important causative agents of acute respiratory disease. The Coxsackievirus and adenovirus receptor (CAR) is the primary receptor for many adenoviruses. We hypothesized that cigarette smoke exposure increases epithelial susceptibility to adenovirus infection by increasing the abundance of apical CAR. Cultured human airway epithelial cells (CaLu-3) were used as a model to investigate the effect of sidestream cigarette smoke (SSS), mainstream cigarette smoke (MSS), or control air exposure on the susceptibility of polarized respiratory epithelia to adenoviral infection. Using a Cultex air-liquid interface exposure system, we have discovered novel differences in epithelial susceptibility between SSS and MSS exposures. SSS exposure upregulates an eight-exon isoform of CAR and increases adenoviral entry from the apical surface whilst MSS exposure is similar to control air exposure. Additionally, the level of cellular glycogen synthase kinase 3β (GSK3β) is downregulated by SSS exposure and treatment with a specific GSK3β inhibitor recapitulates the effects of SSS exposure on CAR expression and viral infection. This is the first time that SSS exposure has been shown to directly enhance the susceptibility of a polarized epithelium to infection by a common respiratory viral pathogen. This work provides a novel understanding of the impact of SSS on the burden of respiratory viral infections and may lead to new strategies to alter viral infections. Moreover, since GSK3β inhibitors are under intense clinical investigation as therapeutics for a diverse range of diseases, studies such as these might provide insight to extend the use of clinically relevant therapeutics and

  18. Misbalance in type III collagen formation/degradation as a novel serological biomarker for penetrating (Montreal B3) Crohn's disease.

    Science.gov (United States)

    van Haaften, W T; Mortensen, J H; Karsdal, M A; Bay-Jensen, A C; Dijkstra, G; Olinga, P

    2017-07-01

    Misbalances in extracellular matrix turnover are key factors in the development of stricturing (Montreal B2) and penetrating (Montreal B3) Crohn's disease. To determine whether serological markers for collagen formation and degradation could serve as biomarkers for complications of Crohn's disease. Serum biomarkers for type I, III, V and VI collagen formation (P1NP, Pro-C3, Pro-C5, Pro-C6) and matrix metalloproteinase mediated degradation (C1M, C3M, C5M and C6M) were measured in a retrospective, single centre cohort of 112 patients with Crohn's disease in the terminal ileum (nonstricturing/nonpenetrating: n=40, stricturing: n=55, penetrating: n=17) and 24 healthy controls. Active inflammation was defined as CRP >5 mg/L. C3M and Pro-C5 levels were higher in penetrating vs nonpenetrating/nonstricturing and stricturing disease (33.6±5 vs 25.8±2.2 [P=.004] and 27.2±2.3 [P=.018] nmol/L C3M, 1262.7±259.4 vs 902.9±109.9 [P=.005] and 953.0±106.4 [P=.015] nmol/L Pro-C5). C1M (71.2±26.1 vs 46.2±6.2 nmol/L [PCrohn's disease is characterised by increased matrix metalloproteinase-9 degraded type III collagen and formation of type V collagen. Active inflammation in Crohn's disease is characterised by increased formation of type V collagen and increased matrix metalloproteinase mediated breakdown of type I, III collagen. Pro-C3/C3M ratios are superior in differentiating between penetrating Crohn's disease vs inflammatory and stricturing Crohn's disease. © 2017 The Authors. Alimentary Pharmacology and Therapeutics published by John Wiley & Sons Ltd.

  19. Gas-Phase and Microsolvated Glycine Interacting with Boron Nitride Nanotubes. A B3LYP-D2* Periodic Study

    Directory of Open Access Journals (Sweden)

    Albert Rimola

    2014-06-01

    Full Text Available The adsorption of glycine (Gly both in gas-phase conditions and in a microsolvated state on a series of zig-zag (n,0 single-walled boron nitride nanotubes (BNNTs, n = 4, 6, 9 and 15 has been studied by means of B3LYP-D2* periodic calculations. Gas-phase Gly is found to be chemisorbed on the (4,0, (6,0 and (9,0 BNNTs by means of a dative interaction between the NH2 group of Gly and a B atom of the BNNTs, whose computed adsorption energies are gradually decreased by increasing the tube radius. On the (15,0 BNNT, Gly is found to be physisorbed with an adsorption driving force mainly dictated by p-stacking dispersion interactions. Gly adsorption in a microsolvated environment has been studied in the presence of seven water molecules by progressively microsolvating the dry Gly/BNNT interface. The most stable structures on the (6,0, (9,0 and (15,0 BNNTs present the Gly/BNNT interface fully bridged by the water solvent molecules; i.e., no direct contact between Gly and the BNNTs takes place, whereas on the (4,0 BNNT the most stable structure presents a unique direct interaction between the COO− Gly group and a B atom of the nanotube. Further energetic analyses indicate that the (6,0, (9,0 and (15,0 BNNTs exhibit a low water affinity, which favors the Gly/water interactions upon BNNT coadsorption. In contrast, the (4,0 BNNT has been found to show a large water affinity, bringing the replacement of adsorbed water by a microsolvated glycine molecule as an unfavorable process.

  20. Heterochromatinization induced by GAA-repeat hyperexpansion in Friedreich's ataxia can be reduced upon HDAC inhibition by vitamin B3.

    Science.gov (United States)

    Chan, Ping K; Torres, Raul; Yandim, Cihangir; Law, Pui P; Khadayate, Sanjay; Mauri, Marta; Grosan, Crina; Chapman-Rothe, Nadine; Giunti, Paola; Pook, Mark; Festenstein, Richard

    2013-07-01

    Large intronic expansions of the triplet-repeat sequence (GAA.TTC) cause transcriptional repression of the Frataxin gene (FXN) leading to Friedreich's ataxia (FRDA). We previously found that GAA-triplet expansions stimulate heterochromatinization in vivo in transgenic mice. We report here using chromosome conformation capture (3C) coupled with high-throughput sequencing that the GAA-repeat expansion in FRDA cells stimulates a higher-order structure as a fragment containing the GAA-repeat expansion showed an increased interaction frequency with genomic regions along the FXN locus. This is consistent with a more compacted chromatin and coincided with an increase in both constitutive H3K9me3 and facultative H3K27me3 heterochromatic marks in FRDA. Consistent with this, DNase I accessibility in regions flanking the GAA repeats in patients was decreased compared with healthy controls. Strikingly, this effect could be antagonized with the class III histone deactylase (HDAC) inhibitor vitamin B3 (nicotinamide) which activated the silenced FXN gene in several FRDA models. Examination of the FXN locus revealed a reduction of H3K9me3 and H3K27me3, an increased accessibility to DNase I and an induction of euchromatic H3 and H4 histone acetylations upon nicotinamide treatment. In addition, transcriptomic analysis of nicotinamide treated and untreated FRDA primary lymphocytes revealed that the expression of 67% of genes known to be dysregulated in FRDA was ameliorated by the treatment. These findings show that nictotinamide can up-regulate the FXN gene and reveal a potential mechanism of action for nicotinamide in reactivating the epigenetically silenced FXN gene and therefore support the further assessment of HDAC inhibitors (HDACi's) in FRDA and diseases caused by a similar mechanism.

  1. Outcome of a new patient pathway for managing B3 breast lesions by vacuum-assisted biopsy: time to change current UK practice?

    Science.gov (United States)

    Strachan, C; Horgan, K; Millican-Slater, R A; Shaaban, A M; Sharma, N

    2016-03-01

    B3 lesions of the breast represent a difficult management dilemma. The umbrella term 'B3' incorporates lesions with little associated malignancy risk as well as lesions with significant risk of concurrent neoplasia. Diagnosis of B3 lesions in screening populations is largely made on needle core biopsy, which provides little tissue to adequately diagnose pathologically diverse lesions. The advent of vacuum-assisted biopsy (VAB) provides the multidisciplinary team with a more representative pathology sample to direct management. In this unit, in 2009, a pathway to guide management of B3 lesions detected on needle core biopsy in screening patients was implemented to assess whether VAB was a safe and viable alternative to surgery in selected cases.Here we present the 5-year follow-up results of this pathway. 398 patients with B3 lesions were suitable for this pathway, of which 321 went on to have second-line VAB. 24% of these patients subsequently required surgery for malignancy or ongoing concerns, and thus 245 avoided surgery being subsequently referred for 5-year mammographic surveillance or back to screening. Median follow-up was 3 years (IQR 2), and no cancers were detected at the original B3 site during follow-up. We have demonstrated here that with large volume tissue sampling for indeterminate lesions of the breast surgery can be safely avoided in selected B3 lesions with and without atypia. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  2. Enterovirus infection induces cytokine and chemokine expression in insulin-producing cells.

    Science.gov (United States)

    Nair, Sandhya; Leung, Kin-Chuen; Rawlinson, William D; Naing, Zin; Craig, Maria E

    2010-11-01

    Despite evidence supporting an association between enterovirus (EV) infection and type 1 diabetes, the etiological mechanism(s) for EV-induced beta cell destruction is(are) not well understood. In this study, the effects of Coxsackievirus B (CVB) 1-6 on cell lysis and cytokine/chemokine expression in the insulinoma-1 (INS-1) beta cell line were investigated. Cytolysis was assessed using tissue culture infectious dose 50 (TCID(50)). Quantitative RT-PCR was used to measure viral RNA and mRNA of cytokines interferon (IFN)-α, IFN-β, IFN-γ, tumor necrosis factor (TNF)-α, and chemokine (C-X-C motif) ligand 10 (CXCL10), chemokine (C-C motif) ligand 2 (CCL2), and chemokine (C-C motif) ligand 5 (CCL5) in infected INS-1 cells. CVB2, 4, 5, and 6 lysed and replicated in INS-1 cells; TCID(50) was lowest for CVB5 and highest for CVB6. IFN-γ, CXCL10, and CCL5 mRNA levels all increased significantly following infection with CVB2, 4, 5, and 6 (PCVB5 infection (P<0.05), while TNF-α mRNA and IFN-β mRNA (P<0.001) increased with CVB2 infection. Dose-dependent effects of infection on cytokine mRNA levels were observed for all (P<0.01) except IFN-γ. Following inoculation of INS-1 cells with CVB1 and 3, viral RNA was not detected and cytokine/chemokine mRNA levels were unchanged. In conclusion, CVB2, 4, 5, and 6 induce dose-dependent cytokine and chemokine mRNA production from INS-1 cells suggesting that pro-inflammatory cytokine and chemokine secretion by beta cells is a potential mechanism for EV-induced beta cell damage in type 1 diabetes. © 2010 Wiley-Liss, Inc.

  3. Lesions with unclear malignant potential (B3) after minimally invasive breast biopsy: evaluation of vacuum biopsies performed in Switzerland and recommended further management.

    Science.gov (United States)

    Saladin, Camilla; Haueisen, Harald; Kampmann, Gert; Oehlschlegel, Christian; Seifert, B; Rageth, Luzi; Rageth, Christoph; Stadlmann, S; Kubik-Huch, Rahel A

    2016-07-01

    Histopathological B3 lesions after minimal invasive breast biopsy (VABB) are a particular challenge for the clinician, as there are currently no binding recommendations regarding the subsequent procedure. To analyze all B3 lesions, diagnosed at VABB and captured in the national central Swiss MIBB database and to provide a data basis for further management in this subgroup of patients. All 9,153 stereotactically, sonographically, or magnetic resonance imaging (MRI)-guided vacuum-assisted breast biopsies, performed in Switzerland between 2009 and 2011, captured in a central database, were evaluated. The rate of B3 lesions and the definitive pathological findings in patients who underwent surgical resection were analyzed. The B3 rate was 17.0% (1532 of 9000 biopsies with B classification). Among the 521 lesions with a definitive postoperative diagnosis, the malignancy rate (invasive carcinoma or DCIS) was 21.5%. In patients with atypical ductal hyperplasia, papillary lesions, flat epithelial atypia, lobular neoplasia, and radial scar diagnosed by VABB, the malignancy rates were 25.9%, 3.1%, 18.3%, 26.4%, and 11.1%, respectively. B3 lesions, comprising 17%, of all analyzed biopsies, were common and the proportion of malignancies in those lesions undergoing subsequent surgical excision was high (21.5%). © The Foundation Acta Radiologica 2015.

  4. Fourier transform spectroscopy and coupled-channel deperturbation treatment of the A1Sigma+ ~ b3Pi complex of KCs molecule

    CERN Document Server

    Kruzins, A; Nikolayeva, O; Tamanis, M; Ferber, R; Pazyuk, E A; Stolyarov, A V

    2009-01-01

    The laser induced fluorescence (LIF) spectra A1Sigma ~ b3Pi --> X1Sigma+ of KCs dimer were recorded in near infrared region by Fourier Transform Spectrometer with a resolution of 0.03 cm-1. Overall more than 200 LIF spectra were rotationally assigned to 39K133Cs and 41K133Cs isotopomers yielding with the uncertainty of 0.003-0.01 cm-1 more than 3400 rovibronic term values of the strongly mixed singlet A1Sigma+ and triplet b3Pi states. Experimental data massive starts from the lowest vibrational level v_A=0 of the singlet and nonuniformly cover the energy range from 10040 to 13250 cm-1 with rotational quantum numbers J from 7 to 225. Besides of the dominating regular A1Sigma+ ~ b3P Omega=0 interactions the weak and local heterogenous A1S+ ~ b3P Omega=1 perturbations have been discovered and analyzed. Coupled-channel deperturbation analysis of the experimental 39K133Cs e-parity termvalues of the A1S+ ~ b3P complex was accomplished in the framework of the phenomenological 4 x 4 Hamiltonian accounting implicitly ...

  5. Mutagenesis of the yellow fever virus NS2B/3 cleavage site: determinants of cleavage site specificity and effects on polyprotein processing and viral replication.

    Science.gov (United States)

    Chambers, T J; Nestorowicz, A; Rice, C M

    1995-03-01

    The determinants of cleavage site specificity of the yellow fever virus (YF) NS3 proteinase for its 2B/3 cleavage site have been studied by using site-directed mutagenesis. Mutations at residues within the GARR decreases S sequence were tested for effects on cis cleavage of an NS2B-3(181) polyprotein during cell-free translation. At the P1 position, only the conservative substitution R-->K exhibited significant levels of cleavage. Conservative and nonconservative substitutions were tolerated at the P1' and P2 positions, resulting in intermediate levels of cleavage. Substitutions at the P3 and P4 positions had no effects on cleavage efficiency in the cell-free assay. Processing at other dibasic sites was studied by using transient expression of a sig2A-5(356) polyprotein. Cleavage at the 2B/3 site was not required for processing at downstream sites. However, increased accumulation of high-molecular-weight viral polyproteins was generally observed for mutations which reduced cleavage efficiency at the 2B/3 site. Several mutations were also tested for their effects on viral replication. Virus was not recovered from substitutions which blocked or substantially reduced cleavage in the cell-free assay, suggesting that efficient cleavage at the 2B/3 site is required for flavivirus replication.

  6. New procyanidin B3-human salivary protein complexes by mass spectrometry. Effect of salivary protein profile, tannin concentration, and time stability.

    Science.gov (United States)

    Perez-Gregorio, Maria Rosa; Mateus, Nuno; De Freitas, Victor

    2014-10-15

    Several factors could influence the tannin-protein interaction such as the human salivary protein profile, the tannin tested, and the tannin/protein ratio. The goal of this study aims to study the effect of different salivas (A, B, and C) and different tannin concentrations (0.5 and 1 mg/mL) on the interaction process as well as the complex's stability over time. This study is focused on the identification of new procyanidin B3-human salivary protein complexes. Thus, 48 major B3-human salivary protein aggregates were identified regardless of the saliva and tannin concentration tested. A higher number of aggregates was found at lower tannin concentration. Moreover, the number of protein moieties involved in the aggregation process was higher when the tannin concentration was also higher. The selectivity of the different groups of proteins to bind tannin was also confirmed. It was also verified that the B3-human salivary protein complexes formed evolved over time.

  7. Up-regulation of Serum MiR-130b-3p Level is Associated with Renal Damage in Early Lupus Nephritis

    Science.gov (United States)

    Wang, Wanpeng; Mou, Shan; Wang, Ling; Zhang, Minfang; Shao, Xinghua; Fang, Wei; Lu, Renhua; Qi, Chaojun; Fan, Zhuping; Cao, Qin; Wang, Qin; Fang, Yan; Ni, Zhaohui

    2015-08-01

    Systemic lupus erythematosus (SLE) is a common but severe autoimmune systemic inflammatory disease. Lupus nephritis (LN) is a serious complication of SLE,affecting up to 70% of SLE patients. Circulating microRNAs (miRNA) are emerging as biomarkers for pathological conditions and play significant roles in intercellular communication. In present research, serum samples from healthy control, early and late stage LN patients were used to analyze the expression profile of miRNAs by microarray. Subsequent study demonstrated that miR-130b-3p in serum of patients with early stage LN were significantly up-regulated when compared with healthy controls. In addition,we have also observed that the expression of a large amount of circulating microRNAs significantly decreased in patients with late stage LN. The further analysis found that the expression of serum miR-130b-3p was positively correlated with 24-hour proteinuria and renal chronicity index in patients with early stage LN.Transfection of renal tubular cellline(HK-2)with miR-130b-3p mimics can promote epithelial-mesenchymal transition (EMT). The opposite effects were observed when transfected with miR-130b-3p inhibitors. MiR-130b-3p negatively regulated ERBB2IP expression by directly targeting the 3‧-UTR of ERBB2IP The circulating miR-130b-3p might serve as a biomarker and play an important role in renal damage in early stage LN patients.

  8. Retinoid acid-induced microRNA-27b-3p impairs C2C12 myoblast proliferation and differentiation by suppressing α-dystrobrevin

    Energy Technology Data Exchange (ETDEWEB)

    Li, Nan; Tang, Yi; Liu, Bo; Cong, Wei; Liu, Chao, E-mail: liuchao_19760711@yahoo.com; Xiao, Jing, E-mail: xiaoj@dmu.edu.cn

    2017-01-15

    We previously reported that excess retinoic acid (RA) resulted in hypoplastic and derangement of myofilaments in embryonic tongue by inhibiting myogenic proliferation and differentiation through CamKIID pathway. Our further studies revealed that the expression of a series of miRNAs was altered by RA administration in embryonic tongue as well as in C2C12 cells. Thus, if excess RA impairs myogenic proliferation and differentiation through miRNAs is taken into account. In present study, miR-27b-3p was found up-regulated in RA-treated C2C12 cells as in embryonic tongue, and predicted to target the 3′UTR of α-dystrobrevin (DTNA). Luciferase reporter assays confirmed the direct interaction between miR-27b-3p and the 3′UTR of DTNA. MiR-27b-3p mimics recapitulated the RA repression on DTNA expression, C2C12 proliferation and differentiation, while the miR-27b-3p inhibitor circumvented these defects resulting from excess RA. As expected, the effects of siDTNA on C2C12 were coincided with those by RA treatment or miR-27b-3p mimics. Therefore, these findings indicated that excess RA inhibited the myoblast proliferation and differentiation by up-regulating miR-27b-3p to target DTNA, which implied a new mechanism in myogenic hypoplasia. - Highlights: • A mechanism that RA results in tongue deformity by disrupting the myogenesis. • A non-muscle specific miR mediating the RA suppression on tongue myogenesis. • A target gene of non-muscle specific miR involved in RA induced tongue deformity.

  9. Interaction between ADH1B*3 and alcohol-facilitating social environments in alcohol behaviors among college students of african descent.

    Science.gov (United States)

    Desalu, Jessica M; Zaso, Michelle J; Kim, Jueun; Belote, John M; Park, Aesoon

    2017-06-01

    Although alcohol-facilitating social environmental factors, such as alcohol offers and high perceived peer drinking norms, have been extensively studied as determinants of college drinking, their role among college students of African descent remains understudied. Furthermore, gene-environment interaction research suggests that the effects of alcohol-facilitating environments may differ as a function of genetic factors. Specifically, the alcohol dehydrogenase gene's ADH1B*3 allele, found almost exclusively in persons of African descent, may modulate the association of risky social environments with alcohol behaviors. The current study examined whether the ADH1B*3 allele attenuated the relationship between alcohol-facilitating environments (ie, alcohol offers and perceived peer drinking norms) and alcohol behaviors. Participants were 241 undergraduate students who self-identified as being of African descent (mean age = 20 years [SD = 4.11]; 66% female). Significant interaction effects of ADH1B*3 with alcohol offers were found on alcohol use frequency (incidence rate ratio [IRR] = 1.14) and on drinking consequences (IRR = 1.21). ADH1B*3 also interacted with perceived peer norms on drinking consequences (IRR = 1.41). Carriers of the ADH1B*3 allele drank less frequently and experienced fewer negative consequences than non-carriers when exposed to lower levels of alcohol offers and perceived peer drinking. In contrast, in high alcohol-facilitating environments, no protective genetic effect was observed. This study demonstrates that ADH1B*3 may protect college students of African descent against alcohol outcomes, although only in low alcohol-facilitating environments. Findings add to the growing body of knowledge regarding genetic and social determinants of alcohol behaviors among college students of African descent. (Am J Addict 2017;26:349-356). © 2017 American Academy of Addiction Psychiatry.

  10. Isolation of Modulators of the Liver-Specific Organic Anion-Transporting Polypeptides (OATPs) 1B1 and 1B3 from Rollinia emarginata Schlecht (Annonaceae)

    Science.gov (United States)

    Roth, Megan; Araya, Juan J.; Timmermann, Barbara N.

    2011-01-01

    Organic anion-transporting polypeptides 1B1 and 1B3 (OATP1B1 and OATP1B3) are liver-specific transporters that mediate the uptake of a broad range of drugs into hepatocytes, including statins, antibiotics, and many anticancer drugs. Compounds that alter transport by one or both of these OATPs could potentially be used to target drugs to hepatocytes or improve the bioavailability of drugs that are cleared by the liver. In this study, we applied a bioassay-guided isolation approach to identify such compounds from the organic extract of Rollinia emarginata Schlecht (Annonaceae). Fractions of the plant extract were screened for effects on OATP1B1- and OATP1B3-mediated transport of the model substrates estradiol-17β-glucuronide and estrone-3-sulfate. We isolated three compounds, ursolic acid, oleanolic acid, and 8-trans-p-coumaroyloxy-α-terpineol, which inhibited estradiol-17β-glucuronide uptake by OATP1B1 but not OATP1B3. In addition, a rare compound, quercetin 3-O-α-l-arabinopyranosyl(1→2) α-l-rhamnopyranoside, was identified that had distinct effects on each OATP. OATP1B1 was strongly inhibited, as was OATP1B3-mediated transport of estradiol-17β-glucuronide. However, OATP1B3-mediated uptake of estrone-3-sulfate was stimulated 4- to 5-fold. Kinetic analysis of this stimulation revealed that the apparent affinity for estrone-3-sulfate was increased (decreased Km), whereas the maximal rate of transport (Vmax) was significantly reduced. These results demonstrate a mechanism through which the hepatic uptake of drug OATP substrates could be stimulated. PMID:21846839

  11. Serum cholinesterase: a potential assistant biomarker for hand, foot, and mouth disease caused by enterovirus 71 infection.

    Science.gov (United States)

    Cheng, Bang-Ning; Jin, Yu-Lian; Chen, Bi-Quan; Zhu, Li-Yan; Xu, Zi-Cheng; Shen, Tao

    2016-03-29

    Hand, foot, and mouth disease (HFMD) caused by enterovirus 71 (EV71) is a potentially life-threatening infectious disease that commonly occurs in children. Diagnosis of HFMD caused by EV71 largely depends on clinical manifestations and rare serological biomarkers used to identify children suffering from HFMD. Serum cholinesterase (SChE) activity has frequently been reported as a potential biomarker for solid central nervous system tumors, chronic heart failure, and liver cirrhosis. However, its potential value in the diagnosis of neurotropic virus infections, such as HFMD caused by EV71, remains to be determined. In our study, 220 children hospitalized with HFMD caused by EV71, 34 inpatients infected with coxsackievirus A16 (CVA16), and 43 undefined enterovirus-infected HFMD inpatients were recruited at the Anhui Provincial Children's Hospital between January 2011 and December 2012. SChE activity was measured. The non-parametric Mann-Whitney U test showed that SChE activity in children diagnosed with HFMD caused by EV71 was significantly higher than in healthy controls (p  0.05). An important finding was that SChE activity declined in the recovery phase of HFMD caused by EV71 compared to the acute phase (p < 0.001). Elevated SChE activity was observed in patients with severe HFMD caused by EV71. Therefore, SChE might be a potential assistant biomarker for the diagnosis of HFMD caused by EV71 in children.

  12. Notes from the Field: Outbreak of Hand, Foot, and Mouth Disease Caused by Coxsackievirus A6 Among Basic Military Trainees - Texas, 2015.

    Science.gov (United States)

    Banta, Jonathan; Lenz, Brittany; Pawlak, Mary; Laskoski, Kelly; Seykora, Caitlin; Webber, Bryant; Yun, Heather; Ritchie, Simon

    2016-07-08

    On July 7, 2015, a man aged 22 years reported to sick call during basic military training at Lackland Air Force Base (AFB), Texas. He had erythematous, crusted papulovesicular lesions on the extensor surfaces of the upper and lower extremities. The patient was afebrile and otherwise well, and was evaluated later that day by the dermatology service. A viral infection was considered most likely because of the patient's age, absence of fever or constitutional symptoms, and the distribution and morphology of the lesions. The initial differential diagnosis included Henoch-Schönlein purpura, parvovirus B19, and Rocky Mountain spotted fever. However, the clinical signs, including the unique morphology and distribution of grouped vesicles and papules was suggestive of hand, foot, and mouth disease (HFMD), although the patient did not have oral lesions and reported no contact with another person with HFMD. A viral culture and punch biopsy of one of the lesions were obtained.

  13. Staphylococcal Infections

    Science.gov (United States)

    ... arthritis), and a number of skin infections (eg, impetigo, pimples, boils). Staphylococcus aureus also causes toxin-related ... cases clear up in 7 to 10 days. Impetigo is a common and contagious skin infection in ...

  14. Campylobacter Infections

    Science.gov (United States)

    Campylobacter infection is a common foodborne illness. You usually get it from eating contaminated food, especially raw ... reactive arthritis or Guillain-Barre syndrome. To prevent Campylobacter infection, cook poultry thoroughly. Use a separate cutting ...

  15. Rotavirus Infections

    Science.gov (United States)

    ... that causes gastroenteritis. Symptoms include severe diarrhea, vomiting, fever, and dehydration. Almost all children in the U.S. are likely to be infected with rotavirus before their 5th birthday. Infections happen most often ...

  16. Comparison analysis of microRNAs in response to EV71 and CA16 infection in human bronchial epithelial cells by high-throughput sequencing to reveal differential infective mechanisms.

    Science.gov (United States)

    Hu, Yajie; Song, Jie; Liu, Longding; Li, Jing; Tang, Beibei; Zhang, Ying; Wang, Jingjing; Wang, Lichun; Fan, Shengtao; Feng, Ming; Li, Qihan

    2017-01-15

    Hand, foot, and mouth disease (HFMD) mainly caused by Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) infections which presented significantly different clinical manifestations. Nevertheless, the factors underlying these differences remain unclear. Recently, the functions of microRNAs (miRNAs) in pathogen-host interactions have been highlighted. Here, we performed comprehensive miRNA profiling in EV71- and CA16-infected human bronchial epithelial (16HBE) cells at multiple time points using high-throughput sequencing. The results showed that 154 known and 47 novel miRNAs exhibited remarkable differences in expression. Of these, 65 miRNAs, including 58 known and 7 novel miRNAs, presented opposite trends in EV71- and CA16-infected samples. Subsequently, we mainly focused on the 56 known differentially expressed miRNAs by further screening for targets prediction. GO and pathway analysis of these targets demonstrated that 18 biological processes, 7 molecular functions, 1 cellular component and 123 pathways were enriched. Among these pathways, Cadherin signalling pathway, Wnt signalling pathway and angiogenesis showed significant alterations. The regulatory networks of these miRNAs with predicted targets, GOs, pathways and transcription factors were determined, which suggested that miRNAs displayed intricate regulatory mechanisms during the infection phase. Consequently, we specifically analysed the hierarchical GO categories of the predicted targets involved in adhesion. The results indicated that the distinct changes induced by EV71 and CA16 infection may be partly linked to airway epithelial barrier function. Taken together, our data provide useful insights that help elucidate the different host-pathogen interactions following EV71 and CA16 infection and might offer novel therapeutic targets for these infections. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  17. Staph Infections

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Staph Infections KidsHealth / For Teens / Staph Infections What's in ... en español Infecciones por estafilococo What Is a Staph Infection? Staph is the shortened name for Staphylococcus ( ...

  18. SCC-TB, DFT/B3LYP, MP2, AM1, PM3 and RHF study of ethylene oxide and propylene oxide structures, VA and VCD spectra

    DEFF Research Database (Denmark)

    Jalkanen, Karl J.; Frimand, Kenneth

    2002-01-01

    -binding method for equilibrium structures, VA and VCD spectra of ethylene oxide and propylene oxide in the gas-phase. Comparison to conventional methods AM1, PM3, MP2, RHF and DFT/B3LYP is carried out. We report results over a wider range of frequencies than previous work. In particular, we find indications...

  19. Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5)

    NARCIS (Netherlands)

    Bousquet, J.; Farrell, J.; Crooks, G.; Hellings, P.; Bel, E. H.; Bewick, M.; Chavannes, N. H.; de Sousa, J. Correia; Cruz, A. A.; Haahtela, T.; Joos, G.; Khaltaev, N.; Malva, J.; Muraro, A.; Nogues, M.; Palkonen, S.; Pedersen, S.; Robalo-Cordeiro, C.; Samolinski, B.; Strandberg, T.; Valiulis, A.; Yorgancioglu, A.; Zuberbier, T.; Bedbrook, A.; Aberer, W.; Adachi, M.; Agusti, A.; Akdis, C. A.; Akdis, M.; Ankri, J.; Alonso, A.; Annesi-Maesano, I.; Ansotegui, I. J.; Anto, J. M.; Arnavielhe, S.; Arshad, H.; Bai, C.; Baiardini, I.; Bachert, C.; Baigenzhin, A. K.; Barbara, C.; Bateman, E. D.; Beghé, B.; Kheder, A. Ben; Bennoor, K. S.; Benson, M.; Bergmann, K. C.; Bieber, T.; Bindslev-Jensen, C.; Bjermer, L.; Blain, H.; Blasi, F.; Boner, A. L.; Bonini, M.; Bonini, S.; Bosnic-Anticevitch, S.; Boulet, L. P.; Bourret, R.; Bousquet, P. J.; Braido, F.; Briggs, A. H.; Brightling, C. E.; Brozek, J.; Buhl, R.; Burney, P. G.; Bush, A.; Caballero-Fonseca, F.; Caimmi, D.; Calderon, M. A.; Calverley, P. M.; Camargos, P. A. M.; Canonica, G. W.; Camuzat, T.; Carlsen, K. H.; Carr, W.; Carriazo, A.; Casale, T.; Cepeda Sarabia, A. M.; Chatzi, L.; Chen, Y. Z.; Chiron, R.; Chkhartishvili, E.; Chuchalin, A. G.; Chung, K. F.; Ciprandi, G.; Cirule, I.; Cox, L.; Costa, D. J.; Custovic, A.; Dahl, R.; Dahlen, S. E.; Darsow, U.; de Carlo, G.; de Blay, F.; Dedeu, T.; Deleanu, D.; de Manuel Keenoy, E.; Demoly, P.; Denburg, J. A.; Devillier, P.; Didier, A.; Dinh-Xuan, A. T.; Djukanovic, R.; Dokic, D.; Douagui, H.; Dray, G.; Dubakiene, R.; Durham, S. R.; Dykewicz, M. S.; El-Gamal, Y.; Emuzyte, R.; Fabbri, L. M.; Fletcher, M.; Fiocchi, A.; Fink Wagner, A.; Fonseca, J.; Fokkens, W. J.; Forastiere, F.; Frith, P.; Gaga, M.; Gamkrelidze, A.; Garces, J.; Garcia-Aymerich, J.; Gemicioğlu, B.; Gereda, J. E.; González Diaz, S.; Gotua, M.; Grisle, I.; Grouse, L.; Gutter, Z.; Guzmán, M. A.; Heaney, L. G.; Hellquist-Dahl, B.; Henderson, D.; Hendry, A.; Heinrich, J.; Heve, D.; Horak, F.; Hourihane, J. O.' B.; Howarth, P.; Humbert, M.; Hyland, M. E.; Illario, M.; Ivancevich, J. C.; Jardim, J. R.; Jares, E. J.; Jeandel, C.; Jenkins, C.; Johnston, S. L.; Jonquet, O.; Julge, K.; Jung, K. S.; Just, J.; Kaidashev, I.; Kaitov, M. R.; Kalayci, O.; Kalyoncu, A. F.; Keil, T.; Keith, P. K.; Klimek, L.; Koffi N'goran, B.; Kolek, V.; Koppelman, G. H.; Kowalski, M. L.; Kull, I.; Kuna, P.; Kvedariene, V.; Lambrecht, B.; Lau, S.; Larenas-Linnemann, D.; Laune, D.; Le, L. T. T.; Lieberman, P.; Lipworth, B.; Li, J.; Lodrup Carlsen, K.; Louis, R.; MacNee, W.; Magard, Y.; Magnan, A.; Mahboub, B.; Mair, A.; Majer, I.; Makela, M. J.; Manning, P.; Mara, S.; Marshall, G. D.; Masjedi, M. R.; Matignon, P.; Maurer, M.; Mavale-Manuel, S.; Melén, E.; Melo-Gomes, E.; Meltzer, E. O.; Menzies-Gow, A.; Merk, H.; Michel, J. P.; Miculinic, N.; Mihaltan, F.; Milenkovic, B.; Mohammad, G. M. Y.; Molimard, M.; Momas, I.; Montilla-Santana, A.; Morais-Almeida, M.; Morgan, M.; Mösges, R.; Mullol, J.; Nafti, S.; Namazova-Baranova, L.; Naclerio, R.; Neou, A.; Neffen, H.; Nekam, K.; Niggemann, B.; Ninot, G.; Nyembue, T. D.; O'Hehir, R. E.; Ohta, K.; Okamoto, Y.; Okubo, K.; Ouedraogo, S.; Paggiaro, P.; Pali-Schöll, I.; Panzner, P.; Papadopoulos, N.; Papi, A.; Park, H. S.; Passalacqua, G.; Pavord, I.; Pawankar, R.; Pengelly, R.; Pfaar, O.; Picard, R.; Pigearias, B.; Pin, I.; Plavec, D.; Poethig, D.; Pohl, W.; Popov, T. A.; Portejoie, F.; Potter, P.; Postma, D.; Price, D.; Rabe, K. F.; Raciborski, F.; Radier Pontal, F.; Repka-Ramirez, S.; Reitamo, S.; Rennard, S.; Rodenas, F.; Roberts, J.; Roca, J.; Rodriguez Mañas, L.; Rolland, C.; Roman Rodriguez, M.; Romano, A.; Rosado-Pinto, J.; Rosario, N.; Rosenwasser, L.; Rottem, M.; Ryan, D.; Sanchez-Borges, M.; Scadding, G. K.; Schunemann, H. J.; Serrano, E.; Schmid-Grendelmeier, P.; Schulz, H.; Sheikh, A.; Shields, M.; Siafakas, N.; Sibille, Y.; Similowski, T.; Simons, F. E. R.; Sisul, J. C.; Skrindo, I.; Smit, H. A.; Solé, D.; Sooronbaev, T.; Spranger, O.; Stelmach, R.; Sterk, P. J.; Sunyer, J.; Thijs, C.; To, T.; Todo-Bom, A.; Triggiani, M.; Valenta, R.; Valero, A. L.; Valia, E.; Valovirta, E.; van Ganse, E.; van Hage, M.; Vandenplas, O.; Vasankari, T.; Vellas, B.; Vestbo, J.; Vezzani, G.; Vichyanond, P.; Viegi, G.; Vogelmeier, C.; Vontetsianos, T.; Wagenmann, M.; Wallaert, B.; Walker, S.; Wang, D. Y.; Wahn, U.; Wickman, M.; Williams, D. M.; Williams, S.; Wright, J.; Yawn, B. P.; Yiallouros, P. K.; Yusuf, O. M.; Zaidi, A.; Zar, H. J.; Zernotti, M. E.; Zhang, L.; Zhong, N.; Zidarn, M.; Mercier, J.

    2016-01-01

    Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) focuses on the integrated care of chronic diseases. Area 5 (Care Pathways) was initiated using chronic respiratory diseases as a model. The chronic respiratory disease action plan includes (1) AIRWAYS

  20. Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3 Area 5)

    NARCIS (Netherlands)

    Bousquet, J; Farrell, J; Crooks, G; Hellings, P; Bel, E H; Bewick, M; Chavannes, N H; de Sousa, J Correia; Cruz, A A; Haahtela, T; Joos, G; Khaltaev, N; Malva, J; Muraro, A; Nogues, M; Palkonen, S; Pedersen, S; Robalo-Cordeiro, C; Samolinski, B; Strandberg, T; Valiulis, A; Yorgancioglu, A; Zuberbier, T; Bedbrook, A; Aberer, W; Adachi, M; Agusti, A; Akdis, C A; Akdis, M; Ankri, J; Alonso, A; Annesi-Maesano, I; Ansotegui, I J; Anto, J M; Arnavielhe, S; Arshad, H; Bai, C; Baiardini, I; Bachert, C; Baigenzhin, A K; Barbara, C; Bateman, E D; Beghé, B; Kheder, A Ben; Bennoor, K S; Benson, M; Bergmann, K C; Bieber, T; Bindslev-Jensen, C; Bjermer, L; Blain, H; Blasi, F; Boner, A L; Bonini, M; Bonini, S; Bosnic-Anticevitch, S; Boulet, L P; Bourret, R; Bousquet, P J; Braido, F; Briggs, A H; Brightling, C E; Brozek, J; Buhl, R; Burney, P G; Bush, A; Caballero-Fonseca, F; Caimmi, D; Calderon, M A; Calverley, P M; Camargos, P A M; Canonica, G W; Camuzat, T; Carlsen, K H; Carr, W; Carriazo, A; Casale, T; Cepeda Sarabia, A M; Chatzi, L; Chen, Y Z; Chiron, R; Chkhartishvili, E; Chuchalin, A G; Chung, K F; Ciprandi, G; Cirule, I; Cox, L; Costa, D J; Custovic, A; Dahl, R; Dahlen, S E; Darsow, U; De Carlo, G; De Blay, F; Dedeu, T; Deleanu, D; De Manuel Keenoy, E; Demoly, P; Denburg, J A; Devillier, P; Didier, A; Dinh-Xuan, A T; Djukanovic, R; Dokic, D; Douagui, H; Dray, G; Dubakiene, R; Durham, S R; Dykewicz, M S; El-Gamal, Y; Emuzyte, R; Fabbri, L M; Fletcher, M; Fiocchi, A; Fink Wagner, A; Fonseca, J; Fokkens, W J; Forastiere, F; Frith, P; Gaga, M; Gamkrelidze, A; Garces, J; Garcia-Aymerich, J; Gemicioğlu, B; Gereda, J E; González Diaz, S; Gotua, M; Grisle, I; Grouse, L; Gutter, Z; Guzmán, M A; Heaney, L G; Hellquist-Dahl, B; Henderson, D; Hendry, A; Heinrich, J; Heve, D; Horak, F; Hourihane, J O' B; Howarth, P; Humbert, M; Hyland, M E; Illario, M; Ivancevich, J C; Jardim, J R; Jares, E J; Jeandel, C; Jenkins, C; Johnston, S L; Jonquet, O; Julge, K; Jung, K S; Just, J; Kaidashev, I; Kaitov, M R; Kalayci, O; Kalyoncu, A F; Keil, T; Keith, P K; Klimek, L; Koffi N'Goran, B; Kolek, V; Koppelman, G H; Kowalski, M L; Kull, I; Kuna, P; Kvedariene, V; Lambrecht, B; Lau, S; Larenas-Linnemann, D; Laune, D; Le, L T T; Lieberman, P; Lipworth, B; Li, J; Lodrup Carlsen, K; Louis, R; MacNee, W; Magard, Y; Magnan, A; Mahboub, B; Mair, A; Majer, I; Makela, M J; Manning, P; Mara, S; Marshall, G D; Masjedi, M R; Matignon, P; Maurer, M; Mavale-Manuel, S; Melén, E; Melo-Gomes, E; Meltzer, E O; Menzies-Gow, A; Merk, H; Michel, J P; Miculinic, N; Mihaltan, F; Milenkovic, B; Mohammad, G M Y; Molimard, M; Momas, I; Montilla-Santana, A; Morais-Almeida, M; Morgan, M; Mösges, R; Mullol, J; Nafti, S; Namazova-Baranova, L; Naclerio, R; Neou, A; Neffen, H; Nekam, K; Niggemann, B; Ninot, G; Nyembue, T D; O'Hehir, R E; Ohta, K; Okamoto, Y; Okubo, K; Ouedraogo, S; Paggiaro, P; Pali-Schöll, I; Panzner, P; Papadopoulos, N; Papi, A; Park, H S; Passalacqua, G; Pavord, I; Pawankar, R; Pengelly, R; Pfaar, O; Picard, R; Pigearias, B; Pin, I; Plavec, D; Poethig, D; Pohl, W; Popov, T A; Portejoie, F; Potter, P; Postma, D.; Price, D; Rabe, K F; Raciborski, F; Radier Pontal, F; Repka-Ramirez, S; Reitamo, S; Rennard, S; Rodenas, F; Roberts, J; Roca, J; Rodriguez Mañas, L; Rolland, C; Roman Rodriguez, M; Romano, A; Rosado-Pinto, J; Rosario, N; Rosenwasser, L; Rottem, M; Ryan, D; Sanchez-Borges, M; Scadding, G K; Schunemann, H J; Serrano, E; Schmid-Grendelmeier, P; Schulz, H; Sheikh, A; Shields, M; Siafakas, N; Sibille, Y; Similowski, T; Simons, F E R; Sisul, J C; Skrindo, I; Smit, H A|info:eu-repo/dai/nl/067730043; Solé, D; Sooronbaev, T; Spranger, O; Stelmach, R; Sterk, P J; Sunyer, J; Thijs, C; To, T; Todo-Bom, A; Triggiani, M; Valenta, R; Valero, A L; Valia, E; Valovirta, E; Van Ganse, E; van Hage, M; Vandenplas, O; Vasankari, T; Vellas, B; Vestbo, J; Vezzani, G; Vichyanond, P; Viegi, G; Vogelmeier, C; Vontetsianos, T; Wagenmann, M; Wallaert, B; Walker, S; Wang, D Y; Wahn, U; Wickman, M; Williams, D M; Williams, S; Wright, J; Yawn, B P; Yiallouros, P K; Yusuf, O M; Zaidi, A; Zar, H J; Zernotti, M E; Zhang, L; Zhong, N; Zidarn, M; Mercier, J

    2016-01-01

    Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) focuses on the integrated care of chronic diseases. Area 5 (Care Pathways) was initiated using chronic respiratory diseases as a model. The chronic respiratory disease action plan includes (1) AIRWAYS

  1. Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3 : Area 5)

    NARCIS (Netherlands)

    Bousquet, J; Farrell, J; Crooks, G; Hellings, P; Bel, E H; Bewick, M; Chavannes, N H; de Sousa, J Correia; Cruz, A A; Haahtela, T; Joos, G; Khaltaev, N; Malva, J; Muraro, A; Nogues, M; Palkonen, S; Pedersen, S; Robalo-Cordeiro, C; Samolinski, B; Strandberg, T; Valiulis, A; Yorgancioglu, A; Zuberbier, T; Bedbrook, A; Aberer, W; Adachi, M; Agusti, A; Akdis, C A; Akdis, M; Ankri, J; Alonso, A; Annesi-Maesano, I; Ansotegui, I J; Anto, J M; Arnavielhe, S; Arshad, H; Bai, C; Baiardini, I; Bachert, C; Baigenzhin, A K; Barbara, C; Bateman, E D; Beghé, B; Kheder, A Ben; Bennoor, K S; Benson, M; Bergmann, K C; Bieber, T; Bindslev-Jensen, C; Bjermer, L; Blain, H; Blasi, F; Boner, A L; Bonini, M; Bonini, S; Bosnic-Anticevitch, S; Boulet, L P; Bourret, R; Bousquet, P J; Braido, F; Briggs, A H; Brightling, C E; Brozek, J; Buhl, R; Burney, P G; Bush, A; Caballero-Fonseca, F; Caimmi, D; Calderon, M A; Calverley, P M; Camargos, P A M; Canonica, G W; Camuzat, T; Carlsen, K H; Carr, W; Carriazo, A; Casale, T; Cepeda Sarabia, A M; Chatzi, L; Chen, Y. Z.; Chiron, R; Chkhartishvili, E; Chuchalin, A G; Chung, K F; Ciprandi, G; Cirule, I; Cox, L; Costa, D J; Custovic, A; Dahl, R; Dahlen, S E; Darsow, U; De Carlo, G; De Blay, F; Dedeu, T; Deleanu, D; De Manuel Keenoy, E; Demoly, P; Denburg, J A; Devillier, P; Didier, A; Dinh-Xuan, A T; Djukanovic, R; Dokic, D; Douagui, H; Dray, G; Dubakiene, R; Durham, S R; Dykewicz, M S; El-Gamal, Y; Emuzyte, R; Fabbri, L M; Fletcher, M; Fiocchi, A; Fink Wagner, A; Fonseca, J; Fokkens, W J; Forastiere, F; Frith, P; Gaga, M; Gamkrelidze, A; Garces, J; Garcia-Aymerich, J; Gemicioğlu, B; Gereda, J E; González Diaz, S; Gotua, M; Grisle, I; Grouse, L; Gutter, Z; Guzmán, M A; Heaney, L G; Hellquist-Dahl, B; Henderson, D; Hendry, A; Heinrich, J.; Heve, D; Horak, F; Hourihane, J O' B; Howarth, P; Humbert, M; Hyland, M E; Illario, M; Ivancevich, J C; Jardim, J R; Jares, E J; Jeandel, C; Jenkins, C; Johnston, S L; Jonquet, O; Julge, K; Jung, K S; Just, J; Kaidashev, I; Kaitov, M R; Kalayci, O; Kalyoncu, A F; Keil, T; Keith, P K; Klimek, L; Koffi N'Goran, B; Kolek, V; Koppelman, G H; Kowalski, M L; Kull, I; Kuna, P; Kvedariene, V; Lambrecht, B; Lau, S; Larenas-Linnemann, D; Laune, D; Le, L T T; Lieberman, P; Lipworth, B; Li, J.; Lodrup Carlsen, K; Louis, R; MacNee, W; Magard, Y; Magnan, A; Mahboub, B; Mair, A; Majer, I; Makela, M J; Manning, P; Mara, S; Marshall, G D; Masjedi, M R; Matignon, P; Maurer, M.; Mavale-Manuel, S; Melén, E; Melo-Gomes, E; Meltzer, E O; Menzies-Gow, A; Merk, H.; Michel, J P; Miculinic, N; Mihaltan, F; Milenkovic, B; Mohammad, G M Y; Molimard, M; Momas, I; Montilla-Santana, A; Morais-Almeida, M; Morgan, M; Mösges, R; Mullol, J; Nafti, S; Namazova-Baranova, L; Naclerio, R; Neou, A; Neffen, H; Nekam, K; Niggemann, B; Ninot, G; Nyembue, T D; O'Hehir, R E; Ohta, K; Okamoto, Y; Okubo, K; Ouedraogo, S; Paggiaro, P; Pali-Schöll, I; Panzner, P; Papadopoulos, N; Papi, A; Park, H S; Passalacqua, G; Pavord, I; Pawankar, R; Pengelly, R; Pfaar, O; Picard, R; Pigearias, B; Pin, I; Plavec, D; Poethig, D; Pohl, W; Popov, T A; Portejoie, F; Potter, P; Postma, D; Price, D; Rabe, K F; Raciborski, F; Radier Pontal, F; Repka-Ramirez, S; Reitamo, S; Rennard, S; Rodenas, F; Roberts, J; Roca, J; Rodriguez Mañas, L; Rolland, C; Roman-Rodriguez, M.; Romano, A; Rosado-Pinto, J; Rosario, N; Rosenwasser, L; Rottem, M; Ryan, D.; Sanchez-Borges, M; Scadding, G K; Schunemann, H J; Serrano, E; Schmid-Grendelmeier, P; Schulz, H; Sheikh, A; Shields, M; Siafakas, N; Sibille, Y; Similowski, T; Simons, F E R; Sisul, J C; Skrindo, I; Smit, H. A.; Solé, D; Sooronbaev, T; Spranger, O; Stelmach, R; Sterk, P J; Sunyer, J; Thijs, C.; To, T; Todo-Bom, A; Triggiani, M; Valenta, R; Valero, A L; Valia, E; Valovirta, E; Van Ganse, E; van Hage, M; Vandenplas, O; Vasankari, T; Vellas, B; Vestbo, J; Vezzani, G; Vichyanond, P; Viegi, G; Vogelmeier, C; Vontetsianos, T; Wagenmann, M; Wallaert, B; Walker, S; Wang, D. Y.; Wahn, U; Wickman, M; Williams, D M; Williams, S; Wright, J; Yawn, B P; Yiallouros, P K; Yusuf, O M; Zaidi, A; Zar, H J; Zernotti, M E; Zhang, L.; Zhong, N; Zidarn, M; Mercier, J

    2016-01-01

    Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) focuses on the integrated care of chronic diseases. Area 5 (Care Pathways) was initiated using chronic respiratory diseases as a model. The chronic respiratory disease action plan includes (1) AIRWAYS

  2. Genetic characterization of clade B measles viruses isolated in Tunisia and Libya 2002-2009 and a proposed new subtype within the B3 genotype.

    Science.gov (United States)

    Haddad-Boubaker, Sondes; Rezq, Moftah; Smeo, Mohamed-Najeb; Ben Yahia, Ahlem; Abudher, Abdulhafid; Slim, Amin; Ben Ghorbel, Mohamed; Ahmed, Hinda; Rota, Paul; Triki, Hinda

    2010-11-01

    Genetic characterization was conducted on 18 wild-type measles viruses, detected in Tunisia and Libya from 2002 to 2009. Sequence analysis of the 456 nucleotides in the carboxy terminus of the nucleoprotein (N) gene and the entire hemagglutinin (H) gene indicated that all isolates were in genotype B3. All of the viruses from 2002 to 2007 and some of the isolates from 2009 belonged to subtype B3.1. In contrast, 7 of the viruses isolated during 2008 and 2009 were quite divergent from all B3 isolates. The nucleotide sequences of the N gene of these 7 isolates differed from the sequences of the Ibadan and New York reference strain by an average of 3.1 and 4.4%, respectively. The H gene sequences differed by 1.1 and 2.6% with the same reference strains. This is the first report describing the genetic characteristics of measles viruses from clade B isolated in North Africa; the results suggest that these viruses represent a new subtype of genotype B3. Copyright © 2010 Elsevier B.V. All rights reserved.

  3. Magnetic field dependence of rotationally resolved excitation spectra of the 1B3u 000 transition of jet-cooled pyrazine

    NARCIS (Netherlands)

    Jonkman, Harry Th.; Drabe, Karel E.

    1991-01-01

    We report rotationally resolved excitation spectra of the 1B3u 000 transition of jet-cooled pyrazine in magnetic fields up to 50 kG. The emission intensity of every rotational line is found to decrease by a factor of three for magnetic fields larger than about 300 G. For still larger magnetic fields

  4. The Spectrum of the Molecular Eigenstates of Pyrazine and the Reconstruction of Decays of Rotational States of the 1B3u (0-0) Transition of Pyrazine

    NARCIS (Netherlands)

    Meer, Barend J. van der; Jonkman, Harry Th.; Kommandeur, Jan

    1983-01-01

    The spectrum of the molecular eigenstates (ME) belonging to the various rotational members of the 1B3u (0-0) transition of pyrazine was measured with a very narrow band laser in a molecular beam with a Doppler width of 30 MHz. It is shown that, when the ME’s belonging to a single rotational state

  5. Biochemical Characterization of CPS-1, a Subclass B3 Metallo-β-Lactamase from a Chryseobacterium piscium Soil Isolate

    DEFF Research Database (Denmark)

    Gudeta, Dereje Dadi; Pollini, Simona; Docquier, Jean-Denis

    2016-01-01

    CPS-1 is a subclass B3 metallo-β-lactamase from a Chryseobacterium piscium isolated from soil, showing 68 % amino acid identity to GOB-1 enzyme. CPS-1 was overproduced in Escherichia coli Rosetta (DE3), purified by chromatography and biochemically characterized. This enzyme exhibits a broad...

  6. Induction of ErbB-3 expression by alpha6beta4 integrin contributes to tamoxifen resistance in ERbeta1-negative breast carcinomas.

    Directory of Open Access Journals (Sweden)

    Valentina Folgiero

    Full Text Available BACKGROUND: Tamoxifen is still the most widely used drug in hormone therapy for the treatment of breast cancer. Its benefits in adjuvant treatment are well documented in controlled and randomized clinical studies, which have demonstrated an increase in disease-free intervals of patients with positive hormonal receptors. However, the mechanisms involved in endocrine resistance are not clear. Laboratory and clinical data now indicate that bi-directional molecular cross-talk between nuclear or membrane ER and growth factor receptor pathways may be involved in endocrine resistance. We recently found a functional interaction between alpha6beta4 integrin and ErbB-3 receptor to maintain the PI3K/Akt survival pathway of mammary tumour cells. We sought to improve understanding of this process in order to provide the involvement of both receptors insight into mechanism of Tamoxifen resistance. METHODS AND FINDINGS: Using human breast cancer cell lines displaying different levels of alpha6beta4 and ErbB-3 receptors and a series of 232 breast cancer biopsies from patients submitted to adjuvant Tamoxifen monotherapy for five years, we evaluated the functional interaction between both receptors in relationship to Tamoxifen responsiveness. In mammary carcinoma cells, we evidenced that the alpha6beta4 integrin strongly influence Akt phosphorylation through ErbB-3 protein regulation. Moreover, the ErbB-3 inactivation inhibits Akt phosphorylation, induces apoptosis and inhibits in vitro invasion favouring Tamoxifen responsiveness. The analysis of human tumors revealed a significant relationship between alpha6beta4 and ErbB-3 in P-Akt-positive and ERbeta1-negative breast cancers derived from patients with lower disease free survival. CONCLUSIONS: We provided evidence that a strong relationship occurs between alpha6beta4 and ErbB-3 positivity in ERbeta1-negative breast cancers. We also found that the association between ErbB-3 and P-Akt positivity mainly occurs in

  7. Induction of ErbB-3 Expression by α6β4 Integrin Contributes to Tamoxifen Resistance in ERβ1-Negative Breast Carcinomas

    Science.gov (United States)

    Bon, Giulia; Di Carlo, Selene E.; Fabi, Alessandra; Nisticò, Cecilia; Vici, Patrizia; Melucci, Elisa; Buglioni, Simonetta; Perracchio, Letizia; Sperduti, Isabella; Rosanò, Laura; Sacchi, Ada; Mottolese, Marcella; Falcioni, Rita

    2008-01-01

    Background Tamoxifen is still the most widely used drug in hormone therapy for the treatment of breast cancer. Its benefits in adjuvant treatment are well documented in controlled and randomized clinical studies, which have demonstrated an increase in disease-free intervals of patients with positive hormonal receptors. However, the mechanisms involved in endocrine resistance are not clear. Laboratory and clinical data now indicate that bi-directional molecular cross-talk between nuclear or membrane ER and growth factor receptor pathways may be involved in endocrine resistance. We recently found a functional interaction between α6β4 integrin and ErbB-3 receptor to maintain the PI3K/Akt survival pathway of mammary tumour cells. We sought to improve understanding of this process in order to provide the involvement of both receptors insight into mechanism of Tamoxifen resistance. Methods and Findings Using human breast cancer cell lines displaying different levels of α6β4 and ErbB-3 receptors and a series of 232 breast cancer biopsies from patients submitted to adjuvant Tamoxifen monotherapy for five years, we evaluated the functional interaction between both receptors in relationship to Tamoxifen responsiveness. In mammary carcinoma cells, we evidenced that the α6β4 integrin strongly influence Akt phosphorylation through ErbB-3 protein regulation. Moreover, the ErbB-3 inactivation inhibits Akt phosphorylation, induces apoptosis and inhibits in vitro invasion favouring Tamoxifen responsiveness. The analysis of human tumors revealed a significant relationship between α6β4 and ErbB-3 in P-Akt-positive and ERβ1-negative breast cancers derived from patients with lower disease free survival. Conclusions We provided evidence that a strong relationship occurs between α6β4 and ErbB-3 positivity in ERβ1-negative breast cancers. We also found that the association between ErbB-3 and P-Akt positivity mainly occurs in ERβ1-negative breast cancer derived from patients

  8. Induction of ErbB-3 expression by alpha6beta4 integrin contributes to tamoxifen resistance in ERbeta1-negative breast carcinomas.

    Science.gov (United States)

    Folgiero, Valentina; Avetrani, Paolo; Bon, Giulia; Di Carlo, Selene E; Fabi, Alessandra; Nisticò, Cecilia; Vici, Patrizia; Melucci, Elisa; Buglioni, Simonetta; Perracchio, Letizia; Sperduti, Isabella; Rosanò, Laura; Sacchi, Ada; Mottolese, Marcella; Falcioni, Rita

    2008-02-13

    Tamoxifen is still the most widely used drug in hormone therapy for the treatment of breast cancer. Its benefits in adjuvant treatment are well documented in controlled and randomized clinical studies, which have demonstrated an increase in disease-free intervals of patients with positive hormonal receptors. However, the mechanisms involved in endocrine resistance are not clear. Laboratory and clinical data now indicate that bi-directional molecular cross-talk between nuclear or membrane ER and growth factor receptor pathways may be involved in endocrine resistance. We recently found a functional interaction between alpha6beta4 integrin and ErbB-3 receptor to maintain the PI3K/Akt survival pathway of mammary tumour cells. We sought to improve understanding of this process in order to provide the involvement of both receptors insight into mechanism of Tamoxifen resistance. Using human breast cancer cell lines displaying different levels of alpha6beta4 and ErbB-3 receptors and a series of 232 breast cancer biopsies from patients submitted to adjuvant Tamoxifen monotherapy for five years, we evaluated the functional interaction between both receptors in relationship to Tamoxifen responsiveness. In mammary carcinoma cells, we evidenced that the alpha6beta4 integrin strongly influence Akt phosphorylation through ErbB-3 protein regulation. Moreover, the ErbB-3 inactivation inhibits Akt phosphorylation, induces apoptosis and inhibits in vitro invasion favouring Tamoxifen responsiveness. The analysis of human tumors revealed a significant relationship between alpha6beta4 and ErbB-3 in P-Akt-positive and ERbeta1-negative breast cancers derived from patients with lower disease free survival. We provided evidence that a strong relationship occurs between alpha6beta4 and ErbB-3 positivity in ERbeta1-negative breast cancers. We also found that the association between ErbB-3 and P-Akt positivity mainly occurs in ERbeta1-negative breast cancer derived from patients with lower DFS

  9. Correlation of needle core biopsy with excision histology in screen-detected B3 lesions: the Merrion Breast Screening Unit experience.

    LENUS (Irish Health Repository)

    Hayes, B D

    2012-02-01

    AIMS: Needle core biopsy (NCB) is a widely-used technique for non-operative evaluation of screen-detected breast lesions. Although most NCBs are B2 (benign) or B5 (malignant), some fall into the B3 category of "uncertain malignant potential". This study aims to categorise the lesions prompting a B3 NCB in the Merrion Breast Screening Unit, and establish the incidence of malignancy on subsequent excision biopsy. METHODS: Patients attending the Merrion Breast Screening Unit in Dublin between 2000 and 2008 who had a B3 NCB were identified. The NCB pathology reports were reviewed and the diagnosis correlated with excision histology; the latter was classified as benign, atypical or malignant. Lesion-specific positive predictive values (PPVs) for malignancy were derived. RESULTS: 141 patients with a B3 NCB were identified. The most frequent lesions on NCB were radial scar (RS; n = 57), atypical intraductal epithelial proliferation (AIDEP; n = 25) and papillary lesion (n = 24). The final diagnosis was malignant in 22 patients (16%), atypical in 40 (28%) and benign in 79 (56%). Two of the patients with a malignant diagnosis had invasive carcinoma. The lesion-specific PPVs were: lobular neoplasia 50%, AIDEP 32%, columnar cell lesion with atypia 12.5%, RS 12.3%, papillary lesion 8.3%, suspected phyllodes tumour 7.7%, and spindle cell lesion 0%. Atypia on RS NCB predicted an atypical or malignant excision diagnosis, but atypia on papillary lesion NCB did not. CONCLUSIONS: One-sixth of B3 NCBs in this series proved to be malignant on excision. The PPV for malignancy varied according to lesion type.

  10. Genotoxicity Evaluation of Dipotassium -Trioxohydroxytetrafluorotriborate, K2(B3O3F4OH, in Human Lymphocyte Cultures and Mice Reticulocytes

    Directory of Open Access Journals (Sweden)

    Sanin Haveric

    Full Text Available ABSTRACT Genotoxic effects of inorganic molecule dipotassium-trioxohydroxytetrafluorotriborate, K2(B3O3F4OH, a promising new therapeutic for the epidermal changes treatment, have been evaluated. In vitro analysis included evaluation of genotoxic and cytotoxic potential of K2(B3O3F4OH in concentrations of 0.01, 0.02, 0.05 and 0.06 mg/mL applying cytokinesis-block micronucleus cytome assay in human lymphocyte culture. With the increase of concentration the frequency of micronuclei elevated but the differences were not significant. Also, there were no significant differences among the frequencies of nuclear buds and nucleoplasmic bridges between controls and treated cultures. Nuclear division index and nuclear division cytotoxycity index values did not reveal significant cytotoxic effect of K2(B3O3F4OH. In vivo genotoxic effects were analyzed on BALB/c mice applying reticulocytes micronucleus assay. K2(B3O3F4OH was administrated intraperitoneally in final concentrations of 10, 20, 50 and 55 mg/kg. Significant decrease of reticulocytes ratio and increase of micronuclei frequencies against pre-treatments were found for both sampling periods of 48 and 72 hours of the highest applied concentration. This study confirmed that K2(B3O3F4OH is not genotoxic in tested concentrations in vitro as well as in concentrations lower than 55 mg/kg in vivo. This study presents a reliable basis for further pre-clinical and potential clinical investigations.

  11. Correlation of needle core biopsy with excision histology in screen-detected B3 lesions: the Merrion Breast Screening Unit experience.

    Science.gov (United States)

    Hayes, B D; O'Doherty, A; Quinn, C M

    2009-12-01

    Needle core biopsy (NCB) is a widely-used technique for non-operative evaluation of screen-detected breast lesions. Although most NCBs are B2 (benign) or B5 (malignant), some fall into the B3 category of "uncertain malignant potential". This study aims to categorise the lesions prompting a B3 NCB in the Merrion Breast Screening Unit, and establish the incidence of malignancy on subsequent excision biopsy. Patients attending the Merrion Breast Screening Unit in Dublin between 2000 and 2008 who had a B3 NCB were identified. The NCB pathology reports were reviewed and the diagnosis correlated with excision histology; the latter was classified as benign, atypical or malignant. Lesion-specific positive predictive values (PPVs) for malignancy were derived. 141 patients with a B3 NCB were identified. The most frequent lesions on NCB were radial scar (RS; n = 57), atypical intraductal epithelial proliferation (AIDEP; n = 25) and papillary lesion (n = 24). The final diagnosis was malignant in 22 patients (16%), atypical in 40 (28%) and benign in 79 (56%). Two of the patients with a malignant diagnosis had invasive carcinoma. The lesion-specific PPVs were: lobular neoplasia 50%, AIDEP 32%, columnar cell lesion with atypia 12.5%, RS 12.3%, papillary lesion 8.3%, suspected phyllodes tumour 7.7%, and spindle cell lesion 0%. Atypia on RS NCB predicted an atypical or malignant excision diagnosis, but atypia on papillary lesion NCB did not. One-sixth of B3 NCBs in this series proved to be malignant on excision. The PPV for malignancy varied according to lesion type.

  12. EphB3-targeted regulation of miR-149 in the migration and invasion of human colonic carcinoma HCT116 and SW620 cells.

    Science.gov (United States)

    Zhang, Guodong; Liu, Xiaozhu; Li, Yinfeng; Wang, Yan; Liang, Huankun; Li, Kangyan; Li, Laiqing; Chen, Cuicui; Sun, Wenqiao; Ren, Shoulei; Zhu, Pengfei; Zhang, Licheng

    2017-03-01

    microRNAs play key roles during various crucial cell processes such as proliferation, migration, invasion and apoptosis. Also, microRNAs have been shown to possess oncogenic and tumor-suppressive functions in human cancers. Here, we describe the regulation and function of miR-149 in colorectal cancer cell lines. miR-149 expression patterns were detected in human colorectal cell lines and tissue samples, and then focused on its role in regulation of cell growth, migration, invasion, and its target gene identification. Furthermore, the function of the target gene of miR-149 was analyzed in vitro and in vivo. miR-149 expression was downregulated in human colorectal cancer HCT116 and SW620 cell lines compared to the normal colon epithelial NCM460 cell line using quantitative real-time polymerase chain reaction methods. Further studies indicated that introduction of miR-149 was able to suppress cell migration and invasion. Then, EphB3 was identified as a direct target gene of miR-149 in colorectal cancer cells. Moreover, experiments in vitro showed that knockdown expression of EphB3 could suppress cell proliferation and invasion, and ectopic expression of EphB3 restored the phenotypes of CRC cell lines transfected with miR149. In addition, silencing of EphB3 significantly affected cycle progression distribution and increased apoptosis in CRC cell lines. Finally, in vivo results demonstrated that knockdown of EphB3 by siRNA inhibited tumor growth. In conclusion,the important role of miR-149 in colorectal cancer progression suggesting that miR-149 may serve as a therapeutic target for colorectal cancer treatment. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  13. Organic anion transporting polypeptides OATP1B1 and OATP1B3 and their genetic variants influence the pharmacokinetics and pharmacodynamics of raloxifene

    Science.gov (United States)

    2012-01-01

    Background Raloxifene, a selective estrogen receptor modulator, exhibits quite large and unexplained interindividual variability in pharmacokinetics and pharmacodynamics. The aim of this study was to determine the role of organic-anion transporting polypeptides OATP1B1 and OATP1B3 and their genetic variants in the pharmacokinetics and pharmacodynamics of raloxifene. Methods To test the role of OATP1B1 and OATP1B3 transporters on hepatic uptake of raloxifene and its metabolites an in vitro model of Chinese Hamster Ovary cells expressing OATP1B1 or OATP1B3 was employed. The influence of OATP1B1 and OATP1B3 genetic variants on in vivo pharmacokinetics and pharmacodynamics was evaluated in 53 osteoporotic postmenopausal women treated with raloxifene. Results Our in vitro results showed that raloxifene and two of the three metabolites, raloxifene-4'-β-glucuronide (M2) and raloxifene-6,4'-diglucuronide (M3), interact with OATP1B1 and OATP1B3. Higher M3 and total raloxifene serum concentrations in patients correlated with lower serum levels of bone resorption marker, serum C-terminal telopeptide fragments of type I collagen, indicating a higher antiresorptive effect of raloxifene. Higher concentrations of M2 correlated with higher increase of lumbar spine bone mineral density supporting the raloxifene vertebral fracture specific protection effect. Finally, raloxifene, M3 and total raloxifene serum concentrations were significantly higher in patients with SLCO1B1 c.388A > G polymorphism and *1b haplotype implicating a considerable genetic effect on pharmacokinetics and pharmacodynamics of raloxifene. Conclusions These findings indicate that SLCO1B1 c.388A > G polymorphism could play an important role in pharmacokinetics and pharmacodynamics of raloxifene. PMID:22533838

  14. Organic anion transporting polypeptides OATP1B1 and OATP1B3 and their genetic variants influence the pharmacokinetics and pharmacodynamics of raloxifene

    Directory of Open Access Journals (Sweden)

    Trdan Lušin Tina

    2012-04-01

    Full Text Available Abstract Background Raloxifene, a selective estrogen receptor modulator, exhibits quite large and unexplained interindividual variability in pharmacokinetics and pharmacodynamics. The aim of this study was to determine the role of organic-anion transporting polypeptides OATP1B1 and OATP1B3 and their genetic variants in the pharmacokinetics and pharmacodynamics of raloxifene. Methods To test the role of OATP1B1 and OATP1B3 transporters on hepatic uptake of raloxifene and its metabolites an in vitro model of Chinese Hamster Ovary cells expressing OATP1B1 or OATP1B3 was employed. The influence of OATP1B1 and OATP1B3 genetic variants on in vivo pharmacokinetics and pharmacodynamics was evaluated in 53 osteoporotic postmenopausal women treated with raloxifene. Results Our in vitro results showed that raloxifene and two of the three metabolites, raloxifene-4'-β-glucuronide (M2 and raloxifene-6,4'-diglucuronide (M3, interact with OATP1B1 and OATP1B3. Higher M3 and total raloxifene serum concentrations in patients correlated with lower serum levels of bone resorption marker, serum C-terminal telopeptide fragments of type I collagen, indicating a higher antiresorptive effect of raloxifene. Higher concentrations of M2 correlated with higher increase of lumbar spine bone mineral density supporting the raloxifene vertebral fracture specific protection effect. Finally, raloxifene, M3 and total raloxifene serum concentrations were significantly higher in patients with SLCO1B1 c.388A > G polymorphism and *1b haplotype implicating a considerable genetic effect on pharmacokinetics and pharmacodynamics of raloxifene. Conclusions These findings indicate that SLCO1B1 c.388A > G polymorphism could play an important role in pharmacokinetics and pharmacodynamics of raloxifene.

  15. Adenovirus infection in children with acute lower respiratory tract infections in Beijing, China, 2007 to 2012.

    Science.gov (United States)

    Liu, Chunyan; Xiao, Yan; Zhang, Jing; Ren, Lili; Li, Jianguo; Xie, Zhengde; Xu, Baoping; Yang, Yan; Qian, Suyun; Wang, Jianwei; Shen, Kunling

    2015-10-01

    Human adenoviruses (HAdV) play a significant role in pediatric respiratory tract infections. To date, over 60 types of HAdV have been identified. Here, HAdV types are characterized in children in the Beijing area with acute lower respiratory tract infections (ALRTIs) and the clinical features and laboratory findings of hospitalized HAdV-infected cases are described. Respiratory specimens were collected from pediatric patients with ALRTIs in the emergency department or from those admitted to Beijing Children's Hospital between March 2007 and December 2012. Infections with common respiratory viruses were determined by PCR or RT-PCR. HAdV positive samples were further typed by PCR and sequencing. Among 3356 patients with ALRTIs, 194 (5.8 %) were found to have HAdV infection. HAdV infection was primarily confined to children (88.35 %) less than 5 years of age. A total of 11 different types of HAdV were detected throughout the study period, with HAdV-B7 (49.0 %) and HAdV-B3 (26.3 %) as the most prevalent types, followed by HAdV-C2 (7.7 %) and HAdVC1 (4.6 %). Newly emerging and re-emergent types or variants, HAdV-B55 (n = 5), HAdV-C57 (n = 3), and HAdV-B14p1 (n = 1), were identified. Results also included the reported first case of co-infection with HAdV-C2 and HAdV-C57. Clinical entities of patients with single HAdV infection (n = 49) were similar to those with mixed HAdV/respiratory syncytial virus (RSV) infections (n = 41). Patients with HAdV-B7 infection had longer duration of fever and higher serum levels of muscle enzymes than HAdV-B3-infected patients. During the study period, HAdV-B7 and HAdV-B3 were the predominant types identified in pediatric ALRTIs. HAdV-B7 infection tends to have more severe clinical consequences. The presence of newly emerging types or variants and co-infection with different types of HAdV highlights the need for constant and close surveillance of HAdV infection.

  16. 77 FR 28392 - Healthcare Infection Control Practices Advisory Committee (HICPAC)

    Science.gov (United States)

    2012-05-14

    ... HUMAN SERVICES Centers for Disease Control and Prevention Healthcare Infection Control Practices.... L. 92-463), the Centers for Disease Control and Prevention (CDC) announces the following meeting of...., June 15, 2012. Place: CDC, Global Communications Center, Building 19, Auditorium B3, 1600 Clifton Road...

  17. 77 FR 4820 - Healthcare Infection Control Practices Advisory Committee (HICPAC)

    Science.gov (United States)

    2012-01-31

    ... HUMAN SERVICES Centers for Disease Control and Prevention Healthcare Infection Control Practices.... L. 92-463), the Centers for Disease Control and Prevention (CDC) announce the following meeting for...., February 17, 2012. Place: CDC, Global Communications Center, Building 19, Auditorium B3, 1600 Clifton Road...

  18. Alternative Splicing of EZH2 pre-mRNA by SF3B3 Contributes to the Tumorigenic Potential of Renal Cancer.

    Science.gov (United States)

    Chen, Ke; Xiao, Haibing; Zeng, Jin; Yu, Gan; Zhou, Hui; Huang, Chunhua; Yao, Weimin; Xiao, Wei; Hu, Junhui; Guan, Wei; Wu, Lily; Huang, Jiaoti; Huang, Qihong; Xu, Hua; Ye, Zhangqun

    2017-07-01

    Purpose: Deregulation or mutation of the EZH2 gene causes various tumors, including clear cell renal cell carcinoma (ccRCC). Although several splice variants of EZH2 have been identified, little is known about how EZH2 splicing is regulated or the contribution of alternative splicing to its protumorigenic functions.Experimental Design: We conducted RT-PCR, Western blot analysis, and IHC techniques to examine EZH2 and its alternative splicing transcript expression in renal cancer tissue and renal cancer cell lines. Proliferation, migration, clonogenicity, and tumorigenicity of renal cancer cells either exhibiting knockdown of EZH2 or its splicing factor SF3B3 were assessed by CCK8, Transwell assay, and murine xenograft experiments.Results: We found that the inclusion of alternative EZH2 exon 14 was significantly increased in ccRCC samples and renal cancer cell lines. In ccRCC lines, enforced expression of EZH2Δ14 inhibited, and EZH2 promoted, cell growth, migration, proliferation, and tumorigenicity in a xenograft model. Mechanistic studies demonstrated that EZH2Δ14 isoform functions as a dominant-negative inhibitor of full-length EZH2. Coexpression of EZH2Δ14 variant with full-length EZH2 not only abrogated DAB2IP and HOXA9 suppression but also inhibited EZH2-driven tumorigenesis. Strikingly, the splicing factor SF3B3 stimulates inclusion of exon14 and has pro-proliferative activity. Importantly, the upregulation of SF3B3 expression observed in clinical ccRCC samples parallels the increased inclusion of EZH2 exon14, and the SF3B3 level is associated with higher tumor stage and poor overall survival.Conclusions: These results suggest SF3B3 as a key regulator of EZH2 pre-mRNA splicing and SF3B3 may represent a novel prognostic factor and potential therapeutic target in ccRCC. Clin Cancer Res; 23(13); 3428-41. ©2016 AACR. ©2016 American Association for Cancer Research.

  19. Neonatal enterovirus infections reported to the national enterovirus surveillance system in the United States, 1983-2003.

    Science.gov (United States)

    Khetsuriani, Nino; Lamonte, Ashley; Oberste, M Steven; Pallansch, Mark

    2006-10-01

    Neonatal enterovirus (EV) infections lead to a wide range of clinical manifestations, from mild febrile illness to severe, sometimes fatal, sepsislike disease. To determine the relationship of EV serotypes with the risk of neonatal infection and its fatal outcome, we analyzed data reported to the National Enterovirus Surveillance System (NESS) during 1983-2003. Of the 26,737 EV detections reported during this period, neonates accounted for 2544 (11.4% of those with known age). Serotypes most commonly isolated from neonates included echovirus (E) 11 (14.0% of EV with known serotype), coxsackievirus (CV) B2 (8.9%), CVB5 (7.5%), E6, E9 and CVB4 (6.8% each). CVB1-4, E11, and E25 were significantly more common, whereas CVA16, E4, E9, E21, E30, and human parechovirus 1 (formerly E22) were less common among neonates than among persons aged > or =1 month. Fatal outcome was noted for 3.3% of reports, with neonates at a higher risk of death than persons aged > or =1 month (11.5% versus 2.5%; odds ratio [OR] 5.1; 95% confidence interval [CI] = 3.3-7.8). Neonates infected with CVB4 were at a higher risk of death (OR 6.5; 95% CI = 2.4-17.7) than those infected with other EV. EV are important neonatal pathogens associated with high risk of infection and death. Because of the limitations of the NESS (incomplete reporting, limited clinical data, bias towards more severe and younger cases), additional studies are needed to better evaluate the role of different EV in neonatal infections.

  20. [Nosocomial infections].

    Science.gov (United States)

    Kerwat, Klaus; Graf, Jürgen; Wulf, Hinnerk

    2010-01-01

    It is estimated for the year 2006 that around 500,000 to 600,000 nosocomial infections occurred in Germany and that among these 10,000 to 15,000 patients died of the infection. Nosocomial infections in general lengthen the duration of hospitalisation by on average 4 days - with associated extra costs of 4000 to 20,000 Euro per case. About a third of all infections acquired in hospital are considered to be avoidable. However, the classification of an infection as nosocomial does not automatically mean that a causal relationship exists between a medical intervention and the occurrence of the infection. Also a nosocomial infection is not a synonym for medical or nursing errors. The first epidemiological report of the EU emphasises the health-political and health-economical significance of nosocomial infections and classifies the increasing number of infections acquired in hospitals as a most important danger - even higher than the threats of pandemic influenza and HIV. (c) Georg Thieme Verlag Stuttgart New York.

  1. Somatic mutations in ATP1A1 and ATP2B3 lead to aldosterone-producing adenomas and secondary hypertension

    DEFF Research Database (Denmark)

    Beuschlein, Felix; Boulkroun, Sheerazed; Osswald, Andrea

    2013-01-01

    Primary aldosteronism is the most prevalent form of secondary hypertension. To explore molecular mechanisms of autonomous aldosterone secretion, we performed exome sequencing of aldosterone-producing adenomas (APAs). We identified somatic hotspot mutations in the ATP1A1 (encoding an Na+/K+ ATPase α...... subunit) and ATP2B3 (encoding a Ca2+ ATPase) genes in three and two of the nine APAs, respectively. These ATPases are expressed in adrenal cells and control sodium, potassium and calcium ion homeostasis. Functional in vitro studies of ATP1A1 mutants showed loss of pump activity and strongly reduced...... affinity for potassium. Electrophysiological ex vivo studies on primary adrenal adenoma cells provided further evidence for inappropriate depolarization of cells with ATPase alterations. In a collection of 308 APAs, we found 16 (5.2%) somatic mutations in ATP1A1 and 5 (1.6%) in ATP2B3. Mutation...

  2. Effects of Fe substitution on B3-B1 phase transition and structural, vibrational, and electronic properties of ZnS from DFT calculations

    Science.gov (United States)

    Das, Pratik Kr.; Mandal, Nibir; Arya, A.

    2017-02-01

    Naturally occurring zinc sulfide (ZnS) contains a substantial amount of iron (Fe) in its crystal structure. This study explores the possible effects of such Fe impurity on the physical properties of its two phases: B3 and B1, crystallizing in a cubic system with zinc blend (ZB, space group: F-43m) and rock salt (RS, space group: Fm-3m) structures. We have performed ab-initio calculations within density functional theory (DFT) to determine the equilibrium volumes of B3- and B1-ZnS phases, doped with Fe in varying concentrations (0% to 25%), and their corresponding lattice structures. Using the enthalpy cross-over, we determine the pressure-dependent B3 to B1 transition as a function of Fe concentration. Our DFT calculations suggest an inverse relation of the transition pressure with Fe content. For pure ZnS, the transition occurs at 17 GPa, which drops to ˜12 GPa for 25% Fe. This study also provides a first-hand analysis of the elastic constants (C11, C12, and C44) to show the effects of Fe impurity on the mechanical properties of ZnS phases. Their values generally drop due to Fe and the differences widen with increasing pressure. Fe causes large softening of C44, especially for the B1 phase. We have also performed phonon calculations to characterize the vibrational properties and explain the pressure dependent structural instability of the B3- ZnS. Finally, our calculations of the electronic structures show a transition of semi-conductor to conductor behavior of ZnS with incorporation of Fe impurity.

  3. 75 FR 22508 - Airworthiness Directives; Eurocopter France Model AS350B, BA, B1, B2, B3, C, D, and D1; AS 355E...

    Science.gov (United States)

    2010-04-29

    ... D1; and AS 355E, F, F1, F2, N, and NP helicopters with a Goodrich Electric hoist, part number (P/N... Model AS350B, BA, B1, B2, B3, C, D, and D1; AS 355E, F, F1, F2, N, and NP Helicopters AGENCY: Federal...., Washington, DC 20590, between 9 a.m. and 5 p.m., Monday through Friday, except Federal holidays. You may get...

  4. Lentiviral vector-driven inhibition of 5-HT synthesis in B3 bulbo-spinal serotonergic projections - Consequences on nociception, inflammatory and neuropathic pain in rats.

    Science.gov (United States)

    Gautier, Anne; El Ouaraki, Hanady; Bazin, Natacha; Salam, Soha; Vodjdani, Guilan; Bourgoin, Sylvie; Pezet, Sophie; Bernard, Jean-François; Hamon, Michel

    2017-02-01

    Although it is well established that bulbo-spinal serotonergic projections contribute to pain control mechanisms, whether they exert anti- or pro-nociceptive modulations is still a matter of debate. In order to reappraise the role of 5-HT in descending controls, we used RNA interference to selectively inhibit 5-HT synthesis in B3 neurons and assess resulting changes in nociception. Rats were injected into the bulbar B3 group with a recombinant lentiviral vector, LV-shTPH2, encoding RNA interfering with tryptophan hydroxylase 2 expression. Together with the long term disappearance of this enzyme in the whole rostro-caudal extent of B3 group, 5-HT was markedly depleted selectively in the dorsal horn at all levels of the spinal cord. In contrast, immunolabeling of the 5-HT transporter was unaffected by LV-shTPH2 injection, indicating the preservation of serotonergic fibers integrity. Whereas mechanical and thermal nociceptive thresholds were unchanged by 5-HT depletion, marked reductions in intraplantar formalin (but not carrageenin)-evoked nocifensive responses, and, in contrast, significant increases in mechanical and thermal hyperalgesia evoked by sciatic nerve ligation were noted in LV-shTPH2-injected rats versus controls. Parallel changes in c-Fos immunolabeling within the dorsal horn confirmed that bulbo-spinal serotonergic projections modulate pain signaling under these various conditions. These results suggest that serotonergic neurons of the B3 group are only moderately concerned, if any, by acute nociception but exert modulatory influences under pain sensitizing conditions. The opposite changes in formalin injected- versus sciatic nerve ligated rats might be related to the implication of different receptors in 5-HT-mediated modulation of inflammatory versus neuropathic pain. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Semi-experimental equilibrium structure determinations by employing B3LYP/SNSD anharmonic force fields: validation and application to semirigid organic molecules.

    Science.gov (United States)

    Piccardo, Matteo; Penocchio, Emanuele; Puzzarini, Cristina; Biczysko, Malgorzata; Barone, Vincenzo

    2015-03-12

    This work aims at extending the semi-experimental (SE) approach for deriving accurate equilibrium structures to large molecular systems of organic and biological interest. SE equilibrium structures are derived by a least-squares fit of the structural parameters to the experimental ground-state rotational constants of several isotopic species corrected by vibrational contributions computed by quantum mechanical (QM) methods. A systematic benchmark study on 21 small molecules (CCse set) is carried out to evaluate the performance of hybrid density functionals (in particular B3LYP) in the derivation of vibrational corrections to rotational constants. The resulting SE equilibrium structures show a very good agreement with the corresponding geometries obtained employing post-Hartree-Fock vibrational corrections. The use of B3LYP in conjunction with the double-ζ SNSD basis set strongly reduces the computational costs, thus allowing for the evaluation of accurate SE equilibrium structures for medium-sized molecular systems. On these grounds, an additional set of 26 SE equilibrium structures including the most common organic moieties has been set up by collecting the most accurate geometries available in the literature together with new determinations from the present work. The overall set of 47 SE equilibrium structures determined using B3LYP/SNSD vibrational corrections (B3se set) provides a high quality benchmark for validating the structural predictions of other experimental and/or computational approaches. Finally, we present a new strategy (referred to as the template approach) to deal with the cases for which it is not possible to fit all geometrical parameters due to the lack of experimental data.

  6. Loss of Phosphatase and tensin homologue deleted on chromosome 10 engages ErbB3 and IGF-IR signaling to promote antiestrogen resistance in breast cancer

    Science.gov (United States)

    Miller, Todd W.; Pérez-Torres, Marianela; Narasanna, Archana; Guix, Marta; Stål, Olle; Pérez-Tenorio, Gizeh; Gonzalez-Angulo, Ana M.; Hennessy, Bryan T.; Mills, Gordon B.; Kennedy, J. Phillip; Lindsley, Craig W.; Arteaga, Carlos L.

    2009-01-01

    Knockdown of the tumor suppressor phosphatase PTEN with shRNA in three estrogen receptor (ER)-positive breast cancer cell lines resulted in increased PI3K and AKT activities, resistance to tamoxifen and fulvestrant, and hormone-independent growth. PTEN knockdown induced the upregulation of ER transcriptional activity in MCF-7 cells, but decreased ER protein levels and transcriptional activity in T47D and MDA-361 cells. Tamoxifen and fulvestrant treatment inhibited estradiol-induced ER transcriptional activity in all shPTEN cell lines but did not abrogate the increased cell proliferation induced by PTEN knockdown. PTEN knockdown increased basal and ligand-induced activation of the IGF-I and ErbB3 receptor tyrosine kinases, and prolonged the association of the p85 PI3K subunit with the IGF-IR effector IRS-1 and with ErbB3, implicating PTEN in the modulation of signaling upstream of PI3K. Consistent with these data, PTEN levels inversely correlated with levels of tyrosine-phosphorylated IGF-IR in tissue lysate arrays of primary breast cancers. Inhibition of IGF-IR and/or ErbB2-mediated activation of ErbB3 with tyrosine kinase inhibitors restored hormone-dependence and the growth inhibitory effect of tamoxifen and fulvestrant on shPTEN cells, suggesting that co-targeting both ER and receptor tyrosine kinase pathways holds promise for the treatment of patients with ER+, PTEN-deficient breast cancers. PMID:19435893

  7. Expression of CYP6B1 and CYP6B3 cytochrome P450 monooxygenases and furanocoumarin metabolism in different tissues of Papilio polyxenes (Lepidoptera: Papilionidae).

    Science.gov (United States)

    Petersen, R A; Zangerl, A R; Berenbaum, M R; Schuler, M A

    2001-04-27

    The CYP6B1 and CYP6B3 cytochrome P450 monooxygenases in the midgut of the black swallowtail participate in the metabolism of toxic furanocoumarins present in its host plants. In this study, biochemical analyses indicate that the fat body metabolizes significant amounts of the linear furanocoumarins bergapten and xanthotoxin after larvae feed on xanthotoxin. Northern analyses of the combined CYP6B1/3 transcript expression patterns indicate that transcripts in this P450 subfamily are induced in the midgut and fat body by xanthotoxin. Semi-quantitative RT-PCR analyses of individual CYP6B1/CYP6B3 mRNAs indicate that CYP6B1 transcripts are induced by xanthotoxin in all tissues examined and that CYP6B3 transcripts are induced in the fat body only. These results indicate that the fat body participates in the P450-mediated metabolism of excess furanocoumarins unmetabolized by the midgut. Although transcripts of both genes were detected and CYP6B1 transcripts were induced by xanthotoxin in the integument, furanocoumarin metabolism was not detected. Comparison of these P450 promoters with the promoters of alcohol dehydrogenase genes expressed in the fat bodies of several Drosophila species suggest that the xanthotoxin inducibilities of these P450 genes in fat bodies are regulated by elements other than those modulating expression of Adh genes.

  8. Control of Glycosylation-Related Genes by DNA Methylation: the Intriguing Case of the B3GALT5 Gene and Its Distinct Promoters

    Directory of Open Access Journals (Sweden)

    Marco Trinchera

    2014-08-01

    Full Text Available Glycosylation is a metabolic pathway consisting of the enzymatic modification of proteins and lipids through the stepwise addition of sugars that gives rise to glycoconjugates. To determine the full complement of glycoconjugates that cells produce (the glycome, a variety of genes are involved, many of which are regulated by DNA methylation. The aim of the present review is to briefly describe some relevant examples of glycosylation-related genes whose DNA methylation has been implicated in their regulation and to focus on the intriguing case of a glycosyltransferase gene (B3GALT5. Aberrant promoter methylation is frequently at the basis of their modulation in cancer, but in the case of B3GALT5, at least two promoters are involved in regulation, and a complex interplay is reported to occur between transcription factors, chromatin remodelling and DNA methylation of typical CpG islands or even of other CpG dinucleotides. Transcription of the B3GALT5 gene underwent a particular evolutionary fate, so that promoter hypermethylation, acting on one transcript, and hypomethylation of other sequences, acting on the other, cooperate on one gene to obtain full cancer-associated silencing. The findings may also help in unravelling the complex origin of serum CA19.9 antigen circulating in some patients.

  9. Lesions of uncertain malignant potential (B3) on core biopsy in the NHS Breast Screening Programme: is the screening round relevant?

    Science.gov (United States)

    Hunt, R J; Steel, J R; Porter, G J R; Holgate, C S; Watkins, R M

    2012-03-01

    Most women who have screening mammography and undergo subsequent open biopsy following an indeterminate core biopsy result are eventually found to have benign disease. However, a significant number have malignant disease and the rate of malignancy in such cases may be influenced by various factors. This study examined the effect of the type of screening round (prevalent or incident) on the likelihood of breast cancer being present. A total of 199 women who had NHS breast screening mammograms and subsequent indeterminate (B3) core biopsy results followed by excision biopsy over an 11-year period in a single breast screening unit were reviewed. The rate of malignancy following excision of a lesion graded as B3 on core biopsy was 21% for women in the prevalent screening round compared to 33% in subsequent rounds (Fisher's exact test, p=0.038). The incidence of malignancy associated with a B3 core biopsy result appears to be related to the screening round in which the lesion is detected, being approximately 50% higher in the subsequent incident rounds compared to the initial prevalent round. This finding may be useful in formulating management plans for women who have an indeterminate biopsy result.

  10. Spatial separation of covalent, ionic, and metallic interactions in Mg11Rh18B8 and Mg3Rh5B3.

    Science.gov (United States)

    Alekseeva, Anastasia M; Abakumov, Artem M; Leither-Jasper, Andreas; Schnelle, Walter; Prots, Yuri; Tendeloo, Gustaaf Van; Antipov, Eugene V; Grin, Yuri

    2013-12-23

    The crystal structures of Mg11Rh18B8 and Mg3Rh5B3 have been investigated by using single-crystal X-ray diffraction. Mg11Rh18B8: space group P4/mbm; a=17.9949(7), c=2.9271(1) Å; Z=2. Mg3Rh5B3: space group Pmma; a=8.450(2), b=2.8644(6), c=11.602(2) Å; Z=2. Both crystal structures are characterized by trigonal prismatic coordination of the boron atoms by rhodium atoms. The [BRh6] trigonal prisms form arrangements with different connectivity patterns. Analysis of the chemical bonding by means of the electron-localizability/electron-density approach reveals covalent BRh interactions in these arrangements and the formation of B-Rh polyanions. The magnesium atoms that are located inside the polyanions interact ionically with their environment, whereas, in the structure parts, which are mainly formed by Mg and Rh atoms, multicenter (metallic) interactions are observed. Diamagnetic behavior and metallic electron transport of the Mg11Rh18B8 and Mg3Rh5B3 phases are in agreement with the bonding picture and the band structure. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Activation of ErbB3, EGFR and Erk is essential for growth of human breast cancer cell lines with acquired resistance to fulvestrant

    DEFF Research Database (Denmark)

    Frogne, Thomas; Benjaminsen, Rikke V; Sonne-Hansen, Katrine

    2008-01-01

    growth inhibition of two resistant cell lines. These data indicate that ligand activated ErbB3 and EGFR, and Erk signaling play important roles in fulvestrant resistant cell growth. Furthermore, the decreased level of ErbB4 in resistant cells may facilitate heterodimerization of ErbB3 with EGFR and ErbB2......Seven fulvestrant resistant cell lines derived from the estrogen receptor alpha positive MCF-7 human breast cancer cell line were used to investigate the importance of epidermal growth factor receptor (ErbB1-4) signaling. We found an increase in mRNA expression of EGFR and the ErbB3/ErbB4 ligand...... activation was observed only in the parental MCF-7 cells. The downstream kinases pAkt and pErk were increased in five of seven and in all seven resistant cell lines, respectively. Treatment with the EGFR inhibitor gefitinib preferentially inhibited growth and reduced the S phase fraction in the resistant...

  12. Streptococcal Infections

    Science.gov (United States)

    ... fasciitis (flesh-eating disease) Group B strep can cause blood infections, pneumonia and meningitis in newborns. A screening test during ... or already have health problems. Strep B can cause urinary tract infections, blood ... and pneumonia in adults. Antibiotics are used to treat strep ...

  13. ScRu2B3 and Sc2RuB6: Borides Featuring a 2D Infinite Boron Clustering.

    Science.gov (United States)

    Salamakha, Leonid P; Sologub, Oksana; Stöger, Berthold; Rogl, Peter Franz; Waas, Monika; Kapustianyk, Volodymyr B; Bauer, Ernst

    2017-09-05

    Two borides, ScRu2B3 and Sc2RuB6, were obtained by argon-arc melting of the elements followed by annealing at 800 °C. ScRu2B3 exhibits a new structure type with the space group Cmcm (a = 3.0195(2) Å, b = 15.4056(8) Å, c = 5.4492(3) Å; single crystal X-ray data; RF(2) = 0.0105). Sc2RuB6 adopts the Y2ReB6-type structure (space group Pbam; a = 8.8545(2) Å, b = 11.1620(3) Å, c = 3.4760(1) Å; single crystal X-ray data; RF(2) = 0.0185). ScRu2B3 displays an unusual intergrowth of CeCo3B2- and AlB2-related slabs; a striking feature is a boat configuration of puckered boron hexagons within infinite graphite like boron layers (6(3) nets). Sc2RuB6 presents two-dimensional planar nets of condensed boron pentagons, hexagons, and heptagons sandwiched between metal layers. In Sc/Y substituted Y2ReB6-type, Y atoms are distributed exclusively inside the boron heptagons. Exploration of the Sc-Ru-B system at 800 °C including binary boundaries employing EPMA and powder X-ray diffraction technique furthermore rules out the existence of previously reported "ScRuB4" but confirms the formation and crystal structure of Sc2Ru5B4. ScRu4B4 forms in cast alloys (LuRu4B4-type structure; space group I41/acd (No. 142), a = 7.3543(2) Å, c = 14.92137(8) Å). Cell parameters and atomic coordinates have been refined for ScRu2B3, Sc2RuB6, and ScRu4B4 in the scope of the generalized gradient approximation. Ab initio electronic structure calculations indicate a moderate electronic density of states at the Fermi level situated near the upper edge of essentially filled d-bands. Electrical resistivity measurements characterize ScRu2B3 and Sc2RuB6 as metals in concord with electronic band structure calculations.

  14. The anti-erbB3 antibody MM-121/SAR256212 in combination with trastuzumab exerts potent antitumor activity against trastuzumab-resistant breast cancer cells

    Science.gov (United States)

    2013-01-01

    Background Elevated expression of erbB3 receptor has been reported to induce resistance to therapeutic agents, including trastuzumab in erbB2-overexpressing breast cancer. Our recent studies indicate that erbB3 interacts with both erbB2 and IGF-1 receptor to form a heterotrimeric complex in trastuzumab-resistant breast cancer cells. Herein, we investigate the antitumor activity of MM-121/SAR256212, a fully human anti-erbB3 antibody (Ab), against two erbB2-overexpressing breast cancer cell lines resistant to trastuzumab. Methods MTS-based proliferation assays were used to determine cell viability upon treatment of trastuzumab and/or MM-121/SAR256212. Cell cycle progression was examined by flow cytometric analysis. Western blot analyses were performed to determine the expression and activation of proteins. Tumor xenografts were established by inoculation of the trastuzumab-resistant BT474-HR20 cells into nude mice. The tumor-bearing mice were treated with trastuzumab and/or MM-121/SAR256212 via i.p injection to determine the Abs’ antitumor activity. Immunohistochemical analyses were carried out to study the Abs’ inhibitory effects on tumor cell proliferation and induction of apoptosis in vivo. Results MM-121 significantly enhanced trastuzumab-induced growth inhibition in two sensitive and two resistant breast cancer cell lines. MM-121 in combination with trastuzumab resulted in a dramatic reduction of phosphorylated erbB3 (P-erbB3) and Akt (P-Akt) in the in vitro studies. MM-121 combined with trastuzumab did not induce apoptosis in the trastuzumab-resistant cell lines under our cell culture condition, rather induced cell cycle G1 arrest mainly associated with the upregulation of p27kip1. Interestingly, in the tumor xenograft model established from the trastuzumab-resistant cells, MM-121 in combination with trastuzumab as compared to either agent alone dramatically inhibited tumor growth correlated with a significant reduction of Ki67 staining and increase of

  15. IgM-linked SerpinB3 and SerpinB4 in sera of patients with chronic liver disease.

    Science.gov (United States)

    Biasiolo, Alessandra; Tono, Natascia; Ruvoletto, Mariagrazia; Quarta, Santina; Turato, Cristian; Villano, Gianmarco; Beneduce, Luca; Fassina, Giorgio; Merkel, Carlo; Gatta, Angelo; Pontisso, Patrizia

    2012-01-01

    Epidemiological studies indicate that a growing number of cirrhotic patients will develop hepatocellular carcinoma (HCC) in the next decade. Recent findings have demonstrated that Squamous cell carcinoma antigen 1 (SCCA1) and 2 (SCCA2) isoforms, now classified as serpinB3 and serpinB4, are over-expressed in HCC, but not in normal liver. As reported, high levels of circulating SCCA-IgM immunocomplexes in patients with cirrhosis are significantly associated with HCC development. To ascertain whether IgM-linked SCCA isoforms circulate in patients with chronic liver disease, compared to total SCCA-IgM levels. 79 patients with chronic liver disease were studied, including 17 patients with chronic hepatitis, 36 patients with cirrhosis and 26 with HCC. 28 blood donors were used as control. Monoclonal antibodies against serpinB3 and serpinB4 were used as catcher antibodies to set up specific ELISA assays, while total SCCA-IgM immunocomplexes were detected by commercially available ELISA assay. Overall, the results revealed a better diagnostic sensitivity of total SCCA-IgM assay, compared to both serpinB3 and serpinB4 IgM-linked assays. SerpinB4-IgM median values obtained with SCC103 antibody were moderately higher in patients with cirrhosis than in those with HCC, median values: 0.168 (IQR 0.140-0.427) vs. 0.140 (IQR 0.140-0.278), (p = 0.177). A trend toward decreasing serpinB4-IgM/serpinB3-IgM median ratio was observed in patients with advanced liver disease, being 1.08 in patients with HCC, 1.10 in patients with cirrhosis and 1.40 in patients with chronic hepatitis (p = 0.079). IgM-linked SCCA isoforms in serum of patients with chronic liver diseases were quantified for the first time. Although the number of patients was limited, this preliminary study reveals that the relative balance of the two serpin isoforms is altered in HCC and it is characterized by a lower serpinB4-IgM/serpinB3-IgM ratio, determined by lower serpinB4 levels.

  16. IgM-linked SerpinB3 and SerpinB4 in sera of patients with chronic liver disease.

    Directory of Open Access Journals (Sweden)

    Alessandra Biasiolo

    Full Text Available BACKGROUND: Epidemiological studies indicate that a growing number of cirrhotic patients will develop hepatocellular carcinoma (HCC in the next decade. Recent findings have demonstrated that Squamous cell carcinoma antigen 1 (SCCA1 and 2 (SCCA2 isoforms, now classified as serpinB3 and serpinB4, are over-expressed in HCC, but not in normal liver. As reported, high levels of circulating SCCA-IgM immunocomplexes in patients with cirrhosis are significantly associated with HCC development. AIM: To ascertain whether IgM-linked SCCA isoforms circulate in patients with chronic liver disease, compared to total SCCA-IgM levels. METHODOLOGY AND FINDINGS: 79 patients with chronic liver disease were studied, including 17 patients with chronic hepatitis, 36 patients with cirrhosis and 26 with HCC. 28 blood donors were used as control. Monoclonal antibodies against serpinB3 and serpinB4 were used as catcher antibodies to set up specific ELISA assays, while total SCCA-IgM immunocomplexes were detected by commercially available ELISA assay. Overall, the results revealed a better diagnostic sensitivity of total SCCA-IgM assay, compared to both serpinB3 and serpinB4 IgM-linked assays. SerpinB4-IgM median values obtained with SCC103 antibody were moderately higher in patients with cirrhosis than in those with HCC, median values: 0.168 (IQR 0.140-0.427 vs. 0.140 (IQR 0.140-0.278, (p = 0.177. A trend toward decreasing serpinB4-IgM/serpinB3-IgM median ratio was observed in patients with advanced liver disease, being 1.08 in patients with HCC, 1.10 in patients with cirrhosis and 1.40 in patients with chronic hepatitis (p = 0.079. CONCLUSIONS: IgM-linked SCCA isoforms in serum of patients with chronic liver diseases were quantified for the first time. Although the number of patients was limited, this preliminary study reveals that the relative balance of the two serpin isoforms is altered in HCC and it is characterized by a lower serpinB4-IgM/serpinB3-IgM ratio

  17. Cardiac Function Remains Impaired Despite Reversible Cardiac Remodeling after Acute Experimental Viral Myocarditis

    Directory of Open Access Journals (Sweden)

    Peter Moritz Becher

    2017-01-01

    Full Text Available Background. Infection with Coxsackievirus B3 induces myocarditis. We aimed to compare the acute and chronic phases of viral myocarditis to identify the immediate effects of cardiac inflammation as well as the long-term effects after resolved inflammation on cardiac fibrosis and consequently on cardiac function. Material and Methods. We infected C57BL/6J mice with Coxsackievirus B3 and determined the hemodynamic function 7 as well as 28 days after infection. Subsequently, we analyzed viral burden and viral replication in the cardiac tissue as well as the expression of cytokines and matrix proteins. Furthermore, cardiac fibroblasts were infected with virus to investigate if viral infection alone induces profibrotic signaling. Results. Severe cardiac inflammation was determined and cardiac fibrosis was consistently colocalized with inflammation during the acute phase of myocarditis. Declined cardiac inflammation but no significantly improved hemodynamic function was observed 28 days after infection. Interestingly, cardiac fibrosis declined to basal levels as well. Both cardiac inflammation and fibrosis were reversible, whereas the hemodynamic function remains impaired after healed viral myocarditis in C57BL/6J mice.

  18. Saffold virus, a human Theiler's-like cardiovirus, is ubiquitous and causes infection early in life.

    Directory of Open Access Journals (Sweden)

    Jan Zoll

    2009-05-01

    Full Text Available The family Picornaviridae contains well-known human pathogens (e.g., poliovirus, coxsackievirus, rhinovirus, and parechovirus. In addition, this family contains a number of viruses that infect animals, including members of the genus Cardiovirus such as Encephalomyocarditis virus (EMCV and Theiler's murine encephalomyelits virus (TMEV. The latter are important murine pathogens that cause myocarditis, type 1 diabetes and chronic inflammation in the brains, mimicking multiple sclerosis. Recently, a new picornavirus was isolated from humans, named Saffold virus (SAFV. The virus is genetically related to Theiler's virus and classified as a new species in the genus Cardiovirus, which until the discovery of SAFV did not contain human viruses. By analogy with the rodent cardioviruses, SAFV may be a relevant new human pathogen. Thus far, SAFVs have sporadically been detected by molecular techniques in respiratory and fecal specimens, but the epidemiology and clinical significance remained unclear. Here we describe the first cultivated SAFV type 3 (SAFV-3 isolate, its growth characteristics, full-length sequence, and epidemiology. Unlike the previously isolated SAFV-1 and -2 viruses, SAFV-3 showed efficient growth in several cell lines with a clear cytopathic effect. The latter allowed us to conduct a large-scale serological survey by a virus-neutralization assay. This survey showed that infection by SAFV-3 occurs early in life (>75% positive at 24 months and that the seroprevalence reaches >90% in older children and adults. Neutralizing antibodies were found in serum samples collected in several countries in Europe, Africa, and Asia. In conclusion, this study describes the first cultivated SAFV-3 isolate, its full-length sequence, and epidemiology. SAFV-3 is a highly common and widespread human virus causing infection in early childhood. This finding has important implications for understanding the impact of these ubiquitous viruses and their possible

  19. Nail infections.

    Science.gov (United States)

    Jules, K T; Bonar, P L

    1989-04-01

    Nail infections are and will continue to be a diagnostic and therapeutic challenge to all foot physicians. Attention to basic concepts of accurate detailed history and physical examination will aid in the determination of the etiology of these infections. Following basic guidelines of incision and drainage, gram stain, soaks, and antibiotics will be the cornerstone of initial treatment of pyogenic infections. Upon resolution of the acute infection a permanent treatment plan can be constituted based on the etiology. Nail infections of mycotic nature require an understanding by both patient and doctor as to the difficulty and resistance to treatment of this problem. It is the authors' opinion that aggressive persistent treatment will provide the best long-term result when dealing with mycotic infections. This may require nail removal, local and systemic treatment as well as change in shoe environment. As we have seen and is stated throughout this text, the nail and its pathologic processes can be a mirror of systemic disease. Many times a dystrophic infected nail may be the initial clinical presentation of a much more involved disease process. It is the responsibility and duty of all foot physicians to have a total understanding of knowledge of normal and pathologic process that affect the nail plates, nail bed, and surrounding nail proper. I hope this article will stimulate the foot physician to approach the disease of the nail with a high index of suspicion and respect.

  20. Is a multivalent hand, foot, and mouth disease vaccine feasible?

    Science.gov (United States)

    Klein, Michel; Chong, Pele

    2015-01-01

    Enterovirus A infections are the primary cause of hand, foot and mouth disease (HFMD) in infants and young children. Although enterovirus 71 (EV-A71) and coxsackievirus A16 (CV-A16) are the predominant causes of HFMD epidemics worldwide, EV-A71 has emerged as a major neurovirulent virus responsible for severe neurological complications and fatal outcomes. HFMD is a serious health threat and economic burden across the Asia-Pacific region. Inactivated EV-A71 vaccines have elicited protection against EV-A71 but not against CV-A16 infections in large efficacy trials. The current development of a bivalent inactivated EV-A71/CV-A16 vaccine is the next step toward that of multivalent HFMD vaccines. These vaccines should ultimately include other prevalent pathogenic coxsackieviruses A (CV-A6 and CV-A10), coxsackieviruses B (B3 and B5) and echovirus 30 that often co-circulate during HFMD epidemics and can cause severe HFMD, aseptic meningitis and acute viral myocarditis. The prospect and challenges for the development of such multivalent vaccines are discussed. PMID:26009802

  1. Hepatitis B virus infection in Indonesia.

    Science.gov (United States)

    Yano, Yoshihiko; Utsumi, Takako; Lusida, Maria Inge; Hayashi, Yoshitake

    2015-10-14

    Approximately 240 million people are chronically infected with hepatitis B virus (HBV), 75% of whom reside in Asia. Approximately 600000 of infected patients die each year due to HBV-related diseases or hepatocellular carcinoma (HCC). The endemicity of hepatitis surface antigen in Indonesia is intermediate to high with a geographical difference. The risk of HBV infection is high in hemodialysis (HD) patients, men having sex with men, and health care workers. Occult HBV infection has been detected in various groups such as blood donors, HD patients, and HIV-infected individuals and children. The most common HBV subgenotype in Indonesia is B3 followed by C1. Various novel subgenotypes of HBV have been identified throughout Indonesia, with the novel HBV subgenotypes C6-C16 and D6 being successfully isolated. Although a number of HBV subgenotypes have been discovered in Indonesia, genotype-related pathogenicity has not yet been elucidated in detail. Therefore, genotype-related differences in the prognosis of liver disease and their effects on treatments need to be determined. A previous study conducted in Indonesia revealed that hepatic steatosis was associated with disease progression. Pre-S2 mutations and mutations at C1638T and T1753V in HBV/B3 have been associated with advanced liver diseases including HCC. However, drug resistance to lamivudine, which is prominent in Indonesia, remains obscure. Although the number of studies on HBV in Indonesia has been increasing, adequate databases on HBV infection are limited. We herein provided an overview of the epidemiology and clinical characteristics of HBV infection in Indonesia.

  2. The effect of organic anion-transporting polypeptides 1B1, 1B3 and 2B1 on the antitumor activity of flavopiridol in breast cancer cells.

    Science.gov (United States)

    Brenner, Stefan; Riha, Juliane; Giessrigl, Benedikt; Thalhammer, Theresia; Grusch, Michael; Krupitza, Georg; Stieger, Bruno; Jäger, Walter

    2015-01-01

    The contribution of organic anion transporting polypeptides (OATPs) to the cellular uptake of flavopiridol was investigated in OATP1B1-, OATP1B3- and OATP2B1-expressing Chinese hamster ovary (CHO) cells. Uptake of flavopiridol into these cells showed typical Michaelis-Menten kinetics with much higher transport capacity for OATP1B3 compared to OATP1B1 and OATP2B1 (Vmax/Km, 33.9 vs. 8.84 and 2.41 µl/mg/min, respectively). The predominant role of OATPs was further supported by a dramatic inhibition of flavopiridol uptake in the presence of the OATP substrate rifampicin. Uptake of flavopiridol by OATPs also seems to be an important determinant in breast cancer cells. The much higher mRNA level for OATP1B1 found in wild-type compared to ZR-75-1 OATP1B1 knockdown cells correlated with higher flavopiridol initial uptake leading to 4.6-fold decreased IC50 values in the cytotoxicity assay (IC50, 1.45 vs. 6.64 µM). Cell cycle profile also showed a clear incidence for a stronger cell cycle arrest in the G2/M phase for ZR-75-1 wild-type cells compared to OATP1B1 knockdown cells, further indicating an active uptake via OATP1B1. In conclusion, our results revealed OATP1B1, OATP1B3 and OATP2B1 as uptake transporters for flavopiridol in cancer cells, which may also apply in patients during cancer therapy.

  3. Influence of genomic ancestry on the distribution of SLCO1B1, SLCO1B3 and ABCB1 gene polymorphisms among Brazilians.

    Science.gov (United States)

    Sortica, Vinicius de A; Ojopi, Elida B; Genro, Júlia P; Callegari-Jacques, Sidia; Ribeiro-Dos-Santos, Andrea; de Moraes, Manoel Odorico; Romano-Silva, Marco A; Pena, Sérgio D J; Suarez-Kurtz, Guilherme; Hutz, Mara H

    2012-05-01

    The frequency distribution of SNPs and haplotypes in the ABCB1, SLCO1B1 and SLCO1B3 genes varies largely among continental populations. This variation can lead to biases in pharmacogenetic studies conducted in admixed populations such as those from Brazil and other Latin American countries. The aim of this study was to evaluate the influence of self-reported colour, geographical origin and genomic ancestry on distributions of the ABCB1, SLCO1B1 and SLCO1B3 polymorphisms and derived haplotypes in admixed Brazilian populations. A total of 1039 healthy adults from the north, north-east, south-east and south of Brazil were recruited for this investigation. The c.388A>G (rs2306283), c.463C>A (rs11045819) and c.521T>C (rs4149056) SNPs in the SLCO1B1 gene and c.334T>G (rs4149117) and c.699G>A (rs7311358) SNPs in the SLCO1B3 gene were determined by Taqman 5'-nuclease assays. The ABCB1 c.1236C>T (rs1128503), c.2677G>T/A (rs2032582) and c.3435C>T (rs1045642) polymorphisms were genotyped using a previously described single-base extension/termination method. The results showed that genotype and haplotype distributions are highly variable among populations of the same self-reported colour and geographical region. However, genomic ancestry showed that these associations are better explained by a continuous variable. The influence of ancestry on the distribution of alleles and haplotype frequencies was more evident in variants with large differences in allele frequencies between European and African populations. Design and interpretation of pharmacogenetic studies using these transporter genes should include genomic controls to avoid spurious conclusions based on improper matching of study cohorts from Brazilian populations and other highly admixed populations. © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.

  4. Organic anion transporting polypeptide (OATP)1B1 and OATP1B3 as important regulators of the pharmacokinetics of substrate drugs.

    Science.gov (United States)

    Maeda, Kazuya

    2015-01-01

    Nobody doubts the importance of organic anion transporting polypeptide (OATP)1B1 and 1B3 in the clinical pharmacokinetics of substrate drugs. Based on the theory of pharmacokinetics, even if a drug is eliminated from the body by extensive metabolism, the rate-determining process of the hepatic intrinsic clearance of OATP substrates is often hepatic uptake. Because of their broad substrate specificities, once the functions of OATP1B1 or OATP1B3 are altered by several kinds of special occasions such as drug-drug interactions (DDI) and genetic polymorphisms of transporter genes, the hepatic clearance of many kinds of structurally-unrelated drugs is expected to be changed. In some cases, these alterations of pharmacokinetics lead to modified pharmacological effects and adverse reactions such as statin-induced myotoxicity and the glucose-lowering effect of anti-diabetes drugs. Thus, appropriate methods with which to quantitatively predict the changes in plasma and tissue concentrations of drugs are needed in the process of drug development. As for DDI, a static model that takes into consideration of the theoretically-maximum unbound inhibitor concentration is often used for the sensitive detection of possible DDI risks and this method has been adopted in several regulatory guidance/guidelines on DDI. Regarding genetic polymorphisms, the effects of SLCO1B1 c.388A>G and c.521T>C on the pharmacokinetics of substrate drugs have been extensively investigated. Even though there are some discrepancies, c.521T>C generally decreased hepatic uptake activity, while c.388A>G tended to slightly increase it. This article briefly summarizes the current status of research on hepatic OATP1B1 and OATP1B3 and the clinical significance of their functions.

  5. Tapeworm Infection

    Science.gov (United States)

    ... tapeworm (Taenia solium) is greater in areas of Latin America, China, sub-Saharan Africa or Southeast Asia where ... as well as seizures, meningitis, hydrocephalus or dementia. Death can occur in severe cases of infection. Organ ...

  6. Norovirus Infection

    Science.gov (United States)

    ... if you experience severe vomiting, bloody stools, abdominal pain or dehydration. Causes Noroviruses are highly contagious and are shed in the feces of infected humans and animals. Methods of transmission include: Eating contaminated food Drinking ...

  7. MRSA Infection

    Science.gov (United States)

    ... Runny nose MRSA infection Symptoms & causes Diagnosis & treatment Advertisement Mayo Clinic does not endorse companies or products. ... a Job Site Map About This Site Twitter Facebook Google YouTube Pinterest Mayo Clinic is a not- ...

  8. Pinworm Infection

    Science.gov (United States)

    ... and vomiting Pinworm infection Symptoms & causes Diagnosis & treatment Advertisement Mayo Clinic does not endorse companies or products. ... a Job Site Map About This Site Twitter Facebook Google YouTube Pinterest Mayo Clinic is a not- ...

  9. Biofilm Infections

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Jensen, Peter Østrup; Moser, Claus Ernst

    A still increasing interest and emphasis on the sessile bacterial lifestyle biofilms has been seen since it was realized that the vast majority of the total microbial biomass exists as biofilms. Aggregation of bacteria was first described by Leeuwenhoek in 1677, but only recently recognized...... as being important in chronic infection. In 1993 the American Society for Microbiology (ASM) recognized that the biofilm mode of growth was relevant to microbiology. This book covers both the evidence for biofilms in many chronic bacterial infections as well as the problems facing these infections...... such as diagnostics, pathogenesis, treatment regimes and in vitro and in vivo models for studying biofilms. This is the first scientific book on biofilm infections, chapters written by the world leading scientist and clinicians. The intended audience of this book is scientists, teachers at university level as well...

  10. Norovirus Infections

    Science.gov (United States)

    ... get it if you touch a contaminated surface. Norovirus can be serious, especially for young children and older adults. The most common symptoms of norovirus infection are Diarrhea Nausea and vomiting Stomach pain ...

  11. Anaerobic Infections

    Science.gov (United States)

    ... Pediatrician Health Issues Conditions Abdominal ADHD Allergies & Asthma Autism Cancer Chest & Lungs Chronic Conditions Cleft & Craniofacial Developmental ... on the face and neck, sometimes after a dental infection or procedure such as a tooth extraction ...

  12. Shigella Infections

    Science.gov (United States)

    ... your hands before touching other people and before handling food. (Anyone with a diarrhea should not prepare food ... should be kept away from other kids. Proper handling, storage, and preparation of food can also help prevent Shigella infections. Cold foods ...

  13. Hand Infections

    Science.gov (United States)

    ... an infection of the paronychium (pay-roh-NIK-ee-um), which is the area around the fingernail ( ... term?) for single-character wildcard matching. For example, pa?ent would give you results for parent, patent, ...

  14. Campylobacter Infections

    Science.gov (United States)

    ... are the most common Campylobacter species associated with diarrhea . Common ways that a child can get the ... and Symptoms Illness caused by Campylobacter infections includes diarrhea, stomach pain, and fever. Blood may be present ...

  15. The electronic and chemical structure of the a-B3CO0.5:Hy-to-metal interface from photoemission spectroscopy: implications for Schottky barrier heights.

    Science.gov (United States)

    Driver, M Sky; Paquette, Michelle M; Karki, S; Nordell, B J; Caruso, A N

    2012-11-07

    The electronic and chemical structure of the metal-to-semiconductor interface was studied by photoemission spectroscopy for evaporated Cr, Ti, Al and Cu overlayers on sputter-cleaned as-deposited and thermally treated thin films of amorphous hydrogenated boron carbide (a-B(x)C:H(y)) grown by plasma-enhanced chemical vapor deposition. The films were found to contain ~10% oxygen in the bulk and to have approximate bulk stoichiometries of a-B(3)CO(0.5):H(y). Measured work functions of 4.7/4.5 eV and valence band maxima to Fermi level energy gaps of 0.80/0.66 eV for the films (as-deposited/thermally treated) led to predicted Schottky barrier heights of 1.0/0.7 eV for Cr, 1.2/0.9 eV for Ti, 1.2/0.9 eV for Al, and 0.9/0.6 eV for Cu. The Cr interface was found to contain a thick partial metal oxide layer, dominated by the wide-bandgap semiconductor Cr(2)O(3), expected to lead to an increased Schottky barrier at the junction and the formation of a space-charge region in the a-B(3)CO(0.5):H (y) layer. Analysis of the Ti interface revealed a thick layer of metal oxide, comprising metallic TiO and Ti (2)O (3), expected to decrease the barrier height. A thinner, insulating Al(2)O(3) layer was observed at the Al-to-a-B(3)CO(0.5):H(y) interface, expected to lead to tunnel junction behavior. Finally, no metal oxides or other new chemical species were evident at the Cu-to-a-B(3)CO(0.5):H(y) interface in either the core level or valence band photoemission spectra, wherein characteristic metallic Cu features were observed at very thin overlayer coverages. These results highlight the importance of thin-film bulk oxygen content on the metal-to-semiconductor junction character as well as the use of Cu as a potential Ohmic contact material for amorphous hydrogenated boron carbide semiconductor devices such as high-efficiency direct-conversion solid-state neutron detectors.

  16. On a focal point instability in (B3Πg - C3Πu)N2 optogalvanic circuit with hollow cathode

    Science.gov (United States)

    Gencheva, V.

    2016-03-01

    The (B3Πg, v = 0 - C3 Πu, v = 0) N2 dynamic optogalvanic signals have been registered illuminating an Al hollow cathode lamp with a pulsed N2 laser generating at the wavelength of 337.1nm. The dynamic optogalvanic signal (DOGS) at certain discharge current of 8 mA is a harmonic oscillator due to a focal point instability produced by our optogalvanic circuit. This damped harmonic oscillator can be described as a solution of linear second order homogeneous differential equation. The oscillation frequency is estimated from the registered DOGS using Fourier synthesis. The analytical description of the damped harmonic DOGS is obtained.

  17. Evaluation of an ELISA using recombinant Ssλ20ΔB3 antigen for the serological diagnosis of Sarcoptes scabiei infestation in domestic and wild rabbits.

    Science.gov (United States)

    Casais, Rosa; Millán, Javier; Rosell, Joan Maria; Dalton, Kevin P; Prieto, José Miguel

    2015-12-15

    An ELISA, based on the Sarcoptes scabiei Ssλ20ΔB3 inmunodominant antigen, was evaluated for the detection of antibodies to S. scabiei in experimentally infested (n=10), farm (n=109), and wild (n=78) rabbit sera. The S. scabiei antigen Ssλ20ΔB3, a major structural protein present over the entire mite's body, was produced as a recombinant protein in Escherichia coli and purified for its use in the ELISA. The resulting ELISA showed, in experimentally infested domestic rabbits, detectable specific antibody responses (IgG) above the cut off level from week three post-infestation indicating that the assay is able to detect positive rabbits very early during the course of the infestation. The ELISA was validated on a panel of 109 domestic breeding rabbit sera collected from 26 Spanish farms, of which 41 were obtained from rabbits with skin lesions compatible with sarcoptic mange, 26 with skin lesions compatible with psoroptic mange, and 42 from unexposed individuals from mange-free farms. The ELISA in this group was characterized by 95% sensitivity, 97% specificity, and a high degree of repeatability. In the psoroptic mange compatible lesions group, included in the study as control group for cross-reactivity with the closely related mite Psoroptes cuniculi, cross-reacting antibodies to Ssλ20ΔB3 S. scabiei antigen were detected in 42.30% of the rabbit sera. However, mean% OD values of the sarcoptic-mange group (55.61 ± 39.20%) were significantly higher (prabbits from Mallorca Island. The sensitivity of the assay for this group was 100% (4 out of the 4 rabbits with sarcoptic mange compatible lesions and presence of S. scabiei mites were seropositive) and the specificity was 90% (67 out of 74 wild rabbits without detectable mange lesions were seronegative). Although, the total number of tested samples from experimentally infested, farm and wild rabbits was limited, our study showed that the ELISA is able to differentiate between infested and non-infested animals in

  18. Remaining Sites Verification Package for the 126-B-3, 184-B Coal Pit Dumping Area, Waste Site Reclassification Form 2005-028

    Energy Technology Data Exchange (ETDEWEB)

    L. M. Dittmer

    2006-08-07

    The 126-B-3 waste site is the former coal storage pit for the 184-B Powerhouse. During demolition operations in the 1970s, the site was used for disposal of demolition debris from 100-B/C Area facilities. The site has been remediated by removing debris and contaminated soils. The results of verification sampling demonstrated that residual contaminant concentrations do not preclude any future uses and allow for unrestricted use of shallow zone soils. The results also showed that residual contaminant concentrations are protective of groundwater and the Columbia River.

  19. High-power ultraviolet 278 nm laser from fourth-harmonic generation of a Nd:YAG laser in CsB3O5.

    Science.gov (United States)

    Wang, Zhichao; Yang, Feng; Zhang, Guochun; Bo, Yong; Liu, Shanshan; Xie, Shiyong; Xu, Yiting; Zong, Nan; Li, Fangqin; Liu, Biaolong; Xu, Jialin; Peng, Qinjun; Zhang, Jingyuan; Cui, Dafu; Wu, Yicheng; Xu, Zuyan

    2012-06-15

    We demonstrate a high-power UV 278 nm laser by fourth-harmonic generation (FHG) of a 1112 nm Nd:YAG laser in a nonlinear optical (NLO) crystal CsB3O5 (CBO) for the first time, to our best knowledge. A 30 W level diode-pumped Q-switched Nd:YAG laser at 1112 nm with beam quality factor M2=1.2 was used as the fundamental light source at a pulse width of 500 ns. With an LiB3O5 crystal, the 1112 nm laser was first frequency-doubled to 556 nm with an average output power of 13.5 W. It was then frequency doubled again in a CBO crystal to obtain the FHG output at 278 nm. The maximum average output power of the 278 nm laser is up to 1.5 W. The results demonstrated that CBO crystal is a promising NLO material for UV high-power lasers below 300 nm.

  20. Association between IL2/IL21 and SH2B3 polymorphisms and risk of celiac disease: a meta-analysis.

    Science.gov (United States)

    Guo, C C; Huang, W H; Zhang, N; Dong, F; Jing, L P; Liu, Y; Ye, X G; Xiao, D; Ou, M L; Zhang, B H; Wang, M; Liang, W K; Yang, G; Jing, C X

    2015-10-27

    Celiac disease (CD) is a common autoimmune disorder characterized by heightened immunological response to ingested gluten. Certain gene polymorphisms of IL2/IL21 (rs6822844 and rs6840978) and SH2B3 (rs3184504) may influence susceptibility to CD, although the effects remain unclear. We performed a meta-analysis of the associations between rs6822844, rs6840978, and rs3184504 polymorphisms and CD risk. PubMed, EMBASE, and the China National Knowledge Infrastructure were searched. ORs and 95%CIs of each single nucleotide polymorphism (SNP) were estimated using the fixed-effect model if I(2) IL2/IL21 significantly decreased the risk of CD. However, the minor allele A of rs3184504 (A vs G, OR = 1.18, 95%CI = 1.12-1.24, P < 0.001) in SH2B3 significantly increased CD susceptibility. The estimated lambda values were 0.49, 0.50, and 0.53 for rs6822844, rs6840978, and rs3184504, respectively, suggesting that a co-dominant model of genotype effect was most appropriate for the three SNPs. Our results support associations between the three SNPs and CD and provide a strong argument for further research.

  1. Resonance Raman detection of a ferrous five-coordinate nitrosylheme b(3) complex in cytochrome cbb(3) oxidase from Pseudomonas stutzeri.

    Science.gov (United States)

    Pinakoulaki, Eftychia; Stavrakis, Stavros; Urbani, Andrea; Varotsis, Constantinos

    2002-08-14

    Understanding the chemical nature of the nitric oxide (NO) moiety of nitrosylheme copper oxidases is crucial for elucidation of the NO activation process. In the present work, direct resonance Raman spectroscopic observation of both the Fe(2+)-NO and the N-O stretching modes unambiguously establishes the vibrational characteristics of the NO-bound heme moiety in cytochrome cbb(3) from Pseudomonas stutzeri. Addition of NO to fully reduced enzyme causes the rupture of the proximal His-heme b(3) bond resulting in the formation of a five-coordinate heme b(3)(2+)-NO species with nu(Fe-NO) and nu(NO) at 524 and 1679 cm(-1), respectively. The frequencies of the nitrosyl species we detect are very similar to those obtained in other model- and protein heme-NO complexes. To account for this observation, we propose a model describing the oxidation and ligand-binding states in fully reduced cytochrome cbb(3) upon addition of NO.

  2. An outbreak of Kingella kingae infections associated with hand, foot and mouth disease/herpangina virus outbreak in Marseille, France, 2013.

    Science.gov (United States)

    El Houmami, Nawal; Minodier, Philippe; Dubourg, Grégory; Martin-Laval, Alain; Lafont, Elisabeth; Jouve, Jean-Luc; Charrel, Rémi; Raoult, Didier; Fournier, Pierre-Edouard

    2015-03-01

    Outbreaks of invasive Kingella kingae infections recently emerged as a new public health concern in daycare centers in Europe, USA and Israel. Despite this, no trigger factor has been yet identified, preventing the setting up of rational measures of control and prevention. We report an outbreak of K. kingae infections associated with hand, foot and mouth disease/herpangina outbreak, and we define the research and policy priorities. From April 22 to May 07, 2013, 5 toddlers presented successive osteo-articular infections in a daycare center in Marseille, France. Real-time polymerase chain reaction targeting the cpn60 gene of K. kingae was used to investigate suspected cases and the prevalence of oropharyngeal K. kingae carriage of their close contacts. The attack rate of the K. kingae infections outbreak was 23.7% (5/21) with no fatality. Positive real-time polymerase chain reaction targeting the cpn60 gene of K. kingae confirmed the diagnosis in 3 cases and revealed a rate of K. kingae oropharynx carriage in the index classroom of 94.4% (17/18) among daycare attendees not given antibiotic during the previous month, and of 76.9% (10/13) among staff in close contact. The eradication rate of K. kingae was 21.4% (3/14) among classmates after oral administration of rifampicin, and eradication occurred spontaneously in 83.3% (5/6) of the staff. Clinical and epidemiological features of the herpangina outbreak were consistent with that of an emerging European Coxsackievirus-A6 outbreak. Hand, foot and mouth disease/herpangina virus outbreak enables triggering a K. kingae infections outbreak. Our findings offer support for new guidelines of K. kingae infections outbreaks management and emphasize the need for further research.

  3. Cerebral infections

    Energy Technology Data Exchange (ETDEWEB)

    Karampekios, Spyros [University of Crete, Department of Radiology, Heraklion, Crete (Greece); Hesselink, John [UCSD, Department of Radiology, San Diego, CA (United States)

    2005-03-01

    Despite the development of many effective antibiotic therapies and the general improvement in hygiene and health care systems all over the world, the incidence of central nervous system (CNS) infection has increased significantly in the past 15 years. This can be attributed primarily to the acquired immunodeficiency syndrome (AIDS) epidemic and its devastating effect on the immune system and secondarily to various immunosuppressive agents that are being used in aggressive cancer treatment and in organ transplantations. The brain particularly is protected from infection by the calvarium, meninges and blood brain barrier. However, different types of pathogens, including bacteria, viruses, fungi and parasites, can reach the brain hematogenously or, less likely, by direct extension from an adjacent infected focus. The early detection and specific diagnosis of infection are of great importance, since brain infections are potentially treatable diseases. Imaging studies play a crucial role in the diagnostic process, along with the history (exposure to infectious agents), host factors (open head trauma, CSF leak, sinusitis, otitis, immune status), physical examination and laboratory analysis of CSF. (orig.)

  4. Spinal infections

    Energy Technology Data Exchange (ETDEWEB)

    Tali, E. Turgut E-mail: turguttali@gazi.edu.tr

    2004-05-01

    Spinal infections can be thought of as a spectrum of disease comprising spondylitis, discitis, spondylodiscitis, pyogenic facet arthropathy, epidural infections, meningitis, polyradiculopathy and myelitis. Radiological evaluations have gained importance in the diagnosis, treatment planning, treatment and treatment monitoring of the spinal infections. Conventional radiographs are usually the initial imaging study. The sensitivity and specificity of the plain radiographs are very low. The sensitivity of CT is higher while it lacks of specificity. Conventional CT has played minor role for the diagnosis of early spondylitis and disc space infection and for follow-up, researches are going on the value of MDCT. MRI is as sensitive, specific and accurate as combined nuclear medicine studies and the method of choice for the spondylitis. Low signal areas of the vertebral body, loss of definition of the end plates and interruption of the cortical continuity, destruction of the cortical margins are typical on T1WI whereas high signal of affected areas of the vertebral body and disc is typical on T2WI. Contrast is mandatory and increases conspicuity, specificity, and observer confidence in the diagnosis and facilitates the treatment planning. Contrast enhancement is the earliest sign and pathognomonic in the acute inflammatory episode and even in the subtle infection then persists to a varying degree for several weeks or months. The outcome of the treatment is influenced by the type of infection and by the degree of neurologic compromise before treatment. There is an increasing move away from surgical intervention towards conservative therapy, percutaneous drainage of abscess or both. It is therefore critical to monitor treatment response, particularly in the immuno-deficient population.

  5. AtREM1, a member of a new family of B3 domain-containing genes, is preferentially expressed in reproductive meristems.

    Science.gov (United States)

    Franco-Zorrilla, José M; Cubas, Pilar; Jarillo, José A; Fernández-Calvín, Begoña; Salinas, Julio; Martínez-Zapater, José M

    2002-02-01

    We have isolated and characterized AtREM1, the Arabidopsis ortholog of the cauliflower (Brassica oleracea) BoREM1. AtREM1 belongs to a large gene family of more than 20 members in Arabidopsis. The deduced AtREM1 protein contains several repeats of a B3-related domain, and it could represent a new class of regulatory proteins only found in plants. Expression of AtREM1 is developmentally regulated, being first localized in a few central cells of vegetative apical meristems, and later expanding to the whole inflorescence meristem, as well as primordia and organs of third and fourth floral whorls. This specific expression pattern suggests a role in the organization of reproductive meristems, as well as during flower organ development.

  6. High-power Femtosecond Optical Parametric Amplification at 1 kHz in BiB(3)O(6) pumped at 800 nm.

    Science.gov (United States)

    Petrov, Valentin; Noack, Frank; Tzankov, Pancho; Ghotbi, Masood; Ebrahim-Zadeh, Majid; Nikolov, Ivailo; Buchvarov, Ivan

    2007-01-22

    Substantial power scaling of a travelling-wave femtosecond optical parametric amplifier, pumped near 800 nm by a 1 kHz Ti:sapphire laser amplifier, is demonstrated using monoclinic BiB(3)O(6) in a two stage scheme with continuum seeding. Total energy output (signal plus idler) exceeding 1 mJ is achieved, corresponding to an intrinsic conversion efficiency of approximately 32% for the second stage. The tunability extends from 1.1 to 2.9 microm. The high parametric gain and broad amplification bandwidth of this crystal allowed the maintenance of the pump pulse duration, leading to pulse lengths less than 140 fs, both for the signal and idler pulses, even at such high output levels.

  7. AtREM1, a Member of a New Family of B3 Domain-Containing Genes, Is Preferentially Expressed in Reproductive Meristems1

    Science.gov (United States)

    Franco-Zorrilla, José M.; Cubas, Pilar; Jarillo, José A.; Fernández-Calvín, Begoña; Salinas, Julio; Martínez-Zapater, José M.

    2002-01-01

    We have isolated and characterized AtREM1, the Arabidopsis ortholog of the cauliflower (Brassica oleracea) BoREM1. AtREM1 belongs to a large gene family of more than 20 members in Arabidopsis. The deduced AtREM1 protein contains several repeats of a B3-related domain, and it could represent a new class of regulatory proteins only found in plants. Expression of AtREM1 is developmentally regulated, being first localized in a few central cells of vegetative apical meristems, and later expanding to the whole inflorescence meristem, as well as primordia and organs of third and fourth floral whorls. This specific expression pattern suggests a role in the organization of reproductive meristems, as well as during flower organ development. PMID:11842146

  8. Identification of cyc-B3H3 with Three Bridging B–H–B Bonds in a Six-Membered Ring

    Directory of Open Access Journals (Sweden)

    Sheng-Lung Chou

    2017-02-01

    Full Text Available Irradiation of samples of diborane(6, B2H6 and B2D6, separately and together, dispersed in solid neon near 4 K with tunable far-ultraviolet light from a synchrotron yielded new infrared absorption lines that are assigned to several carriers. Besides H, B, BH, BH2, BH3, B2, B2H2, and B2H4, previously identified, a further species is assigned on the basis of quantum-chemical calculations of vibrational wavenumbers and intensities to be cyc-B3H3 (D3h, singlet state in several isotopic variants, which feature three bridging B–H–B bonds in a six-membered ring.

  9. Long isoform of ErbB3 binding protein, p48, mediates protein kinase B/Akt-dependent HDM2 stabilization and nuclear localization

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Chung Kwon; Lee, Sang Bae; Nguyen, Truong L.X. [Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, 440-746 (Korea, Republic of); Lee, Kyung-Hoon [Department of Anatomy, Sungkyunkwan University School of Medicine, Suwon, 440-746 (Korea, Republic of); Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, 440-746 (Korea, Republic of); Um, Sung Hee [Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, 440-746 (Korea, Republic of); Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, 440-746 (Korea, Republic of); Kim, Jihoe [School of Biotechnology, Yeungnam University, Gyeongsan 712-749 (Korea, Republic of); Ahn, Jee-Yin, E-mail: jeeahn@skku.edu [Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, 440-746 (Korea, Republic of); Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, 440-746 (Korea, Republic of)

    2012-01-15

    p48 is a long isoform of the ErbB3 binding protein that has oncogenic functions including promotion of carcinogenesis and induction of malignant transformation through negative regulation of tumor suppressor p53. Here, we show that high level of p48 protein expression leads to enhance HDM2 phosphorylation by Akt and inhibits the self-ubiquitination of HDM2 by up-regulation of Akt activity, thereby promoting its protein stability. Moreover, p48 expression leads to accumulated nuclear localization of HDM2, whereas p48 depletion disturbs its nuclear localization. Hence, higher expression of p48 in cancer cells reduces p53 levels through modulation of HDM2 nuclear localization and protein stability via regulation of its Akt-mediated phosphorylation.

  10. Mo5PB2: a new superconductor in the Cr5B3 structure type with Tc = 9.2 K

    Science.gov (United States)

    McGuire, Michael; Parker, David

    Superconductivity has been reported recently in several ternary silicide-borides adopting the tetragonal Cr5B3 structure type, including Nb5Si3-xBx, Mo5SiB2, and W5SiB2, with critical temperatures ranging from 5.8-7.8 K. Here we report superconductivity with Tc exceeding 9 K in the phosphorus-containing analogue Mo5PB2. We have synthesized polycrystalline samples of the compound, made measurements of electrical resistivity, magnetic susceptibility, and heat capacity, and performed first principles electronic structure calculations. The highest Tc values occur in slightly phosphorus rich samples, with composition near Mo5P1.1B1.9. Together with the measured properties, the calculations suggest the superconductivity in these materials may be multi-band. Research sponsored by the US Department of Energy, Office of Science, Basic Energy Sciences, Materials Sciences and Engineering Division.

  11. Biochemical Analysis of Four Missense Mutations in the HSD17B3 Gene Associated With 46,XY Disorders of Sex Development in Egyptian Patients.

    Science.gov (United States)

    Engeli, Roger T; Tsachaki, Maria; Hassan, Heba A; Sager, Christoph P; Essawi, Mona L; Gad, Yehia Z; Kamel, Alaa K; Mazen, Inas; Odermatt, Alex

    2017-09-01

    Mutations in the HSD17B3 gene are associated with a 46,XY disorder of sexual development (46,XY DSD) as a result of low testosterone production during embryogenesis. To elucidate the molecular basis of the disorder by chemically analyzing four missense mutations in HSD17B3 (T54A, M164T, L194P, G289S) from Egyptian patients with 46,XY DSD. Expression plasmids for wild-type 17β-hydroxysteroid hydrogenase type 3 (17β-HSD3) and mutant enzymes generated by site-directed mutagenesis were transiently transfected into human HEK-293 cells. Protein expression was verified by western blotting and activity was determined by measuring the conversion of radiolabeled Δ4-androstene-3,17-dione to testosterone. Application of a homology model provided an explanation for the observed effects of the mutations. Testosterone formation by wild-type and mutant 17β-HSD3 enzymes was compared. Mutations T54A and L194P, despite normal protein expression, completely abolished 17β-HSD3 activity, explaining their severe 46,XY DSD phenotype. Mutant M164T could still produce testosterone, albeit with significantly lower activity compared with wild-type 17β-HSD3, resulting in ambiguous genitalia or a microphallus at birth. The substitution G289S represented a polymorphism exhibiting comparable activity to wild-type 17β-HSD3. Sequencing of the SRD5A2 gene in three siblings bearing the HSD17B3 G289S polymorphism disclosed the homozygous Y91H mutation in the former gene, thus explaining the 46,XY DSD presentations. Molecular modeling analyses supported the biochemical observations and predicted a disruption of cofactor binding by mutations T54A and M164T and of substrate binding by L196P, resulting in the loss of enzyme activity. In contrast, the G289S substitution was predicted to disturb neither the three-dimensional structure nor enzyme activity. Biochemical analysis of mutant 17β-HSD3 enzymes is necessary to understand genotype-phenotype relationships. Biochemical analysis combined with

  12. Campylobacter Infections

    Science.gov (United States)

    ... contact with fecal matter (poop) from an infected person (especially a child in diapers). Household pets can carry and spread the bacteria to people. ... preparing food. Clean and disinfect toilets after the person with diarrhea uses them. Also, if a pet dog or cat has diarrhea, wash your hands ...

  13. Fusarium Infection

    Science.gov (United States)

    Muhammed, Maged; Anagnostou, Theodora; Desalermos, Athanasios; Kourkoumpetis, Themistoklis K.; Carneiro, Herman A.; Glavis-Bloom, Justin; Coleman, Jeffrey J.

    2013-01-01

    Abstract Fusarium species is a ubiquitous fungus that causes opportunistic infections. We present 26 cases of invasive fusariosis categorized according to the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria of fungal infections. All cases (20 proven and 6 probable) were treated from January 2000 until January 2010. We also review 97 cases reported since 2000. The most important risk factors for invasive fusariosis in our patients were compromised immune system, specifically lung transplantation (n = 6) and hematologic malignancies (n = 5), and burns (n = 7 patients with skin fusariosis), while the most commonly infected site was the skin in 11 of 26 patients. The mortality rates among our patients with disseminated, skin, and pulmonary fusariosis were 50%, 40%, and 37.5%, respectively. Fusarium solani was the most frequent species, isolated from 49% of literature cases. Blood cultures were positive in 82% of both current study and literature patients with disseminated fusariosis, while the remaining 16% had 2 noncontiguous sites of infection but negative blood cultures. Surgical removal of focal lesions was effective in both current study and literature cases. Skin lesions in immunocompromised patients should raise the suspicion for skin or disseminated fusariosis. The combination of medical monotherapy with voriconazole or amphotericin B and surgery in such cases is highly suggested. PMID:24145697

  14. Chlamydia Infections

    Science.gov (United States)

    ... if you have a partner who has a sexually transmitted disease. Pregnant women should get a test when they go to ... partners, or a sex partner who has a sexually transmitted disease Men who have ... of chlamydia? In women, an untreated infection can spread to your uterus ...

  15. Protozoan Infections

    Science.gov (United States)

    1989-01-01

    respond poorly to antimicrobial therapy. Organisms closely related to Leishmania include Trypanosoma cruzi , which causes American trypanosomiasis...1978). Trypanosoma cruzi also does not 22. Protozoan Infections 689 inhibit phagolysosomal fusion, but escapes from the parasitophorous vacuole to...y from solution. Approximately one-third of antileishmanial activity remains, however, when lymphokine preparations are treated with anti -IFN (Nacy et

  16. Baylisascaris Infection

    Centers for Disease Control (CDC) Podcasts

    2012-08-27

    This podcast will educate health care providers on diagnosing baylisascariasis and on providing patients at risk of Baylisascaris infection with prevention messages.  Created: 8/27/2012 by Center for Global Health, Division of Parasitic Diseases and Malaria.   Date Released: 8/28/2012.

  17. The Theobroma cacao B3 domain transcription factor TcLEC2 plays a duel role in control of embryo development and maturation.

    Science.gov (United States)

    Zhang, Yufan; Clemens, Adam; Maximova, Siela N; Guiltinan, Mark J

    2014-04-24

    The Arabidopsis thaliana LEC2 gene encodes a B3 domain transcription factor, which plays critical roles during both zygotic and somatic embryogenesis. LEC2 exerts significant impacts on determining embryogenic potential and various metabolic processes through a complicated genetic regulatory network. An ortholog of the Arabidopsis Leafy Cotyledon 2 gene (AtLEC2) was characterized in Theobroma cacao (TcLEC2). TcLEC2 encodes a B3 domain transcription factor preferentially expressed during early and late zygotic embryo development. The expression of TcLEC2 was higher in dedifferentiated cells competent for somatic embryogenesis (embryogenic calli), compared to non-embryogenic calli. Transient overexpression of TcLEC2 in immature zygotic embryos resulted in changes in gene expression profiles and fatty acid composition. Ectopic expression of TcLEC2 in cacao leaves changed the expression levels of several seed related genes. The overexpression of TcLEC2 in cacao explants greatly increased the frequency of regeneration of stably transformed somatic embryos. TcLEC2 overexpressing cotyledon explants exhibited a very high level of embryogenic competency and when cultured on hormone free medium, exhibited an iterative embryogenic chain-reaction. Our study revealed essential roles of TcLEC2 during both zygotic and somatic embryo development. Collectively, our evidence supports the conclusion that TcLEC2 is a functional ortholog of AtLEC2 and that it is involved in similar genetic regulatory networks during cacao somatic embryogenesis. To our knowledge, this is the first detailed report of the functional analysis of a LEC2 ortholog in a species other then Arabidopsis. TcLEC2 could potentially be used as a biomarker for the improvement of the SE process and screen for elite varieties in cacao germplasm.

  18. Physisorption of aromatic organic contaminants at the surface of hydrophobic/hydrophilic silica geosorbents: a B3LYP-D modeling study.

    Science.gov (United States)

    Rimola, Albert; Civalleri, Bartolomeo; Ugliengo, Piero

    2010-06-28

    The adsorption of benzene and benzene-1,4-diol on two all-silica surface models derived from the framework of sanidine mineral with either hydrophobic or hydrophilic properties has been studied by means of periodic calculations based on local Gaussian basis function and the B3LYP-D functional, which includes dispersion contribution as an empirical correction to the pure B3LYP energy. The aromatic molecules have been docked on different adsorption sites of the two surfaces using the electrostatic potential of the separate parts as a guide to ensure the best matching between electrophilic/nucleophilic regions. The inclusion of dispersion in the definition of the functional method dramatically affects both the intermolecular geometries and the adsorption energies, these latter being, in all cases, underestimated without the inclusion of the dispersive contribution. The adsorption of the aromatic molecules on the hydrophobic silica surface is dictated by dispersion and weak CH...O(Si)O interactions. The entity of the interaction for benzene on the hydrophilic surface is close to the value of the sublimation energy of the benzene molecular crystal, thus showing that adsorbate self-aggregation and adsorption to the silica surface are competing processes. For hydrophilic surfaces dispersion is still large despite the fact that adsorption energies are almost doubled with respect to the hydrophobic surface due to H-bonding interactions through either SiOH...pi (benzene case) or SiOH...OH (benzene-1,4-diol case). The computed infrared spectra of the adsorbed molecules reveal small perturbations in the CH, CCH and CCC ring modes, which are sensitive to the adsorbate/adsorbent features, so that these bands can be used as fingerprints for the interpretation of experimental spectra. The present work may contribute to a better understanding of the sorption of typical organic contaminants in common earth's inorganic soils, which is of relevance for environmental concerns.

  19. Nicotinamide riboside, a form of vitamin B3 and NAD+ precursor, relieves the nociceptive and aversive dimensions of paclitaxel-induced peripheral neuropathy in female rats.

    Science.gov (United States)

    Hamity, Marta V; White, Stephanie R; Walder, Roxanne Y; Schmidt, Mark S; Brenner, Charles; Hammond, Donna L

    2017-05-01

    Injury to sensory afferents may contribute to the peripheral neuropathies that develop after administration of chemotherapeutic agents. Manipulations that increase levels of nicotinamide adenine dinucleotide (NAD) can protect against neuronal injury. This study examined whether nicotinamide riboside (NR), a third form of vitamin B3 and precursor of NAD, diminishes tactile hypersensitivity and place escape-avoidance behaviors in a rodent model of paclitaxel-induced peripheral neuropathy. Female Sprague-Dawley rats received 3 intravenous injections of 6.6 mg/kg paclitaxel over 5 days. Daily oral administration of 200 mg/kg NR beginning 7 days before paclitaxel treatment and continuing for another 24 days prevented the development of tactile hypersensitivity and blunted place escape-avoidance behaviors. These effects were sustained after a 2-week washout period. This dose of NR increased blood levels of NAD by 50%, did not interfere with the myelosuppressive effects of paclitaxel, and did not produce adverse locomotor effects. Treatment with 200 mg/kg NR for 3 weeks after paclitaxel reversed the well-established tactile hypersensitivity in a subset of rats and blunted escape-avoidance behaviors. Pretreatment with 100 mg/kg oral acetyl-L-carnitine (ALCAR) did not prevent paclitaxel-induced tactile hypersensitivity or blunt escape-avoidance behaviors. ALCAR by itself produced tactile hypersensitivity. These findings suggest that agents that increase NAD, a critical cofactor for mitochondrial oxidative phosphorylation systems and cellular redox systems involved with fuel utilization and energy metabolism, represent a novel therapeutic approach for relief of chemotherapy-induced peripheral neuropathies. Because NR is a vitamin B3 precursor of NAD and a nutritional supplement, clinical tests of this hypothesis may be accelerated.

  20. Soluble expression and purifiation of hepatitis B core antigen (HBcAg subgenotype B3 in Escherichia coli using thioredoxin fusion tag

    Directory of Open Access Journals (Sweden)

    Rahmah Waty

    2017-08-01

    Full Text Available Objective: To express HBcAg protein (hepatitis B virus subgenotype B3 in Escherichia coli in soluble form. Methods: HBcAg sequence of hepatitis B virus subgenotype B3 was cloned into plasmid pET32a and introduced to E. coli BL21 (DE3. The E. coli was grown in Luria-Bertani (LB medium supplemented with ampicillin with agitation. Protein expression was induced by adding isopropyl-β-D-thiogalactopyranoside (IPTG at concentrations of 0.1 mmol/L, 0.3 mmol/L, and 0.5 mmol/L at room temperature (28 °C. The bacteria were dissolved in lysis buffer and lysed by freeze-thawing method then sonication. The fusion protein [thioredoxin A-(His6tag-HBcAg] was purified using immobilized metal affinity chromatography. The protein expression was analyzed by SDS-PAGE, dot blot, and western blot. Results: This research showed that DNA sequence of HBcAg could be propagated in pET32a and soluble protein was successfully expressed in E. coli. Induction with 0.3 mmol/L IPTG and 4-hour incubation was the best condition to express the HBcAg protein. SDS-PAGE and dot blot analysis showed that HBcAg protein could be expressed in E. coli. Western blot analysis showed that molecular weight of HBcAg fusion protein was about 38.5 kDa. Conclusions: This study confirmed that HBcAg protein could be expressed in soluble form in E. coli.

  1. Survey of fumonisins B1, B2 and B3 in conventional and organic retail corn products in Spain and Italy and estimated dietary exposure.

    Science.gov (United States)

    D'Arco, G; Fernández-Franzón, M; Font, G; Damiani, P; Mañes, J

    2009-01-01

    A survey was conducted to determine the occurrence of fumonisin B1, B2 and B3 during 2007 in 186 samples of organic and conventional locally available corn products. Samples included baby food (n = 62), corn flour (11), cornflakes (23), pasta (14), cookies (17) and other corn products (59) were obtained from popular markets of Valencia (Spain) and Perugia (Italy). The analytical method used pressurized liquid extraction and liquid chromatography/electrospray ionization tandem mass spectrometry with a triple quadrupole (QqQ) analyser. Of the 104 Spanish samples, 22% contained levels in the range of 2-449 µg kg(-1), 2-229 µg kg(-1) and 6-105 µg kg(-1) for FB1, FB2 and FB3, respectively, while 19 (23%) of the 82 Italian samples were positive with quantifiable levels between 2-235 µg kg(-1), 3-187 µg kg(-1), and 4-40 µg kg(-1) for fumonisins B1, B2 and B3, respectively. Overall, none of the Italian samples and only one organic baby food sample from a Spanish market was above the maximum permitted levels established by European legislation. Fumonisins were found mostly in corn flour followed by cookies and cornflakes. Eleven samples from Spain and nine samples from Italy were organic products, being contaminated the 72% and 77% of the samples, respectively. Analysis of the results showed that levels of fumonisins in corn products were similar in Italy and Spain. The safety of fumonisin intake through corn products was demonstrated by the calculation of the estimated daily intake of both populations considering organic and conventional products separately, which ranged from 1.7 × 10(-3) to 0.72 µg kg(-1) bw day(-1) and comparing them with the provisional maximum total daily intake (PMTDI) of 2 µg kg(-1) bw day(-1) established by the European Union.

  2. Comparative molecular dynamics simulation of Hepatitis C Virus NS3/4A protease (Genotypes 1b, 3a and 4b predicts conformational instability of the catalytic triad in drug resistant strains.

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    Mitchell Kramer

    Full Text Available The protease domain of the Hepatitis C Virus (HCV nonstructural protein 3 (NS3 has been targeted for inhibition by several direct-acting antiviral drugs. This approach has had marked success to treat infections caused by HCV genotype 1 predominant in the USA, Europe, and Japan. However, genotypes 3 and 4, dominant in developing countries, are resistant to a number of these drugs and little progress has been made towards understanding the structural basis of their drug resistivity. We have previously developed a 4D computational methodology, based on 3D structure modeling and molecular dynamics simulation, to analyze the active sites of the NS3 proteases of HCV-1b and 4a in relation to their catalytic activity and drug susceptibility. Here, we improved the methodology, extended the analysis to include genotype 3a (predominant in South Asia including Pakistan, and compared the results of the three genotypes (1b, 3a and 4a. The 4D analyses of the interactions between the catalytic triad residues (His57, Asp81, and Ser139 indicate conformational instability of the catalytic site in HCV-3a and 4a compared to that of HCV-1b NS3 protease. The divergence is gradual and genotype-dependent, with HCV-1b being the most stable, HCV-4a being the most unstable and HCV-3a representing an intermediate state. These results suggest that the structural dynamics behavior, more than the rigid structure, could be related to the altered catalytic activity and drug susceptibility seen in NS3 proteases of HCV-3a and 4a.

  3. Comparative Molecular Dynamics Simulation of Hepatitis C Virus NS3/4A Protease (Genotypes 1b, 3a and 4a) Predicts Conformational Instability of the Catalytic Triad in Drug Resistant Strains

    Science.gov (United States)

    Kramer, Mitchell; Halleran, Daniel; Rahman, Moazur; Iqbal, Mazhar; Anwar, Muhammad Ikram; Sabet, Salwa; Ackad, Edward; Yousef, Mohammad

    2014-01-01

    The protease domain of the Hepatitis C Virus (HCV) nonstructural protein 3 (NS3) has been targeted for inhibition by several direct-acting antiviral drugs. This approach has had marked success to treat infections caused by HCV genotype 1 predominant in the USA, Europe, and Japan. However, genotypes 3 and 4, dominant in developing countries, are resistant to a number of these drugs and little progress has been made towards understanding the structural basis of their drug resistivity. We have previously developed a 4D computational methodology, based on 3D structure modeling and molecular dynamics simulation, to analyze the active sites of the NS3 proteases of HCV-1b and 4a in relation to their catalytic activity and drug susceptibility. Here, we improved the methodology, extended the analysis to include genotype 3a (predominant in South Asia including Pakistan), and compared the results of the three genotypes (1b, 3a and 4a). The 4D analyses of the interactions between the catalytic triad residues (His57, Asp81, and Ser139) indicate conformational instability of the catalytic site in HCV-3a and 4a compared to that of HCV-1b NS3 protease. The divergence is gradual and genotype-dependent, with HCV-1b being the most stable, HCV-4a being the most unstable and HCV-3a representing an intermediate state. These results suggest that the structural dynamics behavior, more than the rigid structure, could be related to the altered catalytic activity and drug susceptibility seen in NS3 proteases of HCV-3a and 4a. PMID:25111232

  4. Infective endocarditis.

    Science.gov (United States)

    Ferro, José M; Fonseca, Ana Catarina

    2014-01-01

    Infective endocarditis is a serious disease of the endocardium of the heart and cardiac valves, caused by a variety of infectious agents, ranging from streptococci to rickettsia. The proportion of cases associated with rheumatic valvulopathy and dental surgery has decreased in recent years, while endocarditis associated with intravenous drug abuse, prosthetic valves, degenerative valve disease, implanted cardiac devices, and iatrogenic or nosocomial infections has emerged. Endocarditis causes constitutional, cardiac and multiorgan symptoms and signs. The central nervous system can be affected in the form of meningitis, cerebritis, encephalopathy, seizures, brain abscess, ischemic embolic stroke, mycotic aneurysm, and subarachnoid or intracerebral hemorrhage. Stroke in endocarditis is an ominous prognostic sign. Treatment of endocarditis includes prolonged appropriate antimicrobial therapy and in selected cases, cardiac surgery. In ischemic stroke associated with infective endocarditis there is no indication to start antithrombotic drugs. In previously anticoagulated patients with an ischemic stroke, oral anticoagulants should be replaced by unfractionated heparin, while in intracranial hemorrhage, all anticoagulation should be interrupted. The majority of unruptured mycotic aneurysms can be treated by antibiotics, but for ruptured aneurysms, endovascular or neurosurgical therapy is indicated. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. A prognostic model of triple-negative breast cancer based on miR-27b-3p and node status.

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    Songjie Shen

    Full Text Available Triple-negative breast cancer (TNBC is an aggressive but heterogeneous subtype of breast cancer. This study aimed to identify and validate a prognostic signature for TNBC patients to improve prognostic capability and to guide individualized treatment.We retrospectively analyzed the prognostic performance of clinicopathological characteristics and miRNAs in a training set of 58 patients with invasive ductal TNBC diagnosed between 2002 and 2012. A prediction model was developed based on independent clinicopathological and miRNA covariates. The prognostic value of the model was further validated in a separate set of 41 TNBC patients diagnosed between 2007 and 2008.Only lymph node status was marginally significantly associated with poor prognosis of TNBC (P = 0.054, whereas other clinicopathological factors, including age, tumor size, histological grade, lymphovascular invasion, P53 status, Ki-67 index, and type of surgery, were not. The expression levels of miR-27b-3p, miR-107, and miR-103a-3p were significantly elevated in the metastatic group compared with the disease-free group (P value: 0.008, 0.005, and 0.050, respectively. The Cox proportional hazards regression analysis revealed that lymph node status and miR-27b-3p were independent predictors of poor prognosis (P value: 0.012 and 0.027, respectively. A logistic regression model was developed based on these two independent covariates, and the prognostic value of the model was subsequently confirmed in a separate validation set. The two different risk groups, which were stratified according to the model, showed significant differences in the rates of distant metastasis and breast cancer-related death not only in the training set (P value: 0.001 and 0.040, respectively but also in the validation set (P value: 0.013 and 0.012, respectively.This model based on miRNA and node status covariates may be used to stratify TNBC patients into different prognostic subgroups for potentially

  6. The Role of TRAF4 and B3GAT1 Gene Expression in the Food Hypersensitivity and Insect Venom Allergy in Mastocytosis.

    Science.gov (United States)

    Górska, Aleksandra; Gruchała-Niedoszytko, Marta; Niedoszytko, Marek; Maciejewska, Agnieszka; Chełmińska, Marta; Skrzypski, Marcin; Wasąg, Bartosz; Kaczkan, Małgorzata; Lange, Magdalena; Nedoszytko, Bogusław; Pawłowski, Ryszard; Małgorzewicz, Sylwia; Jassem, Ewa

    2016-12-01

    Mastocytosis is an uncommon disease classified as a myeloproliferative neoplasm, however, its symptoms are broad and place patients at crossroads between dermatology, hematology and allergology. Patients with mastocytosis often suffer from symptoms resulting from the activation and release of mediators from the mast cells, such as generalized itching, redness, headache, abdominal cramps, diarrhea, bone pain or arthritis, hypotension and shock. The possible severe, fatal or near fatal reactions caused by food hypersensitivity are reasons for the research focused on marker identification. The aim of the study was to analyse the gene expression differences in mastocytosis patients with and without food and drug hypersensitivity and insect venom allergy (IVA). A total of 57 Caucasian patients with mastocytosis were studied [median age 41.8; range 18-77 years; 15 (26.3 %) males and 42 (73.7 %) females]. Quantitative RT-PCRs of 11 genes plus ribosomal 18S RNA were run. Symptoms of food hypersensitivity were found in 12 patients (21 %), including 3 patients (13 %) with cutaneous mastocytosis (CM), and 9 (28 %) with indolent systemic mastocytosis (ISM). IVA was confirmed in 13 patients (22.8 %) including 6 patients (10.5 %) with CM, and 7 patients (12.3 %) with ISM. Drug hypersensitivity was diagnosed in 10 patients (17.5 %). Significant differences in the gene expression were found for TRAF4 (p = 0.008) in the comparison of the mastocytosis patients with and without concomitant food hypersensitivity. Furthermore significant differences were found in gene expression for B3GAT1 (p = 0.003) in patients with IVA compared to patients without insect sting anaphylaxis in the medical history. The expression of studied genes did not differ according to the presence of drug hypersensitivity. The TRAF4 expression was higher in mastocytosis patients with food hypersensitivity in their medical history, the B3GAT1 expression was lower in mastocytosis patients with IVA in

  7. The EGFR/ErbB3 Pathway Acts as a Compensatory Survival Mechanism upon c-Met Inhibition in Human c-Met+ Hepatocellular Carcinoma.

    Directory of Open Access Journals (Sweden)

    Steven N Steinway

    Full Text Available c-Met, a high-affinity receptor for Hepatocyte Growth Factor (HGF, plays a critical role in tumor growth, invasion, and metastasis. Hepatocellular carcinoma (HCC patients with activated HGF/c-Met signaling have a significantly worse prognosis. Targeted therapies using c-Met tyrosine kinase inhibitors are currently in clinical trials for HCC, although receptor tyrosine kinase inhibition in other cancers has demonstrated early success. Unfortunately, therapeutic effect is frequently not durable due to acquired resistance.We utilized the human MHCC97-H c-Met positive (c-Met+ HCC cell line to explore the compensatory survival mechanisms that are acquired after c-Met inhibition. MHCC97-H cells with stable c-Met knockdown (MHCC97-H c-Met KD cells were generated using a c-Met shRNA vector with puromycin selection and stably transfected scrambled shRNA as a control. Gene expression profiling was conducted, and protein expression was analyzed to characterize MHCC97-H cells after blockade of the c-Met oncogene. A high-throughput siRNA screen was performed to find putative compensatory survival proteins, which could drive HCC growth in the absence of c-Met. Findings from this screen were validated through subsequent analyses.We have previously demonstrated that treatment of MHCC97-H cells with a c-Met inhibitor, PHA665752, results in stasis of tumor growth in vivo. MHCC97-H c-Met KD cells demonstrate slower growth kinetics, similar to c-Met inhibitor treated tumors. Using gene expression profiling and siRNA screening against 873 kinases and phosphatases, we identified ErbB3 and TGF-α as compensatory survival factors that are upregulated after c-Met inhibition. Suppressing these factors in c-Met KD MHCC97-H cells suppresses tumor growth in vitro. In addition, we found that the PI3K/Akt signaling pathway serves as a negative feedback signal responsible for the ErbB3 upregulation after c-Met inhibition. Furthermore, in vitro studies demonstrate that

  8. Fish tapeworm infection

    Science.gov (United States)

    Fish tapeworm infection is an intestinal infection with the tapeworm parasite found in fish. ... The fish tapeworm ( Diphyllobothrium latum ) is the largest parasite that infects humans. Humans become infected when they eat raw or undercooked ...

  9. Yeast Infection (Vaginal)

    Science.gov (United States)

    ... vaginal discharge with a cottage cheese appearance Complicated yeast infection You might have a complicated yeast infection ... have an uncomplicated or a complicated infection. Uncomplicated yeast infection For mild to moderate symptoms and infrequent ...

  10. Tratamiento de las fracturas periprotésicas de cadera tipos B2 y B3 con tallos no cementados de fijación distal. [Treatment of types B2 and B3 periprosthetic hip fractures with distal fixation cementless stem].

    Directory of Open Access Journals (Sweden)

    Sebastian Pereira

    2016-11-01

    Full Text Available Introducción: La fractura periprotésica se encuentra en tercer lugar como causa mas frecuente de revisión de cadera por detrás del aflojamiento aséptico y la infección. Aquellas que se presentan asociadas a un tallo flojo (B2 o a un déficit de capital óseo (B3, deben ser tratadas con la revisión femoral. Materiales y Método: Se estudiaron retrospectivamente 38 pacientes con fracturas periprotésicas de fémur B2 y B3 tratadas con tallos no cementados de fijación distal sin injerto óseo ni placas de osteosíntesis. El tiempo de seguimiento promedio fue de 2.5 años (rango, 1.5 a10. Resultados: El puntaje promedio alcanzado en el HHS fue de 69 puntos (rango, 57-91. En todos los casos (100% se logró la consolidación ósea. La sobrevida libre de revisión fue del 94.8%. Las complicaciones fueron; 1 (2.6% hundimiento del tallo mayor a 5mm, 1 (2.6% luxación, 2 (5.2% infecciones , 1 (2.6% hematoma de la herida. Conclusiones: La técnica de revisión con tallos no cementados de fijación distal sin el aporte de injerto óseo  ha demostrados ser un método eficaz para el tratamiento de las fracturas periprotésicas de  cadera B2 y B3.

  11. Theoretical Calculation of Jet Fuel Thermochemistry. 1; Tetrahydrodicylopentadiene (JP10) Thermochemistry Using the CBS-QB3 and G3(MP2)//B3LYP Methods

    Science.gov (United States)

    Zehe, Michael J.; Jaffe, Richard L.

    2010-01-01

    High-level ab initio calculations have been performed on the exo and endo isomers of gas-phase tetrahydrodicyclopentadiene (THDCPD), a principal component of the jet fuel JP10, using the Gaussian Gx and Gx(MPx) composite methods, as well as the CBS-QB3 method, and using a variety of isodesmic and homodesmotic reaction schemes. The impetus for this work is to help resolve large discrepancies existing between literature measurements of the formation enthalpy Delta (sub f)H deg (298) for exo-THDCPD. We find that use of the isodesmic bond separation reaction C10H16 + 14CH4 yields 12C2H6 yields results for the exo isomer (JP10) in between the two experimentally accepted values, for the composite methods G3(MP2), G3(MP2)//B3LYP, and CBS-QB3. Application of this same isodesmic bond separation scheme to gas-phase adamantane yields a value for Delta (sub f)H deg (298) within 5 kJ/mol of experiment. Isodesmic bond separation calculations for the endo isomer give a heat of formation in excellent agreement with the experimental measurement. Combining our calculated values for the gas-phase heat of formation with recent measurements of the heat of vaporization yields recommended values for Delta (sub f)H deg (298)liq of -126.4 and -114.7 kJ/mol for the exo and endo isomers, respectively.

  12. Theoretical calculation of jet fuel thermochemistry. 1. Tetrahydrodicylopentadiene (JP10) thermochemistry using the CBS-QB3 and G3(MP2)//B3LYP methods.

    Science.gov (United States)

    Zehe, Michael J; Jaffe, Richard L

    2010-07-02

    High-level ab initio calculations have been performed on the exo and endo isomers of gas-phase tetrahydrodicyclopentadiene (THDCPD), a principal component of the jet fuel JP10, using the Gaussian G(x) and G(x)(MP(x)) composite methods, as well as the CBS-QB3 method, and using a variety of isodesmic and homodesmotic reaction schemes. The impetus for this work is to help resolve large discrepancies existing between literature measurements of the formation enthalpy Delta(f)H degrees (298) for exo-THDCPD. We find that use of the isodesmic bond separation reaction C(10)H(16) + 14CH(4) --> 12C(2)H(6) yields results for the exo isomer (JP10) in between the two experimentally accepted values, for the composite methods G3(MP2), G3(MP2)//B3LYP, and CBS-QB3. Application of this same isodesmic bond separation scheme to gas-phase adamantane yields a value for Delta(f)H degrees (298) within 5 kJ/mol of experiment. Isodesmic bond separation calculations for the endo isomer give a heat of formation in excellent agreement with the experimental measurement. Combining our calculated values for the gas-phase heat of formation with recent measurements of the heat of vaporization yields recommended values for Delta(f)H degrees (298)liq of -126.4 and -114.7 kJ/mol for the exo and endo isomers, respectively.

  13. B3LYP density functional calculations on the ground-state structure, elastic properties, and compression mechanism of α-ZrW2O8

    Science.gov (United States)

    Figueirêdo, C. A.; Perottoni, C. A.

    2007-05-01

    The structure of α-ZrW2O8 was optimized at different pressures and its elastic constants were calculated at the B3LYP density functional level of theory. Overall, the relative stiffnesses of the atomic bonds (and linkages), ranked in terms of bond compressibilities, decrease according to the sequence W-O>Zr⋯W>Zr-O . The tetrahedra around tungsten atoms are found to be much stiffer than the ZrO6 octahedra. These latter are, in fact, more compressible than the α-ZrW2O8 unit cell. The elastic constants calculated in the athermal limit are in excellent agreement with recent experimental results obtained near 0K . The α-ZrW2O8 compression mechanism around W1 and W2 atoms is quite different. While the former can be described essentially in terms of a correlated polyhedral rotation, the latter involves correlated rotation of the first coordination polyhedra and translation of WO4 units downward along the ⟨111⟩ axis. These modes of deformation should bear some resemblance to the low-energy modes responsible for the negative thermal expansion in zirconium tungstate, and thus could give some insight on the microscopic mechanism behind this phenomenon.

  14. The molecular structure of the borate mineral inderite Mg(H4B3O7)(OH) · 5H2O--a vibrational spectroscopic study.

    Science.gov (United States)

    Frost, Ray L; López, Andrés; Xi, Yunfei; Lima, Rosa Malena Fernandes; Scholz, Ricardo; Granja, Amanda

    2013-12-01

    We have undertaken a study of the mineral inderite Mg(H4B3O7)(OH) · 5H2O a hydrated hydroxy borate mineral of magnesium using scanning electron microscopy, thermogravimetry and vibrational spectroscopic techniques. The structure consists of [Formula: see text] soroborate groups and Mg(OH)2(H2O)4 octahedra interconnected into discrete molecules by the sharing of two OH groups. Thermogravimetry shows a mass loss of 47.2% at 137.5 °C, proving the mineral is thermally unstable. Raman bands at 954, 1047 and 1116 cm(-1) are assigned to the trigonal symmetric stretching mode. The two bands at 880 and 916 cm(-1) are attributed to the symmetric stretching mode of the tetrahedral boron. Both the Raman and infrared spectra of inderite show complexity. Raman bands are observed at 3052, 3233, 3330, 3392 attributed to water stretching vibrations and 3459 cm(-1) with sharper bands at 3459, 3530 and 3562 cm(-1) assigned to OH stretching vibrations. Vibrational spectroscopy is used to assess the molecular structure of inderite. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5).

    Science.gov (United States)

    Bousquet, J; Farrell, J; Crooks, G; Hellings, P; Bel, E H; Bewick, M; Chavannes, N H; de Sousa, J Correia; Cruz, A A; Haahtela, T; Joos, G; Khaltaev, N; Malva, J; Muraro, A; Nogues, M; Palkonen, S; Pedersen, S; Robalo-Cordeiro, C; Samolinski, B; Strandberg, T; Valiulis, A; Yorgancioglu, A; Zuberbier, T; Bedbrook, A; Aberer, W; Adachi, M; Agusti, A; Akdis, C A; Akdis, M; Ankri, J; Alonso, A; Annesi-Maesano, I; Ansotegui, I J; Anto, J M; Arnavielhe, S; Arshad, H; Bai, C; Baiardini, I; Bachert, C; Baigenzhin, A K; Barbara, C; Bateman, E D; Beghé, B; Kheder, A Ben; Bennoor, K S; Benson, M; Bergmann, K C; Bieber, T; Bindslev-Jensen, C; Bjermer, L; Blain, H; Blasi, F; Boner, A L; Bonini, M; Bonini, S; Bosnic-Anticevitch, S; Boulet, L P; Bourret, R; Bousquet, P J; Braido, F; Briggs, A H; Brightling, C E; Brozek, J; Buhl, R; Burney, P G; Bush, A; Caballero-Fonseca, F; Caimmi, D; Calderon, M A; Calverley, P M; Camargos, P A M; Canonica, G W; Camuzat, T; Carlsen, K H; Carr, W; Carriazo, A; Casale, T; Cepeda Sarabia, A M; Chatzi, L; Chen, Y Z; Chiron, R; Chkhartishvili, E; Chuchalin, A G; Chung, K F; Ciprandi, G; Cirule, I; Cox, L; Costa, D J; Custovic, A; Dahl, R; Dahlen, S E; Darsow, U; De Carlo, G; De Blay, F; Dedeu, T; Deleanu, D; De Manuel Keenoy, E; Demoly, P; Denburg, J A; Devillier, P; Didier, A; Dinh-Xuan, A T; Djukanovic, R; Dokic, D; Douagui, H; Dray, G; Dubakiene, R; Durham, S R; Dykewicz, M S; El-Gamal, Y; Emuzyte, R; Fabbri, L M; Fletcher, M; Fiocchi, A; Fink Wagner, A; Fonseca, J; Fokkens, W J; Forastiere, F; Frith, P; Gaga, M; Gamkrelidze, A; Garces, J; Garcia-Aymerich, J; Gemicioğlu, B; Gereda, J E; González Diaz, S; Gotua, M; Grisle, I; Grouse, L; Gutter, Z; Guzmán, M A; Heaney, L G; Hellquist-Dahl, B; Henderson, D; Hendry, A; Heinrich, J; Heve, D; Horak, F; Hourihane, J O' B; Howarth, P; Humbert, M; Hyland, M E; Illario, M; Ivancevich, J C; Jardim, J R; Jares, E J; Jeandel, C; Jenkins, C; Johnston, S L; Jonquet, O; Julge, K; Jung, K S; Just, J; Kaidashev, I; Kaitov, M R; Kalayci, O; Kalyoncu, A F; Keil, T; Keith, P K; Klimek, L; Koffi N'Goran, B; Kolek, V; Koppelman, G H; Kowalski, M L; Kull, I; Kuna, P; Kvedariene, V; Lambrecht, B; Lau, S; Larenas-Linnemann, D; Laune, D; Le, L T T; Lieberman, P; Lipworth, B; Li, J; Lodrup Carlsen, K; Louis, R; MacNee, W; Magard, Y; Magnan, A; Mahboub, B; Mair, A; Majer, I; Makela, M J; Manning, P; Mara, S; Marshall, G D; Masjedi, M R; Matignon, P; Maurer, M; Mavale-Manuel, S; Melén, E; Melo-Gomes, E; Meltzer, E O; Menzies-Gow, A; Merk, H; Michel, J P; Miculinic, N; Mihaltan, F; Milenkovic, B; Mohammad, G M Y; Molimard, M; Momas, I; Montilla-Santana, A; Morais-Almeida, M; Morgan, M; Mösges, R; Mullol, J; Nafti, S; Namazova-Baranova, L; Naclerio, R; Neou, A; Neffen, H; Nekam, K; Niggemann, B; Ninot, G; Nyembue, T D; O'Hehir, R E; Ohta, K; Okamoto, Y; Okubo, K; Ouedraogo, S; Paggiaro, P; Pali-Schöll, I; Panzner, P; Papadopoulos, N; Papi, A; Park, H S; Passalacqua, G; Pavord, I; Pawankar, R; Pengelly, R; Pfaar, O; Picard, R; Pigearias, B; Pin, I; Plavec, D; Poethig, D; Pohl, W; Popov, T A; Portejoie, F; Potter, P; Postma, D; Price, D; Rabe, K F; Raciborski, F; Radier Pontal, F; Repka-Ramirez, S; Reitamo, S; Rennard, S; Rodenas, F; Roberts, J; Roca, J; Rodriguez Mañas, L; Rolland, C; Roman Rodriguez, M; Romano, A; Rosado-Pinto, J; Rosario, N; Rosenwasser, L; Rottem, M; Ryan, D; Sanchez-Borges, M; Scadding, G K; Schunemann, H J; Serrano, E; Schmid-Grendelmeier, P; Schulz, H; Sheikh, A; Shields, M; Siafakas, N; Sibille, Y; Similowski, T; Simons, F E R; Sisul, J C; Skrindo, I; Smit, H A; Solé, D; Sooronbaev, T; Spranger, O; Stelmach, R; Sterk, P J; Sunyer, J; Thijs, C; To, T; Todo-Bom, A; Triggiani, M; Valenta, R; Valero, A L; Valia, E; Valovirta, E; Van Ganse, E; van Hage, M; Vandenplas, O; Vasankari, T; Vellas, B; Vestbo, J; Vezzani, G; Vichyanond, P; Viegi, G; Vogelmeier, C; Vontetsianos, T; Wagenmann, M; Wallaert, B; Walker, S; Wang, D Y; Wahn, U; Wickman, M; Williams, D M; Williams, S; Wright, J; Yawn, B P; Yiallouros, P K; Yusuf, O M; Zaidi, A; Zar, H J; Zernotti, M E; Zhang, L; Zhong, N; Zidarn, M; Mercier, J

    2016-01-01

    Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) focuses on the integrated care of chronic diseases. Area 5 (Care Pathways) was initiated using chronic respiratory diseases as a model. The chronic respiratory disease action plan includes (1) AIRWAYS integrated care pathways (ICPs), (2) the joint initiative between the Reference site MACVIA-LR (Contre les MAladies Chroniques pour un VIeillissement Actif) and ARIA (Allergic Rhinitis and its Impact on Asthma), (3) Commitments for Action to the European Innovation Partnership on Active and Healthy Ageing and the AIRWAYS ICPs network. It is deployed in collaboration with the World Health Organization Global Alliance against Chronic Respiratory Diseases (GARD). The European Innovation Partnership on Active and Healthy Ageing has proposed a 5-step framework for developing an individual scaling up strategy: (1) what to scale up: (1-a) databases of good practices, (1-b) assessment of viability of the scaling up of good practices, (1-c) classification of good practices for local replication and (2) how to scale up: (2-a) facilitating partnerships for scaling up, (2-b) implementation of key success factors and lessons learnt, including emerging technologies for individualised and predictive medicine. This strategy has already been applied to the chronic respiratory disease action plan of the European Innovation Partnership on Active and Healthy Ageing.

  16. Tuning the LUMO level of organic photovoltaic solar cells by conjugately fusing graphene flake: A DFT-B3LYP study

    Science.gov (United States)

    Ganji, M. Darvish; Tajbakhsh, M.; Kariminasab, M.; Alinezhad, H.

    2016-07-01

    The efficiency of polymer solar cells can be essentially enhanced by improving the performance of electron acceptor materials especially by increasing its lowest unoccupied molecular orbital (LUMO) level. To this aim, the electronic properties of an extremely π-extended system, graphene flake and functionalized graphene flake with phenyl-C-butyric methyl ester (PCBM) group, were investigated and compared with those of C60 ones. Several properties of phenyl-C61-butyric methyl ester ([C60]PCBM) derivatives have been calculated and compared against the experimental and other theoretical results. All geometrical and electronic structures calculations were carried out by using the density functional theory (DFT) method at the B3LYP level of theory. The results show that the phenyl ring of [C60]PCBM was substituted with the methoxy groups to increase the LUMO level of the respective system which is in agreement with other studies. We found that graphene flake functionalized by methoxy-PCBM group offer significant increase in the value of the LUMO energy level in comparison with C60 counterpart. Furthermore, the electrophilicity of this compound is lower than that of the other counterparts, which results in higher open circuit voltage (Voc) value in the photovoltaic device. These findings could provide fundamental insights in improving the Voc value as well as raising the LUMO levels of electron acceptor materials and may also serve as an alternative strategy to increase open circuit voltage in polymer solar cells.

  17. UGT1A1, SLCO1B1, and SLCO1B3 polymorphisms vs. neonatal hyperbilirubinemia: is there an association?

    Science.gov (United States)

    Alencastro de Azevedo, Laura; Reverbel da Silveira, Themis; Carvalho, Clarissa Gutierrez; Martins de Castro, Simone; Giugliani, Roberto; Matte, Ursula

    2012-08-01

    Jaundice is a physiological phenomenon; however, severe hyperbilirubinemia occurs in only 5 to 6% of the healthy newborn population. It has been suggested that genetic variation could enhance the risk of hyperbilirubinemia when coexpressed with other icterogenic conditions. The study included newborns with a gestational age of greater than 35 wk and weights greater than 2,000 g with indications for phototherapy. The polymorphisms from UGT1A1 (rs8175347), SLCO1B1 (rs4149056 and rs2306283), and SLCO1B3 (rs17680137 and rs2117032) were analyzed by capillary electrophoresis and hydrolysis probes. A total of 167 hyperbilirubinemic infants and 247 control subjects were enrolled. The gender, ABO incompatibility, birth weight, and gestational age differed between the groups, but the allelic and genotypic frequency of the polymorphisms from SLCO1B genes did not. In logistic regression, the ABO incompatibility, gestational age, and polymorphic T allele of rs2117032 remained in the model. The presence of this polymorphism seemed to provide protection from hyperbilirubinemia. The individuals who were homozygous for the G allele of rs2306283 and who were glucose 6-phosphate-dehydrogenase deficient were more frequent among the cases. Although genetic variation accounts for a good part of this condition, the association between different polymorphisms and environmental factors has yet to be explained.

  18. Multiple temperature effects on up-conversion fluorescences of Er3+-Y b3+-Mo6+ codoped TiO2 and high thermal sensitivity

    Directory of Open Access Journals (Sweden)

    B. S. Cao

    2015-08-01

    Full Text Available We report multiple temperature effects on green and red up-conversion emissions in Er3+-Y b3+-Mo6+ codoped TiO2 phosphors. With increasing temperature, the decrease of the red emission from 4F9/2→4I15/2, the increase of green emission from 2H11/2→4I15/2 and another unchanged green emission from 4S3/2→4I15/2 were simultaneously observed, which are explained by steady-state rate equations analysis. Due to different evolution with temperature of the two green emissions, higher thermal sensitivity of optical thermal sensor was obtained based on the transitions with the largest fluorescence intensity ratio. Two parameters, maximum theoretical sensitivity (Smax and optimum operating temperature (Tmax are given to describe thermal sensing properties of the produced sensors. The intensity ratio and energy difference ΔE of a pair of energy levels are two main factors for the sensitivity and accuracy of sensors, which should be referred to design sensors with optimized sensing properties.

  19. Observation of Ortho-Para Dependence of Pressure Broadening Coefficient in Acetylene νb{1}+νb{3} Vibration Band Using Dual-Comb Spectroscopy

    Science.gov (United States)

    Iwakuni, Kana; Okubo, Sho; Inaba, Hajime; Onae, Atsushi; Hong, Feng-Lei; Sasada, Hiroyuki; Yamada, Koichi MT

    2016-06-01

    We observe that the pressure-broadening coefficients depend on the ortho-para levels. The spectrum is taken with a dual-comb spectrometer which has the resolution of 48 MHz and the frequency accuracy of 8 digit when the signal-to-noise ratio is more than 20. In this study, about 4.4-Tz wide spectra of the P(31) to R(31) transitions in the νb{1}+νb{3} vibration band of 12C_2H_2 are observed at the pressure of 25, 60, 396, 1047, 1962 and 2654 Pa. Each rotation-vibration absorption line is fitted to Voight function and we determined pressure-broadening coefficients for each rotation-vibration transition. The Figure shows pressure broadening coefficient as a function of m. Here m is J"+1 for R and -J" for P-branch. The graph shows obvious dependence on ortho and para. We fit it to Pade function considering the population ratio of three-to-one for the ortho and para levels. This would lead to detailed understanding of the pressure boarding mechanism. S. Okubo et al., Applied Physics Express 8, 082402 (2015)

  20. TINAGL1 and B3GALNT1 are potential therapy target genes to suppress metastasis in non-small cell lung cancer.

    Science.gov (United States)

    Umeyama, Hideaki; Iwadate, Mitsuo; Taguchi, Y-h

    2014-01-01

    Non-small cell lung cancer (NSCLC) remains lethal despite the development of numerous drug therapy technologies. About 85% to 90% of lung cancers are NSCLC and the 5-year survival rate is at best still below 50%. Thus, it is important to find drugable target genes for NSCLC to develop an effective therapy for NSCLC. Integrated analysis of publically available gene expression and promoter methylation patterns of two highly aggressive NSCLC cell lines generated by in vivo selection was performed. We selected eleven critical genes that may mediate metastasis using recently proposed principal component analysis based unsupervised feature extraction. The eleven selected genes were significantly related to cancer diagnosis. The tertiary protein structure of the selected genes was inferred by Full Automatic Modeling System, a profile-based protein structure inference software, to determine protein functions and to specify genes that could be potential drug targets. We identified eleven potentially critical genes that may mediate NSCLC metastasis using bioinformatic analysis of publically available data sets. These genes are potential target genes for the therapy of NSCLC. Among the eleven genes, TINAGL1 and B3GALNT1 are possible candidates for drug compounds that inhibit their gene expression.

  1. Virus Infection

    Directory of Open Access Journals (Sweden)

    Hiroshi Abe

    2013-01-01

    Full Text Available Of 168 patients with chronic hepatitis B virus (HBV infection-related liver disease, 20 patients who had received 100 mg of lamivudine plus 10 mg/day of adefovir dipivoxil (ADV (ADV group and 124 patients who had received 0.5 mg/day of entecavir or 100 mg/day of lamivudine (non-ADV group for >1 year were enrolled. For comparative analyses, 19 well-matched pairs were obtained from the groups by propensity scores. At the time of enrollment, serum creatinine and phosphate concentrations were similar between the ADV and non-ADV groups; however, urinary phosphate ( and serum bone-specific alkaline phosphatase (BAP ( concentrations were significantly higher in the ADV group than in the non-ADV group. Serum BAP was significantly higher at the time of enrollment than before ADV administration in the ADV group (, although there was no significant change in serum BAP concentration in the non-ADV group. There was a significant positive correlation between the period of ADV therapy and ΔBAP (, . Serum BAP concentration increased before increase in serum creatinine concentration and was useful for early detection of adverse events and for developing adequate measures for continuing ADV for chronic HBV infection-related liver disease.

  2. Integral cross sections for the direct excitation of the A 3 (sigma) u +, B 3 (pi) g, W 3 (delta) u, B' 3 (sigma) u -, a' 1 (sigma) u -, a 1 (pi) g, w 1 (delta) u, and C 3 (pi) u electronic states in

    Science.gov (United States)

    Johnson, P. V.; Malone, C. P.; Kanik, I.

    2005-01-01

    Integral cross sections for electron impact excitation out of the ground state (X 1(sigma)g +) to the A 3(sigma)u +, B 3(pi)g, W 3(delta)u, B' 3(sigma)u -, a' 1(sigma)u -, a 1(pi)g, w 1(delta)u, and states in N2 are reported at incident energies ranging between 10 and 100 eV. These data have been derived by integrating differential cross sections previously reported by this group. New differential cross section measurements for the a 1(pi)g state at 200 eV are also presented to extend the range of the reported integral cross sections for this state, which is responsible for the emissions of the Lyman-Birge-Hopfield band system (a 1(pi)g (rightwards arrow) X 1(sigma)g +). The present results are compared and critically evaluated against existing cross sec In general, the present cross sections are smaller than previous results at low impact energies from threshold through the excitation function peak regions. These lower cross sections have potentially significant implications on our understanding of UV emissions in the atmospheres of Earth and Titan.

  3. Meta-analysis of genome-wide association studies identifies common susceptibility polymorphisms for colorectal and endometrial cancer near SH2B3 and TSHZ1

    Science.gov (United States)

    Cheng, Timothy HT; Thompson, Deborah; Painter, Jodie; O’Mara, Tracy; Gorman, Maggie; Martin, Lynn; Palles, Claire; Jones, Angela; Buchanan, Daniel D.; Ko Win, Aung; Hopper, John; Jenkins, Mark; Lindor, Noralane M.; Newcomb, Polly A.; Gallinger, Steve; Conti, David; Schumacher, Fred; Casey, Graham; Giles, Graham G; Pharoah, Paul; Peto, Julian; Cox, Angela; Swerdlow, Anthony; Couch, Fergus; Cunningham, Julie M; Goode, Ellen L; Winham, Stacey J; Lambrechts, Diether; Fasching, Peter; Burwinkel, Barbara; Brenner, Hermann; Brauch, Hiltrud; Chang-Claude, Jenny; Salvesen, Helga B.; Kristensen, Vessela; Darabi, Hatef; Li, Jingmei; Liu, Tao; Lindblom, Annika; Hall, Per; de Polanco, Magdalena Echeverry; Sans, Monica; Carracedo, Angel; Castellvi-Bel, Sergi; Rojas-Martinez, Augusto; Aguiar Jnr, Samuel; Teixeira, Manuel R.; Dunning, Alison M; Dennis, Joe; Otton, Geoffrey; Proietto, Tony; Holliday, Elizabeth; Attia, John; Ashton, Katie; Scott, Rodney J; McEvoy, Mark; Dowdy, Sean C; Fridley, Brooke L; Werner, Henrica MJ; Trovik, Jone; Njolstad, Tormund S; Tham, Emma; Mints, Miriam; Runnebaum, Ingo; Hillemanns, Peter; Dörk, Thilo; Amant, Frederic; Schrauwen, Stefanie; Hein, Alexander; Beckmann, Matthias W; Ekici, Arif; Czene, Kamila; Meindl, Alfons; Bolla, Manjeet K; Michailidou, Kyriaki; Tyrer, Jonathan P; Wang, Qin; Ahmed, Shahana; Healey, Catherine S; Shah, Mitul; Annibali, Daniela; Depreeuw, Jeroen; Al-Tassan, Nada A.; Harris, Rebecca; Meyer, Brian F.; Whiffin, Nicola; Hosking, Fay J; Kinnersley, Ben; Farrington, Susan M.; Timofeeva, Maria; Tenesa, Albert; Campbell, Harry; Haile, Robert W.; Hodgson, Shirley; Carvajal-Carmona, Luis; Cheadle, Jeremy P.; Easton, Douglas; Dunlop, Malcolm; Houlston, Richard; Spurdle, Amanda; Tomlinson, Ian

    2015-01-01

    High-risk mutations in several genes predispose to both colorectal cancer (CRC) and endometrial cancer (EC). We therefore hypothesised that some lower-risk genetic variants might also predispose to both CRC and EC. Using CRC and EC genome-wide association series, totalling 13,265 cancer cases and 40,245 controls, we found that the protective allele [G] at one previously-identified CRC polymorphism, rs2736100 near TERT, was associated with EC risk (odds ratio (OR) = 1.08, P = 0.000167); this polymorphism influences the risk of several other cancers. A further CRC polymorphism near TERC also showed evidence of association with EC (OR = 0.92; P = 0.03). Overall, however, there was no good evidence that the set of CRC polymorphisms was associated with EC risk, and neither of two previously-reported EC polymorphisms was associated with CRC risk. A combined analysis revealed one genome-wide significant polymorphism, rs3184504, on chromosome 12q24 (OR = 1.10, P = 7.23 × 10−9) with shared effects on CRC and EC risk. This polymorphism, a missense variant in the gene SH2B3, is also associated with haematological and autoimmune disorders, suggesting that it influences cancer risk through the immune response. Another polymorphism, rs12970291 near gene TSHZ1, was associated with both CRC and EC (OR = 1.26, P = 4.82 × 10−8), with the alleles showing opposite effects on the risks of the two cancers. PMID:26621817

  4. Small tyrosine kinase inhibitors interrupt EGFR signaling by interacting with erbB3 and erbB4 in glioblastoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Carrasco-Garcia, Estefania; Saceda, Miguel [Instituto de Biologia Molecular y Celular, Universidad Miguel Hernandez, 03202 Elche (Alicante) (Spain); Unidad de Investigacion, Hospital General Universitario de Elche, 03203 Elche (Alicante) (Spain); Grasso, Silvina; Rocamora-Reverte, Lourdes; Conde, Mariano; Gomez-Martinez, Angeles [Instituto de Biologia Molecular y Celular, Universidad Miguel Hernandez, 03202 Elche (Alicante) (Spain); Garcia-Morales, Pilar [Instituto de Biologia Molecular y Celular, Universidad Miguel Hernandez, 03202 Elche (Alicante) (Spain); Unidad de Investigacion, Hospital General Universitario de Elche, 03203 Elche (Alicante) (Spain); Ferragut, Jose A. [Instituto de Biologia Molecular y Celular, Universidad Miguel Hernandez, 03202 Elche (Alicante) (Spain); Martinez-Lacaci, Isabel, E-mail: imlacaci@umh.es [Instituto de Biologia Molecular y Celular, Universidad Miguel Hernandez, 03202 Elche (Alicante) (Spain); Unidad AECC de Investigacion Traslacional en Cancer, Hospital Universitario Virgen de la Arrixaca, 30120 Murcia (Spain)

    2011-06-10

    Signaling through the epidermal growth factor receptor (EGFR) is relevant in glioblastoma. We have determined the effects of the EGFR inhibitor AG1478 in glioblastoma cell lines and found that U87 and LN-229 cells were very sensitive to this drug, since their proliferation diminished and underwent a marked G{sub 1} arrest. T98 cells were a little more refractory to growth inhibition and A172 cells did not undergo a G{sub 1} arrest. This G{sub 1} arrest was associated with up-regulation of p27{sup kip1}, whose protein turnover was stabilized. EGFR autophosphorylation was blocked with AG1478 to the same extent in all the cell lines. Other small-molecule EGFR tyrosine kinase inhibitors employed in the clinic, such as gefitinib, erlotinib and lapatinib, were able to abrogate proliferation of glioblastoma cell lines, which underwent a G{sub 1} arrest. However, the EGFR monoclonal antibody, cetuximab had no effect on cell proliferation and consistently, had no effect on cell cycle either. Similarly, cetuximab did not inhibit proliferation of U87 {Delta}EGFR cells or primary glioblastoma cell cultures, whereas small-molecule EGFR inhibitors did. Activity of downstream signaling molecules of EGFR such as Akt and especially ERK1/2 was interrupted with EGFR tyrosine kinase inhibitors, whereas cetuximab treatment could not sustain this blockade over time. Small-molecule EGFR inhibitors were able to prevent phosphorylation of erbB3 and erbB4, whereas cetuximab only hindered EGFR phosphorylation, suggesting that EGFR tyrosine kinase inhibitors may mediate their anti-proliferative effects through other erbB family members. We can conclude that small-molecule EGFR inhibitors may be a therapeutic approach for the treatment of glioblastoma patients.

  5. Escherichia coli Infections.

    Science.gov (United States)

    Makvana, Sejal; Krilov, Leonard R

    2015-04-01

    Virulent strains of Escherichia coli are responsible for most diarrheal infections, meningitis, septicemia, and urinary tract infections in children worldwide. Clinicians must learn to recognize, treat, and prevent these infections. After completing this article, readers should be able to: 1. Describe the epidemiology of E coli infections. 2. Recognize the clinical features of E coli infections, including the O157: H7 strain. 3. Appropriately treat children with various types of E coli infections. 4. Understand ways to prevent E coli infections.

  6. Monkeypoxvirus infections.

    Science.gov (United States)

    Pattyn, S R

    2000-04-01

    During and after the smallpox eradication campaign, human cases of monkeypox appeared in West and Central Africa, as isolated cases or as small epidemics. Since inter-human transmission has never or only very exceptionally been documented, monkeypox does not represent a serious threat to humans. The virus reservoir is among tree squirrels living in the tropical rain forests of Africa and humans are infected by hunting, killing and skinning these animals. However, the modernization of society lessens human contact with the virus reservoir. Since the eradication of smallpox, stocks of variola virus have been maintained; whether these stocks should now be destroyed is a political question, which is seriously compromised by mistrust between countries.

  7. Arenavirus Infections

    Directory of Open Access Journals (Sweden)

    Salim Mattar V

    2017-05-01

    Full Text Available The infectious syndromes associated with arenaviruses in South America are four: febrile syndrome of viral origin; Haemorrhagic fevers with or without neurological involvement; Aseptic meningitis and meningo-encephalitis. Among the Arenavirus of the new world is the Tacaribe complex where the viruses are found: Junín (Argentina, Guanarito (Venezuela, Machupo (Bolivia and Sabiá (Brazil, which are characterized by hemorrhagic fevers. In Colombia the arenavirus Pichindé was isolated in 1965, from the rodent Oryzomys albigularis, in the valley of Pichindé (Valle del Cauca. This arenavirus produces a persistent infection in its host and is not pathogenic for the man. There is evidence of the circulation of the Guanarito virus in rodents from Córdoba, but there are no cases diagnosed in humans; In Colombia, the genome of the lymphocytic choriomeningitis virus was detected in the brains of rodents Mus musculus. The diagnosis is based on the knowledge of local epidemiology and the suspicion of a patient with fever in endemic areas, where infections such as malaria, dengue and leptospirosis, sepsis of bacterial origin and rickectomy have been excluded. Virus isolation in the feverish period is the gold standart, but it implies contact with the virus that is highly infectious, which represents a public health problem. Serology has been used for diagnosis, but there is no commercial evidence and only research groups and large public health laboratories have these tests. Most of the patients present a moderate severity, which needs adequate hydration, antipyretics and anti-inflammatories. All patients with severe signs should be aggressively treated. The use of drugs has not demonstrated a decrease in mortality but a significant reduction in viremia.

  8. Structural insight into the specificity of the B3 DNA-binding domains provided by the co-crystal structure of the C-terminal fragment of BfiI restriction enzyme.

    Science.gov (United States)

    Golovenko, Dmitrij; Manakova, Elena; Zakrys, Linas; Zaremba, Mindaugas; Sasnauskas, Giedrius; Gražulis, Saulius; Siksnys, Virginijus

    2014-04-01

    The B3 DNA-binding domains (DBDs) of plant transcription factors (TF) and DBDs of EcoRII and BfiI restriction endonucleases (EcoRII-N and BfiI-C) share a common structural fold, classified as the DNA-binding pseudobarrel. The B3 DBDs in the plant TFs recognize a diverse set of target sequences. The only available co-crystal structure of the B3-like DBD is that of EcoRII-N (recognition sequence 5'-CCTGG-3'). In order to understand the structural and molecular mechanisms of specificity of B3 DBDs, we have solved the crystal structure of BfiI-C (recognition sequence 5'-ACTGGG-3') complexed with 12-bp cognate oligoduplex. Structural comparison of BfiI-C-DNA and EcoRII-N-DNA complexes reveals a conserved DNA-binding mode and a conserved pattern of interactions with the phosphodiester backbone. The determinants of the target specificity are located in the loops that emanate from the conserved structural core. The BfiI-C-DNA structure presented here expands a range of templates for modeling of the DNA-bound complexes of the B3 family of plant TFs.

  9. MOLECULAR MODELING STUDY OF THE CONTRIBUTIONS OF SIDE AMINO ACID RESIDUES OF POLYMYXIN B3 TO ITS BINDING WITH E.COLI OUTER MEMBRANE LIPOPOLYSACCHARIDE

    Directory of Open Access Journals (Sweden)

    Lisnyak Yu. V.

    2014-12-01

    Full Text Available Last decades, antimicrobial peptides (AMPs are the subject of intense investigations aimed to develop effective drugs against extremely resistant nosocomial bacterial pathogens (especially Gram-negative bacteria. In particular, there has been greatly renewed interest to polymyxins, the representatives of AMPs which are specific and highly potent against Gram-negative bacteria, but have potential nephrotoxic side effect. A prerequisite of purposeful enhancement of therapeutic properties of polymyxins is a detailed knowledge of the molecular mechanisms of their interactions with cell targets. Lipopolysaccharide (LPS, the main component of the outer leaflet of outer membrane of gram-negative bacteria, is a primary cell target of polymyxins. The aim of the paper was to study the peculiarities of molecular interactions of polymyxin В3 with lipopolysaccharide of the outer membrane of gram-negative bacterium. Materials and methods The complexes of polymyxin В3 (PmВ3 and its alaninederivatives with E. coli outer membrane lipopolysaccharide were built and studied by molecular modeling methods (minimization, simulated annealing, docking. Atom coordinates of polymyxin В3 and LPS structures were taken from nuclear magnetic resonance and X-ray crystallography experiments, respectively. The AMBER03 force field was used with a 1.05 nm force cutoff. Longrange electrostatic interactions were treated by the Particle Mesh Ewald method. Results and discussion Alanine scanning of PmВ3 molecule has been carried out and the role of its side amino acid residues in the formation of complex with lipopolysaccharide has been investigated. It has been shown that substitutions of polymyxin’s Dab residues in positions 1, 3, 5, 8 and 9 for alanine markedly reduce the binding energy of PmB3-LPS complex, where as the similar substitutions of residues in positions 2, 6, 7 and 10 leave the binding energy virtually unchanged. Structural aspects of antimicrobial action of

  10. Conjugated polymers based on benzo[2,1-b:3,4-b']dithiophene with low-lying highest occupied molecular orbital energy levels for organic photovoltaics.

    Science.gov (United States)

    Xiao, Shengqiang; Stuart, Andrew C; Liu, Shubin; You, Wei

    2009-07-01

    Fusing bithiophene units with a benzo moiety, benzo[2,1-b:3,4-b']dithiophene (BDT), was projected by theoretical calculations to lower the highest occupied molecular orbital (HOMO) energy level of the resulting polymers compared with that of the bithiophene unit, which would enhance the open circuit voltage of bulk heterojunction photovoltaic cells fabricated from BDT-based polymers blended with PCBM. The homopolymer of BDT (HMPBDT) and alternating copolymer of BDT with 2,1,3-benzothiadiazole (PBDT-BT) were therefore synthesized and fully characterized. Both the homopolymer (HMPBDT) and the copolymer (PBDT-BT) were experimentally confirmed to have low HOMO energy levels (-5.70 eV for HMPBDT and -5.34 eV for PBDT-BT). Introducing the acceptor moiety (2,1,3-benzothiadiazole) successfully lowered the optical band gap of the copolymer from 2.31 eV (HMPBDT) to 1.78 eV (PBDT-BT). Bulk heterojunction photovoltaic devices were fabricated from blends of these structurally related polymers with PBCM to investigate the photovoltaic performances. The optimized device of HMPBDT:PCBM (1:3, 180 nm) exhibited an improved open circuit voltage (V(oc)) of 0.76 V, a short circuit current (J(sc)) of 0.34 mA/cm(2), and a fill factor (FF) of 0.40, offering an overall efficiency of 0.10%. The observed large phase separation of the thin film by AFM and the large band gap were accountable for the small current. The optimized device of PBDT-BT:PCBM (1:3, 55 nm) demonstrated a better efficiency of 0.6%, with V(oc) = 0.72 V, J(sc) = 2.06 mA/cm(2), and FF = 0.42. The much improved current was attributed to the lower bandgap and better film morphology. However, the low hole mobility limited the thickness of the PBDT-BT:PCBM film, making inaccessible the thicker film which would utilize more light and enhance the current. Further improvements are expected if the mobility and film morphology can be improved by the new materials design, together with low band gap and low HOMO energy level.

  11. Interstellar H adsorption and H₂ formation on the crystalline (010) forsterite surface: a B3LYP-D2* periodic study.

    Science.gov (United States)

    Navarro-Ruiz, Javier; Sodupe, Mariona; Ugliengo, Piero; Rimola, Albert

    2014-09-07

    The physisorption/chemisorption of atomic hydrogen on a slab model of the Mg2SiO4 forsterite (010) surface mimicking the interstellar dust particle surface has been modeled using a quantum mechanical approach based on periodic B3LYP-D2* density functional calculations (DFT) combined with flexible polarized Gaussian type basis sets, which allows a balanced description of the hydrogen/surface interactions for both minima and activated complexes. Physisorption of hydrogen is barrierless, very weak and occurs either close to surface oxygen atoms or on Mg surface ions. The contribution of dispersion interactions accounts for almost half of the adsorption energy. Both the hydrogen adsorption energy and barrier to hydrogen jump between equivalent surface sites are overestimated compared to experimental results meant to simulate the interstellar conditions in the laboratory. The hydrogen atom exclusively chemisorbs at the oxygen site of the forsterite (010) surface, forming a SiOH surface group and its spin density being entirely transferred to the neighboring Mg ion. Barrier for chemisorption allows rapid attachment of H at the surface at 100 K, but prevents the same process from occurring at 10 K. From this H-chemisorbed state, the second hydrogen chemisorption mainly occurs on the neighboring Mg ion, thus forming a Mg-H surface group, giving rise to a surface species stabilized by favorable electrostatic interactions between the OHH-Mg pair. The formation of molecular hydrogen at the (010) forsterite surface adopting a Langmuir-Hinshelwood mechanism takes place either starting from two physisorbed H atoms with an almost negligible kinetic barrier through a spin-spin coupling driven reaction or from two chemisorbed H atoms with a barrier surmountable even at T higher than 10 K. We also suggest that a nanosized model of the interstellar dust built from a replica of the forsterite unit cell is able to adsorb half the energy released by the H2 formation by increasing its

  12. Safety and efficacy of uric acid in patients with acute stroke (URICO-ICTUS): a randomised, double-blind phase 2b/3 trial.

    Science.gov (United States)

    Chamorro, Angel; Amaro, Sergio; Castellanos, Mar; Segura, Tomás; Arenillas, Juan; Martí-Fábregas, Joan; Gállego, Jaime; Krupinski, Jurek; Gomis, Meritxell; Cánovas, David; Carné, Xavier; Deulofeu, Ramón; Román, Luis San; Oleaga, Laura; Torres, Ferran; Planas, Anna M

    2014-05-01

    Uric acid is an antioxidant with neuroprotective effects in experimental models of stroke. We assessed whether uric acid therapy would improve functional outcomes at 90 days in patients with acute ischaemic stroke. URICO-ICTUS was a randomised, double-blind, placebo-controlled, phase 2b/3 trial that recruited patients with acute ischaemic stroke admitted to ten Spanish stroke centres. Patients were included if they were aged 18 years or older, had received alteplase within 4·5 h of symptom onset, and had an eligible National Institutes of Health Stroke Scale (NIHSS) score (>6 and ≤25) and premorbid (assessed by anamnesis) modified Rankin Scale (mRS) score (≤2). Patients were randomly allocated (1:1) to receive uric acid 1000 mg or placebo (both infused intravenously in 90 min during the infusion of alteplase), stratified by centre and baseline stroke severity. The primary outcome was the proportion of patients with excellent outcome (ie, an mRS score of 0-1, or 2 if premorbid score was 2) at 90 days, analysed in the target population (all randomly assigned patients who had been correctly diagnosed with ischaemic stroke and had begun study medication). The study is registered with ClinicalTrials.gov, number NCT00860366. Between July 1, 2011, and April 30, 2013, we randomly assigned 421 patients, of whom 411 (98%) were included in the target population (211 received uric acid and 200 received placebo). 83 (39%) patients who received uric acid and 66 (33%) patients who received placebo had an excellent outcome (adjusted risk ratio 1·23 [95% CI 0·96-1·56]; p=0·099). No clinically relevant or statistically significant differences were reported between groups with respect to death (28 [13%] patients who received uric acid vs 31 [16%] who received placebo), symptomatic intracerebral haemorrhage (nine [4%] vs six [3%]), and gouty arthritis (one [<1%] vs four [2%]). 516 adverse events occurred in the uric acid group and 532 in the placebo group, of which 61 (12

  13. Hantavirus Infections

    Directory of Open Access Journals (Sweden)

    Camilo Guzmán T

    2017-05-01

    Full Text Available Hantaviruses are the causative agents of hantavirus pulmonary syndrome in humans in the Americas; The primary reservoirs are in the rodents of the subfamily Sigmodontinae. In South America, cases of hantavirus pulmonary syndrome caused by numerous viral genotypes have been diagnosed. In Colombia, different serological studies have reported the circulation of hantavirus in humans and rodents. These viruses act in an intimate association with a rodent species that serves as a reservoir and have a distribution around the wild rodent, being limited to a specific geographic region. In South America, the first HPS-associated hantavirus was described in 1993 in Brazil and was called Juquitiva and from 1993 to 2012, more than 1400 cases had been identified in Brazil. This syndrome should be suspected in all patients with respiratory distress syndrome of unclear etiology, in areas endemic for the disease, especially if accompanied by fever, marked leukocytosis and thrombocytopenia and bilateral interstitial infiltrates. Hemorrhagic febrile syndrome has not yet been described in the Americas. There are no clinical or laboratory signs that are pathognomonic of hantavirus infection. The treatment is based on adequate hydration, use of antipyretics and anti-inflammatories and patients with signs of severity should establish a more aggressive management. Triage is indispensable, patients with co-morbidities have a higher mortality risk and therefore should be hospitalized. Future research in Colombia should be directed to multidisciplinary studies that include viral isolation, different clinical forms of case presentation, epidemiological differences, risk factors, and taxonomy of viruses and rodents.

  14. Characterization of a monoclonal antibody against the 3D polymerase of enterovirus 71 and its use for the detection of human enterovirus A infection.

    Science.gov (United States)

    Kiener, Tanja K; Lim, Xiao Fang; Jia, Qiang; Meng, Tao; Chow, Vincent Tak Kwong; Kwang, Jimmy

    2012-03-01

    Over the last decade, frequent epidemic outbreaks of hand, foot and mouth disease have been observed in the Asia-Pacific region. Hand, foot and mouth disease is caused by different viruses from the enterovirus family, mainly coxsackievirus A16 and enterovirus 71 (EV71) from the human enterovirus A family. Severe disease and neurological complications are associated more often with EV71 infection, and can lead occasionally to fatal brain stem encephalitis in young children. The rapid progression and high mortality of severe hand, foot and mouth disease makes the direct detection of antigens early in infection essential. The best method for virus detection is the use of specific monoclonal antibodies. The generation and characterization of a monoclonal antibody specific for the 3D polymerase of human enterovirus A and the development of a virus detection dot blot assay are described. A recombinant 3CD protein from EV71 C4 strain was used as an immunogen to generate monoclonal antibodies (MAbs). Screening of hybridoma cells led to the isolation of monoclonal antibody 4B12 of the immunoglobulin IgG1 isotype. MAb 4B12 recognizes the linear epitope DFEQALFS close to the active site of the 3D polymerase, corresponding to amino acid positions 53-60 of 3D and 1784-1791 of enterovirus 71 polyprotein. The presence of 3D polymerase and its precursor 3CD proteinase in purified virus particles was confirmed. MAb 4B12 was used successfully to detect all enterovirus 71 subgenotypes in a denaturing dot blot assay with a sensitivity of 10 pg of 3D protein and 10(4) tissue culture infective dose of virus particles. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Imaging of deep venous thrombosis in patients using a radiolabelled anti-D-dimer Fab' fragment ({sup 99m}Tc-DI-DD3B6/22-80B3): results of a phase I trial

    Energy Technology Data Exchange (ETDEWEB)

    Macfarlane, David [University of Queensland, School of Medicine, Brisbane (Australia); Socrates, Angelides; Larcos, George [University of Sydney, Department of Medicine, Sydney (Australia)]|[Westmead Hospital, Department of Nuclear Medicine and Ultrasound, Westmead (Australia)]|[Westmead Hospital, Centre for Biomedical Imaging and Research, Westmead (Australia); Eisenberg, Paul [Amgen Inc, Thousand Oaks, CA (United States); Roach, Paul [University of Sydney, Department of Medicine, Sydney (Australia)]|[Royal North Shore Hospital, Nuclear Medicine, St. Leonards (Australia); Gerometta, Michael [Agen Biomedical Pty Ltd, Brisbane (Australia); Smart, Richard; Tsui, Wendy [St. George Hospital, Nuclear Medicine Department, Sydney (Australia)]|[University of New South Wales, Department of Medicine, Sydney (Australia); Scott, Andrew M. [Austin Hospital, Centre for PET, Melbourne (Australia)]|[Ludwig Institute, Melbourne (Australia)

    2009-02-15

    {sup 99m}Tc-DI-DD3B6/22-80B3 (ThromboView registered, hereafter abbreviated to {sup 99m}Tc-DI-80B3 Fab') is a radiolabelled humanised monoclonal Fab' fragment with affinity and specificity for D-dimer domains of cross-linked fibrin. Detection of thromboembolic events has been demonstrated in canine models. The study objectives were evaluation of safety and characterisation of biodistribution, immunogenicity and pharmacokinetic profile of increasing doses of {sup 99m}Tc-DI-80B3 Fab' in subjects with acute lower-limb DVT. Twenty-six patients with acute lower limb DVT were enrolled. Of these, 21 received a single intravenous dose of 0.5 mg (n = 6), 1.0 mg (n = 9) or 2 mg (n = 6) {sup 99m}Tc-DI-80B3 Fab'. Blood and urine samples and gamma camera images were collected to 24 h after administration for pharmacokinetic and dosimetry analysis. Vital signs, electrocardiography, hematological and biochemical data and human anti-human antibody (HAHA) levels were monitored for up to 30 days following administration. Patients were assigned to either planar or single photon emission computed tomographic (SPECT) imaging of the thorax at 4 h following injection. Thirty-five adverse events were reported in 15 of the 21 subjects. Those deemed possibly related to administration of {sup 99m}Tc-DI-80B3 Fab' included mild hypertension, mild elevation of LD (lactate dehydrogenase) and moderate elevation of ALT (alanine transaminase). HAHA assays remained negative. Pharmacokinetics and organ dosimetry were comparable to prior normal volunteer data. Localisation of Thromboview registered to sites of known thrombus was evident as early as 30 min post-injection. In subjects with acute DVT, {sup 99m}Tc-DI-80B3 Fab' was well tolerated with favourable characteristics for the detection of acute venous thrombosis. (orig.)

  16. Salmonella Infections (For Parents)

    Science.gov (United States)

    ... Needs a Kidney Transplant Vision Facts and Myths Salmonella Infections KidsHealth > For Parents > Salmonella Infections Print A ... Last? Can Salmonella Infections Be Prevented? What Is Salmonella ? Salmonella is a kind of bacteria , with many ...

  17. Metabolic Imaging of Infection

    NARCIS (Netherlands)

    Lawal, Ismaheel; Zeevaart, JanRijn; Ebenhan, Thomas; Ankrah, Alfred; Vorster, Mariza; Kruger, Hendrik G.; Govender, Thavendran; Sathekge, Mike

    2017-01-01

    Metabolic imaging has come to occupy a prominent place in the diagnosis and management of microbial infection. Molecular probes available for infection imaging have undergone a rapid evolution starting with nonspecific agents that accumulate similarly in infection, sterile inflammation, and

  18. Listeria Infection (Listeriosis)

    Science.gov (United States)

    Listeria infection Overview Listeria infection is a foodborne bacterial illness that can be very serious for pregnant women and people with impaired immune systems. Listeria infection is most commonly contracted by eating improperly ...

  19. Enterococcus faecalis infective endocarditis

    DEFF Research Database (Denmark)

    Dahl, Anders; Bruun, Niels Eske

    2013-01-01

    Enterococcus faecalis infective endocarditis (IE) is a disease of increasing importance, with more patients infected, increasing frequency of health-care associated infections and increasing incidence of antimicrobial resistances. The typical clinical presentation is a subacute course with fever...

  20. Infections and Pregnancy

    Science.gov (United States)

    During pregnancy, some common infections like the common cold or a skin infection do not usually cause serious problems. ... of the infections that can be dangerous during pregnancy include Bacterial vaginosis (BV) Group B strep (GBS) ...

  1. Group B Strep Infection

    Science.gov (United States)

    ... org editorial staff Home Diseases and Conditions Group B Strep Infection Condition Group B Strep Infection Share Print Group B Strep Infection Table of Contents1. Overview2. Symptoms3. Diagnosis4. ...

  2. Variability of the blazar 4C 38.41 (B3 1633+382) from GHz frequencies to GeV energies

    Science.gov (United States)

    Raiteri, C. M.; Villata, M.; Smith, P. S.; Larionov, V. M.; Acosta-Pulido, J. A.; Aller, M. F.; D'Ammando, F.; Gurwell, M. A.; Jorstad, S. G.; Joshi, M.; Kurtanidze, O. M.; Lähteenmäki, A.; Mirzaqulov, D. O.; Agudo, I.; Aller, H. D.; Arévalo, M. J.; Arkharov, A. A.; Bach, U.; Benítez, E.; Berdyugin, A.; Blinov, D. A.; Blumenthal, K.; Buemi, C. S.; Bueno, A.; Carleton, T. M.; Carnerero, M. I.; Carosati, D.; Casadio, C.; Chen, W. P.; Di Paola, A.; Dolci, M.; Efimova, N. V.; Ehgamberdiev, Sh. A.; Gómez, J. L.; González, A. I.; Hagen-Thorn, V. A.; Heidt, J.; Hiriart, D.; Holikov, Sh.; Konstantinova, T. S.; Kopatskaya, E. N.; Koptelova, E.; Kurtanidze, S. O.; Larionova, E. G.; Larionova, L. V.; León-Tavares, J.; Leto, P.; Lin, H. C.; Lindfors, E.; Marscher, A. P.; McHardy, I. M.; Molina, S. N.; Morozova, D. A.; Mujica, R.; Nikolashvili, M. G.; Nilsson, K.; Ovcharov, E. P.; Panwar, N.; Pasanen, M.; Puerto-Gimenez, I.; Reinthal, R.; Richter, G. M.; Ros, J. A.; Sakamoto, T.; Schwartz, R. D.; Sillanpää, A.; Smith, N.; Takalo, L. O.; Tammi, J.; Taylor, B.; Thum, C.; Tornikoski, M.; Trigilio, C.; Troitsky, I. S.; Umana, G.; Valcheva, A. T.; Wehrle, A. E.

    2012-09-01

    Context. After years of modest optical activity, the quasar-type blazar 4C 38.41 (B3 1633+382) experienced a large outburst in 2011, which was detected throughout the entire electromagnetic spectrum, renewing interest in this source. Aims: We present the results of low-energy multifrequency monitoring by the GLAST-AGILE Support Program (GASP) of the Whole Earth Blazar Telescope (WEBT) consortium and collaborators, as well as those of spectropolarimetric/spectrophotometric monitoring at the Steward Observatory. We also analyse high-energy observations of the Swift and Fermi satellites. This combined study aims to provide insights into the source broad-band emission and variability properties. Methods: We assemble optical, near-infrared, millimetre, and radio light curves and investigate their features and correlations. In the optical, we also analyse the spectroscopic and polarimetric properties of the source. We then compare the low-energy emission behaviour with that at high energies. Results: In the optical-UV band, several results indicate that there is a contribution from a quasi-stellar-object (QSO) like emission component, in addition to both variable and polarised jet emission. In the optical, the source is redder-when-brighter, at least for R ≳ 16. The optical spectra display broad emission lines, whose flux is constant in time. The observed degree of polarisation increases with flux and is higher in the red than the blue. The spectral energy distribution reveals a bump peaking around the U band. The unpolarised emission component is likely thermal radiation from the accretion disc that dilutes the jet polarisation. We estimate its brightness to be RQSO ~ 17.85-18 and derive the intrinsic jet polarisation degree. We find no clear correlation between the optical and radio light curves, while the correlation between the optical and γ-ray flux apparently fades in time, likely because of an increasing optical to γ-ray flux ratio. Conclusions: As suggested

  3. Luminescent properties of Li2 (Ca0.99, Eu0.01) SiO4: B3+ particles as a potential bluish green phosphor for ultraviolet light-emitting diodes

    Science.gov (United States)

    Yao, Shanshan; Chen, Donghua

    2007-12-01

    In our study, the 1% mol Eu2+ doped Li2CaSiO4: B3+ phosphors were prepared by the combustion method as fluorescent material for ultraviolet, light-emitting diodes (UV-LEDs) used as a light source. The properties of Li2 (Ca0.99, Eu0.01) SiO4: B3+ phosphors with urea concentration, doping boric acid and a series of initiating combustion temperature were investigated. The crystallization and particle sizes of Li2 (Ca0.99, Eu0.01) SiO4: B3+ has been investigated by using powder X-ray diffraction (XRD) and transmission electron microscopy (TEM). Luminescence measurements showed that the phosphors can be efficiently excited by UV to the visible region, and exhibited bluish green light with a peak of 480 nm. The results showed that the boric acid was effective in improving the luminescence intensity of Li2 (Ca0.99, Eu0.01) SiO4: B3+ and the optimum molar ratio of boric acid to calcium nitrate was about 0.06. The optimized phosphors Li2 (Ca0.99, Eu0.01) SiO4: B0.063+ showed 180% improved emission intensity compared with that of the Li2 (Ca0.99, Eu0.01) SiO4 phosphors under ultraviolet (λex =287 nm) excitation.

  4. Probing the nitrite and nitric oxide reductase activity of cbb3 oxidase: resonance Raman detection of a six-coordinate ferrous heme-nitrosyl species in the binuclear b3/CuB center.

    Science.gov (United States)

    Loullis, Andreas; Pinakoulaki, Eftychia

    2015-12-21

    In this work we report the first spectroscopic evidence demonstrating that cbb3 oxidase catalyzes the reduction of nitrite to nitrous oxide under reducing anaerobic conditions. The reaction proceeds through the formation of a ferrous six-coordinate heme b3-nitrosyl species that has been characterized by resonance Raman spectroscopy.

  5. Safety, pharmacokinetic and dosimetry evaluation of the proposed thrombus imaging agent {sup 99m}Tc-DI-DD-3B6/22-80B3 Fab'

    Energy Technology Data Exchange (ETDEWEB)

    Macfarlane, David J. [Royal Brisbane and Women' s Hospital, Department of Nuclear Medicine, Brisbane (Australia); Smart, Richard C. [St George Hospital, Department of Nuclear Medicine, Sydney (Australia); Tsui, Wendy W. [St George Hospital, Department of Nuclear Medicine, Sydney (Australia); University of New South Wales, School of Medicine, Sydney (Australia); Gerometta, Michael [AGEN Biomedical Limited, Research and Development, Brisbane (Australia); Eisenberg, Paul R. [Eli Lilly Company, Lilly Research Laboratories, Indianapolis (United States); Scott, Andrew M. [Austin Health, Centre for PET, Melbourne (Australia); Ludwig Institute for Cancer Research, Melbourne (Australia)

    2006-06-15

    {sup 99m}Tc-DI-DD-3B6/22-80B3 (Thromboview, hereafter abbreviated to {sup 99m}Tc-DI-80B3 Fab') is a humanised, radiolabelled monoclonal antibody Fab' fragment with high affinity and specificity for the D-dimer domain of cross-linked fibrin. The purpose of this study was to evaluate the safety, pharmacokinetics and dosimetry of four increasing doses of {sup 99m}Tc-DI-80B3 Fab' in healthy volunteers. Thirty-two healthy volunteers (18-70 years; 16 male, 16 female) received a single intravenous injection of 0.5, 1.0, 2.0 or 4.0 mg of {sup 99m}Tc-DI-80B3 Fab'. Safety outcomes (vital signs, electrocardiography, haematology, biochemistry, adverse events and development of human anti-human antibodies) were assessed up to 30 days post injection. Blood and urine samples were collected up to 48 h post injection. Gamma camera images were acquired at 0.5, 1, 2, 4, 6 and 24 h post injection. Dosimetry was performed using standard MIRD methodology. No adverse events considered to be drug related were observed. Human anti-human antibody was not detectable in any subject during the follow-up period. {sup 99m}Tc-DI-80B3 Fab' had a rapid initial plasma clearance (t{sub 1/2}{alpha}=1 h). The pharmacokinetic profile of the Fab' fragment was generally linear across the four dose cohorts. By 24 h, 30-35% of the administered radioactivity appeared in the urine. There was marked renal accumulation with time, but no specific uptake was identified within other normal tissues. The effective dose was 9 mSv/750 MBq. (orig.)

  6. Synthesis and up-conversion luminescence of Er(3+) and Y b(3+) codoped nanocrystalline tetra- (KLaP4O12) and pentaphosphates (LaP5O14).

    Science.gov (United States)

    Marciniak, L; Stefanski, M; Tomala, R; Hreniak, D; Strek, W

    2015-09-07

    The up-converting nanocrystals of KLa0.95Er0.05Y bxP4O12 and La0.95-xEr0.05Y bxP5O14 were prepared using co-precipitation method. The spectroscopic properties of these materials were investigated in a function of Y b(3+) concentration. The up-conversion emission, power dependence of emission intensities, and the luminescence decay times were investigated. It was found that the green to red and (2)H11/2 → (4)I15/2 to (4)S3/2 → (4)I15/2 emission intensity ratio were strongly affected by the Y b(3+) concentration. Moreover, the order of up-conversion emission and threshold power rises up with Y b(3+) concentration for (4)S3/2 → (4)I15/2 transition. The luminescence decay time of the (4)S3/2 → (4)I15/2 emission increases with Y b(3+) concentration while the (4)F9/2 → (4)I15/2 emission is independent of dopant concentration. The influence of the Y b(3+) concentration on the up-conversion emission intensities was discussed in terms of concentration dependent hetero looped photon avalanche process. A comparison of the up-conversion properties of KLa0.95Er0.05Y bxP4O12 and La0.95-xEr0.05Y bxP5O14 nanocrystals was presented.

  7. Musculoskeletal infections: ultrasound appearances

    Energy Technology Data Exchange (ETDEWEB)

    Chau, C.L.F. [Department of Radiology, North District Hospital, NTEC, Fanling, NT, Hong Kong (China)]. E-mail: c8681@yahoo.com; Griffith, J.F. [Department of Diagnostic Radiology and Organ Imaging, Prince of Wales Hospital, NTEC, Shatin, NT, Hong Kong (China)

    2005-02-01

    Musculoskeletal infections are commonly encountered in clinical practice. This review will discuss the ultrasound appearances of a variety of musculoskeletal infections such as cellulitis, infective tenosynovitis, pyomyositis, soft-tissue abscesses, septic arthritis, acute and chronic osteomyelitis, and post-operative infection. The peculiar sonographic features of less common musculoskeletal infections, such as necrotizing fasciitis, and rice body formation in atypical mycobacterial tenosynovitis, and bursitis will also be presented.

  8. Shewanella putrefaciens infective endocarditis

    Directory of Open Access Journals (Sweden)

    Jonathan Constant

    2014-11-01

    Full Text Available Shewanella putrefaciens rarely causes infection in humans. In the last few decades a growing number of cases have been described. The following report outlines the case of a 40-year-old immunocompetent white man with S. putrefaciens infective endocarditis. This is the first known case of infective endocarditis due to an apparently monomicrobial S. putrefaciens infection, and the second known case of S. putrefaciens-related infective endocarditis worldwide.

  9. Postoperative pelvic infections.

    Science.gov (United States)

    Faro, Constance; Faro, Sebastian

    2008-12-01

    Infectious morbidity affecting the postoperative course has long been a concern for obstetricians and gynecologists. The incidence of postoperative infections approaches 38%. The third most common nosocomial infection is surgical site infection. The realm of postoperative infections includes obstetric and gynecologic sources. An understanding of the basic fundamentals of the vaginal flora and addressing host and surgical risk factors can aid in prevention of postoperative infections, which result in significant morbidity and mortality.

  10. Rhinovirus genome evolution during experimental human infection.

    Directory of Open Access Journals (Sweden)

    Samuel Cordey

    Full Text Available Human rhinoviruses (HRVs evolve rapidly due in part to their error-prone RNA polymerase. Knowledge of the diversity of HRV populations emerging during the course of a natural infection is essential and represents a basis for the design of future potential vaccines and antiviral drugs. To evaluate HRV evolution in humans, nasal wash samples were collected daily for five days from 15 immunocompetent volunteers experimentally infected with a reference stock of HRV-39. In parallel, HeLa-OH cells were inoculated to compare HRV evolution in vitro. Nasal wash in vivo assessed by real-time PCR showed a viral load that peaked at 48-72 h. Ultra-deep sequencing was used to compare the low-frequency mutation populations present in the HRV-39 inoculum in two human subjects and one HeLa-OH supernatant collected 5 days post-infection. The analysis revealed hypervariable mutation locations in VP2, VP3, VP1, 2C and 3C genes and conserved regions in VP4, 2A, 2B, 3A, 3B and 3D genes. These results were confirmed by classical sequencing of additional samples, both from inoculated volunteers and independent cell infections, and suggest that HRV inter-host transmission is not associated with a strong bottleneck effect. A specific analysis of the VP1 capsid gene of 15 human cases confirmed the high mutation incidence in this capsid region, but not in the antiviral drug-binding pocket. We could also estimate a mutation frequency in vivo of 3.4x10(-4 mutations/nucleotides and 3.1x10(-4 over the entire ORF and VP1 gene, respectively. In vivo, HRV generate new variants rapidly during the course of an acute infection due to mutations that accumulate in hot spot regions located at the capsid level, as well as in 2C and 3C genes.

  11. Experimental Infection of Sheep using Infective Larvae (L3 ...

    African Journals Online (AJOL)

    Experimental Infection of Sheep using Infective Larvae (L3) harvested from the Faeces of Naturally Infected Swayne's Hartebeest ( Alcelaphus buselaphus swaynei ) at Senkele Swayne's Hartebeest Sanctuary, Ethiopia.

  12. Combustion synthesis and luminescent properties of a new material Li 2(Ba 0.99,Eu 0.01)SiO 4:B 3+ for ultraviolet light emitting diodes

    Science.gov (United States)

    Yao, Shanshan; Chen, Donghua

    2008-04-01

    Using urea as fuel and boric as flux, a novel bluish green emitting phosphor Li 2(Ba 0.99,Eu 0.01)SiO 4:B 3+ has been successfully synthesized using a combustion method. The material has potential application as the fluorescent material for ultraviolet light-emitting diodes (UV-LEDs). The dependence of the properties of Li 2(Ba 0.99,Eu 0.01)SiO 4:B 3+ phosphors upon urea concentration, boric acid doping and initiating combustion temperature were investigated. The crystallization and particle sizes of Li 2(Ba 0.99,Eu 0.01)SiO 4:B 3+ have been investigated by using powder X-ray diffraction (XRD) and transmission electron microscopy (TEM). Luminescence measurements showed that the phosphors can be efficiently excited by ultraviolet (UV) to visible region, emitting a bluish green light with peak wavelength of 490 nm. The results showed that the boric acid was effective in improving the luminescence intensity of Li 2(Ba 0.99,Eu 0.01)SiO 4 and the optimum molar ratio of boric acid to barium nitrate was about 0.06. The optimized phosphors Li 2(Ba 0.99,Eu 0.01)SiO 4:B 0.063+ showed 160% improved emission intensity compared with that of the Li 2(Ba 0.99,Eu 0.01)SiO 4 phosphors under UV ( λex=350 nm) excitation.

  13. Learn About Cronobacter Infection

    Science.gov (United States)

    ... this? Submit What's this? Submit Button Past Emails Learn About Cronobacter Infection Language: English (US) Español (Spanish) ... but infections in young infants can be deadly. Learn what steps you can take to protect your ...

  14. Salivary gland infections

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/001041.htm Salivary gland infections To use the sharing features on this page, please enable JavaScript. Salivary gland infections affect the glands that produce spit (saliva). ...

  15. Urinary tract infection - children

    Science.gov (United States)

    UTI - children; Cystitis - children; Bladder infection - children; Kidney infection - children; Pyelonephritis - children ... They may occur often around age 3, as children begin toilet training. Boys who are not circumcised ...

  16. Pediatric Urinary Tract