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Sample records for play important functional

  1. Play's Importance in School

    Science.gov (United States)

    Sandberg, Anette; Heden, Rebecca

    2011-01-01

    The purpose of this study is to contribute knowledge on and gain an understanding of elementary school teachers' perspectives on the function of play in children's learning processes. The study is qualitative with a hermeneutical approach and has George Herbert Mead as a theoretical frame of reference. Interviews have been carried out with seven…

  2. The Importance of Being Playful.

    Science.gov (United States)

    Bodrova, Elena; Leong, Deborah J.

    2003-01-01

    Recent research provides evidence of the strong connections between quality of play in preschool years and children's readiness for school instruction. Mature play, characterized by imaginary situations, multiple roles, clearly defined rules, flexible themes, language development, length of play, helps students' cognitive development. (Contains 12…

  3. Dimer monomer transition and dimer re-formation play important role for ATM cellular function during DNA repair.

    Science.gov (United States)

    Du, Fengxia; Zhang, Minjie; Li, Xiaohua; Yang, Caiyun; Meng, Hao; Wang, Dong; Chang, Shuang; Xu, Ye; Price, Brendan; Sun, Yingli

    2014-10-03

    The ATM protein kinase, is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks, mediates responses to ionizing radiation in mammalian cells. Here we show that ATM is held inactive in unirradiated cells as a dimer and phosphorylates the opposite strand of the dimer in response to DNA damage. Cellular irradiation induces rapid intermolecular autophosphorylation of serine 1981 that causes dimer dissociation and initiates cellular ATM kinase activity. ATM cannot phosphorylate the substrates when it could not undergo dimer monomer transition. After DNA repair, the active monomer will undergo dephosphorylation to form dimer again and dephosphorylation is critical for dimer re-formation. Our work reveals novel function of ATM dimer monomer transition and explains why ATM dimer monomer transition plays such important role for ATM cellular activity during DNA repair.

  4. Dimer monomer transition and dimer re-formation play important role for ATM cellular function during DNA repair

    Energy Technology Data Exchange (ETDEWEB)

    Du, Fengxia [Laboratory of Genome Variations and Precision Bio-Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101 (China); Zhang, Minjie [Laboratory of Genome Variations and Precision Bio-Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Li, Xiaohua; Yang, Caiyun [Laboratory of Genome Variations and Precision Bio-Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101 (China); Meng, Hao; Wang, Dong; Chang, Shuang [Laboratory of Genome Variations and Precision Bio-Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Xu, Ye [Department of Radiation Oncology, Division of Genomic Stability, Dana Farber Cancer Institute, Harvard Medical School, MA 02134 (United States); Price, Brendan, E-mail: Brendan_Price@dfci.harvard.edu [Department of Radiation Oncology, Division of Genomic Stability, Dana Farber Cancer Institute, Harvard Medical School, MA 02134 (United States); Sun, Yingli, E-mail: sunyl@big.ac.cn [Laboratory of Genome Variations and Precision Bio-Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101 (China)

    2014-10-03

    Highlights: • ATM phosphorylates the opposite strand of the dimer in response to DNA damage. • The PETPVFRLT box of ATM plays a key role in its dimer dissociation in DNA repair. • The dephosphorylation of ATM is critical for dimer re-formation after DNA repair. - Abstract: The ATM protein kinase, is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks, mediates responses to ionizing radiation in mammalian cells. Here we show that ATM is held inactive in unirradiated cells as a dimer and phosphorylates the opposite strand of the dimer in response to DNA damage. Cellular irradiation induces rapid intermolecular autophosphorylation of serine 1981 that causes dimer dissociation and initiates cellular ATM kinase activity. ATM cannot phosphorylate the substrates when it could not undergo dimer monomer transition. After DNA repair, the active monomer will undergo dephosphorylation to form dimer again and dephosphorylation is critical for dimer re-formation. Our work reveals novel function of ATM dimer monomer transition and explains why ATM dimer monomer transition plays such important role for ATM cellular activity during DNA repair.

  5. Role Playing, Issue Importance, and Attitude Change.

    Science.gov (United States)

    Sarup, Gian

    1981-01-01

    Contrasted three major theories on attitude change: cognitive dissonance, incentive, and social judgment. Results from student questionnaires provided little support for cognitive dissonance. Also provided credible, though overlapping, evidence for incentive and social judgment theories. Improvised role playing produced more change than did…

  6. Preschoolers' Free Play--Connections with Emotional and Social Functioning

    Science.gov (United States)

    Veiga, Guida; Neto, Carlos; Rieffe, Carolien

    2016-01-01

    Play has an important role in various aspects of children's development. However, time for free play has declined substantially over the last decades. To date, few studies have focused on the relationship between opportunities for free play and children's social functioning. The aims of this study are to examine whether children´s free play is…

  7. Smoking status and gene susceptibility play important roles in the development of chronic obstructive pulmonary disease and lung function decline: A population-based prospective study.

    Science.gov (United States)

    Zhao, Junling; Li, Miao; Chen, Jinkun; Wu, Xiaomei; Ning, Qin; Zhao, Jianping; Xu, Yongjian; Xie, Jungang; Yu, Jun

    2017-06-01

    We conducted this study to identify the influences and synergistic effects of smoking status and polymorphisms in hedgehog interacting protein (HHIP) on chronic obstructive pulmonary disease (COPD) and lung function decline. A cohort containing 306 COPD patients and 743 healthy subjects was recruited from 25,000 subjects. All selected subjects had chronic cough for over 2 years or a smoking history above 20 pack-years. After 8 years, all subjects were divided into 2 cohorts according to whether they had quit smoking or not. A follow-up of all patients was completed after another period of 10 years. Three variants in HHIP were genotyped to investigate the impacts of gene susceptibility on the development of COPD and lung function decline. During the follow-up tests, forced expiratory volume in 1 s (FEV1) ratios decreased more significantly in COPD patients than in healthy subjects. For variant rs7654947, FEV1 decreased more significantly in CC and CT subjects than in TT subjects. FEV1 in COPD patients with a CC genotype from smoking cohorts reduced markedly when compared to ex-smoking cohorts (case, 30.75% vs. 35.5%; total, 28% vs. 32%). Our results showed that smoking and HHIP variant rs7654947 were associated with COPD development and lung function decline. Moreover, we found that cigarette smoking and gene susceptibility have cooperative effects on COPD risk and lung function decline.

  8. Upregulation of PDZK1 by Calculus Bovis Sativus May Play an Important Role in Restoring Biliary Transport Function in Intrahepatic Cholestasis

    Directory of Open Access Journals (Sweden)

    Dong Xiang

    2017-01-01

    Full Text Available Intrahepatic cholestasis is a main cause of hepatic accumulation of bile acids leading to liver injury, fibrosis, and liver failure. Our previous studies proved that Calculus Bovis Sativus (CBS can restore biliary transport function through upregulating the multidrug resistance-associated protein 2 (MRP2 and breast cancer resistance protein (BCRP in 17α-ethynylestradiol- (EE- induced intrahepatic cholestasis rats. The regulation mechanism of CBS on these transporters, however, remains unclear. This study was designed to evaluate the possible relationship between the effect of CBS on transport activities and the regulation of CBS on the expression of PDZK1, a mainly scaffold protein which can regulate MRP2 and BCRP. Intrahepatic cholestasis model was induced in rats with injection of EE for five consecutive days and then the biliary excretion rates and cumulative biliary excretions were measured. The mRNA and protein expression levels of PDZK1 were detected by reverse transcription-quantitative real-time polymerase chain reaction, western blot, and immunohistochemical analysis. When treated with CBS, cumulative biliary excretions and mRNA and protein expressions of PDZK1 were significantly increased in intrahepatic cholestasis rats. This study demonstrated that CBS exerted a beneficial effect on EE-induced intrahepatic cholestasis rats by restoring biliary transport function, which may result from the upregulation of PDZK1 expression.

  9. Executive Functions Development and Playing Games

    Science.gov (United States)

    Petty, Ana Lucia; de Souza, Maria Thereza C. Coelho

    2012-01-01

    The aim of this paper is to discuss executive functions and playing games, considering Piaget's work (1967) and the neuropsychological framework (Barkley, 1997, 2000; Cypel, 2007). Two questions guide the discussion: What are the intersections between playing games and the development of executive functions? Can we stimulate children with learning…

  10. Preschoolers’ free play - connections with emotional and social functioning

    Directory of Open Access Journals (Sweden)

    Guida Veiga

    2016-04-01

    Full Text Available Play has an important role in various aspects of children’s development. However, time for free play has declined substantially over the last decades. To date, few studies have focused on the relationship between opportunities for free play and children’s social functioning. The aims of this study are to examine whether children´s free play is related to their social functioning and whether this relationship is mediated by children´s emotional functioning. Seventy-eight children (age, 55- 77 months were tested on their theory of mind and emotion understanding. Parents reported on their children’s time for free play, empathic abilities, social competence and externalizing behaviors. The main findings showed that free play and children’s theory of mind are negatively related to externalizing behaviors. Empathy was strongly related to children’s social competence, but free play and social competence were not associated. Less time for free play is related to more disruptive behaviors in preschool children, however certain emotional functioning skills influence these behaviors independently of the time children have for free play. These outcomes suggest that free play might help to prevent the development of disruptive behaviors, but future studies should further examine the causality of this relationship.

  11. Copy number variation plays an important role in clinical epilepsy

    Science.gov (United States)

    Olson, Heather; Shen, Yiping; Avallone, Jennifer; Sheidley, Beth R.; Pinsky, Rebecca; Bergin, Ann M.; Berry, Gerard T.; Duffy, Frank H.; Eksioglu, Yaman; Harris, David J.; Hisama, Fuki M.; Ho, Eugenia; Irons, Mira; Jacobsen, Christina M.; James, Philip; Kothare, Sanjeev; Khwaja, Omar; Lipton, Jonathan; Loddenkemper, Tobias; Markowitz, Jennifer; Maski, Kiran; Megerian, J. Thomas; Neilan, Edward; Raffalli, Peter C.; Robbins, Michael; Roberts, Amy; Roe, Eugene; Rollins, Caitlin; Sahin, Mustafa; Sarco, Dean; Schonwald, Alison; Smith, Sharon E.; Soul, Janet; Stoler, Joan M.; Takeoka, Masanori; Tan, Wen-Han; Torres, Alcy R.; Tsai, Peter; Urion, David K.; Weissman, Laura; Wolff, Robert; Wu, Bai-Lin; Miller, David T.; Poduri, Annapurna

    2015-01-01

    Objective To evaluate the role of copy number abnormalities detectable by chromosomal microarray (CMA) testing in patients with epilepsy at a tertiary care center. Methods We identified patients with ICD-9 codes for epilepsy or seizures and clinical CMA testing performed between October 2006 and February 2011 at Boston Children’s Hospital. We reviewed medical records and included patients meeting criteria for epilepsy. We phenotypically characterized patients with epilepsy-associated abnormalities on CMA. Results Of 973 patients who had CMA and ICD-9 codes for epilepsy or seizures, 805 patients satisfied criteria for epilepsy. We observed 437 copy number variants (CNVs) in 323 patients (1–4 per patient), including 185 (42%) deletions and 252 (58%) duplications. Forty (9%) were confirmed de novo, 186 (43%) were inherited, and parental data were unavailable for 211 (48%). Excluding full chromosome trisomies, CNV size ranged from 18 kb to 142 Mb, and 34% were over 500 kb. In at least 40 cases (5%), the epilepsy phenotype was explained by a CNV, including 29 patients with epilepsy-associated syndromes and 11 with likely disease-associated CNVs involving epilepsy genes or “hotspots.” We observed numerous recurrent CNVs including 10 involving loss or gain of Xp22.31, a region described in patients with and without epilepsy. Interpretation Copy number abnormalities play an important role in patients with epilepsy. Given that the diagnostic yield of CMA for epilepsy patients is similar to the yield in autism spectrum disorders and in prenatal diagnosis, for which published guidelines recommend testing with CMA, we recommend the implementation of CMA in the evaluation of unexplained epilepsy. PMID:24811917

  12. Affordances for Risky Play in Preschool: The Importance of Features in the Play Environment

    Science.gov (United States)

    Sandseter, Ellen Beate Hansen

    2009-01-01

    The purpose of this article is to qualitatively explore the affordances for risky play in two different preschool outdoor environments, an ordinary preschool playground and a nature playground, based on Gibson ("The ecological approach to visual perception," 1979) theory of affordances and Heft's and Kyttea's (Heft in "Children's…

  13. An Important Role Culture Plays in Communicative Learning

    Institute of Scientific and Technical Information of China (English)

    马晓霞

    2005-01-01

    This paper presents a study of the effects of cultural background on the communicative approach exemplified by the teaching of Integrated Skills of English (ISE).It proceeds from the interpretation of culture in light of linguis tic and pedagogic perspectives,then target on how cultural knowledge affects the communicative approach with the actual examples from ISE,and concludes that greater importance should be attached to EFL teaching

  14. Parent participation plays an important part in promoting physical activity

    Directory of Open Access Journals (Sweden)

    Anna-Karin Lindqvist

    2015-08-01

    Full Text Available Although physical activity (PA is an important and modifiable determinant of health, in Sweden only 15% of boys and 10% of girls aged 15 years old achieve the recommended levels of PA 7 days per week. Adolescents’ PA levels are associated with social influence exerted by parents, friends, and teachers. The purpose of this study was to describe parents’ experiences of being a part of their adolescents’ empowerment-inspired PA intervention. A qualitative interview study was performed at a school in the northern part of Sweden. A total of 10 parents were interviewed, and the collected data were analyzed with qualitative content analysis. Three subthemes were combined into one main theme, demonstrating that parents are one important part of a successful PA intervention. The life of an adolescent has many options and demands that make it difficult to prioritize PA. Although parents felt that they were important in supporting their adolescent, a successful PA intervention must have multiple components. Moreover, the parents noted that the intervention had a positive effect upon not only their adolescents’, but also their own PA. Interventions aimed at promoting PA among adolescents should include measures to stimulate parent participation, have an empowerment approach, and preferably be school-based.

  15. Vegetation plays an important role in mediating future water resources

    Science.gov (United States)

    Ukkola, A. M.; Keenan, T. F.; Kelley, D. I.; Prentice, I. C.

    2016-09-01

    Future environmental change is expected to modify the global hydrological cycle, with consequences for the regional distribution of freshwater supplies. Regional precipitation projections, however, differ largely between models, making future water resource projections highly uncertain. Using two representative concentration pathways and nine climate models, we estimate 21st century water resources across Australia, employing both a process-based dynamic vegetation model and a simple hydrological framework commonly used in water resource studies to separate the effects of climate and vegetation on water resources. We show surprisingly robust, pathway-independent regional patterns of change in water resources despite large uncertainties in precipitation projections. Increasing plant water use efficiency (due to the changing atmospheric CO2) and reduced green vegetation cover (due to the changing climate) relieve pressure on water resources for the highly populated, humid coastal regions of eastern Australia. By contrast, in semi-arid regions across Australia, runoff declines are amplified by CO2-induced greening, which leads to increased vegetation water use. These findings highlight the importance of including vegetation dynamics in future water resource projections.

  16. Relationships between symbolic play, functional play, verbal and non-verbal ability in young children.

    Science.gov (United States)

    Lewis, V; Boucher, J; Lupton, L; Watson, S

    2000-01-01

    It is well established that certain aspects of play in young children are related to their emerging linguistic skills. The present study examined the relationships between functional play, symbolic play, non-verbal ability, and expressive and receptive language in normally developing children aged between 1 and 6 years using standardized assessment procedures, including a recently developed Test of Pretend Play (ToPP). When effects of chronological age were partialled out, symbolic play remained significantly correlated with both expressive and receptive language, but not with functional play or non-verbal ability; and functional play was only correlated significantly with expressive language. It is concluded that ToPP will provide practitioners with a useful way of assessing symbolic ability in children between the ages of 1 and 6 years, and will contribute to the assessment and diagnosis of a number of communication difficulties, and have implications for intervention.

  17. Importance and Functions of Grasslands

    Directory of Open Access Journals (Sweden)

    Lucien CARLIER

    2009-06-01

    Full Text Available Grasslands, mixture of grass, clover and other leguminous species, dicotyledonous, herbs and shrubs, contribute to a high degree to the struggle against erosion and to the regularizing of water regimes, to the purification of fertilizers and pesticides and to biodiversity and they have aesthetic role and recreational function as far as they provide public access that other agricultural uses do not allow. Grassland will continue to be an important form of land use in Europe, but with increased diversity in management objectives and systems used. Besides its role as basic nutrient for herbivores and ruminants, grasslands have opportunities for an adding value by exploiting positive health characteristics in animal products from grassland and through the delivery of environmental benefits. But even for grassland it is very difficult to create a good frame for its different tasks (1 the provision of forage for livestock, (2 protection and conservation of soil and water resources, (3 furnishing a habitat for wildlife, both flora and fauna and (4 contribution to the attractiveness of the landscape. Nevertheless it is the only crop able to fulfil so many tasks and to fit so many requirements. In this article the focus is limited to the grass and clover components of the grasslands.

  18. The importance of play in adulthood. An interview with Joan M. Erikson. Interview by Daniel Benveniste.

    Science.gov (United States)

    Erikson, J M

    1998-01-01

    Joan M. Erikson (1902-1997) was an artist, a writer, a mother, and the wife and collaborator of Erik H. Erikson (1902-1994), one of the most important and influential psychoanalysts in the world. The following is an edited dialogue on one of her favorite topics--The Importance of Play in Adulthood. It features her thoughts on the subject and reminiscences of the ways she played throughout her life. She muses on play in relation to humor, fun, the role of the fool, and more. The article was a project undertaken in the spirit of play and it will hopefully evoke further playful musings in the minds of readers.

  19. Homeodomain-interacting protein kinase 2 plays an important role in normal terminal erythroid differentiation.

    Science.gov (United States)

    Hattangadi, Shilpa M; Burke, Karly A; Lodish, Harvey F

    2010-06-10

    Gene-targeting experiments report that the homeodomain-interacting protein kinases 1 and 2, Hipk1 and Hipk2, are essential but redundant in hematopoietic development because Hipk1/Hipk2 double-deficient animals exhibit severe defects in hematopoiesis and vasculogenesis, whereas the single knockouts do not. These serine-threonine kinases phosphorylate and consequently modify the functions of several important hematopoietic transcription factors and cofactors. Here we show that Hipk2 knockdown alone plays a significant role in terminal fetal liver erythroid differentiation. Hipk1 and Hipk2 are highly induced during primary mouse fetal liver erythropoiesis. Specific knockdown of Hipk2 inhibits terminal erythroid cell proliferation (explained in part by impaired cell-cycle progression as well as increased apoptosis) and terminal enucleation as well as the accumulation of hemoglobin. Hipk2 knockdown also reduces the transcription of many genes involved in proliferation and apoptosis as well as important, erythroid-specific genes involved in hemoglobin biosynthesis, such as alpha-globin and mitoferrin 1, demonstrating that Hipk2 plays an important role in some but not all aspects of normal terminal erythroid differentiation.

  20. Mitochondria play an important role in the cell proliferation suppressing activity of berberine

    Science.gov (United States)

    Yan, Xiao-Jin; Yu, Xuan; Wang, Xin-Pei; Jiang, Jing-Fei; Yuan, Zhi-Yi; Lu, Xi; Lei, Fan; Xing, Dong-Ming

    2017-01-01

    After being studied for approximately a century, berberine (BBR) has been found to act on various targets and pathways. A great challenge in the pharmacological analysis of BBR at present is to identify which target(s) plays a decisive role. In the study described herein, a rescue experiment was designed to show the important role of mitochondria in BBR activity. A toxic dose of BBR was applied to inhibit cell proliferation and mitochondrial activity, then α-ketobutyrate (AKB), an analogue of pyruvate that serves only as an electron receptor of NADH, was proven to partially restore cell proliferation. However, mitochondrial morphology damage and TCA cycle suppression were not recovered by AKB. As the AKB just help to regenerate NAD+, which is make up for part function of mitochondrial, the recovered cell proliferation stands for the contribution of mitochondria to the activity of BBR. Our results also indicate that BBR suppresses tumour growth and reduces energy charge and mitochondrial DNA (mtDNA) copy number in a HepG2 xenograft model. In summary, our study suggests that mitochondria play an important role in BBR activity regarding tumour cell proliferation and metabolism. PMID:28181523

  1. Entamoeba mitosomes play an important role in encystation by association with cholesteryl sulfate synthesis.

    Science.gov (United States)

    Mi-ichi, Fumika; Miyamoto, Tomofumi; Takao, Shouko; Jeelani, Ghulam; Hashimoto, Tetsuo; Hara, Hiromitsu; Nozaki, Tomoyoshi; Yoshida, Hiroki

    2015-06-01

    Hydrogenosomes and mitosomes are mitochondrion-related organelles (MROs) that have highly reduced and divergent functions in anaerobic/microaerophilic eukaryotes. Entamoeba histolytica, a microaerophilic, parasitic amoebozoan species, which causes intestinal and extraintestinal amoebiasis in humans, possesses mitosomes, the existence and biological functions of which have been a longstanding enigma in the evolution of mitochondria. We previously demonstrated that sulfate activation, which is not generally compartmentalized to mitochondria, is a major function of E. histolytica mitosomes. However, because the final metabolites of sulfate activation remain unknown, the overall scheme of this metabolism and the role of mitosomes in Entamoeba have not been elucidated. In this study we purified and identified cholesteryl sulfate (CS) as a final metabolite of sulfate activation. We then identified the gene encoding the cholesteryl sulfotransferase responsible for synthesizing CS. Addition of CS to culture media increased the number of cysts, the dormant form that differentiates from proliferative trophozoites. Conversely, chlorate, a selective inhibitor of the first enzyme in the sulfate-activation pathway, inhibited cyst formation in a dose-dependent manner. These results indicate that CS plays an important role in differentiation, an essential process for the transmission of Entamoeba between hosts. Furthermore, we show that Mastigamoeba balamuthi, an anaerobic, free-living amoebozoan species, which is a close relative of E. histolytica, also has the sulfate-activation pathway in MROs but does not possess the capacity for CS production. Hence, we propose that a unique function of MROs in Entamoeba contributes to its adaptation to its parasitic life cycle.

  2. Logoplaste : how business models can play an important role in the achievement of sustained competitive advantage

    OpenAIRE

    Pita, Miguel Vieira

    2011-01-01

    Dissertation title: Logoplaste: How Business Models can play an important role in the achievement of Sustained Competitive Advantage Author: Miguel Vieira Pita The following dissertation gives focus to the case study of Logoplaste, a successful Portuguese company where strategy plays an important role in the short and long term success of the company. Focusing on writing a dissertation that gives highlight to the creation and development of the firm’s valuable resources and ...

  3. Museologia i patrimoni historicoeducatiu. Importància i funció dels materials lúdics Museology and historical educational heritage. The importance and function of materials for play Museología y patrimonio histórico-educativo. La importancia y el papel de los materiales lúdicos

    Directory of Open Access Journals (Sweden)

    Andrés Payà Rico

    2011-12-01

    conception, is related to play activities. These have always formed a part of educational spaces. Consequently, games and related materials should be carefully considered in any educational project of a museographic or heritage nature. In this paper, we study the function of these materials in educational museums, and in projects and activities related to historical educational heritage. We briefly summarize the place that games have played in these institutions and educational experiences. Finally, we establish a taxonomy or typology to classify play that may serve to unify criteria and establish guidelines for recovering, studying and disseminating these elements more effectively.Uno de los aspectos de la cultura material de la escuela y de la historia educativa, en su concepción más global, continuamente presente en los diferentes espacios pedagógicos, ha sido el relativo a la actividad lúdica. Por ello, se hace necesario tener muy en cuenta el juego y los materiales que lo acompañan en cualquier proyecto educativo de carácter museográfico o patrimonial. En este artículo, estudiamos el papel que tienen estos materiales en los museos educativos, así como en los proyectos y acciones relativas al patrimonio histórico-educativo. Realizamos un breve repaso del lugar que ha “jugado el juego” en estas instituciones y experiencias educativas para, finalmente, establecer una taxonomía o tipología de clasificación lúdica que pueda servir para unificar criterios y establecer unas orientaciones para su mejor recuperación, estudio y difusión.

  4. Entamoeba mitosomes play an important role in encystation by association with cholesteryl sulfate synthesis

    Science.gov (United States)

    Mi-ichi, Fumika; Miyamoto, Tomofumi; Takao, Shouko; Jeelani, Ghulam; Hashimoto, Tetsuo; Hara, Hiromitsu; Nozaki, Tomoyoshi; Yoshida, Hiroki

    2015-01-01

    Hydrogenosomes and mitosomes are mitochondrion-related organelles (MROs) that have highly reduced and divergent functions in anaerobic/microaerophilic eukaryotes. Entamoeba histolytica, a microaerophilic, parasitic amoebozoan species, which causes intestinal and extraintestinal amoebiasis in humans, possesses mitosomes, the existence and biological functions of which have been a longstanding enigma in the evolution of mitochondria. We previously demonstrated that sulfate activation, which is not generally compartmentalized to mitochondria, is a major function of E. histolytica mitosomes. However, because the final metabolites of sulfate activation remain unknown, the overall scheme of this metabolism and the role of mitosomes in Entamoeba have not been elucidated. In this study we purified and identified cholesteryl sulfate (CS) as a final metabolite of sulfate activation. We then identified the gene encoding the cholesteryl sulfotransferase responsible for synthesizing CS. Addition of CS to culture media increased the number of cysts, the dormant form that differentiates from proliferative trophozoites. Conversely, chlorate, a selective inhibitor of the first enzyme in the sulfate-activation pathway, inhibited cyst formation in a dose-dependent manner. These results indicate that CS plays an important role in differentiation, an essential process for the transmission of Entamoeba between hosts. Furthermore, we show that Mastigamoeba balamuthi, an anaerobic, free-living amoebozoan species, which is a close relative of E. histolytica, also has the sulfate-activation pathway in MROs but does not possess the capacity for CS production. Hence, we propose that a unique function of MROs in Entamoeba contributes to its adaptation to its parasitic life cycle. PMID:25986376

  5. TGF-β signaling plays an important role in resisting γ-irradiation

    Energy Technology Data Exchange (ETDEWEB)

    An, You Sun; Kim, Mi-Ra [Division of Radiation Effects, Korea Institute of Radiation and Medical Sciences, Seoul (Korea, Republic of); Lee, Seung-Sook [Laboratory of Experimental Pathology, Korea Institute of Radiation and Medical Sciences, Seoul (Korea, Republic of); Lee, Yun-Sil [College of Pharmacy and Division of Life Science and Pharmaceuticals, Ewha Womans University, Seoul (Korea, Republic of); Chung, Eunkyung [Department of Genetic Engineering, College of Life Science, Kyung-Hee University, Yongin, Gyeonggi-do (Korea, Republic of); Song, Jie-Young [Division of Radiation Cancer Research, Korea Institute of Radiation and Medical Sciences, Seoul (Korea, Republic of); Lee, Jeeyong, E-mail: jeeyongl@gmail.com [Division of Radiation Effects, Korea Institute of Radiation and Medical Sciences, Seoul (Korea, Republic of); Yi, Jae Youn, E-mail: yjy_71@kcch.re.kr [Division of Radiation Effects, Korea Institute of Radiation and Medical Sciences, Seoul (Korea, Republic of)

    2013-02-15

    Transforming growth factor-β1 (TGF-β1) regulates various biological processes, including differentiation, bone remodeling and angiogenesis, and is particularly important as a regulator of homeostasis and cell growth in normal tissue. Interestingly, some studies have reported that TGF-β1 induces apoptosis through induction of specific genes, whereas others suggest that TGF-β1 inhibits apoptosis and facilitates cell survival. Resolving these discrepancies, which may reflect differences in cellular context, is an important research priority. Here, using the parental mink lung epithelial cell line, Mv1Lu, and its derivatives, R1B and DR26, lacking TGF-β receptors, we investigated the involvement of TGF-β signaling in the effects of γ-irradiation. We found that canonical TGF-β signaling played an important role in protecting cells from γ-irradiation. Introduction of functional TGF-β receptors or constitutively active Smads into R1B and DR26 cell lines reduced DNA fragmentation, Caspase-3 cleavage and γ-H2AX foci formation in γ-irradiated cells. Notably, we also found that de novo protein synthesis was required for the radio-resistant effects of TGF-β1. Our data thus indicate that TGF-β1 protected against γ-irradiation, decreasing DNA damage and reducing apoptosis, and thereby enhanced cell survival. - Highlights: ► TGF-β1 pretreatment inhibits γ-irradiation-induced apoptosis. ► TGF-β signaling reduces γ-irradiation-induced γ-H2AX foci formation. ► de novo protein synthesis is necessary for TGF-β1-induced radio-resistance.

  6. Functional importance of PAI-1 glycosylation

    DEFF Research Database (Denmark)

    Christensen, Anni; Naessens, Dominik; Skottrup, Peter Durand

    Structure-function studies of plasminogen activator inhibitor-1 (PAI-1) have previously been performed mostly with non-glycosylated material expressed in E. coli. We have now studied the importance of PAI-1 glycosylation for its functional properties. PAI-1 has 3 potential sites for N-linked glyc...

  7. Taurine plays an important role in the protection of spermatogonia from oxidative stress.

    Science.gov (United States)

    Higuchi, Masato; Celino, Fritzie T; Shimizu-Yamaguchi, Sonoko; Miura, Chiemi; Miura, Takeshi

    2012-12-01

    It has been demonstrated that taurine has various physiological functions in the body. We demonstrated that taurine is abundant in the serum, liver, muscle and testis of the Japanese eel (Anguilla japonica). In the eel testis, taurine is found mainly in spermatogonia and is weakly expressed also in the Sertoli cells. We have further found in the eel testis that taurine is actively accumulated via the sodium/chloride-dependent taurine transporter (TauT; SLC6A6), which is expressed in germ cells. In our current study, the effects of taurine on the anti-oxidant response were examined. Taurine was found to promote the total superoxide dismutase (SOD) activity in the testis. Moreover, our results indicate that taurine does not affect the mRNA levels of copper-zinc (Cu/Zn) SOD or manganese SOD, but promotes the translation of Cu/Zn SOD. Overall, our present data suggest that taurine may modulate Cu/Zn SOD at the translational level and thereby may play an important role in the protection of germ cells from oxidative stress.

  8. PRI Play Important Role in West-East Project · Interview with PIR Director Xue Zhenkui

    Institute of Scientific and Technical Information of China (English)

    Xiao Lu

    2002-01-01

    @@ Pipeline Research Institute of CNPC (PRI) is playing a more and more important role in the oil and natural gas pipeline industrial development in the present-day China. The pipeline technology and equipment developed by PRI have proven costeffective and extremely useful in the country's WestEast gas transmission pipeline project

  9. LvDJ-1 plays an important role in resistance against Vibrio alginolyticus in Litopenaeus vannamei.

    Science.gov (United States)

    Huang, Mingzhu; Liu, Yuan; Xie, Chenying; Wang, Wei-Na

    2015-05-01

    DJ-1 was first identified as an oncogene that transformed mouse NIH3T3 cells in cooperation with activated Ras. It has since exhibited a variety of functions in a range of organisms. In this study, the DJ-1 gene in Litopenaeus vannamei (LvDJ-1) was identified and characterized. A recombinant protein LvDJ-1 was produced in Pichia pastoris. LvDJ-1 expression in vivo was knocked down by dsRNA-mediated RNA interference (RNAi), which led to significantly decreased levels of LvDJ-1 mRNA and protein. When the L. vannamei were challenged with RNAi and Vibrio alginolyticus, the transcription and expression of copper zinc superoxide dismutase (LvCZSOD) in the hepatopancreas were dramatically lower in shrimp with knocked down LvDJ-1 than in controls. Transcription and expression of P53 (LvP53) were significantly higher in shrimp lacking LvDJ-1 than in controls. Hepatopancreas samples were analyzed using real time polymerase chain reaction and Western blot. Moreover, blood samples from the shrimp, assessed with flow cytometry, showed significant increases in respiratory burst and apoptosis in those lacking LvDJ-1 compared to the controls. Cumulative mortality in the shrimp lacking LvDJ-1 was significantly different from that in the control group after challenge with V. alginolyticus. Altogether, the results prove that LvDJ-1 regulates apoptosis and antioxidant activity, and that these functions play an important role in L. vannamei resistance against V. alginolyticus.

  10. Intensity of guitar playing as a function of auditory feedback.

    Science.gov (United States)

    Johnson, C I; Pick, H L; Garber, S R; Siegel, G M

    1978-06-01

    Subjects played an electric guitar while auditory feedback was attenuated or amplified at seven sidetone levels varying 10-dB steps around a comfortable listening level. The sidetone signal was presented in quiet (experiment I) and several levels of white noise (experiment II). Subjects compensated for feedback changes, demonstrating a sidetone amplification as well as a Lombard effect. The similarity of these results to those found previously for speech suggests that guitar playing can be a useful analog for the function of auditory feedback in speech production. Unlike previous findings for speech, the sidetone-amplification effect was not potentiated by masking, consistent with a hypothesis that potentiation in speech is attributable to interference with bone conduction caused by the masking noise.

  11. Importance sampling the Rayleigh phase function

    DEFF Research Database (Denmark)

    Frisvad, Jeppe Revall

    2011-01-01

    Rayleigh scattering is used frequently in Monte Carlo simulation of multiple scattering. The Rayleigh phase function is quite simple, and one might expect that it should be simple to importance sample it efficiently. However, there seems to be no one good way of sampling it in the literature. Thi....... This paper provides the details of several different techniques for importance sampling the Rayleigh phase function, and it includes a comparison of their performance as well as hints toward efficient implementation.......Rayleigh scattering is used frequently in Monte Carlo simulation of multiple scattering. The Rayleigh phase function is quite simple, and one might expect that it should be simple to importance sample it efficiently. However, there seems to be no one good way of sampling it in the literature...

  12. Functional anatomy of the soft palate applied to wind playing.

    Science.gov (United States)

    Evans, Alison; Ackermann, Bronwen; Driscoll, Tim

    2010-12-01

    Wind players must be able to sustain high intraoral pressures in order to play their instruments. Prolonged exposure to these high pressures may lead to the performance-related disorder velopharyngeal insufficiency (VPI). This disorder occurs when the soft palate fails to completely close the air passage between the oral and nasal cavities in the upper respiratory cavity during blowing tasks, this closure being necessary for optimum performance on a wind instrument. VPI is potentially career threatening. Improving music teachers' and students' knowledge of the mechanism of velopharyngeal closure may assist in avoiding potentially catastrophic performance-related disorders arising from dysfunction of the soft palate. In the functional anatomy of the soft palate as applied to wind playing, seven muscles of the soft palate involved in the velopharyngeal closure mechanism are reviewed. These are the tensor veli palatini, levator veli palatini, palatopharyngeus, palatoglossus, musculus uvulae, superior pharyngeal constrictor, and salpingopharyngeus. These muscles contribute to either a palatal or a pharyngeal component of velopharyngeal closure. This information should guide further research into targeted methods of assessment, management, and treatment of VPI in wind musicians.

  13. The MBD4 Gene Plays an Important Role in Porcine Adipocyte Differentiation

    Directory of Open Access Journals (Sweden)

    Lian-Jiang Zhang

    2014-09-01

    Full Text Available Background: MBD4 (methyl-CpG binding domain protein 4 is an important G: T glycosylase that can identify T-G mismatches. It plays a role in active demethylation through base excision repair. Overexpression of MBD4 gene can cause the demethylation of numerous genes, and the remethylation of MBD4-associated genes can occur when the MBD4 gene is knocked out. To date, the functions and regulatory mechanisms of the MBD4 gene in the differentiation of porcine preadipocytes have not been clearly established. Methods: Subcutaneous fat cells from 1- to 7-day-old Junmu-1 piglets were cultured in vitro, induced to differentiate, and then identified. A real-time fluorescence-based quantitative polymerase chain reaction (PCR analysis was conducted to detect MBD4 messenger RNA (mRNA expression. Cells were treated with MBD4-siRNA (small interfering RNA and induced to differentiate. Changes in the lipid droplets were observed by oil red O staining. Changes in the mRNA and protein expression levels of MBD4 and the adipose differentiation-associated genes C/EBPα (CCAAT-enhancer-binding protein alpha, PPARγ (peroxisome proliferator-activated receptor gamma, and aP2 (adipocyte protein 2 were detected. In addition, the bisulfite sequencing method was used to detect changes in methylation in the promoters of certain genes associated with adipose differentiation. Results: Levels of MBD4 mRNA and protein expression varied with time over the course of the porcine adipocyte differentiation, with the highest levels of this expression observed on day two of the differentiation process. After silencing MBD4 and inducing differentiation, the production of lipid droplets decreased, the mRNA expression levels of C/EBPα, PPARγ, and aP2 were significantly reduced, and DNA methylation modification levels were significantly elevated in the examined promoter regions. Conclusion: The silencing of the MBD4 gene can influence the DNA methylation levels of preadipocyte

  14. Fact or fiction? A longitudinal study of play and the development of reflective functioning.

    Science.gov (United States)

    Tessier, V P; Normandin, L; Ensink, K; Fonagy, P

    2016-01-01

    In Fonagy and Target's (1996, 2000) developmental model of mentalization, play is theorized as a precursor of later mentalization and reflective function (RF); however, the relationship between play and later mentalization and RF has yet to be empirically tested. These processes are particularly important in the context of trauma, but an empirical model of the relationships among mentalization, play, and trauma is currently lacking. The aim of this longitudinal study was to examine whether children's capacity to engage in pretend play, to symbolize, and to make play narratives was associated with later RF in those children. Thirty-nine sexually abused children and 21 nonabused children (aged 3 to 8) participated in the study. The Children's Play Therapy Instrument was used to assess children's free play. Three years after the play assessment, children's RF was assessed using the Child Attachment Interview, coded with the Child and Adolescent Reflective Functioning Scale. Pretend play completion was associated with later other-understanding. Play was also found to mediate the relationship between sexual abuse and children's later mentalization regarding others. These findings are consistent with Fonagy and Target's emphasis on the role of pretend play in the development of a nuanced sense of the qualities of the mind and reality. In sum, the findings lend support to Fonagy and Target's account of playing with reality, and the development of mentalization suggests that it may be more than "fiction." Furthermore, these results suggest that children's ability to create meaningful and coherent play sequences after sexual abuse is associated with the development of a better understanding of their relationships with others. Clinical implications and future directions are discussed.

  15. The terminal structure plays an important role in the biological activity of cecropin CMIV

    Institute of Scientific and Technical Information of China (English)

    窦非; 谢维; 董雪吟; 徐贤秀

    1999-01-01

    Antibacterial peptides have received increasing attention as a new pharmaceutical substance. But the molecular mechanism of lysis is still poorly understood. CMIV gene and mutant CMIV gene in GST fusion system were expressed. After cleaving with different cleavage reagents, the peptide with an excess of N-terminus and with an un-amidated C-terminus stopped the activity while the peptide with an excess Asn at the C-terminus had the activity level the same as natural CMIV. The results showed that the terminal structure of cecropin CMIV played an important role in its biological activity.

  16. Boron Plays an Important Role in the Regulation of Plant Cell Growth

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Boron is an essential nutrition for higher plants.However, the primary function of boron remains a matter of discussion.Boron may function by forming complexes with compounds having cis-hydroxyl groups(diols), e.g., pectic materials in cell walls, glycoproteins or glycolipids in membranes and o-diphenols.The well-defined functions of boron are its involvement in maintaining cell wall structure and both the structural and the functional integrity of plasma membrane.Lack of boron causes an increase in the leakage of ions and compounds which reflects the impairment of plasma membrane.Boron is functionally important in forming a pectic network in cell wall which is responsible for the extensibility of cell wall and consequently regulates cell growth.

  17. Functional importance of PAI-1 glycosylation

    DEFF Research Database (Denmark)

    Christensen, Anni; Naessens, Dominik; Skottrup, Peter

    2001-01-01

    Structure-function studies of plasminogen activator inhibitor-1 (PAI-1) have previously been performed mostly with non-glycosylated material expressed in E. coli. We have now studied the importance of PAI-1 glycosylation for its functional properties. PAI-1 has 3 potential sites for N......-linked glycosylation. Biochemical analysis of PAI-1 variants with substitutions of the Asn residues in each of these sites and expression in human embryonic kidney 293 (HEK293) cells showed that only Asn211 and Asn 267, but not Asn331 are glycosylated, and revealed a differential composition of the carbohydrate...... attached at the 2 sites. Analysing the susceptibility of glycosylated and non-glycosylated PAI-1 to activity neutralisation by monoclonal antibodies, we found that the IC50-values for neutralisation by some monoclonal antibodies differed strongly between glycosylated and non-glycosylated PAI-1. The most...

  18. Acute Effects of Exercise, Physically Active Video Game Play, and Inactive Video Game Play on Executive Functioning Skills in Children

    OpenAIRE

    Flynn, Rachel Marie

    2013-01-01

    Interactive media plays a central role in children's lives, however limited research has examined the impact of interactive media on children's cognitive development. Past research has suggested that exercise and video game play can improve executive functioning (EF) skills in both the short and long term. EF is a cluster of higher order cognitive skills, including selective attention and inhibition, which work together to coordinate higher order functioning. Interventions that improve EF ...

  19. AtTMEM18 plays important roles in pollen tube and vegetative growth in Arabidopsis

    Institute of Scientific and Technical Information of China (English)

    Xiao-Ying Dou; Ke-Zhen Yang; Zhao-Xia Ma; Li-Qun Chen; Xue-Qin Zhang; Jin-Rong Bai; De Ye

    2016-01-01

    In flowering plants, pol en tube growth is essential for delivery of male gametes into the female gametophyte or embryo sac for double fertilization. Although many genes have been identified as being involved in the process, the molecular mechanisms of pol en tube growth remains poorly understood. In this study, we identified that the Arabidopsis Transmembrane Protein 18 (AtTMEM18) gene played important roles in pol en tube growth. The AtTMEM18 shares a high similarity with the Transmembrane 18 proteins (TMEM18s) that are conserved in most eukaryotes and may play important roles in obesity in humans. Mutation in the AtTMEM18 by a Ds insertion caused abnormal cal ose deposition in the pol en grains and had a significant impact on pol en germination and pol en tube growth. AtTMEM18 is expressed in pol en grains, pol en tubes, root tips and other vegetative tissues. The pol en-rescued assays showed that the mutation in AtTMEM18 also caused defects in roots, stems, leaves and transmitting tracts. AtTMEM18-GFP was located around the nuclei. Genetic assays demonstrated that the localization of AtTMEM18 around the nuclei in the generative cel s of pol en grains was essential for the male fertility. Furthermore, expression of the rice TMEM18-homologous protein (OsTMEM18) driven by LAT52 promoter could recover the fertility of the Arabidopsis attmem18 mutant. These results suggested that the TMEM18 is important for plant growth in Arabidopsis.

  20. Clinically important factors influencing endothelial function.

    Science.gov (United States)

    Vapaatalo, H; Mervaala, E

    2001-01-01

    The endothelium, a continuous cellular monolayer lining the blood vessels, has an enormous range of important homeostatic roles. It serves and participates in highly active metabolic and regulatory functions including control of primary hemostasis, blood coagulation and fibrinolysis, platelet and leukocyte interactions with the vessel wall, interaction with lipoprotein metabolism, presentation of histocompatibility antigens, regulation of vascular tone and growth and further of blood pressure. Many crucial vasoactive endogenous compounds like prostacyclin, thromboxane, nitric oxide, endothelin, angiotensin, endothelium derived hyperpolarizing factor, free radicals and bradykinin are formed in the endothelial cells to control the functions of vascular smooth muscle cells and of circulating blood cells. These versatile and complex systems and cellular interactions are extremely vulnerable. The balances may be disturbed by numerous endogenous and exogenous factors including psychological and physical stress, disease states characterized by vasospasm, inflammation, leukocyte and platelet adhesion and aggregation, thrombosis, abnormal vascular proliferation, atherosclerosis and hypertension. The endothelial cells are also the site of action of many drugs and exogenous toxic substances (e.g. smoking, alcohol). As markers and assays for endothelial dysfunction, direct measurement of nitric oxide, its metabolites from plasma and urine, functional measurement of vascular nitric oxide dependent responses and assay of different circulating markers have been used. In numerous pathological conditions (e.g. atherosclerosis, hypertension, congestive heart failure, hyperhomocysteinemia, diabetes, renal failure, transplantation, liver cirrhosis) endothelial dysfunction has been described to exist. Some of them, as well as hormonal and nutritional factors and drug treatment will be discussed in this short review.

  1. Mechanical factors play an important role in pectus excavatum with thoracic scoliosis

    Directory of Open Access Journals (Sweden)

    Wang Yuncang

    2012-11-01

    Full Text Available Abstract Background This study investigated the incidence, imaging characteristics and mechanical factors in scoliotic patients with pectus excavatum. Methods A total of 142 scoliostic patients with pectus excavatum were evaluated prior to operation. The evaluation included a complete physical exam, phenotype and severity of the pectus excavatum, incidence and severity of scoliosis, and analysis of radiological images, including calculation of the Haller index. Results Twenty five out of 142 patients (17.61% with pectus excavatum had scoliosis with a Cobb angle >10 degrees, and in 80.00% of the cases the spinal column was bent to the right. Seventeen patients had bent-to-the-right spines that involved the 6th to 10 th thoracic vertebrae. We found that 23 out of 25 patients with a Cobb angle more than 10° were teenagers and adults. The incidence of scoliosis was only 6.06% in the children under 11 years whereas it was 21.79% in the teenage group. Conclusions Mechanical forces appear to play a role in the coexistence of pectus excavatum and scoliosis. There is a relationship between age, severity (Haller index, asymmetry and scoliosis. The heart and mediastinum play a role in providing an outward force to the left of the sternum which may be an important reason for the coexistence of pectus excavatum and scoliosis, but the correlation needs further proof.

  2. Phosphorus plays an important role in enhancing biodiesel productivity of Chlorella vulgaris under nitrogen deficiency.

    Science.gov (United States)

    Chu, Fei-Fei; Chu, Pei-Na; Cai, Pei-Jie; Li, Wen-Wei; Lam, Paul K S; Zeng, Raymond J

    2013-04-01

    To investigate the role of phosphorus in lipid production under nitrogen starvation conditions, five types of media possessing different nitrogen and phosphorus concentrations or their combination were prepared to culture Chlorella vulgaris. It was found that biomass production under nitrogen deficient condition with sufficient phosphorus supply was similar to that of the control (with sufficient nutrition), resulting in a maximum lipid productivity of 58.39 mg/L/day. Meanwhile, 31P NMR showed that phosphorus in the medium was transformed and accumulated as polyphosphate in cells. The uptake rate of phosphorus in cells was 3.8 times higher than the uptake rate of the control. This study demonstrates that phosphorus plays an important role in lipid production of C. vulgaris under nitrogen deficient conditions and implies a potential to combine phosphorus removal from wastewater with biodiesel production via microalgae.

  3. An Na+/H+ antiporter gene from wheat plays an important role in stress tolerance

    Indian Academy of Sciences (India)

    Jia Ning Yu; Jian Huang; Zi Ning Wang; Jin Song Zhang; Shou Yi Chen

    2007-09-01

    A vacuole Na+/H+ antiporter gene TaNHX2 was obtained by screening the wheat cDNA library and by the 5′-RACE method. The expression of TaNHX2 was induced in roots and leaves by treatment with NaCl, polyethylene glycol (PEG), cold and abscisic acid (ABA). When expressed in a yeast mutant (nhx1), TaNHX2 suppressed the salt sensitivity of the mutant, which was deficient in vacuolar Na+/H+ antiporter, and caused partial recovery of growth of nhx1 in NaCl and LiCl media. The survival rate of yeast cells was improved by overexpressing the TaNHX2 gene under NaCl, KCl, sorbitol and freezing stresses when compared with the control. The results imply that TaNHX2 might play an important role in salt and osmotic stress tolerance in plant cells.

  4. Surface proteins of Staphylococcus aureus play an important role in experimental skin infection.

    Science.gov (United States)

    Kwiecinski, Jakub; Jin, Tao; Josefsson, Elisabet

    2014-12-01

    Staphylococcus aureus is the most common cause of skin infections that range from mild diseases up to life-threatening conditions. Mechanisms of S. aureus virulence in those infections remain poorly studied. To investigate the impact of S. aureus surface proteins on skin infection, we used mouse models of skin abscess formation and skin necrosis, induced by a subcutaneous injection of bacteria. In the skin abscess model, a sortase-deficient S. aureus strain lacking all of its cell-wall anchored proteins was less virulent than its wild-type strain. Also, strains specifically lacking protein A, fibronecting binding proteins, clumping factor A or surface protein SasF were impaired in their virulence. When a model of dermonecrosis was studied, the S. aureus surface proteins could not be shown to be involved. In summary, surface proteins play an important role in virulence of S. aureus skin abscess infections, but not in formation of skin necrosis.

  5. [Does the diuretic effect of calcium inhibitors play an important role in the hypertensive efficacy?].

    Science.gov (United States)

    Maldonado Martin, A; Gil Extremera, B; Rubio Luengo, M A

    1995-04-08

    Calcium ions play an important role in the pathophysiology of hypertension. Calcium antagonists, a group of first line drugs in the treatment of hypertension, reduce the intracellular content of calcium in vascular smooth muscle cells, and decrease the peripheral vascular resistance and blood pressure. These drugs differ from other vasodilators in that they also have natriuretic effects; thus they can affect the kidney on three levels: Renal haemodynamics are affected by increased renal blood flow, and increased glomerular filtration rate. Changes in the renin-angiotensin system can decrease aldosterone secretion. Finally, they affect sodium management by acting directly on the renal tubule, increasing sodium excretion and inhibiting tubular reabsorption of this ion. The natriuretic effect of calcium antagonists is independent of the subject's sodium balance. The vasodilating action of these drugs is therefore accompanied by a natriuretic effect that makes satisfactory control of hypertension possible without placing the patient on a low-salt or salt-free diet.

  6. The ZupT transporter plays an important role in zinc homeostasis and contributes to Salmonella enterica virulence

    Science.gov (United States)

    Cerasi, Mauro; Liu, Janet Z.; Ammendola, Serena; Poe, Adam J.; Petrarca, Patrizia; Pesciaroli, Michele; Pasquali, Paolo; Raffatellu, Manuela; Battistoni, Andrea

    2014-01-01

    Zinc is an essential metal for cellular homeostasis and function in both eukaryotes and prokaryotes. To acquire this essential nutrient, bacteria employ transporters characterized by different affinity for the metal. Several studies have investigated the role of the high affinity transporter ZnuABC in the bacterial response to zinc shortage, showing that this transporter has a key role in adapting bacteria to zinc starvation. In contrast, the role of the low affinity zinc importer ZupT has been the object of limited investigations. Here we show that a Salmonella strain lacking ZupT is impaired in its ability to grow in metal devoid environments and that a znuABC zupT strain exhibits a severe growth defect in zinc devoid media, is hypersensitive to oxidative stress and contains reduced level of intracellular free zinc. Moreover, we show that ZupT plays a role also in the ability of S. Typhimurim to colonize the host tissues. During systemic infections, the single zupT mutant strain was attenuated only in Nramp1+/+ mice, but competition experiments between znuABC and znuABC zupT mutants revealed that ZupT contributes to metal uptake in vivo independently from the presence a functional Nramp1 transporter. Altogether, the here reported results show that ZupT plays an important role in Salmonella zinc homeostasis, being involved in metal import both in vitro and in infected animals. PMID:24430377

  7. How Much Do We Know about the Importance of Play in Child Development? Review of Research.

    Science.gov (United States)

    Tsao, Ling-Ling

    2002-01-01

    Discusses children's play in conjunction with intellectual development, language, and social benefits. Suggests that play develops personality, encourages personal relations, stimulates creativity, adds to happiness, and advances learning. Encourages parents and teachers to provide children with richly varied play experiences to promote cognition,…

  8. Transcription Factor ets-2 Plays an Important Role in the Pathogenesis of Pulmonary Fibrosis

    Science.gov (United States)

    Baran, Christopher P.; Fischer, Sara N.; Nuovo, Gerard J.; Kabbout, Mohamed N.; Hitchcock, Charles L.; Bringardner, Benjamin D.; McMaken, Sara; Newland, Christie A.; Cantemir-Stone, Carmen Z.; Phillips, Gary S.; Ostrowski, Michael C.

    2011-01-01

    Ets-2 is a ubiquitous transcription factor activated after phosphorylation at threonine-72. Previous studies highlighted the importance of phosphorylated ets-2 in lung inflammation and extracellular matrix remodeling, two pathways involved in pulmonary fibrosis. We hypothesized that phosphorylated ets-2 played an important role in pulmonary fibrosis, and we sought to determine the role of ets-2 in its pathogenesis. We challenged ets-2 (A72/A72) transgenic mice (harboring a mutated form of ets-2 at phosphorylation site threonine-72) and ets-2 (wild-type/wild-type [WT/WT]) control mice with sequential intraperitoneal injections of bleomycin, followed by quantitative measurements of lung fibrosis and inflammation and primary cell in vitro assays. Concentrations of phosphorylated ets-2 were detected via the single and dual immunohistochemical staining of murine lungs and lung sections from patients with idiopathic pulmonary fibrosis. Ets-2 (A72/A72) mice were protected from bleomycin-induced pulmonary fibrosis, compared with ets-2 (WT/WT) mice. This protection was characterized by decreased lung pathological abnormalities and the fibrotic gene expression of Type I collagen, Type III collagen, α–smooth muscle actin, and connective tissue growth factor. Immunohistochemical staining of lung sections from bleomycin-treated ets-2 (WT/WT) mice and from patients with idiopathic pulmonary fibrosis demonstrated increased staining of phosphorylated ets-2 that colocalized with Type I collagen expression and to fibroblastic foci. Lastly, primary lung fibroblasts from ets-2 (A72/A72) mice exhibited decreased expression of Type I collagen in response to stimulation with TGF-β, compared with fibroblasts from ets-2 (WT/WT) mice. These data indicate the importance of phosphorylated ets-2 in the pathogenesis of pulmonary fibrosis through the expression of Type I collagen and (myo)fibroblast activation. PMID:21562315

  9. Importance and functions of European grasslands.

    Science.gov (United States)

    Carlier, L; De Vliegher, A; Van Cleemput, O; Boeckx, P

    2005-01-01

    The European agricultural policy is not simple and needs to accommodate also social and environmental requirements. Grassland will continue to be an important form of land use in Europe, but with increased diversity in management objectives and systems used. Besides its role as basic nutrient for herbivores and ruminants grasslands have opportunities for adding value by exploiting positive health characteristics in animal products from grassland and through the delivery of environmental benefits. In fact grasslands contribute to a high degree to the struggle against erosion and to the regularizing of water regimes, to the purification of fertilizers and pesticides and to biodiversity. Finally they have aesthetic role and recreational function as far as they provide public access that other agricultural uses do not allow. But even for grassland it is very difficult to create a good frame for its different tasks (1) the provision of forage for livestock, (2) protection and conservation of soil and water resources, (3) furnishing a habitat for wildlife, both flora and fauna and (4) contribution to the attractiveness of the landscape. Nevertheless it is the only crop, able to fulfil so many tasks and to fit so many requirements.

  10. Did large animals play an important role in global biogeochemical cycling in the past?

    Science.gov (United States)

    Doughty, C.

    2014-12-01

    In the late Pleistocene (~50-10,000 years ago), ninety-seven genera of large animals (>44kg) (megafauna) went extinct, concentrated in the Americas and Australia. The loss of megafauna had major effects on ecosystem structure, seed dispersal and land surface albedo. However, the impact of this dramatic extinction on ecosystem nutrient biogeochemistry, through the lateral transport of dung and bodies, has never been explored. Here we explore these nutrient impacts using a novel mathematical framework that analyses this lateral transport as a diffusion-like process and demonstrates that large animals play a disproportionately large role in the horizontal transfer of nutrients across landscapes. For example, we estimate that the extinction of the Amazonian megafauna led to a >98% reduction in the lateral transfer flux of the limiting nutrient phosphorus (P) with similar, though less extreme, decreases in all continents outside of Africa. This resulted in strong decreases in phosphorus availability in Eastern Amazonia away from fertile floodplains, a decline which may still be ongoing, and current P limitation in the Amazon basin may be partially a relic of an ecosystem without the functional connectedness it once had. More broadly, the Pleistocene megafaunal extinctions resulted in major and ongoing disruptions to terrestrial biogeochemical cycling at continental scales and increased nutrient heterogeneity globally.

  11. Daily temperature extremes play an important role in predicting thermal effects.

    Science.gov (United States)

    Ma, Gang; Hoffmann, Ary A; Ma, Chun-Sen

    2015-07-01

    Organisms in natural environments experience diel temperature fluctuations, including sporadic extreme conditions, rather than constant temperatures. Studies based mainly on model organisms have tended to focus on responses to average temperatures or short-term heat stress, which overlooks the potential impact of daily fluctuations, including stressful daytime periods and milder night-time periods. Here, we focus on daily maximum temperatures, while holding night-time temperatures constant, to specifically investigate the effects of high temperature on demographic parameters and fitness in the English grain aphid Sitobion avenae. We then compared the observed effects of different daily maximum temperatures with predictions from constant temperature-performance expectations. Moderate daily maximum temperatures depressed aphid performance while extreme conditions had dramatic effects, even when mean temperatures were below the critical maximum. Predictions based on daily average temperature underestimated negative effects of temperature on performance by ignoring daily maximum temperature, while predictions based on daytime maximum temperatures overestimated detrimental impacts by ignoring recovery under mild night-time temperatures. Our findings suggest that daily maximum temperature will play an important role in regulating natural population dynamics and should be considered in predictions. These findings have implications for natural population dynamics, particularly when considering the expected increase in extreme temperature events under climate change.

  12. Biotransformation effect of Bombyx Mori L. may play an important role in treating diabetic nephropathy.

    Science.gov (United States)

    Zhang, Lei; Zhang, La; Li, Yin; Guo, Xin-Feng; Liu, Xu-Sheng

    2016-11-01

    Compared with herbal drugs, medicine processed from animals (animal medicine) was thought to have more bioactive substances and higher activities. Biotransformation effect often plays an important role in their effect. However, researches about effect of animal medicine on diabetic nephropathy and applying animal medicine as natural bio-transformer were seldom reported. The purpose of this paper was to reveal the use of Bombyx Mori L. on diabetic nephropathy from ancient to modern times. The classical literature indicated that Saosi Decoction (), which contains Bombyx Mori L. or silkworm cocoon, was applied to treat disorders congruent with modern disease diabetic nephropathy from the Ming to Qing Dynasty in ancient China. Modern studies showed that Bombyx Mori L. contains four main active constituents. Among these, 1-deoxynojirimycin (1-DNJ) and quercetin showed promising potential to be new agents in diabetic nephropathy treatment. The concentrations of 1-DNJ and the activities of quercetin in Bombyx Mori L. are higher than in mulberry leaves, because of the biotransformation in the Bombyx Mori L. body. However, these specifific components need further human and mechanistic studies to determine their therapeutic potential for this challenging condition.

  13. MiR-378 Plays an Important Role in the Differentiation of Bovine Preadipocytes

    Directory of Open Access Journals (Sweden)

    Si-Yuan Liu

    2015-07-01

    Full Text Available Background: Adipocyte, the main cellular component of white adipose tissue, plays a vital role in energy balance in higher eukaryotes. In recent years, adipocytes have also been identified as a major endocrine organ involved in immunological responses, vascular diseases, and appetite regulation. In farm animals, fat content and categories are closely correlated with meat quality. MicroRNAs (miRNAs, a class of endogenous single-stranded non-coding RNA molecules, participate in the regulation of adipocyte differentiation and adipogenesis through regulating the transcription or translation of target mRNAs. MiR-378 plays an important role in a number of biological processes, including cell growth, cell differentiation, tumor cell survival and angiogenesis. Methods: In the present study, bioinformatics analysis and dual-luciferase reporter assay were used to identify and validate the target genes of miR-378. In vitro cell transfection, quantitative reverse transcription polymerase chain reaction (RT-qPCR, western blot analysis, Oil Red O staining, and triglyceride content measurement were conducted to analyze the effects of miR-378 on bovine preadipocyte differentiation. Results: MiR-378 was induced during adipocyte differentiation. In the differentiated adipocytes overexpressing miR-378, the volume of lipid droplets was enlarged, and the triglyceride content was increased. Moreover, the mRNA expression levels of the adipocyte differentiation marker genes, peroxisome proliferator-activated receptor gamma (PPARγ and sterol regulatory element-binding protein (SREBP, were significantly elevated in the differentiated, mature adipocytes. In contrast, the mRNA expression level of preadipocyte factor 1 (Pref-1 was markedly reduced. E2F transcription factor 2 (E2F2 and Ras-related nuclear (RAN-binding protein 10 (RANBP10 were the two target genes of miR-378. The mRNA expression levels of E2F2 and RANBP10 did not significantly change in bovine preadipocytes

  14. Does elevated osteopontin level play an important role in the development of scoliosis in bipedal mice?

    Science.gov (United States)

    Xie, Ning; Li, Mo; Wu, Tao; Liu, Jun; Wang, Binbin; Tang, Feng

    2015-07-01

    Previous studies implied indirectly that an elevated osteopontin (OPN) level might play a key role in the pathomechanism of adolescent idiopathic scoliosis. Nonetheless, up to now, no direct evidence was proposed to determine this issue. The aim was to determine the role of OPN in the pathomechanism of scoliosis. This was an experimental study to investigate the role of OPN in a bipedal mouse scoliosis model. All procedures were performed under the approval and supervision of the Institutional Animal Care and Use Committee of our university. A new bipedal mouse model with elevated OPN level was established in this study. Amputation of forelimbs and tail was performed on 80 male C3H/HeJ mice at the age of 3 weeks. Then, these mice were randomly divided into two groups: Group A consisted of 40 mice treated with OPN 40 mg/kg daily and Group B consisted of the remaining 40 mice treated with saline. Then, 40 quadruped mice with saline were included in Group C. Body length, X-rays, and computed tomographic scans were obtained at the twentieth week. Then, scoliosis incidence, curve magnitude, and circulating OPN level were compared among groups. Osteopontin level was significantly higher in Group A compared with that in Groups B and C. Spine deformity was identified in 37 mice in Group A, 21 mice in Group B, and 5 mice in Group C. The average Cobb angle was 29.8° in Group A, 20.9° in Group B, and 17.5° in Group C. Although no significant difference of body length was found, significant statistical difference was noted in terms of scoliosis incidence and curve magnitude, among the three groups. The results of the present study indicated that the elevated OPN level might play an important role in the etiopathogenesis of scoliosis, that is, it not only raises the risk for scoliosis in bipedal mice but also contributes to curve progression. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. PGK1, a glucose metabolism enzyme, may play an important role in rheumatoid arthritis.

    Science.gov (United States)

    Zhao, Yan; Yan, Xinfeng; Li, Xia; Zheng, Yabing; Li, Shufeng; Chang, Xiaotian

    2016-10-01

    Some studies have indicated that glucose metabolism plays an important role in the pathogenesis of rheumatoid arthritis (RA). This study aimed to find the novel genes affecting glucose metabolism in RA. Synovial tissues of collagen-induced arthritis (CIA) were analyzed with Rat Glucose Metabolism RT(2) Profiler™ PCR Array to screen those genes with special expressions in glucose metabolism. Real-time PCR, western blotting, and ELISA were used to confirm the result in synovial tissues and blood of human RA. Culture synovial fibroblast cells (RASF) was treated with siRNA to suppress expressions of the target genes. CCK-8 cell proliferation assay and two-compartment transwell system were performed to examine cell proliferation and cell migration of the treated RASF. Both PCR array and real-time PCR detected the up-regulation of ENO1, HK2, and PGK1 and the down-regulation of PCK1 and PDK4 in synovial tissues of CIA rats. Real-time PCR and western blotting detected the increased expression of ENO1 and PGK1 in RA synovial tissues. ELISA detected a high level of PGK1 in the blood of RA patients. Decreased cell proliferation and cell migration capabilities were significantly detected in RASF following treatment of anti-PGK1 siRNA. IL-1β and IFN-γ rather than TNF-α and IL-1α levels were significantly declined in supernatants of the treated RASF. PGK1, a glycolytic enzyme catalyzing the conversion of 3-phosphoglycerate into 2-phosphoglycerate, has increased expression in synovial tissues and blood of RA, which may be involved in pro-inflammation and synovial hyperplasia of the disease.

  16. Male Parent Plays More Important Role in Heat Tolerance in Three-Line Hybrid Rice

    Directory of Open Access Journals (Sweden)

    Fu Guan-fu

    2015-05-01

    Full Text Available Ten F1 combinations with their male and female parents were employed to evaluate their heat tolerance during the flowering and early grain filling stages. The rice plants were subjected to heat stress (39 °C–43 °C for 1–15 d during flowering. Based on the heat stress index, heat tolerance was only observed in the F1 combinations H2 (K22A × R207, H3 (Bobai A × R207 and H4 (Bobai A × Minghui 63, whereas the others received above 0.5000 of heat stress index. Both parents of the tolerant combination (heat-tolerant × heat-tolerant possessed heat tolerance, whereas the susceptible combinations were crossed by heat-tolerant (sterile lines × heat-susceptible (restorer lines, heat-susceptible × heat-tolerant, or heat-susceptible × heat-susceptible parents. This result indicated that heat tolerance in rice was controlled by recessive genes. Thus, both parents should possess high temperature tolerance to develop heat-tolerant F1 combinations. Furthermore, the heat stress index of F1 combinations was significantly correlated with the heat stress index of restorer lines but not with the heat stress index of maintainer lines. This result suggested that male parents play a more important role in heat-tolerant combinations than female parents. Therefore, the heat susceptibility of the hybrid rice in China is mainly due to the wide application of low-heat-tolerant restorer lines with high yield in three-line hybrid rice breeding.

  17. Subequatorial cytoplasm plays an important role in ectoderm patterning in the sea urchin embryo.

    Science.gov (United States)

    Kominami, Tetsuya; Akagawa, Megumi; Takata, Hiromi

    2006-02-01

    To gain information on the process of ectoderm patterning, the animal halves of sea urchin embryos were isolated at various stages, and their morphology was examined when control embryos developed into pluteus larvae. The animal halves separated at the 8-cell stage developed into 'dauerblastula', without showing any conspicuous ectoderm differentiation. In contrast, some of the animal halves isolated at the 60-cell stage (after the sixth cleavage) formed a ciliated band and oral opening, suggesting that some patterning signal was transmitted from the vegetal to animal hemisphere during early cleavage. Further patterning of the animal hemisphere did not seem to occur until hatching, since both the animal halves isolated at the 60-cell stage and hatching stage showed the same degree of ectoderm patterning. After hatching, the later animal halves were isolated, the more patterned ectoderm they formed. The animal halves isolated just prior to gastrulation differentiated well-patterned ectoderm. It is of note, however, that the level of separation was a more crucial factor than the timing of separation; even the animal fragments of newly hatched embryos differentiated well-patterned ectoderm if they had been separated at a subequatorial level. This suggests that the signal for ectoderm patterning is transmitted over the equator after hatching, and once the cells in the supra-equatorial region receive the signal, they, in turn, can transmit the signal upwardly. Interestingly, if the third cleavage plane was shifted toward the vegetal pole, the isolated animal pole-side fragments developed into 'embryoids' with fully patterned ectoderm. These results indicate that not the micromere descendants but the subequatorial cytoplasm plays an important role in ectoderm patterning.

  18. Stereotypy in Autism: The Importance of Function

    Science.gov (United States)

    Cunningham, Allison B.; Schreibman, Laura

    2008-01-01

    We argue for the utility of a functional definition of stereotypy based on evidence of both sensory automatic and socially mediated reinforcement contingencies in the occurrence of stereotypy in children with autism. A predetermined sensory function of stereotypy is often invoked in the behavioral literature and the term "self-stimulatory…

  19. Intercellular Trogocytosis Plays an Important Role in Modulation of Immune Responses

    Institute of Scientific and Technical Information of China (English)

    Khawaja Ashfaque Ahmed; Manjunatha Ankathatti Munegowda; Yufeng Xie; Jim Xiang

    2008-01-01

    Intercellular communication is an important means of molecular information transfer through exchange of membrane proteins from cells to cells. Advent of the latest analytical and imaging tools has allowed us to enhance our understanding of the cellular communication through the intercellular exchange of intact membrane patches, also called trogocytosis, which is a ubiquitous phenomenon. Immune responses against pathogens or any foreign antigens require fine immune regulation, where cellular communications are mediated by either soluble or cell surface molecules. It has been demonstrated that the membrane molecule transfer between immune cells such as dendritic and T cells can be derived through internalization/recycling pathway, dissociation-associated pathway, uptake of exosomes and membrane nanotube formations. Recent evidence implicates the trogocytosis as an important mechanism of the immune system to modulate immune responses. Exchange of membrane molecules/ antigens between immune cells has been observed for a long time, but the mechanisms and functional consequences of these transfers remain unclear. In this review, we discuss the possible mechanisms of trogocytosis and its physiological relevance to immune system, with special reference to T cells and the stimulatory or suppressive immune responses derived from T cells with acquired dendritic cell membrane molecules. Cellular & Molecular Immunology. 2008;5(4):261-269.

  20. Playing in childhood: importance and singularities for children with visual impairment

    Directory of Open Access Journals (Sweden)

    Tania Mara Zancanaro Pieczkowski

    2017-01-01

    Full Text Available This study investigated what kind of playing and how visually impaired children play in the family and educational contexts, aiming at understanding playing and the role of toys in these children‟s development. The study was based on the historical-cultural perspective, mainly considering Vygotsky‟s studies. Empirical material was collected from five families with blind or short-sighted children and from the specialized institution these children attend. We adopted semi-structured interviews with parents and educators and observation of the relevant contexts. The data collected was categorized and theorized through content analysis. We concluded that the mediation of another person during playing enables the visually impaired child to develop confidence to explore the physical space, objects and to elaborate concepts.

  1. Gravity Plays an Important Role in Muscle Development and the Differentiation of Contractile Protein Phenotype

    Science.gov (United States)

    Adams, Gregory A.; Haddad, Fadia; Baldwin, Kenneth M.

    2003-01-01

    Several muscles in the body exist mainly to work against gravity. Whether gravity is important in the development of these muscles is not known. By examining the basic proteins that compose muscle, questions about the role of gravity in muscle development can be answered. Myosin heavy chains (MHCs) are a family of proteins critically important for muscle contraction. Several types of MHCs exist (e.g., neonatal, slow, fast), and each type is produced by a particular gene. Neonatal MHCs are produced early in life. Slow MHCs are important in antigravity muscles, and fast MHCs are found in fast-twitch power muscles. The gene that is turned on or expressed will determine which MHC is produced. Early in development, antigravity skeletal muscles (muscles that work against gravity) normally produce a combination of the neonatal/embryonic MHCs. The expression of these primitive MHCs is repressed early in development; and the adult slow and fast MHC genes become fully expressed. We tested the hypothesis that weightbearing activity is critical for inducing the normal expression of the slow MHC gene typically expressed in adult antigravity muscles. Also, we hypothesized that thyroid hormone, but not opposition to gravity, is necessary for expressing the adult fast IIb MHC gene essential for high-intensity muscle performance. Groups of normal thyroid and thyroid-deficient neonatal rats were studied after their return from the 16-day Neurolab mission and compared to matched controls. The results suggest: (1) Weightlessness impaired body and limb skeletal muscle growth in both normal and thyroid-deficient animals. Antigravity muscles were impaired more than those used primarily for locomotion andor nonweightbearing activity. (2) Systemic and muscle expression of insulin-like growth factor-I (IGF-I), an important body and tissue growth factor, was depressed in flight animals. (3) Normal slow, type I MHC gene expression was markedly repressed in the normal thyroid flight group. (4

  2. The Function of Play in Bruno Munari’s Children’s Books. A Historical Overview

    Directory of Open Access Journals (Sweden)

    Marnie Campagnaro

    2016-11-01

    Full Text Available The ludic dimension of Bruno Munari’s prolific children’s book publishing activity plays an important role, as far as narration and visual arts are concerned. Since the 1940s, and for the following 50 years, books, play and education were fundamental reference points in the artistic production and critical thinking of this Milanese artist. Munari cultivated these influences with extraordinary results in his picturebooks. The following analysis of some of Munari’s texts offers a historical-critical perspective on the value, function and representation of play in this vast production. The present research relies on three main analytical categories: co-authorship, disorientation and the experience of the limit.

  3. Soil water content plays an important role in soil-atmosphere exchange of carbonyl sulfide (OCS)

    Science.gov (United States)

    Yi, Zhigang; Behrendt, Thomas; Bunk, Rüdiger; Wu, Dianming; Kesselmeier, Jürgen

    2016-04-01

    Carbonyl sulfide (OCS) is a quite stable gas in the troposphere and is transported up to the stratosphere, where it contributes to the sulfate aerosol layer (Crutzen 1976). The tropospheric concentration seems to be quite constant, indicating a balance between sinks and sources. Recent work by Sandoval-Soto et al. (2005) demonstrated the enormous strength of the vegetation sink and the urgent needs to understand the sinks and sources. The role of soils is a matter of discussion (Kesselmeier et al., 1999; Van Diest and Kesselmeier, 2008; Maseyk et al., 2014; Whelan et al., 2015). To better understand the influence of soil water content and OCS mixing ratio on OCS fluxes, we used an OCS analyzer (LGR COS/CO Analyzer 907-0028, Los Gatos, CA, USA) coupled with automated soil chamber system (Behrendt et al., 2014) to measure the OCS fluxes with a slow drying of four different types of soil (arable wheat soil in Mainz, blueberry soil in Waldstein, spruce soil in Waldstein and needle forest soil in Finland). Results showed that OCS fluxes as well as the optimum soil water content for OCS uptake varied significantly for different soils. The net production rates changed significantly with the soil drying out from 100% to about 5% water holding capacity (WHC), implying that soil water content play an important role in the uptake processes. The production and uptake processes were distinguished by the regression of OCS fluxes under different OCS mixing ratios. OCS compensation points (CP) were found to differ significantly for different soil types and water content, with the lowest CP at about 20% WHC, implying that when estimating the global budgets of OCS, especially for soils fluxes, soil water content should be taken into serious consideration. References Crutzen, P. J. 1976, Geophys. Res. Lett., 3, 73-76. Sandoval-Soto, L. et al., 2005, Biogeosciences, 2, 125-132. Kesselmeier, J. et al., 1999, J. Geophys. Res., 104, 11577-11584. Van Diest, H. and Kesselmeier, J. 2008

  4. Functional Importance of Mobile Ribosomal Proteins.

    Science.gov (United States)

    Chang, Kai-Chun; Wen, Jin-Der; Yang, Lee-Wei

    2015-01-01

    Although the dynamic motions and peptidyl transferase activity seem to be embedded in the rRNAs, the ribosome contains more than 50 ribosomal proteins (r-proteins), whose functions remain largely elusive. Also, the precise forms of some of these r-proteins, as being part of the ribosome, are not structurally solved due to their high flexibility, which hinders the efforts in their functional elucidation. Owing to recent advances in cryo-electron microscopy, single-molecule techniques, and theoretical modeling, much has been learned about the dynamics of these r-proteins. Surprisingly, allosteric regulations have been found in between spatially separated components as distant as those in the opposite sides of the ribosome. Here, we focus on the functional roles and intricate regulations of the mobile L1 and L12 stalks and L9 and S1 proteins. Conformational flexibility also enables versatile functions for r-proteins beyond translation. The arrangement of r-proteins may be under evolutionary pressure that fine-tunes mass distributions for optimal structural dynamics and catalytic activity of the ribosome.

  5. Estimating the Importance of Differential Item Functioning.

    Science.gov (United States)

    Rudas, Tamas; Zwick, Rebecca

    1997-01-01

    The mixture index of fit (T. Rudas et al, 1994) is used to estimate the fraction of a population for which differential item functioning (DIF) occurs, and this approach is compared to the Mantel Haenszel test of DIF. The proposed noniterative procedure provides information about data portions contributing to DIF. (SLD)

  6. Estimating the Importance of Differential Item Functioning.

    Science.gov (United States)

    Rudas, Tamas; Zwick, Rebecca

    1997-01-01

    The mixture index of fit (T. Rudas et al, 1994) is used to estimate the fraction of a population for which differential item functioning (DIF) occurs, and this approach is compared to the Mantel Haenszel test of DIF. The proposed noniterative procedure provides information about data portions contributing to DIF. (SLD)

  7. 78 FR 77771 - Culturally Significant Object Imported for Exhibition Determinations: “Love and Play: A Pair of...

    Science.gov (United States)

    2013-12-24

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF STATE Culturally Significant Object Imported for Exhibition Determinations: ``Love and Play: A Pair of Paintings by..., I hereby determine that the object to be included in the exhibition ``Love and Play: A Pair...

  8. Critical importance of RAB proteins for synaptic function.

    Science.gov (United States)

    Mignogna, Maria Lidia; D'Adamo, Patrizia

    2017-02-01

    Neurons are highly polarized cells that exhibit one of the more complex morphology and function. Neuronal intracellular trafficking plays a key role in dictating the directionality and specificity of vesicle formation, transport and fusion, allowing the transmission of information in sophisticate cellular network. Thus, the integrity of protein trafficking and spatial organization is especially important in neuronal cells. RAB proteins, small monomeric GTPases belonging to the RAS superfamily, spatially and temporally orchestrate specific vesicular trafficking steps. In this review we summarise the known roles of RAB GTPases involved in the maintenance of neuronal vesicular trafficking in the central nervous system. In particular, we discriminate the axonal pre-synaptic trafficking and dendritic post-synaptic trafficking, to better underlie how a correct orchestration of vesicle movement is necessary to maintain neuronal polarity and then, to permit an accurate architecture and functionality of synaptic activity.

  9. The importance and possibilities of role playing on children surgery classes

    Directory of Open Access Journals (Sweden)

    Goremykin I.V.

    2014-03-01

    Full Text Available This article analyzes the first experience in the implementation into the pedagogical process of one of the methods of active training — role playing. The need for intensification of medical education process is linked primarily to the rapid increase in the volume required to provide students with information and the lack of training time. The analysis showed that the game significantly increases the level of students' knowledge, but require substantial modernization of the educational process.

  10. Molecular identification of three novel glutaredoxin genes that play important roles in antioxidant defense in Helicoverpa armigera.

    Science.gov (United States)

    Zhang, Song-Dou; Shen, Zhong-Jian; Liu, Xiao-Ming; Li, Zhen; Zhang, Qing-Wen; Liu, Xiao-Xia

    2016-08-01

    Glutaredoxins (Grxs), also known as thioltransferases, play key roles in maintaining intracellular redox balance and protecting cells from oxidative damage in plants and mammals. We tested whether Grxs play important roles in antioxidant defense in insects using the moth, Helicoverpa armigera. We obtained the full-length cDNA sequences of three novel Grx genes, named HaGrx, HaGrx3, and HaGrx5. Sequence analysis indicated that HaGrx shared a high amino acid identity (58%-78%) and a CPYC motif of conserved redox activity with homologues from other selected insect species. In contrast, HaGrx3 and HaGrx5 both shared a CGF(S/G) motif, a conserved catalytic domain, with other orthologous genes. Quantitative real-time PCR results revealed that HaGrx, HaGrx3, and HaGrx5 exhibited temporally- and spatially-dependent patterns of expression. The mRNA expression of HaGrx, HaGrx3, and HaGrx5 was induced by various temperature stresses and H2O2 treatments. We further investigated the knockdown of HaGrx, HaGrx3, and HaGrx5 in H. armigera larvae and found that most of the selected antioxidant genes were up regulated. However, Tpx was down regulated, and further interpretation of the complementary functions of these antioxidant genes is still required. We also determined the effect of HaGrx, HaGrx3, and HaGrx5 knockdown on antioxidant enzymatic activity and metabolite content. The enzymatic activities of SOD, CAT, and POD, and the metabolite contents of hydrogen peroxide, ascorbate, protein carbonyl, and total GSH increased after RNAi mediated knockdown of HaGrx, HaGrx3, and HaGrx5. These results supported our hypothesis that HaGrx, HaGrx3, and HaGrx5 play important roles in antioxidant defense of Helicoverpa armigera and provided a theoretical basis for further in-depth study of physiological function in the insect glutaredoxin family genes.

  11. NAC transcription factors play an important role in ethylene biosynthesis, reception and signaling of tomato fruit ripening.

    Science.gov (United States)

    Kou, Xiaohong; Liu, Chen; Han, Lihua; Wang, Shuang; Xue, Zhaohui

    2016-06-01

    NAC proteins comprise a large family of transcription factors that play important roles in diverse physiological processes during development. To explore the role of NAC transcription factors in the ripening of fruits, we predicted the secondary and tertiary structure as well as regulative function of the SNAC4 (SlNAC48, Accession number: NM 001279348.2) and SNAC9 (SlNAC19, Accession number: XM 004236996.2) transcription factors in tomato. We found that the tertiary structure of SNAC9 was similar to that of ATNAP, which played an important role in the fruit senescence and was required for ethylene stimulation. Likewise, the bio-function prediction results indicated that SNAC4 and SNAC9 participated in various plant hormone signaling and senescence processes. More information about SNACs was obtained by the application of VIGS (virus-induced gene silencing). The silencing of SNAC4 and SNAC9 dramatically repressed the LeACS2, LeACS4 and LeACO1 expression, which consequently led to the inhibition of the ripening process. The silencing of SNACs down-regulated the mRNA levels of the ethylene perception genes and, at the same time, suppressed the expression of ethylene signaling-related genes except for LeERF2 which was induced by the silencing of SNAC4. The expressions of LeRIN were different in two silenced fruits. In addition, the silencing of SNAC4 reduced its mRNA level, while the silencing of SNAC9 induced its expression. Furthermore, the silencing of LeACS4, LeACO1 and LeERF2 reduced the expression of SNAC4 and SNAC9, while the silencing of NR induced the expression of all of them. In particular, these results indicate that SNAC transcription factors bind to the promoter of the ethylene synthesis genes in vitro. This experimental evidence demonstrates that SNAC4 and SNAC9 could positively regulate the tomato fruit ripening process by functioning upstream of ethylene synthesis genes. These outcomes will be helpful to provide a theoretical foundation for further

  12. Dysregulation of JAM-A plays an important role in human tumor progression.

    Science.gov (United States)

    Zhao, Chen; Lu, Funian; Chen, Hongxia; Zhao, Xianda; Sun, Jun; Chen, Honglei

    2014-01-01

    Junctional adhesion molecule A (JAM-A) is a transmembrane protein that belongs to the immunoglobulin (Ig) superfamily. Evidence determines that JAM-A plays a role in numerous cellular processes, including tight junction assembly, leukocyte migration, platelet activation, angiogenesis and virus binding. Recent research suggests that JAM-A is dysregulated in various cancers and is vital for tumor progression. JAM-A is implicated in carcinogenesis via different signal pathways such as TGF-β1 signaling. Furthermore, JAM-A expression in cancers is usually associated with certain outcome of patients and might be a prognostic indicator. In this review, the correlation between JAM-A expression and human cancers will be described.

  13. The First Extracellular Domain Plays an Important Role in Unitary Channel Conductance of Cx50 Gap Junction Channels.

    Directory of Open Access Journals (Sweden)

    Xiaoling Tong

    Full Text Available Gap junction (GJ channels provide direct passage for ions and small molecules to be exchanged between neighbouring cells and are crucial for many physiological processes. GJ channels can be gated by transjunctional voltage (known as Vj-gating and display a wide range of unitary channel conductance (γj, yet the domains responsible for Vj-gating and γj are not fully clear. The first extracellular domain (E1 of several connexins has been shown to line part of their GJ channel pore and play important roles in Vj-gating properties and/or ion permeation selectivity. To test roles of the E1 of Cx50 GJ channels, we generated a chimera, Cx50Cx36E1, where the E1 domain of Cx50 was replaced with that of Cx36, a connexin showing quite distinct Vj-gating and γj from those of Cx50. Detailed characterizations of the chimera and three point mutants in E1 revealed that, although the E1 domain is important in determining γj, the E1 domain of Cx36 is able to effectively function within the context of the Cx50 channel with minor changes in Vj-gating properties, indicating that sequence differences between the E1 domains in Cx36 and Cx50 cannot account for their drastic differences in Vj-gating and γj. Our homology models of the chimera and the E1 mutants revealed that electrostatic properties of the pore-lining residues and their contribution to the electric field in the pore are important factors for the rate of ion permeation of Cx50 and possibly other GJ channels.

  14. Exosomes play an important role in the process of psoralen reverse multidrug resistance of breast cancer.

    Science.gov (United States)

    Wang, Xiaohong; Xu, Chengfeng; Hua, Yitong; Sun, Leitao; Cheng, Kai; Jia, Zhongming; Han, Yong; Dong, Jianli; Cui, Yuzhen; Yang, Zhenlin

    2016-12-01

    Release of exosomes have been shown to play critical roles in drug resistance by delivering cargo. Targeting the transfer of exosomes from resistant cells to sensitive cells may be an approach to overcome some cases of drug resistance. In this study, we investigated the potential role of exosomes in the process of psoralen reverse multidrug resistance of MCF-7/ADR cells. Exosomes were isolated by differential centrifugation of culture media from MCF-7/ADR cells (ADR/exo) and MCF-7 parental cells (S/exo). Exosomes were characterized by morphology, exosomal markers and size distribution. The ability of ADR/exo to transfer multidrug resistance was assessed by MTT and real-time quantitative PCR. The different formation and secretion of exosomes were detected by immunofluorescence and transmission electron microscopy. Then we performed comparative transcriptomic analysis using RNA-Seq technology and real-time quantitative PCR to better understand the gene expression regulation in exosmes formation and release after psoralen treatment. Our data showed that exosomes derived from MCF-7/ADR cells were able to promote active sequestration of drugs and could induce a drug resistance phenotype by transferring drug-resistance-related gene MDR-1 and P-glycoprotein protein. Psoralen could reduce the formation and secretion of exosomes to overcome drug resistance. There were 21 differentially expressed genes. Gene ontology (GO) pathway analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the most significantly expressed genes were linked to PPAR and P53 signaling pathways which were related to exosomes formation, secretion and cargo sorting. Psoralen can affect the exosomes and induce the reduction of resistance transmission via exosomes might through PPAR and P53 signaling pathways, which might provide a novel strategy for breast cancer resistance to chemotherapy in the future.

  15. Chemokines and their receptors play important roles in thedevelopment of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    The chemokine system consists of four differentsubclasses with over 50 chemokines and 19 receptors.Their functions in the immune system have beenwell elucidated and research during the last decadesunveils their new roles in hepatocellular carcinoma(HCC). The chemokines and their receptors in themicroenvironment influence the development of HCC by several aspects including: inflammation, effects onimmune cells, angiogenesis, and direct effects on HCCcells. Regarding these aspects, pre-clinical research bytargeting the chemokine system has yielded promisingdata, and these findings bring us new clues in thechemokine-based therapies for HCC.

  16. Proteins Play Important Role in Intercellular Adhesion Affecting on Fruit Textural Quality

    DEFF Research Database (Denmark)

    Bahadur Adhikari, Khem; Shomer, Ilan

    2012-01-01

    Fruit textural quality is becoming a major quality parameter for export, postharvest preservation, handling and processing. The main determinant of textural quality is intercellular adhesion (ICA) as attributed by the cell wall (CW) and its components. The importance of CW protein in ICA......H 3.5 ( pKa) incubated fruits (~2 N). The protein bands at ~29 kDa, ~75 kDa, ~32 kDa and 87 kDa were exclusively or prominently found in ICA strengthened fruits (pH 3.5

  17. The kidneys play an important role in the clearance of rFVIIa in rats

    DEFF Research Database (Denmark)

    Vestergaard, Bill; Appa, Rupa S.; Lykkesfeldt, Jens

    2014-01-01

    study was to evaluate the importance of the kidneys in the clearance process of rFVIIa after iv administration to rats using a nephrectomy model. MATERIALS AND METHODS: A nephrectomized rat model was established and validated using inulin, a compound primarily cleared by the kidneys, as a test substance...... of mixed effects methods, where a pharmacokinetic model was used to simultaneously model all data from healthy, sham operated, and nephrectomized rats. RESULTS: Nephrectomized animals showed stable rectal temperature, SpO2 and pulse and as expected, clearance of inulin was essentially abolished compared...

  18. Isomerization of Asp residues plays an important role in αA-crystallin dissociation.

    Science.gov (United States)

    Takata, Takumi; Fujii, Noriko

    2016-03-01

    Aged cataract formation is caused by the accumulative precipitation of lens proteins incorporating diverse post-translational modifications. α-Crystallin, a major structural and functional lens protein, consists of a large polymeric structure that is dissociated and insolubilized with accumulative post-translational modifications. One such modification, isomerization of Asp, was recently identified in αB-crystallin monomers derived from aged lens. However, the distributions of Asp isomers in each lens fraction remain unknown. Here, α-crystallin fractions from aged lens were separated into heteropolymeric and monomeric forms to determine the Asp isomerization ratios in each fraction. Lens of four different ages were homogenized and centrifuged, and the soluble fraction was applied to size-exclusion chromatography. The heteropolymeric α-crystallin and monomeric crystallin fractions were obtained and concentrated. After trypsin digestion, each fraction was independently applied to liquid chromatography equipped with mass spectrometry to extract α-crystallin-derived peptides containing Asp isomers. The results showed that Asp58, Asp84 and Asp151 of αA-crystallin were highly isomerized in the monomeric fraction, but not isomerized to the same level in the heteropolymeric fraction. Each type of Asp isomerization increased in an age-dependent manner, was site-specific and was similar to previous results from lens water-insoluble fractions. These results imply that isomerization of Asp residues leads to dissociation of αA-crystallin from the heteropolymeric state and induces insolubilization in aged lens. Taken together, our findings suggest that isomerization of Asp might disrupt the higher order polymeric state of α-crystallin, resulting in decreased solubility and function, ultimately contributing to lens protein impairment and cataract formation with aging. © 2015 Federation of European Biochemical Societies.

  19. HIBADH Plays an Important Role in the Course of Liver Cell Necrosis

    Institute of Scientific and Technical Information of China (English)

    2014-01-01

    Objective To observe the biological function of human 3-hydroxyisobutyrate dehydrogenase (HIBADH). Methods Human 3-hydroxyisobutyrate dehydrogenase (HIBADH, 3-hydroxy-2-methyl propanoate: NAD+oxidoreductase) recombinant protein was expressed inE. coli BL21,and puriifed by Ni+ column. The special antisera was obtained from rabbits immunized by this purified antigen. On the distribution of HIBADH, it was found that HIBADH over-expressed in the injured liver cells when serious hepatitis occurred. The phenomenon was conifrmed in the animal models of SD rats with acute liver cell injury induced by CCl4, but this phenomenon did not exist in the models induced by endotoxin combined with galactosamine. Further more, HIBADH’s overexpression in liver cells will induce cell necrosis through the pathway of oxidative stress. Results When the liver cells injured by drug or other chemical materials, HIBADH will be compensationally over-expressed for the deifciency of energy, so liver cells can make enough ATP through brand-chain amino acid catabolism. However, the overexpression of HIBADH will be harmful for liver cells through the product of much more active oxygens which will induce the cell necrosis. Conclusions HIBADH over-expression is a signal of the liver cell metabolism injury, and it can aggravate the liver cell injury through oxidative stress.

  20. Cholesterol-rich lipid rafts play an important role in the Cyprinid herpesvirus 3 replication cycle.

    Science.gov (United States)

    Brogden, Graham; Adamek, Mikołaj; Proepsting, Marcus J; Ulrich, Reiner; Naim, Hassan Y; Steinhagen, Dieter

    2015-09-30

    The Cyprinus herpesvirus 3 (CyHV-3) is a member of the new Alloherpesviridae virus family in the Herpesvirales order. CyHV-3 has been implicated in a large number of disease outbreaks in carp populations causing up to 100% mortality. The aim of this study was to investigate the requirement of cholesterol-rich lipid rafts in CyHV-3 entry and replication in carp cells. Plasma membrane cholesterol was depleted from common carp brain (CCB) cells with methyl-β-cyclodextrin (MβCD). Treated and non-treated cells were infected with CyHV-3 and virus binding and infection parameters were assessed using RT-qPCR, immunocytochemistry and virus titration. The effect of cholesterol reduction severely stunted virus entry in vitro, however after cholesterol replenishment virus entry and subsequent replication rates were similar to the control infection. Furthermore, cholesterol depletion did not significantly influence virus binding and the subsequent post-entry replication stage, however had an impact on virus egress. Comparative analysis of the lipid compositions of CyHV-3 and CCB membrane fractions revealed strong similarities between the lipid composition of the CyHV-3 and CCB lipid rafts. The results presented here show that cholesterol-rich lipid rafts are important for the CyHV-3 replication cycle especially during entry and egress.

  1. Transposons play an important role in the evolution and diversification of centromeres among closely related species

    Directory of Open Access Journals (Sweden)

    Scott eJackson

    2015-04-01

    Full Text Available Centromeres are important chromosomal regions necessary for eukaryotic cell segregation and replication. Due to high amounts of tandem repeats and transposons, centromeres have been difficult to sequence in most multicellular organisms, thus their sequence structure and evolution are poorly understood. In this study, we analyzed transposons in the centromere 8 (Cen8 from the African cultivated rice (O. glaberrima and two subspecies of the Asian cultivated rice (O. sativa, indica and japonica. We detected much higher transposon contents (>69% in centromere regions than in the whole genomes of O. sativa ssp japonica and O. glaberrima (~35%. We compared the three Cen8s and identified numerous recent insertions of transposons that were frequently organized into multiple-layer nested blocks, similar to nested transposons in maize. Except for the Hopi retrotransposon, all LTR retrotransposons were shared but exhibit different abundances amongst the three Cen8s. Even though a majority of the transposons were located in intergenic regions, some gene-related transposons were found and may be involved in gene diversification. Chromatin immunoprecipitated (ChIP data analysis revealed that 165 families from both Class I and Class II transposons were found in CENH3-associated chromatin sequences. These results indicate essential roles for transposons in centromeres and that the rapid divergence of the Cen8 sequences between the two cultivated rice species was primarily caused by recent transposon insertions.

  2. Specific subunits of heterotrimeric G proteins play important roles during nodulation in soybean.

    Science.gov (United States)

    Choudhury, Swarup Roy; Pandey, Sona

    2013-05-01

    Heterotrimeric G proteins comprising Gα, Gβ, and Gγ subunits regulate many fundamental growth and development processes in all eukaryotes. Plants possess a relatively limited number of G-protein components compared with mammalian systems, and their detailed functional characterization has been performed mostly in Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa). However, the presence of single Gα and Gβ proteins in both these species has significantly undermined the complexity and specificity of response regulation in plant G-protein signaling. There is ample pharmacological evidence for the role of G proteins in regulation of legume-specific processes such as nodulation, but the lack of genetic data from a leguminous species has restricted its direct assessment. Our recent identification and characterization of an elaborate G-protein family in soybean (Glycine max) and the availability of appropriate molecular-genetic resources have allowed us to directly evaluate the role of G-protein subunits during nodulation. We demonstrate that all G-protein genes are expressed in nodules and exhibit significant changes in their expression in response to Bradyrhizobium japonicum infection and in representative supernodulating and nonnodulating soybean mutants. RNA interference suppression and overexpression of specific G-protein components results in lower and higher nodule numbers, respectively, validating their roles as positive regulators of nodule formation. Our data further show preferential usage of distinct G-protein subunits in the presence of an additional signal during nodulation. Interestingly, the Gα proteins directly interact with the soybean nodulation factor receptors NFR1α and NFR1β, suggesting that the plant G proteins may couple with receptors other than the canonical heptahelical receptors common in metazoans to modulate signaling.

  3. Biodiversity and ecosystem functioning in coastal lagoons: Does microbial diversity play any role?

    Science.gov (United States)

    Danovaro, Roberto; Pusceddu, Antonio

    2007-10-01

    Although prokaryotes are small in size, they are a significant biomass component in aquatic ecosystems and play a major role in biogeochemical processes. It is generally assumed that the relative importance of prokaryotes to material and energy fluxes is maximized in low-productivity (oligotrophic) ecosystems and decreases in high-productivity (eutrophic) ecosystems. Lagoon and coastal ecosystems are extremely dynamic, typically highly productive and dominated by macro-size organisms (both macrofauna and macrophytes). As such, their functional characteristics are typically evaluated from a "macrobial" perspective. An efficient ecosystem functioning, with fast nutrient cycling, high productivity, low C accumulation and lack of hypoxic/dystrophic crises is, however, intimately dependent on the interaction between microbial and macrobial organisms. We make here an attempt to relate prokaryote biodiversity (genotype richness, using fingerprinting techniques, ARISA) and ecosystem functioning (using a series of parameters including meiofaunal biomass, prokaryote C production and organic matter turnover rates) in different Mediterranean lagoon systems. The lagoons differed significantly with each other for all the variables. While no relationships were observed between the environmental characteristics of the lagoons and the bacterial diversity, the latter was significantly and positively correlated with the functioning and efficiency of the lagoons. The investigation of the links between microbial diversity and functioning in lagoons is still at its infancy, but these preliminary results suggest that a better understanding of the role of prokaryote diversity on ecosystem functioning and efficiency could open new perspectives for the conservation and management of these highly productive and vulnerable ecosystems.

  4. Multidrug Resistance-Associated Protein 3 Plays an Important Role in Protection against Acute Toxicity of Diclofenac.

    Science.gov (United States)

    Scialis, Renato J; Csanaky, Iván L; Goedken, Michael J; Manautou, José E

    2015-07-01

    Diclofenac (DCF) is a nonsteroidal anti-inflammatory drug commonly prescribed to reduce pain in acute and chronic inflammatory diseases. One of the main DCF metabolites is a reactive diclofenac acyl glucuronide (DCF-AG) that covalently binds to biologic targets and may contribute to adverse drug reactions arising from DCF use. Cellular efflux of DCF-AG is partially mediated by multidrug resistance-associated proteins (Mrp). The importance of Mrp2 during DCF-induced toxicity has been established, yet the role of Mrp3 remains largely unexplored. In the present work, Mrp3-null (KO) mice were used to study the toxicokinetics and toxicodynamics of DCF and its metabolites. DCF-AG plasma concentrations were 90% lower in KO mice than in wild-type (WT) mice, indicating that Mrp3 mediates DCF-AG basolateral efflux. In contrast, there were no differences in DCF-AG biliary excretion between WT and KO, suggesting that only DCF-AG basolateral efflux is compromised by Mrp3 deletion. Susceptibility to toxicity was also evaluated after a single high DCF dose. No signs of injury were detected in livers and kidneys; however, ulcers were found in the small intestines. Furthermore, the observed intestinal injuries were consistently more severe in KO compared with WT. DCF covalent adducts were observed in liver and small intestines; however, staining intensity did not correlate with the severity of injuries, implying that tissues respond differently to covalent modification. Overall, the data provide strong evidence that (1) in vivo Mrp3 plays an important role in DCF-AG disposition and (2) compromised Mrp3 function can enhance injury in the gastrointestinal tract after DCF treatment.

  5. Bacillus subtilis SbcC protein plays an important role in DNA inter-strand cross-link repair

    Directory of Open Access Journals (Sweden)

    Krisnamurthy Mahalakshmi

    2006-06-01

    Full Text Available Abstract Background Several distinct pathways for the repair of damaged DNA exist in all cells. DNA modifications are repaired by base excision or nucleotide excision repair, while DNA double strand breaks (DSBs can be repaired through direct joining of broken ends (non homologous end joining, NHEJ or through recombination with the non broken sister chromosome (homologous recombination, HR. Rad50 protein plays an important role in repair of DNA damage in eukaryotic cells, and forms a complex with the Mre11 nuclease. The prokaryotic ortholog of Rad50, SbcC, also forms a complex with a nuclease, SbcD, in Escherichia coli, and has been implicated in the removal of hairpin structures that can arise during DNA replication. Ku protein is a component of the NHEJ pathway in pro- and eukaryotic cells. Results A deletion of the sbcC gene rendered Bacillus subtilis cells sensitive to DNA damage caused by Mitomycin C (MMC or by gamma irradiation. The deletion of the sbcC gene in a recN mutant background increased the sensitivity of the single recN mutant strain. SbcC was also non-epistatic with AddAB (analog of Escherichia coli RecBCD, but epistatic with RecA. A deletion of the ykoV gene encoding the B. subtilis Ku protein in a sbcC mutant strain did not resulted in an increase in sensitivity towards MMC and gamma irradiation, but exacerbated the phenotype of a recN or a recA mutant strain. In exponentially growing cells, SbcC-GFP was present throughout the cells, or as a central focus in rare cases. Upon induction of DNA damage, SbcC formed 1, rarely 2, foci on the nucleoids. Different to RecN protein, which forms repair centers at any location on the nucleoids, SbcC foci mostly co-localized with the DNA polymerase complex. In contrast to this, AddA-GFP or AddB-GFP did not form detectable foci upon addition of MMC. Conclusion Our experiments show that SbcC plays an important role in the repair of DNA inter-strand cross-links (induced by MMC, most likely

  6. The novel zinc cluster regulator Tog1 plays important roles in oleate utilization and oxidative stress response in Saccharomyces cerevisiae

    Energy Technology Data Exchange (ETDEWEB)

    Thepnok, Piyasuda; Ratanakhanokchai, Khanok; Soontorngun, Nitnipa, E-mail: nitnipa.soo@kmutt.ac.th

    2014-08-08

    Highlights: • TOG1 deletion results in defective growth on non-fermentable carbon sources. • Removal of TOG1 sensitizes cells to oxidative stress. • Tog1 directly binds and activates expression of oleate utilizing genes. • The Δtog1 cells display reduced peroxisomal content in oleate culture. • S. cerevisiae zinc cluster Tog1 is a novel activator of oleate utilization. - Abstract: Many zinc cluster proteins have been shown to play a role in the transcriptional regulation of glucose-repressible genes during glucose exhaustion and diauxic shift. Here, we studied an additional member of this family called Yer184c (herein called Tog1) for transcriptional regulator of oleate. Our results showed that a Δtog1 strain displays impaired growth with several non-fermentable carbons. Tog1 is also implicated in oxidative stress tolerance. Importantly, during the glucose–oleate shift, combined results from quantitative real time-PCR and chromatin immunoprecipitation (ChIP) experiments showed that Tog1 acts as a direct activator of oleate utilizing genes, encoded key enzymes in β-Oxidation and NADPH regeneration (POX1, FOX2, POT1 and IDP2), the glyoxylate shunt (MLS1 and ICL1), and gluconeogenesis (PCK1 and FBP1). A transmission electron microscopy (TEM) analysis of the Δtog1 strain assayed with oleate also revealed a substantial decrease in peroxisome abundance that is vital for fatty acid oxidation. Overall, our results clearly demonstrated that Tog1 is a newly characterized zinc cluster regulator that functions in the complex network of non-fermentable carbon metabolism in Saccharomycescerevisiae.

  7. Adaptive bandwidth measurements of importance functions for speech intelligibility prediction.

    Science.gov (United States)

    Whitmal, Nathaniel A; DeRoy, Kristina

    2011-12-01

    The Articulation Index (AI) and Speech Intelligibility Index (SII) predict intelligibility scores from measurements of speech and hearing parameters. One component in the prediction is the "importance function," a weighting function that characterizes contributions of particular spectral regions of speech to speech intelligibility. Previous work with SII predictions for hearing-impaired subjects suggests that prediction accuracy might improve if importance functions for individual subjects were available. Unfortunately, previous importance function measurements have required extensive intelligibility testing with groups of subjects, using speech processed by various fixed-bandwidth low-pass and high-pass filters. A more efficient approach appropriate to individual subjects is desired. The purpose of this study was to evaluate the feasibility of measuring importance functions for individual subjects with adaptive-bandwidth filters. In two experiments, ten subjects with normal-hearing listened to vowel-consonant-vowel (VCV) nonsense words processed by low-pass and high-pass filters whose bandwidths were varied adaptively to produce specified performance levels in accordance with the transformed up-down rules of Levitt [(1971). J. Acoust. Soc. Am. 49, 467-477]. Local linear psychometric functions were fit to resulting data and used to generate an importance function for VCV words. Results indicate that the adaptive method is reliable and efficient, and produces importance function data consistent with that of the corresponding AI/SII importance function.

  8. Young Mothers' Play with Their Toddlers: Individual Variability as a Function of Psychosocial Factors

    Science.gov (United States)

    Driscoll, Joan Riley; Easterbrooks, M. Ann

    2007-01-01

    There is no one style of parenting which characterizes young mothers as a group. In addition, life circumstances play an important role in shaping maternal behaviour. The aim of this study was to identify patterns of maternal play behaviour and contextual (social and personal) factors associated with these different patterns. In this study, 107…

  9. Children's Right to Play: An Examination of the Importance of Play in the Lives of Children Worldwide. Working Papers in Early Childhood Development, No. 57

    Science.gov (United States)

    Lester, Stuart; Russell, Wendy

    2010-01-01

    In this working paper, Wendy Russell and Stuart Lester of the UK's University of Gloucestershire discuss why play is fundamental to the health and well-being of children. They argue that both state signatories to the United Nations Convention on the Rights of the Child (Article 31 of which enshrines the right to play) and adults generally should…

  10. Mitochondrial cholesterol: mechanisms of import and effects on mitochondrial function.

    Science.gov (United States)

    Martin, Laura A; Kennedy, Barry E; Karten, Barbara

    2016-04-01

    Mitochondria require cholesterol for biogenesis and membrane maintenance, and for the synthesis of steroids, oxysterols and hepatic bile acids. Multiple pathways mediate the transport of cholesterol from different subcellular pools to mitochondria. In steroidogenic cells, the steroidogenic acute regulatory protein (StAR) interacts with a mitochondrial protein complex to mediate cholesterol delivery to the inner mitochondrial membrane for conversion to pregnenolone. In non-steroidogenic cells, several members of a protein family defined by the presence of a StAR-related lipid transfer (START) domain play key roles in the delivery of cholesterol to mitochondrial membranes. Subdomains of the endoplasmic reticulum (ER), termed mitochondria-associated ER membranes (MAM), form membrane contact sites with mitochondria and may contribute to the transport of ER cholesterol to mitochondria, either independently or in conjunction with lipid-transfer proteins. Model systems of mitochondria enriched with cholesterol in vitro and mitochondria isolated from cells with (patho)physiological mitochondrial cholesterol accumulation clearly demonstrate that mitochondrial cholesterol levels affect mitochondrial function. Increased mitochondrial cholesterol levels have been observed in several diseases, including cancer, ischemia, steatohepatitis and neurodegenerative diseases, and influence disease pathology. Hence, a deeper understanding of the mechanisms maintaining mitochondrial cholesterol homeostasis may reveal additional targets for therapeutic intervention. Here we give a brief overview of mitochondrial cholesterol import in steroidogenic cells, and then focus on cholesterol trafficking pathways that deliver cholesterol to mitochondrial membranes in non-steroidogenic cells. We also briefly discuss the consequences of increased mitochondrial cholesterol levels on mitochondrial function and their potential role in disease pathology.

  11. Executive function predicts the development of play skills for verbal preschoolers with autism spectrum disorders.

    Science.gov (United States)

    Faja, Susan; Dawson, Geraldine; Sullivan, Katherine; Meltzoff, Andrew N; Estes, Annette; Bernier, Raphael

    2016-12-01

    Executive function and play skills develop in early childhood and are linked to cognitive and language ability. The present study examined these abilities longitudinally in two groups with autism spectrum disorder-a group with higher initial language (n = 30) and a group with lower initial language ability (n = 36). Among the lower language group, concurrent nonverbal cognitive ability contributed most to individual differences in executive function and play skills. For the higher language group, executive function during preschool significantly predicted play ability at age 6 over and above intelligence, but early play did not predict later executive function. These results suggested that factors related to the development of play and executive function differ for subgroups of children with different language abilities and that early executive function skills may be critical in order for verbal children with autism to develop play. Autism Res 2016, 9: 1274-1284. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

  12. Nano Structure Plays an Important Role in the Present and Future Anode Materials of Li-ion Batteries

    Institute of Scientific and Technical Information of China (English)

    Tsutomu; Takamura

    2007-01-01

    1 ResultsLi-ion batteries are the most promising secondary batteries for IT and EV applications, where it is required to increase the capacity and power capability to a great extent. In responding to the demand we have been studied on the anode materials especially paying attention on the improved graphite active materials and modified silicon. In both cases we realized that the nano-structured design plays an important role. In this paper the examples of nano-size structure working in the actual materi...

  13. The effects of fantastical pretend-play on the development of executive functions: An intervention study.

    Science.gov (United States)

    Thibodeau, Rachel B; Gilpin, Ansley T; Brown, Melissa M; Meyer, Brooke A

    2016-05-01

    Although recent correlational studies have found a relationship between fantasy orientation (FO; i.e., a child's propensity to play in a fantastical realm) and higher order cognitive skills called executive functions (EFs), no work has addressed the causality and directionality of this relationship. The current study experimentally examined the directionality of the observed relationship between FO and EF development in preschool-aged children through an innovative play intervention employing a randomized controlled design. A sample of 110 children between the ages of 3 and 5years were randomly assigned to one of three conditions: fantastical pretend-play intervention, non-imaginative play intervention, or business-as-usual control. Results revealed that children who participated in a 5-week fantastical pretend-play intervention showed improvements in EFs, whereas children in the other two conditions did not. Within the fantastical pretend-play condition, children who were highly engaged in the play and those who were highly fantastical demonstrated the greatest gains in EFs. These data provide evidence for the equifinal relationship between fantasy-oriented play and EF development, such that engaging in fantasy-oriented play may be one of many ways to directly enhance EF development.

  14. Importance of predictor variables for models of chemical function

    Data.gov (United States)

    U.S. Environmental Protection Agency — Importance of random forest predictors for all classification models of chemical function. This dataset is associated with the following publication: Isaacs , K., M....

  15. The pleiotropic CymR regulator of Staphylococcus aureus plays an important role in virulence and stress response.

    Directory of Open Access Journals (Sweden)

    Olga Soutourina

    2010-05-01

    Full Text Available We have characterized a novel pleiotropic role for CymR, the master regulator of cysteine metabolism. We show here that CymR plays an important role both in stress response and virulence of Staphylococcus aureus. Genes involved in detoxification processes, including oxidative stress response and metal ion homeostasis, were differentially expressed in a DeltacymR mutant. Deletion of cymR resulted in increased sensitivity to hydrogen peroxide-, disulfide-, tellurite- and copper-induced stresses. Estimation of metabolite pools suggests that this heightened sensitivity could be the result of profound metabolic changes in the DeltacymR mutant, with an increase in the intracellular cysteine pool and hydrogen sulfide formation. Since resistance to oxidative stress within the host organism is important for pathogen survival, we investigated the role of CymR during the infectious process. Our results indicate that the deletion of cymR promotes survival of S. aureus inside macrophages, whereas virulence of the DeltacymR mutant is highly impaired in mice. These data indicate that CymR plays a major role in virulence and adaptation of S. aureus for survival within the host.

  16. An active factor from tomato root exudates plays an important role in efficient establishment of mycorrhizal symbiosis.

    Directory of Open Access Journals (Sweden)

    Shubin Sun

    Full Text Available Root exudates play an important role in the early signal exchange between host plants and arbuscular mycorrhizal fungi. M161, a pre-mycorrhizal infection (pmi mutant of the tomoto (Solanum lycopersicum cultivar Micro-Tom, fails to establish normal arbuscular mycorrhizal symbioses, and produces exudates that are unable to stimulate hyphal growth and branching of Glomus intraradices. Here, we report the identification of a purified active factor (AF that is present in the root exudates of wild-type tomato, but absent in those of M161. A complementation assay using the dual root organ culture system showed that the AF could induce fungal growth and branching at the pre-infection stage and, subsequently, the formation of viable new spores in the M161 background. Since the AF-mediated stimulation of hyphal growth and branching requires the presence of the M161 root, our data suggest that the AF is essential but not sufficient for hyphal growth and branching. We propose that the AF, which remains to be chemically determined, represents a plant signal molecule that plays an important role in the efficient establishment of mycorrhizal symbioses.

  17. SDF-1 and CXCR4 play an important role in adult SVZ lineage cell proliferation and differentiation.

    Science.gov (United States)

    Zhu, Chang; Yao, Wen-Long; Tan, Wei; Zhang, Chuan-Han

    2017-02-15

    Evidence has shown that stromal cell-derived factor (SDF-1/CXCL12) plays an important role in maintaining adult neural progenitor cells (NPCs). SDF-1 is also known to enhance recovery by recruiting NPCs to damaged regions and recent studies have revealed that SDF-1α exhibits pleiotropism, thereby differentially affecting NPC subpopulations. In this study, we investigated the role of SDF-1 in in vitro NPC self-renewal, proliferation and differentiation, following treatment with different concentrations of SDF-1 or a CXCR4 antagonist, AMD3100. We observed that AMD3100 inhibited the formation of primary neurospheres. However, SDF-1 and AMD3100 exhibited no effect on proliferation upon inclusion of growth factors in the media. Following growth factor withdrawal, AMD3100 and SDF-1 treatment resulted in differential effects on NPC proliferation. SDF-1, at a concentration of 500ng/ml, resulted in an increase in the relative proportion of oligodendrocytes following growth factor withdrawal-induced differentiation. Using CXCR4 knockout mice, we observed that SDF-1 affected NPC proliferation in the sub-ventricular zone (SVZ). We also investigated the occurrence of differential CXCR4 expression at different stages during lineage progression. These results clearly indicate that signaling interactions between SDF-1 and CXCR4 play an important role in adult SVZ lineage cell proliferation and differentiation.

  18. Play with online virtual pets as a method to improve mirror neuron and real world functioning in autistic children.

    Science.gov (United States)

    Altschuler, Eric Lewin

    2008-01-01

    Autism is a severe disease with no known cause and no cure or treatment. Recently, ourselves and subsequently others found that so-called "mirror neurons" - neurons that respond not only when a person moves, but upon observation of movement in another - are dysfunctional in autistic children. Here I suggest an easy, simple, inexpensive and fun method to improve mirror neuron functioning in autistic children, increase appreciation in autistic children for the theory of mind and thinking of others, and most importantly hopefully to improve real world functioning: play with virtual online pets that are the "embodiment" of a stuffed animal the child has. Adoption and then care and play with online pets forces, in a fun way, one to think about the world through the eyes and needs of the pet. A simple method to test this play with online virtual pet therapy is described.

  19. The Function of Play in Bruno Munari’s Children’s Books. A Historical Overview

    OpenAIRE

    Marnie Campagnaro

    2016-01-01

    The ludic dimension of Bruno Munari’s prolific children’s book publishing activity plays an important role, as far as narration and visual arts are concerned. Since the 1940s, and for the following 50 years, books, play and education were fundamental reference points in the artistic production and critical thinking of this Milanese artist. Munari cultivated these influences with extraordinary results in his picturebooks. The following analysis of some of Munari’s texts offers a historical-cri...

  20. Assessment cognitive functions in children with visual impairment by playing method

    Directory of Open Access Journals (Sweden)

    Statiev S. I.

    2010-05-01

    Full Text Available The cognitive functions of children are considered with paropsiss by a playing method. In research 10 children with a paropsis (experimental group and 10 children (control group took part without a paropsis. Age of children - 5-6 years. Directions are rotined adaptation of children to the environment. It is well-proven that a playing method gives the clear estimation of development of cognitive functions for children with paropsiss. In future a method allows to conduct rehabilitation measures on the improvement of the state of visual analyzer of children.

  1. Mast cells play an important role in chlamydia pneumoniae lung infection by facilitating immune cell recruitment into the airway.

    Science.gov (United States)

    Chiba, Norika; Shimada, Kenichi; Chen, Shuang; Jones, Heather D; Alsabeh, Randa; Slepenkin, Anatoly V; Peterson, Ellena; Crother, Timothy R; Arditi, Moshe

    2015-04-15

    Mast cells are known as central players in allergy and anaphylaxis, and they play a pivotal role in host defense against certain pathogens. Chlamydia pneumoniae is an important human pathogen, but it is unclear what role mast cells play during C. pneumoniae infection. We infected C57BL/6 (wild-type [WT]) and mast cell-deficient mice (Kit(W-sh/W-sh) [Wsh]) with C. pneumoniae. Wsh mice showed improved survival compared with WT mice, with fewer cells in Wsh bronchoalveolar lavage fluid (BALF), despite similar levels of cytokines and chemokines. We also found a more rapid clearance of bacteria from the lungs of Wsh mice compared with WT mice. Cromolyn, a mast cell stabilizer, reduced BALF cells and bacterial burden similar to the levels seen in Wsh mice; conversely, Compound 48/80, a mast cell degranulator, increased the number of BALF cells and bacterial burden. Histology showed that WT lungs had diffuse inflammation, whereas Wsh mice had patchy accumulations of neutrophils and perivascular accumulations of lymphocytes. Infected Wsh mice had reduced amounts of matrix metalloprotease-9 in BALF and were resistant to epithelial integral membrane protein degradation, suggesting that barrier integrity remains intact in Wsh mice. Mast cell reconstitution in Wsh mice led to enhanced bacterial growth and normal epithelial integral membrane protein degradation, highlighting the specific role of mast cells in this model. These data suggest that mast cells play a detrimental role during C. pneumoniae infection by facilitating immune cell infiltration into the airspace and providing a more favorable replicative environment for C. pneumoniae.

  2. Fission yeast ATF/CREB family protein Atf21 plays important roles in production of normal spores.

    Science.gov (United States)

    Morita, Tomohiko; Yamada, Takatomi; Yamada, Shintaro; Matsumoto, Kouji; Ohta, Kunihiro

    2011-02-01

    Activating transcription factor/cAMP response element binding protein (ATF/CREB) family transcription factors play central roles in maintaining cellular homeostasis. They are activated in response to environmental stimuli, bind to CRE sequences in the promoters of stress-response genes and regulate transcription. Although ATF/CREB proteins are widely conserved among most eukaryotes, their characteristics are highly diverse. Here, we investigated the functions of a fission yeast ATF/CREB protein Atf21 to find out its unique properties. We show that Atf21 is dispensable for the adaptive response to several stresses such as nitrogen starvation and for meiotic events including nuclear divisions. However, spores derived from atf21Δ mutants are not as mature as wild-type ones and are unable to form colonies under nutrition-rich conditions. Furthermore, we demonstrate that the Atf21 protein, which is scarce in early meiosis, gradually accumulates as meiosis proceeds; it reaches maximum levels approximately 8 h after nitrogen starvation and is present during germination. These results suggest that Atf21 is expressed and functions long after nitrogen starvation. Given that other well-characterized fission yeast ATF/CREB proteins Atf1 and Pcr1 accumulate and function promptly upon exposure to environmental stresses, we propose that Atf21 is a distinct member of the ATF/CREB family in fission yeast. © 2010 The Authors. Journal compilation © 2010 by the Molecular Biology Society of Japan/Blackwell Publishing Ltd.

  3. The Photographic History of Greenland's Glaciers - and how the historical data plays an important role in today's glacier research

    Science.gov (United States)

    Bjork, A. A.; Kjeldsen, K. K.; Korsgaard, N. J.; Aagaard, S.; Andresen, C. S.; Bamber, J. L.; van den Broeke, M.; Colgan, W. T.; Funder, S.; Khan, S. A.; Larsen, N. K.; Machguth, H.; Nuth, C.; Schomacker, A.; Kjaer, K. H.

    2015-12-01

    As the Greenland Ice Sheet and Greenland's glaciers are continuing to loss mass at high rates, knowledge of their past response to climatic changes is ever important. By harvesting the archives for images, both terrestrial and airborne, we are able to expand the record of glacier observation by several decades, thus supplying crucial knowledge on glacier behavior to important climatic transitions such as the end of the Little Ice Age and the early 20th Century warming. Here we show how a large collection of historical aerial images portray the glacial response to the Little Ice Age deglaciation in Greenland and document frontal change throughout the 20th Century. A detailed story of the LIA-deglaciation is told by supplementing with terrestrial photos that capture the onset of retreat and high resolution aerial images that portray geomorphological evidence of the Little Ice Age maximum extent. This work is the result of several generations of Greenland researches and their efforts to portray and document the state of the glaciers, and highlights that while interpretations and conclusions may be challenged and changed through time, the raw observations remain extremely valuable. Finally, we also show how archival data besides photos may play an important role in future glacier research in Greenland.

  4. Geographic location, sex and nutritional status play an important role in body image concerns among Brazilian adolescents.

    Science.gov (United States)

    Laus, Maria Fernanda; Miranda, Valter Paulo Neves; Almeida, Sebastião Sousa; Braga Costa, Telma Maria; Ferreira, Maria Elisa Caputo

    2013-03-01

    This study compared body image concerns among adolescents from different geographic locations in Brazil, and the influence of sex and nutritional status. Seven hundred eighty-eight adolescents completed the Body Shape Questionnaire (BSQ) and had their weight and height measured. There were significant cross-regional differences in BSQ scores. Also, body image concerns were more prevalent among girls and among overweight adolescents. It is suggested that sex and nutritional status may play an important role in body image concerns, which is more common between adolescents from urban areas. Furthermore, our findings contribute to the literature by examining patterns of body image concerns within subgroups of adolescents who have received little research attention on these issues.

  5. A Petunia homeodomain-leucine zipper protein, PhHD-Zip, plays an important role in flower senescence.

    Directory of Open Access Journals (Sweden)

    Xiaoxiao Chang

    Full Text Available Flower senescence is initiated by developmental and environmental signals, and regulated by gene transcription. A homeodomain-leucine zipper transcription factor, PhHD-Zip, is up-regulated during petunia flower senescence. Virus-induced gene silencing of PhHD-Zip extended flower life by 20% both in unpollinated and pollinated flowers. Silencing PhHD-Zip also dramatically reduced ethylene production and the abundance of transcripts of genes involved in ethylene (ACS, ACO, and ABA (NCED biosynthesis. Abundance of transcripts of senescence-related genes (SAG12, SAG29 was also dramatically reduced in the silenced flowers. Over-expression of PhHD-Zip accelerated petunia flower senescence. Furthermore, PhHD-Zip transcript abundance in petunia flowers was increased by application of hormones (ethylene, ABA and abiotic stresses (dehydration, NaCl and cold. Our results suggest that PhHD-Zip plays an important role in regulating petunia flower senescence.

  6. The Functionality of Facial Appearance and Its Importance to a Korean Population

    Directory of Open Access Journals (Sweden)

    Young Jun Kim

    2013-11-01

    Full Text Available BackgroundMany people have an interest in the correction of facial scars or deformities caused by trauma. The increasing ability to correct such flaws has been one of the reasons for the increase in the popularity of facial plastic surgery. In addition to its roles in communication, breathing, eating, olfaction and vision, the appearance of the face also plays an important role in human interactions, including during social activities. However, studies on the importance of the functional role of facial appearance. As a function of the face are scare. Therefore, in the present study, we evaluated the importance of the functions of the face in Korea.MethodsWe conducted an online panel survey of 300 participants (age range, 20-70 years. Each respondent was administered the demographic data form, Facial Function Assessment Scale, Rosenberg Self-Esteem Scale, and standard gamble questionnaires.ResultsIn the evaluation on the importance of facial functions, a normal appearance was considered as important as communication, breathing, speech, and vision. Of the 300 participants, 85% stated that a normal appearance is important in social activities.ConclusionsThe results of this survey involving a cross-section of the Korean population indicated that a normal appearance was considered one of the principal facial functions. A normal appearance was considered more important than the functions of olfaction and expression. Moreover, a normal appearance was determined to be an important facial function for leading a normal life in Korea.

  7. RIN1-Ras-ERK pathway plays an important role in carcinogenesis in colon cancer cell line LoVo.

    Science.gov (United States)

    Inoue, Takeshi; Goi, Takanori; Hirono, Yasuo; Katayama, Kanji; Yamaguchi, Akio

    2011-01-01

    The RIN1 protein has SH2, three domains, and H-Ras binding domains; thus, it is presumed to be an important molecule in an intracellular signaling pathway. We examined the effect of the introduction of a membrane protein-encoding, mutated (S351A)RIN1 gene into a colon cancer. In the LoVo colon cancer cell line, endogenous RIN1 protein was strongly expressed in the cytoplasmic fraction, and the RIN1 protein in the cytoplasmic fraction was strongly bound to the 14-3-3 protein. In the mutated (S351A)RIN1-transfected LoVo cells, the mutated (S351A)RIN1 protein was identified in the cell membrane, and was bound to HRas protein. Also, in vitro the proliferative capacity of the mutated (S351A)RIN1-transfected LoVo cells was significantly inhibited, compared with that of their empty vector-transfected counterparts. In the mutated (S351A)RIN1-transfected LoVo cells, the phosphorylation of ERK1/2 proteins downstream of the H-Ras molecule was inhibited, compared with the counterparts. This study is the first to show that the localization of RIN1 protein plays an important role in the carcinogenesis in colon cancer cells LoVo (i.e., signal transduction in the Ras-ERK pathway).

  8. Nutrition metabolism plays an important role in the alternate bearing of the olive tree (Olea europaea L..

    Directory of Open Access Journals (Sweden)

    Mine Turktas

    Full Text Available The olive tree (Olea europaea L. is widely known for its strong tendency for alternate bearing, which severely affects the fruit yield from year to year. Microarray based gene expression analysis using RNA from olive samples (on-off years leaves and ripe-unripe fruits are particularly useful to understand the molecular mechanisms influencing the periodicity in the olive tree. Thus, we carried out genome wide transcriptome analyses involving different organs and temporal stages of the olive tree using the NimbleGen Array containing 136,628 oligonucleotide probe sets. Cluster analyses of the genes showed that cDNAs originated from different organs could be sorted into separate groups. The nutritional control had a particularly remarkable impact on the alternate bearing of olive, as shown by the differential expression of transcripts under different temporal phases and organs. Additionally, hormonal control and flowering processes also played important roles in this phenomenon. Our analyses provide further insights into the transcript changes between "on year" and "off year" leaves along with the changes from unrpipe to ripe fruits, which shed light on the molecular mechanisms underlying the olive tree alternate bearing. These findings have important implications for the breeding and agriculture of the olive tree and other crops showing periodicity. To our knowledge, this is the first study reporting the development and use of an olive array to document the gene expression profiling associated with the alternate bearing in olive tree.

  9. Cyclic electron flow plays an important role in photoprotection for the resurrection plant Paraboea rufescens under drought stress.

    Science.gov (United States)

    Huang, Wei; Yang, Shi-Jian; Zhang, Shi-Bao; Zhang, Jiao-Lin; Cao, Kun-Fang

    2012-04-01

    Resurrection plants could survive severe drought stress, but the underlying mechanism for protecting their photosynthetic apparatus against drought stress is unclear. Cyclic electron flow (CEF) has been documented as a crucial mechanism for photoprotection in Arabidopsis and tobacco. We hypothesized that CEF plays an important role in protecting photosystem I (PSI) and photosystem II (PSII) against drought stress for resurrection plants. To address this hypothesis, the effects of mild drought stress on light energy distribution in PSII and P700 redox state were examined in a resurrection plant Paraboea rufescens. Cyclic electron flow was not activated below the photosynthetic photon flux density (PPFD) of 400 μmol m⁻² s⁻¹ in leaves without drought stress. However, CEF was activated under low light in leaves with mild drought stress, and the effective quantum yield of PSII significantly decreased. Meanwhile, non-photochemical quenching (NPQ) was significantly stimulated not only under high light but also under low light. Compared with the control, the fraction of overall P700 that cannot be oxidized in a given state (PSI acceptor side limitation) under high light was maintained at low level of 0.1 in leaves with water deficit, indicating that the over-reduction of the PSI acceptor side was prevented by the significant stimulation of CEF. Furthermore, methyl viologen could significantly increase the PSII photo-inhibition induced by high light compared with chloramphenicol. These results suggested that CEF is an important mechanism for protecting PSI and PSII from drought stress in resurrection plants.

  10. Does gender play a role in functional asymmetry of ventromedial prefrontal cortex?

    Science.gov (United States)

    Tranel, Daniel; Damasio, Hanna; Denburg, Natalie L; Bechara, Antoine

    2005-12-01

    We found previously in a lesion study that the right-sided sector of the ventromedial prefrontal cortices (VMPCs) was critical for social/emotional functioning and decision-making, whereas the left side appeared to be less important. It so happened that all but one of the subjects in that study were men, and the one woman did not fit the pattern very well. This prompted a follow-up investigation, in which we explored the following question: Does gender play a role in the development of defects in social conduct, emotional functioning and decision-making, following unilateral VMPC damage? We culled from our Patient Registry same-sex pairs of men or women patients who had comparable unilateral VMPC damage in either the left or right hemisphere. Two male pairs and one female pair were formed, and we included two additional women with unilateral right VMPC damage (8 patients in all). The domains of measurement covered social conduct, emotional processing and personality, and decision-making. We found a systematic effect of gender on the pattern of left-right asymmetry in VMPC. In men, there were severe defects following unilateral right VMPC damage, but not following left-sided damage. In women, there were defects following unilateral left VMPC damage; following right-sided damage, however, defects were mild or absent. The findings suggest that men and women may use different strategies to solve similar problems--e.g. men may use a more holistic, gestalt-type strategy, and women may use a more analytic, verbally-mediated strategy. Such differences could reflect asymmetric, gender-related differences in the neurobiology of left and right VMPC sectors.

  11. Ruminal Prevotella spp. may play an important role in the conversion of plant lignans into human health beneficial antioxidants.

    Directory of Open Access Journals (Sweden)

    Ana L B Schogor

    Full Text Available Secoisolariciresinol diglucoside (SDG, the most abundant lignan in flaxseed, is metabolized by the ruminal microbiota into enterolignans, which are strong antioxidants. Enterolactone (EL, the main mammalian enterolignan produced in the rumen, is transferred into physiological fluids, with potentially human health benefits with respect to menopausal symptoms, hormone-dependent cancers, cardiovascular diseases, osteoporosis and diabetes. However, no information exists to our knowledge on bacterial taxa that play a role in converting plant lignans into EL in ruminants. In order to investigate this, eight rumen cannulated cows were used in a double 4 × 4 Latin square design and fed with four treatments: control with no flax meal (FM, or 5%, 10% and 15% FM (on a dry matter basis. Concentration of EL in the rumen increased linearly with increasing FM inclusion. Total rumen bacterial 16S rRNA concentration obtained using Q-PCR did not differ among treatments. PCR-T-RFLP based dendrograms revealed no global clustering based on diet indicating between animal variation. PCR-DGGE showed a clustering by diet effect within four cows that had similar basal ruminal microbiota. DNA extracted from bands present following feeding 15% FM and absent with no FM supplementation were sequenced and it showed that many genera, in particular Prevotella spp., contributed to the metabolism of lignans. A subsequent in vitro study using selected pure cultures of ruminal bacteria incubated with SDG indicated that 11 ruminal bacteria were able to convert SDG into secoisolariciresinol (SECO, with Prevotella spp. being the main converters. These data suggest that Prevotella spp. is one genus playing an important role in the conversion of plant lignans to human health beneficial antioxidants in the rumen.

  12. The importance of team functioning to natural resource planning outcomes.

    Science.gov (United States)

    Stern, Marc J; Predmore, S Andrew

    2012-09-15

    In its recent history, the U.S. Forest Service is among many federal land management agencies struggling with questions concerning why its planning procedures are sometimes inefficient, perform poorly in the eyes of the public, and fail to deliver outputs that advance agency mission. By examining a representative sample of National Environmental Policy Act (NEPA) processes conducted by the agency between 2007 and 2009, we provide new insights into what drives outcomes in these planning processes. We examined team leaders' perceptions of the following outcomes: achievement of agency goals and NEPA mandates, process efficiency, public relations, and team outcomes. The most consistently important predictors of positive outcomes were team harmony and a clearly empowered team leader. Other factors, such as perceptions of the use of best science, a clear and unambiguous purpose and need, team turnover (personnel changes during the process), extra-agency engagement, and intra-agency relations, were also important, but played a less consistent role. The findings suggest the importance of empowering team leaders and team members through enhancing elements of discretion, responsibility, clear role definition, collaborative interdisciplinary deliberation, and perceived self-efficacy. The results also suggest the importance of genuine concern and respect for participating publics and effective inter-agency coordination. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. The Proapoptotic Bcl-2 Protein Bax Plays an Important Role in the Pathogenesis of Reovirus Encephalitis ▿

    Science.gov (United States)

    Berens, Heather M.; Tyler, Kenneth L.

    2011-01-01

    Encephalitis induced by reovirus serotype 3 (T3) strains results from the apoptotic death of infected neurons. Extrinsic apoptotic signaling is activated in reovirus-infected neurons in vitro and in vivo, but the role of intrinsic apoptosis signaling during encephalitis is largely unknown. Bax plays a key role in intrinsic apoptotic signaling in neurons by allowing the release of mitochondrial cytochrome c. We found Bax activation and cytochrome c release in neurons following infection of neonatal mice with T3 reoviruses. Bax−/− mice infected with T3 Abney (T3A) have reduced central nervous system (CNS) tissue injury and decreased apoptosis, despite viral replication that is similar to that in wild-type (WT) Bax+/+ mice. In contrast, in the heart, T3A-infected Bax−/− mice have viral growth, caspase activation, and injury comparable to those in WT mice, indicating that the role of Bax in pathogenesis is organ specific. Nonmyocarditic T3 Dearing (T3D)-infected Bax−/− mice had delayed disease and enhanced survival compared to WT mice. T3D-infected Bax−/− mice had significantly lower viral titers and levels of activated caspase 3 in the brain despite unaffected transneuronal spread of virus. Cytochrome c and Smac release occurred in some reovirus-infected neurons in the absence of Bax; however, this was clearly reduced compared to levels seen in Bax+/+ wild-type mice, indicating that Bax is necessary for efficient activation of proapoptotic mitochondrial signaling in infected neurons. Our studies suggest that Bax is important for reovirus growth and pathogenesis in neurons and that the intrinsic pathway of apoptosis, mediated by Bax, is important for full expression of disease, CNS tissue injury, apoptosis, and viral growth in the CNS of reovirus-infected mice. PMID:21307199

  14. Adhesive ability means inhibition activities for lactobacillus against pathogens and S-layer protein plays an important role in adhesion.

    Science.gov (United States)

    Zhang, Wenming; Wang, Haifeng; Liu, Jianxin; Zhao, Yunhao; Gao, Kan; Zhang, Juan

    2013-08-01

    Eighty-five strains of lactobacillus were isolated from the pig intestine and identified by sequencing analysis based on 16S rRNA gene, from which five lactobacillus strains with high adhesive ability were selected. The inhibition ability of the five lactobacillus strains with or without S-layer proteins against adherence of Escherichia coli K88 and Salmonella enteritidis 50335 to Caco-2 was evaluated in vitro with Lactobacillus rhamnosus GG strain (LGG) as a positive control. In addition, tolerance of lactobacilli to heat, acid, bile, Zn(2+) and Cu(2+) were assessed. All five selected strains, Lactobacillus salivarius ZJ614 (JN981856), Lactobacillus reuteri ZJ616 (JN981858), L. reuteri ZJ617 (JN981859), L. reuteri ZJ621 (JN981863) and L. reuteri ZJ623 (JN981865), showed inhibition against the two pathogens, E. coli K88 and S. enteritidis 50335. L. reuteri ZJ621 showed higher inhibition ability than the others to S. enteritidis 50335 (P S-layer protein, the inhibition activities of the lactobacilli against pathogens decreased significantly (P S-layer proteins plays an important role.

  15. Notch and Wnt/β-catenin signaling pathway play important roles in activating liver cancer stem cells

    Science.gov (United States)

    Wang, Ronghua; Sun, Qian; Wang, Peng; Liu, Man; Xiong, Si; Luo, Jing; Huang, Hai; Du, Qiang; Geller, David A.; Cheng, Bin

    2016-01-01

    Human hepatocellular carcinoma (HCC) is driven and maintained by liver cancer stem cells (LCSCs) that display stem cell properties. These LCSCs are promoted by the intersecting of Notch and Wnt/β-Catenin signaling pathways. In this study, we demonstrate that LCSCs with markers CD90, CD24, CD13, and CD133 possess stem properties of self-renewal and tumorigenicity in NOD/SCID mice. The increased expression of these markers was correlated with advanced disease stage, larger tumors, and worse overall survival in 61 HCC cases. We also found that both Notch and Wnt/β-catenin signaling pathways played important roles in increasing the stem-ness characteristics of LCSCs. Our data suggested that Notch1 was downstream of Wnt/β-catenin. The active form of Notch1 intracellular domain (NICD) expression depended on Wnt/β-catenin pathway activation. Moreover, Notch1 negatively contributed to Wnt/β-catenin signaling modulation. Knock down of Notch1 with lentivirus N1ShRNA up-regulated the active form of β-catenin. Ectopic expression of NICD with LV-Notch1 in LCSCs attenuated β-catenin/TCF dependent luciferase activity significantly. In addition, there was a non-proteasome mediated feedback loop between Notch1 and Wnt/β-catenin signaling in LCSCs. The central role of Notch and the Wnt/β-catenin signaling pathway in LCSCs may provide an attractive therapeutic strategy against HCC. PMID:26735577

  16. Does arsenic play an important role in the soil microbial community around a typical arsenic mining area?

    Science.gov (United States)

    Wu, Fan; Wang, Jun-Tao; Yang, Jun; Li, Jing; Zheng, Yuan-Ming

    2016-06-01

    Arsenic (As) can cause serious hazards to human health, especially in mining areas. Soil bacterial communities, which are critical parts of the soil ecosystem, were analyzed directly for soil environmental factors. As a consequence, it is of great significance to understand the ecological risk of arsenic contamination on bacteria, especially at the local scale. In this study, 33 pairs of soil and grain samples were collected from the corn and paddy fields around an arsenic mining area in Shimen County in Hunan Province, China. Significant differences were found between the soil nitrogen, As concentrations, and bacteria activities among these two types of land use. According to the structural equation model (SEM) analysis, compared with other environmental factors, soil As was not the key factor affecting the bacterial community, even when grain As was beyond the threshold of the national food hygiene standards of China. In the corn field, soil pH was the main factor dominating the bacterial richness, composition and grain As. Meanwhile, in the paddy field the soil total nitrogen (TN) and total carbon (TC) were the main factors impacting the bacterial richness, and the bacterial community composition was mainly affected by pH. The interactions between grain As and soil As were weak in the corn field. The bacterial communities played important roles in the food chain risk of As. The local policy of transforming paddy soil to dry land could greatly reduce the health risk of As through the food chain.

  17. Physiological analyses indicate superoxide dismutase, catalase, and phytochelatins play important roles in Pb tolerance in Eremochloa ophiuroides.

    Science.gov (United States)

    Li, Xi; Cen, Huameng; Chen, Youxiang; Xu, Siying; Peng, Lingli; Zhu, Hanmingyue; Li, Yiqiao

    2016-01-01

    Phytoremediation is considered to be a promising approach to restore or stabilize soil contaminated by lead (Pb). Turfgrasses, due to their high biomass yields, are considered to be suitable for use in phytoextraction of soil contaminated with heavy metal. It has been demonstrated that centipedegrass (Eremochloa ophiuroides (Munro) Hack., Poaceae) is a good turfgrass for restore of soil contaminated by Pb. However, the enhanced tolerant mechanisms in metallicolous (M) centipedegrass accessions remain unknown. In this study, we made a comparative study of growth performance, Pb accumulation, antioxidant levels, and phytochelatin concentrations in roots and shoots from M and nonmetallicolous (NM) centipedegrass accessions. Results showed that turf quality and growth rate were less repressed in M accessions than in NM accession. Pb stress caused generation of reactive oxygen species in centipedegrass with relatively lower levels in M accessions. Antioxidant activity analysis indicated that superoxide dismutase and catalase played important roles in Pb tolerance in M accessions. M accessions accumulated more Pb in roots and shoots. Greatly increased phytochelatins and less repressed sulfur contents in roots and shoots of M accessions indicated that they correlated with Pb accumulation and tolerance in centipedegrass.

  18. Notch and Wnt/β-catenin signaling pathway play important roles in activating liver cancer stem cells.

    Science.gov (United States)

    Wang, Ronghua; Sun, Qian; Wang, Peng; Liu, Man; Xiong, Si; Luo, Jing; Huang, Hai; Du, Qiang; Geller, David A; Cheng, Bin

    2016-02-02

    Human hepatocellular carcinoma (HCC) is driven and maintained by liver cancer stem cells (LCSCs) that display stem cell properties. These LCSCs are promoted by the intersecting of Notch and Wnt/β-Catenin signaling pathways. In this study, we demonstrate that LCSCs with markers CD90, CD24, CD13, and CD133 possess stem properties of self-renewal and tumorigenicity in NOD/SCID mice. The increased expression of these markers was correlated with advanced disease stage, larger tumors, and worse overall survival in 61 HCC cases. We also found that both Notch and Wnt/β-catenin signaling pathways played important roles in increasing the stem-ness characteristics of LCSCs. Our data suggested that Notch1 was downstream of Wnt/β-catenin. The active form of Notch1 intracellular domain (NICD) expression depended on Wnt/β-catenin pathway activation. Moreover, Notch1 negatively contributed to Wnt/β-catenin signaling modulation. Knock down of Notch1 with lentivirus N1ShRNA up-regulated the active form of β-catenin. Ectopic expression of NICD with LV-Notch1 in LCSCs attenuated β-catenin/TCF dependent luciferase activity significantly. In addition, there was a non-proteasome mediated feedback loop between Notch1 and Wnt/β-catenin signaling in LCSCs. The central role of Notch and the Wnt/β-catenin signaling pathway in LCSCs may provide an attractive therapeutic strategy against HCC.

  19. The functional importance of co-evolving residues in proteins.

    Science.gov (United States)

    Sandler, Inga; Zigdon, Nitzan; Levy, Efrat; Aharoni, Amir

    2014-02-01

    Computational approaches for detecting co-evolution in proteins allow for the identification of protein-protein interaction networks in different organisms and the assignment of function to under-explored proteins. The detection of co-variation of amino acids within or between proteins, moreover, allows for the discovery of residue-residue contacts and highlights functional residues that can affect the binding affinity, catalytic activity, or substrate specificity of a protein. To explore the functional impact of co-evolutionary changes in proteins, a combined experimental and computational approach must be recruited. Here, we review recent studies that apply computational and experimental tools to obtain novel insight into the structure, function, and evolution of proteins. Specifically, we describe the application of co-evolutionary analysis for predicting high-resolution three-dimensional structures of proteins. In addition, we describe computational approaches followed by experimental analysis for identifying specificity-determining residues in proteins. Finally, we discuss studies addressing the importance of such residues in terms of the functional divergence of proteins, allowing proteins to evolve new functions while avoiding crosstalk with existing cellular pathways or forming reproductive barriers and hence promoting speciation.

  20. Carbon nanotubes play an important role in the spatial arrangement of calcium deposits in hydrogels for bone regeneration.

    Science.gov (United States)

    Cancian, Giulia; Tozzi, Gianluca; Hussain, Amirul Ashraf Bin; De Mori, Arianna; Roldo, Marta

    2016-08-01

    Age related bone diseases such as osteoporosis are considered among the main causes of reduced bone mechanical stability and bone fractures. In order to restore both biological and mechanical function of diseased/fractured bones, novel bioactive scaffolds that mimic the bone structure are constantly under development in tissue engineering applications. Among the possible candidates, chitosan-based thermosensitive hydrogel scaffolds represent ideal systems due to their biocompatibility, biodegradability, enhanced antibacterial properties, promotion of osteoblast formation and ease of injection, which makes them suitable for less invasive surgical procedures. As a main drawback, these chitosan systems present poor mechanical performance that could not support load-bearing applications. In order to produce more mechanically-competent biomaterials, the combined addition of hydroxyapatite and carbon nanotubes (CNTs) is proposed in this study. Specifically, the aim of this work is to develop thermosensitive chitosan hydrogels containing stabilised single-walled and multi-walled CNTs, where their effect on the mechanical/physiochemical properties, calcium deposition patterns and ability to provide a platform for the controlled release of protein drugs was investigated. It was found that the addition of CNTs had a significant effect on the sol-gel transition time and significantly increased the resistance to compression for the hydrogels. Moreover, in vitro calcification studies revealed that CNTs played a major role in the spatial arrangements of newly formed calcium deposits in the composite materials studied, suggesting that they may have a role in the way the repair of fragile and/or fractured bones occurs in vivo.

  1. Induction of C-Mip by IL-17 Plays an Important Role in Adriamycin-Induced Podocyte Damage

    Directory of Open Access Journals (Sweden)

    Yanbo Liu

    2015-07-01

    Full Text Available Background/Aims: Although the disturbance of T lymphocyte and glomerular podocyte exerts a crucial function in the pathogenesis of proteinuria, the potential link is still unclear. Methods: The balance of Treg and Th17 cells, and the expression of IL-17/IL-17R and c-mip were investigated in adrimycin-induced nephropathy (AN mice. The effect and mechanism of IL-17 on podocyte were explored in cultured podocytes. Results: The proportion of Th17 cells in peripheral blood mononuclear cells, the amount of IL-17 in serum and kidney cortical homogenates, and the expression of IL-17R and c-mip in glomerular podocyte were increased obviously in AN mice. In cultured podocytes, recombinant IL-17 led to an induction of apoptosis and cytoskeletal disorganization, an overproduction of c-mip while down-regulation of phosphor-nephrin, and an increased binding of c-mip to NF-κB/RelA. Silence of c-mip prevented podocyte apoptosis and reduction of phosphor-nephrin by prompting nuclear translocation of NF-κB/RelA in IL-17 treated cells. Persistent activation of NF-κB up-regulated pro-survival protein Bcl-2 and decreased podocyte apoptosis, but had no effect on phosphor-nephrin level. Conclusion: These findings demonstrated that induction of IL-17 released by Th17 cells plays a key role in podocytopathy most likely through down-regulation of phosphor-nephrin and Bcl-2 level via overproduction of c-mip.

  2. Orexin receptor-1 in the locus coeruleus plays an important role in cue-dependent fear memory consolidation.

    Science.gov (United States)

    Soya, Shingo; Shoji, Hirotaka; Hasegawa, Emi; Hondo, Mari; Miyakawa, Tsuyoshi; Yanagisawa, Masashi; Mieda, Michihiro; Sakurai, Takeshi

    2013-09-01

    The noradrenergic (NA) projections arising from the locus ceruleus (LC) to the amygdala and bed nucleus of the stria terminalis have been implicated in the formation of emotional memory. Since NA neurons in the LC (LC-NA neurons) abundantly express orexin receptor-1 (OX1R) and receive prominent innervation by orexin-producing neurons, we hypothesized that an OX1R-mediated pathway is involved in the physiological fear learning process via regulation of LC-NA neurons. To evaluate this hypothesis, we examined the phenotype of Ox1r(-/-) mice in the classic cued and contextual fear-conditioning test. We found that Ox1r(-/-) mice showed impaired freezing responses in both cued and contextual fear-conditioning paradigms. In contrast, Ox2r(-/-) mice showed normal freezing behavior in the cued fear-conditioning test, while they exhibited shorter freezing time in the contextual fear-conditioning test. Double immunolabeling of Fos and tyrosine hydroxylase showed that double-positive LC-NA neurons after test sessions of both cued and contextual stimuli were significantly fewer in Ox1r(-/-) mice. AAV-mediated expression of OX1R in LC-NA neurons in Ox1r(-/-) mice restored the freezing behavior to the auditory cue to a comparable level to that in wild-type mice in the test session. Decreased freezing time during the contextual fear test was not affected by restoring OX1R expression in LC-NA neurons. These observations support the hypothesis that the orexin system modulates the formation and expression of fear memory via OX1R in multiple pathways. Especially, OX1R in LC-NA neurons plays an important role in cue-dependent fear memory formation and/or retrieval.

  3. Importance of clinical examination in diagnostics of Osgood-Schlatter Disease in boys playing soccer or basketball

    Directory of Open Access Journals (Sweden)

    Amela Halilbasic

    2012-04-01

    Full Text Available Introduction: Osgood–Schlatter disease is an irritation of the patellar tendon at the tibial tubercle. Sports with jumps, running, and repeated contractions of knee extension apparatus are considered to be importantexternal risk-factors which could cause Osgood–Schlatter disease.Objectives of the study are to draw attention to the importance of clinical examination in diagnostics of Osgood–Schlatter disease in boys playing soccer or basketball.Methods: The research included data obtained from 120 boys, average age of 14 years. Examinees were split into two groups, one with young athletes which regularly have soccer or basketball trainings and thesecond one with boys who do not participating in sports. We performed anthropological measurements and clinical examinations of both knees and hips for both groups. For the statistical analysis we used pointbiserialcorrelation coefficient.Results: Based on clinical examination, Osgood–Schlatter disease was diagnosed in 51 examinees (42.5%. In “athletic group” Osgood–Schlatter disease had 31 boys or 52%, comparing with “non-athletic group” wherewe found 20 adolescents with disease (33%. Number of boys with Osgood–Schlatter disease was higher for 19% in “athletic group” comparing with “non-athletic group”. Comparing incidence rate for boys in both groups with diagnosed II and III level of Osgood–Schlatter disease we found that rate is higher in “athletic group” 2.25 times comparing with “non-athletic group”.Conclusions: Clinical examination is critical method in the process of diagnosing Osgood–Schlatter disease especially for identifying II and III level of this disease.

  4. Can Brazil play a more important role in global tuberculosis drug production? An assessment of current capacity and challenges.

    Science.gov (United States)

    Gemal, Andre; Keravec, Joel; Menezes, Alexandre; Trajman, Anete

    2013-03-27

    Despite the existence of effective treatment, tuberculosis is still a global public health issue. The World Health Organization recommends a six-month four-drug regimen in fixed-dose combination formulation to treat drug sensitive tuberculosis, and long course regimens with several second-line drugs to treat multi-drug resistant tuberculosis. To achieve the projected tuberculosis elimination goal by 2050, it will be essential to ensure a non-interrupted supply of quality-assured tuberculosis drugs. However, quality and affordable tuberculosis drug supply is still a significant challenge for National Tuberculosis Programs. Quality drug production requires a combination of complex steps. The first challenge is to guarantee the quality of tuberculosis active pharmaceutical ingredients, then ensure an adequate manufacturing process, according to international standards, to guarantee final product's safety, efficacy and quality. Good practices for storage, transport, distribution and quality control procedures must follow. In contrast to other high-burden countries, Brazil produces tuberculosis drugs through a strong network of public sector drug manufacturers regulated by a World Health Organization-certified national sanitary authority. The installed capacity for production surpasses the 71,000 needed treatments in the country. However, in order to be prepared to act as a global supplier, important bottlenecks are to be overcome. This article presents an in-depth analysis of the current status of production of tuberculosis drugs in Brazil and the bottlenecks and opportunities for the country to sustain national demand and play a role as a potential global supplier. Raw material and drug production, quality control, international certification and pre-qualification, political commitment and regulatory aspects are discussed, as well recommendations for tackling these bottlenecks. This discussion becomes more important as new drugs and regimens to treat tuberculosis are

  5. Proteins of the corneal stroma: importance in visual function.

    Science.gov (United States)

    Xuan, Meng; Wang, Shurong; Liu, Xin; He, Yuxi; Li, Ying; Zhang, Yan

    2016-04-01

    The human cornea, consisting of five layers, is the transparent tissue that refracts and transmits light to the lens and retina, providing about two thirds of the refractive power of the eye. The stroma layer comprises nearly 90 % of the thickness of the cornea and thus plays a pivotal role in normal visual function. The bulk of this layer is constituted by proteins in the extracellular martrix secreted by the corneal epithelial, stroma, and endothelial cells. Clinical research has shown that corneal stroma diseases are common and involve conditions such as infections, injuries, and genetic defects, which cause severe visual disturbances or even blindness. To improve our understanding of the basic molecular mechanisms involved in the physiological and pathological activities of the corneal stroma, its proteins have been brought into the limelight to determine their crucial and irreplaceable roles. The data presented in a previous study have demonstrated the presence of 1679 proteins in the stroma, and this data set has subsequently been perfected by utilizing a highly sensitive isobaric peptide-labeling approach. According to their manifestations, these proteins can be classified as a gel-like organic material composed of proteoglycans, enzymes, and hemocyanin-binding proteins and a network of filaments composed of collagen, elastin, keratin, vimentin, and interconnected filaments comprising fibronectin and laminin. The aim of this review is to describe some corneal stroma proteins by highlighting their major functions and valuable applications in ophthalmologic research toward the better characterization and treatment of eye diseases.

  6. Radiative lifetimes and cooling functions for astrophysically important molecules

    CERN Document Server

    Tennyson, Jonathan; Naim, Omree K; Yurchenko, Sergei N

    2016-01-01

    Extensive line lists generated as part of the ExoMol project are used to compute lifetimes for individual rotational, rovibrational and rovibronic excited states, and temperature-dependent cooling functions by summing over all dipole-allowed transitions for the states concerned. Results are presented for SiO, CaH, AlO, ScH, H$_2$O and methane. The results for CH$_4$ are particularly unusual with 4 excited states with no dipole-allowed decay route and several others where these decays lead to exceptionally long lifetimes. These lifetime data should be useful in models of masers and estimates of critical densities, and can provide a link with laboratory measurements. Cooling functions are important in stellar and planet formation.

  7. Enhancing playful teachers' perception of the importance of ICT use in the classroom: The role of risk taking as a mediator

    National Research Council Canada - National Science Library

    Goodwin, ALin; Low, Ee Ling; Ng, Pak Tee; Yeung, Alexander S; Cai, Li

    2015-01-01

    ... (SEM) found that the effect of cognitive playfulness on the perceived importance of ICT was mediated by risk taking orientation, but the mediation effect was not observed with perceived competence in ICT use...

  8. The Efficacy of Exergames Played Proximally and over the Internet on Cognitive Functioning for Online Physical Education

    Science.gov (United States)

    Kooiman, Brian J.; Sheehan, Dwayne P.

    2014-01-01

    Exergames (active video games that require kinesthetic movement) played in proximity to other players or against a gaming machine have been linked to positive increases in cognitive functioning. This study tested to see if remote exergame play over the Internet had an impact similar to exergames that are played in proximity. The study shows that…

  9. MusicGlove: motivating and quantifying hand movement rehabilitation by using functional grips to play music.

    Science.gov (United States)

    Friedman, Nizan; Chan, Vicky; Zondervan, Danny; Bachman, Mark; Reinkensmeyer, David J

    2011-01-01

    People with stroke typically must perform much of their hand exercise at home without professional assistance as soon as two weeks after the stroke. Without feedback and encouragement, individuals often lose motivation to practice using the affected hand, and this disuse contributes to further declines in hand function. We developed the MusicGlove as a way to facilitate and motivate at home practice of hand movement. This low-cost device uses music as an interactive and motivating medium to guide hand exercise and to quantitatively assess hand movement recovery. It requires the user to practice functional movements, including pincer grip, key-pinch grip, and finger-thumb opposition, by using those movements to play different musical notes, played along to songs displayed by an interactive computer game. We report here the design of the glove and the results of a single-session experiment with 10 participants with chronic stroke. We found that the glove is well suited for use by people with an impairment level quantified by a Box and Blocks score of at least around 7; that the glove can be used to obtain a measure of hand dexterity (% of notes hit) that correlates strongly with the Box and Blocks score; and that the incorporation of music into training significantly improved both objective measures of hand motor performance and self-ratings of motivation for training in the single session.

  10. THE IMPORTANCE OF COMMUNICATION IN THE FUNCTIONING OF AN ORGANIZATION

    Directory of Open Access Journals (Sweden)

    Zvonimir Jurković

    2012-12-01

    Full Text Available Organizations cannot exist without communication. Every human action is a kind of communication, and thus “not communicating” is also a form of communication. Efficient communication is the foundation for the internal organization development, but also a key factor of existence in an uncertain environment. Therefore, communication is an important aspect of manager behaviour as well as of the functioning of the entire organizational system. Business communication takes place both within and outside of organizations. A communication event within an organization can have two routes: a formal and an informal one. To make the organizational communication more successful, it is necessary for all participants and organization employees to have adequate language skills, to conduct interactive exercises and to possess intercultural awareness.

  11. The functional importance of disease-associated mutation

    Directory of Open Access Journals (Sweden)

    Klein Teri E

    2002-09-01

    Full Text Available Abstract Background For many years, scientists believed that point mutations in genes are the genetic switches for somatic and inherited diseases such as cystic fibrosis, phenylketonuria and cancer. Some of these mutations likely alter a protein's function in a manner that is deleterious, and they should occur in functionally important regions of the protein products of genes. Here we show that disease-associated mutations occur in regions of genes that are conserved, and can identify likely disease-causing mutations. Results To show this, we have determined conservation patterns for 6185 non-synonymous and heritable disease-associated mutations in 231 genes. We define a parameter, the conservation ratio, as the ratio of average negative entropy of analyzable positions with reported mutations to that of every analyzable position in the gene sequence. We found that 84.0% of the 231 genes have conservation ratios less than one. 139 genes had eleven or more analyzable mutations and 88.0% of those had conservation ratios less than one. Conclusions These results indicate that phylogenetic information is a powerful tool for the study of disease-associated mutations. Our alignments and analysis has been made available as part of the database at http://cancer.stanford.edu/mut-paper/. Within this dataset, each position is annotated with the analysis, so the most likely disease-causing mutations can be identified.

  12. Playing piano can improve upper extremity function after stroke: case studies.

    Science.gov (United States)

    Villeneuve, Myriam; Lamontagne, Anouk

    2013-01-01

    Music-supported therapy (MST) is an innovative approach that was shown to improve manual dexterity in acute stroke survivors. The feasibility of such intervention in chronic stroke survivors and its longer-term benefits, however, remain unknown. The objective of this pilot study was to estimate the short- and long-term effects of a 3-week piano training program on upper extremity function in persons with chronic stroke. A multiple pre-post sequential design was used, with measurements taken at baseline (week0, week3), prior to (week6) and after the intervention (week9), and at 3-week follow-up (week12). Three persons with stroke participated in the 3-week piano training program that combined structured piano lessons to home practice program. The songs, played on an electronic keyboard, involved all 5 digits of the affected hand and were displayed using a user-friendly MIDI program. After intervention, all the three participants showed improvements in their fine (nine hole peg test) and gross (box and block test) manual dexterity, as well as in the functional use of the upper extremity (Jebsen hand function test). Improvements were maintained at follow-up. These preliminary results support the feasibility of using an MST approach that combines structured lessons to home practice to improve upper extremity function in chronic stroke.

  13. Playing Piano Can Improve Upper Extremity Function after Stroke: Case Studies

    Directory of Open Access Journals (Sweden)

    Myriam Villeneuve

    2013-01-01

    Full Text Available Music-supported therapy (MST is an innovative approach that was shown to improve manual dexterity in acute stroke survivors. The feasibility of such intervention in chronic stroke survivors and its longer-term benefits, however, remain unknown. The objective of this pilot study was to estimate the short- and long-term effects of a 3-week piano training program on upper extremity function in persons with chronic stroke. A multiple pre-post sequential design was used, with measurements taken at baseline (week0, week3, prior to (week6 and after the intervention (week9, and at 3-week follow-up (week12. Three persons with stroke participated in the 3-week piano training program that combined structured piano lessons to home practice program. The songs, played on an electronic keyboard, involved all 5 digits of the affected hand and were displayed using a user-friendly MIDI program. After intervention, all the three participants showed improvements in their fine (nine hole peg test and gross (box and block test manual dexterity, as well as in the functional use of the upper extremity (Jebsen hand function test. Improvements were maintained at follow-up. These preliminary results support the feasibility of using an MST approach that combines structured lessons to home practice to improve upper extremity function in chronic stroke.

  14. Colonic miRNA expression/secretion, regulated by intestinal epithelial PepT1, plays an important role in cell-to-cell communication during colitis.

    Directory of Open Access Journals (Sweden)

    Saravanan Ayyadurai

    Full Text Available PepT1 is a member of the proton-oligopeptide cotransporter family SLC15, which mediates the transport of di/tripeptides from intestinal lumen into epithelial cells. MicroRNAs (miRNAs, a small noncoding RNAs (21-23 nucleotides, post-transcriptionally regulate gene expression by binding to the 3'-untranslated regions (UTRs of their target mRNAs. Although the role of most miRNAs remains elusive, they have been implicated in vital cellular functions such as intestinal epithelial cells differentiation, proliferation, and apoptosis. In the present study, we investigated the effect of intestinal epithelial PepT1 expression on microRNA (miRNA expression/secretion in the colons of control mice and in mice with experimentally induced colonic inflammation (colitis. The colonic miRNA expression was deregulated in both colitis and control mice but the deregulation of miRNA expression/secretion was specific to colonic tissue and did not affect other tissues such as spleen and liver. Intestinal epithelial PepT1-dependent deregulation of colonic miRNA expression not only affects epithelial cells but also other cell types, such as intestinal macrophages. Importantly, we found the miRNA 23b which was known to be involved in inflammatory bowel disease was secreted and transported between cells to impose a gene-silencing effect on recipient intestinal macrophages. Based on our data, we may conclude that the expression of a specific protein, PepT1, in the intestine affects local miRNA expression/secretion in the colon on a tissue specific manner and may play an important role during the induction and progression of colitis. Colonic miRNA expression/secretion, regulated by intestinal epithelial PepT1, could play a crucial role in cell-to-cell communication during colitis.

  15. CD44 plays a functional role in Helicobacter pylori-induced epithelial cell proliferation.

    Directory of Open Access Journals (Sweden)

    Nina Bertaux-Skeirik

    2015-02-01

    Full Text Available The cytotoxin-associated gene (Cag pathogenicity island is a strain-specific constituent of Helicobacter pylori (H. pylori that augments cancer risk. CagA translocates into the cytoplasm where it stimulates cell signaling through the interaction with tyrosine kinase c-Met receptor, leading cellular proliferation. Identified as a potential gastric stem cell marker, cluster-of-differentiation (CD CD44 also acts as a co-receptor for c-Met, but whether it plays a functional role in H. pylori-induced epithelial proliferation is unknown. We tested the hypothesis that CD44 plays a functional role in H. pylori-induced epithelial cell proliferation. To assay changes in gastric epithelial cell proliferation in relation to the direct interaction with H. pylori, human- and mouse-derived gastric organoids were infected with the G27 H. pylori strain or a mutant G27 strain bearing cagA deletion (∆CagA::cat. Epithelial proliferation was quantified by EdU immunostaining. Phosphorylation of c-Met was analyzed by immunoprecipitation followed by Western blot analysis for expression of CD44 and CagA. H. pylori infection of both mouse- and human-derived gastric organoids induced epithelial proliferation that correlated with c-Met phosphorylation. CagA and CD44 co-immunoprecipitated with phosphorylated c-Met. The formation of this complex did not occur in organoids infected with ∆CagA::cat. Epithelial proliferation in response to H. pylori infection was lost in infected organoids derived from CD44-deficient mouse stomachs. Human-derived fundic gastric organoids exhibited an induction in proliferation when infected with H. pylori that was not seen in organoids pre-treated with a peptide inhibitor specific to CD44. In the well-established Mongolian gerbil model of gastric cancer, animals treated with CD44 peptide inhibitor Pep1, resulted in the inhibition of H. pylori-induced proliferation and associated atrophic gastritis. The current study reports a unique

  16. Repetitive sequences and epigenetic modification: inseparable partners play important roles in the evolution of plant sex chromosomes.

    Science.gov (United States)

    Li, Shu-Fen; Zhang, Guo-Jun; Yuan, Jin-Hong; Deng, Chuan-Liang; Gao, Wu-Jun

    2016-05-01

    The present review discusses the roles of repetitive sequences played in plant sex chromosome evolution, and highlights epigenetic modification as potential mechanism of repetitive sequences involved in sex chromosome evolution. Sex determination in plants is mostly based on sex chromosomes. Classic theory proposes that sex chromosomes evolve from a specific pair of autosomes with emergence of a sex-determining gene(s). Subsequently, the newly formed sex chromosomes stop recombination in a small region around the sex-determining locus, and over time, the non-recombining region expands to almost all parts of the sex chromosomes. Accumulation of repetitive sequences, mostly transposable elements and tandem repeats, is a conspicuous feature of the non-recombining region of the Y chromosome, even in primitive one. Repetitive sequences may play multiple roles in sex chromosome evolution, such as triggering heterochromatization and causing recombination suppression, leading to structural and morphological differentiation of sex chromosomes, and promoting Y chromosome degeneration and X chromosome dosage compensation. In this article, we review the current status of this field, and based on preliminary evidence, we posit that repetitive sequences are involved in sex chromosome evolution probably via epigenetic modification, such as DNA and histone methylation, with small interfering RNAs as the mediator.

  17. Repression of ARF10 by microRNA160 plays an important role in the mediation of leaf water loss.

    Science.gov (United States)

    Liu, Xin; Dong, Xiufen; Liu, Zihan; Shi, Zihang; Jiang, Yun; Qi, Mingfang; Xu, Tao; Li, Tianlai

    2016-10-01

    Solanum lycopersicum auxin response factor 10 (SlARF10) is post-transcriptionally regulated by Sl-miR160. Overexpression of a Sl-miR160-resistant SlARF10 (mSlARF10) resulted in narrower leaflet blades with larger stomata but lower densities. 35S:mSlARF10-6 plants with narrower excised leaves had greater water loss, which was in contrast to the wild type (WT). Further analysis revealed that the actual water loss was not consistent with the calculated stomatal water loss in 35S:mSlARF10-6 and the WT under the dehydration treatment, indicating that there is a difference in hydraulic conductance. Pretreatment with abscisic acid (ABA) and HgCl2 confirmed higher hydraulic conductance in 35S:mSlARF10, which is related to the larger stomatal size and higher activity of aquaporins (AQPs). Under ABA treatment, 35S:mSlARF10-6 showed greater sensitivity, and the stomata closed rapidly. Screening by RNA sequencing revealed that five AQP-related genes, fourteen ABA biosynthesis/signal genes and three stomatal development genes were significantly altered in 35S:mSlARF10-6 plants, and this result was verified by qRT-PCR. The promoter analysis showed that upregulated AQPs contain AuxRE and ABRE, implying that these elements may be responsible for the high expression levels of AQPs in 35S:mSlARF10-6. The three most upregulated AQPs (SlTIP1-1-like, SlPIP2;4 and SlNIP-type-like) were chosen to confirm AuxRE and ABRE function. Promoters transient expression demonstrated that the SlPIP2;4 and SlNIP-type-like AuxREs and SlPIP2;4 and SlTIP1-1-like ABREs could significantly enhance the expression of the GUS reporter in 35S:mSlARF10-6, confirming that AuxRE and ABRE may be the main factors inducing the expression of AQPs. Additionally, two upregulated transcription factors in 35S:mSlARF10-6, SlARF10 and SlABI5-like were shown to directly bind to those elements in an electromobility shift assay and a yeast one-hybrid assay. Furthermore, transient expression of down-regulated ARF10 or up

  18. Proteomics Profiling Reveals Carbohydrate Metabolic Enzymes and 14-3-3 Proteins Play Important Roles for Starch Accumulation during Cassava Root Tuberization.

    Science.gov (United States)

    Wang, Xuchu; Chang, Lili; Tong, Zheng; Wang, Dongyang; Yin, Qi; Wang, Dan; Jin, Xiang; Yang, Qian; Wang, Liming; Sun, Yong; Huang, Qixing; Guo, Anping; Peng, Ming

    2016-01-01

    Cassava is one of the most important root crops as a reliable source of food and carbohydrates. Carbohydrate metabolism and starch accumulation in cassava storage root is a cascade process that includes large amounts of proteins and cofactors. Here, comparative proteomics were conducted in cassava root at nine developmental stages. A total of 154 identified proteins were found to be differentially expressed during starch accumulation and root tuberization. Many enzymes involved in starch and sucrose metabolism were significantly up-regulated, and functional classification of the differentially expressed proteins demonstrated that the majority were binding-related enzymes. Many proteins were took part in carbohydrate metabolism to produce energy. Among them, three 14-3-3 isoforms were induced to be clearly phosphorylated during storage root enlargement. Overexpression of a cassava 14-3-3 gene in Arabidopsis thaliana confirmed that the older leaves of these transgenic plants contained higher sugar and starch contents than the wild-type leaves. The 14-3-3 proteins and their binding enzymes may play important roles in carbohydrate metabolism and starch accumulation during cassava root tuberization. These results not only deepened our understanding of the tuberous root proteome, but also uncovered new insights into carbohydrate metabolism and starch accumulation during cassava root enlargement.

  19. Fluidic interconnections for microfluidic systems: A new integrated fluidic interconnection allowing plug 'n' play functionality

    DEFF Research Database (Denmark)

    Perozziello, Gerardo; Bundgaard, Frederik; Geschke, Oliver

    2008-01-01

    A crucial challenge in packaging of microsystems is microfluidic interconnections. These have to seal the ports of the system, and have to provide the appropriate interface to other devices or the external environment. Integrated fluidic interconnections appear to be a good solution...... for interconnecting polymer microsystems in terms of cost, space and performance. Following this path we propose a new reversible, integrated fluidic interconnection composed of custom-made cylindrical rings integrated in a polymer house next to the fluidic network. This allows plug 'n' play functionality between...... external metal ferrules and the system. Theoretical calculations are made to dimension and model the integrated fluidic interconnection. Leakage tests are performed on the interconnections, in order to experimentally confirm the model, and detect its limits....

  20. A petunia ocs element binding factor, PhOBF1, plays an important role in antiviral RNA silencing

    Science.gov (United States)

    Virus-induced gene silencing (VIGS) is a common strategy of reverse genetics for characterizing function of genes in plant. The detailed mechanism governing RNA silencing efficiency triggered by virus is largely unclear. Here, we revealed that a petunia (Petunia hybrida) ocs element binding factor, ...

  1. Holistic marketing and its importance in the functioning of universities

    Directory of Open Access Journals (Sweden)

    I.P. Chajka

    2013-09-01

    Full Text Available The aim of the article is to study holistic marketing concept for its further implementation into activities of national enterprises including universities.The results of the analysis. Implementation of holistic marketing into activities of the company means to move away from traditional, built on a rigid hierarchy and subordination forms of management of production processes. Holistic marketing requires promotion of democracy, decentralization, development initiatives from below, involvement in decision-making of all stakeholders. Another important aspect of holistic marketing is to establish constant feedback to management, interactivity of all elements of the system recognizing the importance of each element.Thus, holistic marketing is a model of integrated planning, development and implementation of marketing programs, processes and activities with deprivation of rigid centralization. Holistic marketing leaves open the possibility for inherent mobility and, consequently, of its internal creative self-configuration potential.The mature state of governance in holistic marketing should be a situation where parts and wholes equal, there is no greater and smaller, important and not important. Each element of the holistic marketing has its meaning, functions that are considered as a whole. The prospect of such a system would be to totality the point where each element of the system becomes equal for the entire system.Authors propose the following principles of holistic marketing implementation into universities activities:independent decision-making;decentralization of management, providing an opportunity to decide the course of individual processes, promotion marketing activity of each participant in the process;the establishment and ongoing support of feedback between elements of the operation of the business;the freedom of each participant in the process, etc.Choosing the strategy of holistic marketing concept at a high school constantly

  2. Optimizing health system response to patient's needs: an argument for the importance of functioning information.

    Science.gov (United States)

    Hopfe, Maren; Prodinger, Birgit; Bickenbach, Jerome E; Stucki, Gerold

    2017-06-06

    Current health systems are increasingly challenged to meet the needs of a growing number of patients living with chronic and often multiple health conditions. The primary outcome of care, it is argued, is not merely curing disease but also optimizing functioning over a person's life span. According to the World Health Organization, functioning can serve as foundation for a comprehensive picture of health and augment the biomedical perspective with a broader and more comprehensive picture of health as it plays out in people's lives. The crucial importance of information about patient's functioning for a well-performing health system, however, has yet to be sufficiently appreciated. This paper argues that functioning information is fundamental in all components of health systems and enhances the capacity of health systems to optimize patients' health and health-related needs. Beyond making sense of biomedical disease patterns, health systems can profit from using functioning information to improve interprofessional collaboration and achieve cross-cutting disease treatment outcomes. Implications for rehabilitation Functioning is a key health outcome for rehabilitation within health systems. Information on restoring, maintaining, and optimizing human functioning can strengthen health system response to patients' health and rehabilitative needs. Functioning information guides health systems to achieve cross-cutting health outcomes that respond to the needs of the growing number of individuals living with chronic and multiple health conditions. Accounting for individuals functioning helps to overcome fragmentation of care and to improve interprofessional collaboration across settings.

  3. The importance of measuring psychosocial functioning in schizophrenia

    Directory of Open Access Journals (Sweden)

    Dias Vasco

    2011-06-01

    Full Text Available Abstract Background Schizophrenia is among the most disabling of mental illnesses and frequently causes impaired functioning. We explore issues of definition and terminology, and the relationship between social functioning, cognition, and psychopathology considering relevant research findings. Methods The present article describes measures of social functioning and outlines their psychometric properties. It considers their usefulness in research and clinical settings. Treatment aims and objectives are explored in the context of cognitive and social functioning. Finally, we identify areas for developing research and refining the measurement of social functioning. Results The definition and measurement of social functioning in schizophrenia remains a complex and disputed area. The relationships between symptoms, cognitive functioning and social functioning are complex but we are beginning to understand them better. Scales for measuring functioning in clinical practice must be brief and sensitive to change and the Personal and Social Performance (PSP scale may offer several advantages in these regards. Brief cognitive assessments focusing upon the domains most commonly affected in schizophrenia, such as verbal memory and executive functions, should be coadministered with measures of functioning. Conclusions The use of validated scales for schizophrenia that are sensitive to change over the course of the illness and its treatment, should allow for a better understanding of patients' functional disabilities, enabling better and more comprehensive monitoring and evaluation of both pharmacological and non-pharmacological treatment strategies.

  4. estimating an aggregate import demand function for ghana

    African Journals Online (AJOL)

    Administrator

    80% of shocks to real exchange rates, merchandise imports and GDP respectively, are attributed to own shocks. ... the United Kingdom and Germany as the main export markets. .... period stock of imported merchandise if posi- tive, and the ...

  5. Nod-Like Receptor Protein-3 Inflammasome Plays an Important Role during Early Stages of Wound Healing

    Science.gov (United States)

    Weinheimer-Haus, Eileen M.; Mirza, Rita E.; Koh, Timothy J.

    2015-01-01

    The Nod-like receptor protein (NLRP)-3 inflammasome/IL-1β pathway is involved in the pathogenesis of various inflammatory skin diseases, but its biological role in wound healing remains to be elucidated. Since inflammation is typically thought to impede healing, we hypothesized that loss of NLRP-3 activity would result in a downregulated inflammatory response and accelerated wound healing. NLRP-3 null mice, caspase-1 null mice and C57Bl/6 wild type control mice (WT) received four 8 mm excisional cutaneous wounds; inflammation and healing were assessed during the early stage of wound healing. Consistent with our hypothesis, wounds from NLRP-3 null and caspase-1 null mice contained lower levels of the pro-inflammatory cytokines IL-1β and TNF-α compared to WT mice and had reduced neutrophil and macrophage accumulation. Contrary to our hypothesis, re-epithelialization, granulation tissue formation, and angiogenesis were delayed in NLRP-3 null mice and caspase-1 null mice compared to WT mice, indicating that NLRP-3 signaling is important for early events in wound healing. Topical treatment of excisional wounds with recombinant IL-1β partially restored granulation tissue formation in wounds of NLRP-3 null mice, confirming the importance of NLRP-3-dependent IL-1β production during early wound healing. Despite the improvement in healing, angiogenesis and levels of the pro-angiogenic growth factor VEGF were further reduced in IL-1β treated wounds, suggesting that IL-1β has a negative effect on angiogenesis and that NLRP-3 promotes angiogenesis in an IL-1β-independent manner. These findings indicate that the NLRP-3 inflammasome contributes to the early inflammatory phase following skin wounding and is important for efficient healing. PMID:25793779

  6. Nod-like receptor protein-3 inflammasome plays an important role during early stages of wound healing.

    Science.gov (United States)

    Weinheimer-Haus, Eileen M; Mirza, Rita E; Koh, Timothy J

    2015-01-01

    The Nod-like receptor protein (NLRP)-3 inflammasome/IL-1β pathway is involved in the pathogenesis of various inflammatory skin diseases, but its biological role in wound healing remains to be elucidated. Since inflammation is typically thought to impede healing, we hypothesized that loss of NLRP-3 activity would result in a downregulated inflammatory response and accelerated wound healing. NLRP-3 null mice, caspase-1 null mice and C57Bl/6 wild type control mice (WT) received four 8 mm excisional cutaneous wounds; inflammation and healing were assessed during the early stage of wound healing. Consistent with our hypothesis, wounds from NLRP-3 null and caspase-1 null mice contained lower levels of the pro-inflammatory cytokines IL-1β and TNF-α compared to WT mice and had reduced neutrophil and macrophage accumulation. Contrary to our hypothesis, re-epithelialization, granulation tissue formation, and angiogenesis were delayed in NLRP-3 null mice and caspase-1 null mice compared to WT mice, indicating that NLRP-3 signaling is important for early events in wound healing. Topical treatment of excisional wounds with recombinant IL-1β partially restored granulation tissue formation in wounds of NLRP-3 null mice, confirming the importance of NLRP-3-dependent IL-1β production during early wound healing. Despite the improvement in healing, angiogenesis and levels of the pro-angiogenic growth factor VEGF were further reduced in IL-1β treated wounds, suggesting that IL-1β has a negative effect on angiogenesis and that NLRP-3 promotes angiogenesis in an IL-1β-independent manner. These findings indicate that the NLRP-3 inflammasome contributes to the early inflammatory phase following skin wounding and is important for efficient healing.

  7. OsRRMh, a Spen-Like Gene, Plays an Important Role During the Vegetative to Reproductive Transition in Rice

    Institute of Scientific and Technical Information of China (English)

    Derui Liu; Xiuling Cai

    2013-01-01

    OsRRMh, a homologue of OsRRM, encodes a Spen-like protein, and is composed of two N-terminal RNA recognition motifs (RRM) and one C-terminal Spen paralogue and an orthologue C-terminal domain (SPOC). The gene has been found to be constitutively expressed in the root, stem, leaf, spikelet, and immature seed, and alternative splicing patterns were confirmed in different tissues, which may indicate diverse functions for OsRRMh. The OsRRMh dsRNAi lines exhibited late-flowering and a larger panicle phenotype. When full-length OsRRMh and/or its SPOC domain were overexpressed, the fertility rate and number of spikelets per panicle were both markedly reduced. Also, overexpression of OsRRMh in the Arabidopsis fpa mutant did not restore the normal flowering time, and it delayed flowering in Col plants. Therefore, we propose that OsRRMh may confer one of its functions in the vegetative-to-reproductive transition in rice (Oryza sativa L. subsp. japonica cv. Zhonghua No. 11 (ZH11)).

  8. The mitochondrial protein Mcu1 plays important roles in carbon source utilization, filamentation, and virulence in Candida albicans.

    Science.gov (United States)

    Guan, Guobo; Wang, Haitao; Liang, Weihong; Cao, Chengjun; Tao, Li; Naseem, Shamoon; Konopka, James B; Wang, Yue; Huang, Guanghua

    2015-08-01

    The fungus Candida albicans is both a pathogen and a commensal in humans. The ability to utilize different carbon sources available in diverse host niches is vital for both commensalism and pathogenicity. N-acetylglucosamine (GlcNAc) is an important signaling molecule as well as a carbon source in C. albicans. Here, we report the discovery of a novel gene MCU1 essential for GlcNAc utilization. Mcu1 is located in mitochondria and associated with multiple energy- and metabolism-related proteins including Por1, Atp1, Pet9, and Mdh1. Consistently, inactivating Por1 impaired GlcNAc utilization as well. Deletion of MCU1 also caused defects in utilizing non-fermentable carbon sources and amino acids. Furthermore, MCU1 is required for filamentation in several inducing conditions and virulence in a mouse systemic infection model. We also deleted TGL99 and GUP1, two genes adjacent to MCU1, and found that the gup1/gup1 mutant exhibited mild defects in the utilization of several carbon sources including GlcNAc, maltose, galactose, amino acids, and ethanol. Our results indicate that MCU1 exists in a cluster of genes involved in the metabolism of carbon sources. Given its importance in metabolism and lack of a homolog in humans, Mcu1 could be a potential target for developing antifungal agents.

  9. 'Serious thigh muscle strains': beware the intramuscular tendon which plays an important role in difficult hamstring and quadriceps muscle strains.

    Science.gov (United States)

    Brukner, Peter; Connell, David

    2016-02-01

    Why do some hamstring and quadriceps strains take much longer to repair than others? Which injuries are more prone to recurrence? Intramuscular tendon injuries have received little attention as an element in 'muscle strain'. In thigh muscles, such as rectus femoris and biceps femoris, the attached tendon extends for a significant distance within the muscle belly. While the pathology of most muscle injures occurs at a musculotendinous junction, at first glance the athlete appears to report pain within a muscle belly. In addition to the musculotendinous injury being a site of pathology, the intramuscular tendon itself is occasionally injured. These injuries have a variety of appearances on MRIs. There is some evidence that these injuries require a prolonged rehabilitation time and may have higher recurrence rates. Therefore, it is important to recognise the tendon component of a thigh 'muscle strain'.

  10. Arabidopsis NIP3;1 Plays an Important Role in Arsenic Uptake and Root-to-Shoot Translocation under Arsenite Stress Conditions.

    Science.gov (United States)

    Xu, Wenzhong; Dai, Wentao; Yan, Huili; Li, Sheng; Shen, Hongling; Chen, Yanshan; Xu, Hua; Sun, Yangyang; He, Zhenyan; Ma, Mi

    2015-05-01

    In Arabidopsis, the nodulin 26-like intrinsic protein (NIP) subfamily of aquaporin proteins consists of nine members, five of which (NIP1;1, NIP1;2, NIP5;1, NIP6;1, and NIP7;1) were previously identified to be permeable to arsenite. However, the roles of NIPs in the root-to-shoot translocation of arsenite in plants remain poorly understood. In this study, using reverse genetic strategies, Arabidopsis NIP3;1 was identified to play an important role in both the arsenic uptake and root-to-shoot distribution under arsenite stress conditions. The nip3;1 loss-of-function mutants displayed obvious improvements in arsenite tolerance for aboveground growth and accumulated less arsenic in shoots than those of the wild-type plants, whereas the nip3;1 nip1;1 double mutant showed strong arsenite tolerance and improved growth of both roots and shoots under arsenite stress conditions. A promoter-β-glucuronidase analysis revealed that NIP3;1 was expressed almost exclusively in roots (with the exception of the root tips), and heterologous expression in the yeast Saccharomyces cerevisiae demonstrated that NIP3;1 was able to mediate arsenite transport. Taken together, our results suggest that NIP3;1 is involved in arsenite uptake and root-to-shoot translocation in Arabidopsis, probably as a passive and bidirectional arsenite transporter.

  11. Protein kinase a dependent phosphorylation of apical membrane antigen 1 plays an important role in erythrocyte invasion by the malaria parasite.

    Directory of Open Access Journals (Sweden)

    Kerstin Leykauf

    2010-06-01

    Full Text Available Apicomplexan parasites are obligate intracellular parasites that infect a variety of hosts, causing significant diseases in livestock and humans. The invasive forms of the parasites invade their host cells by gliding motility, an active process driven by parasite adhesion proteins and molecular motors. A crucial point during host cell invasion is the formation of a ring-shaped area of intimate contact between the parasite and the host known as a tight junction. As the invasive zoite propels itself into the host-cell, the junction moves down the length of the parasite. This process must be tightly regulated and signalling is likely to play a role in this event. One crucial protein for tight-junction formation is the apical membrane antigen 1 (AMA1. Here we have investigated the phosphorylation status of this key player in the invasion process in the human malaria parasite Plasmodium falciparum. We show that the cytoplasmic tail of P. falciparum AMA1 is phosphorylated at serine 610. We provide evidence that the enzyme responsible for serine 610 phosphorylation is the cAMP regulated protein kinase A (PfPKA. Importantly, mutation of AMA1 serine 610 to alanine abrogates phosphorylation of AMA1 in vivo and dramatically impedes invasion. In addition to shedding unexpected new light on AMA1 function, this work represents the first time PKA has been implicated in merozoite invasion.

  12. Isoleucine at position 150 of Cyt2Aa toxin from Bacillus thuringiensis plays an important role during membrane binding and oligomerization

    Directory of Open Access Journals (Sweden)

    Wanwarang Pathaichindachote

    2013-03-01

    Full Text Available Cyt2Aa2 is a mosquito larvicidal and cytolytic toxin producedby Bacillus thuringiensis subsp. darmstadiensis. The toxin becomesinactive when isoleucine at position 150 was replacedby alanine. To investigate the functional role of this position,Ile150 was substituted with Leu, Phe, Glu and Lys. All mutantproteins were produced at high level, solubilized in carbonatebuffer and yielded protease activated product similar to thoseof the wild type. Intrinsic fluorescence spectra analysis suggestedthat these mutants retain similar folding to the wildtype. However, mosquito larvicidal and hemolytic activitiesdramatically decreased for the I150K and were completelyabolished for I150A and I150F mutants. Membrane bindingand oligomerization assays demonstrated that only I150E andI150L could bind and form oligomers on lipid membrane similarto that of the wild type. Our results suggest that amino acidat position 150 plays an important role during membranebinding and oligomerization of Cyt2Aa2 toxin. [BMB Reports2013; 46(3: 175-180

  13. Pili play an important role in enhancing the bacterial clearance from the middle ear in a mouse model of acute otitis media with Moraxella catarrhalis.

    Science.gov (United States)

    Kawano, Toshiaki; Hirano, Takashi; Kodama, Satoru; Mitsui, Marcelo Takahiro; Ahmed, Kamruddin; Nishizono, Akira; Suzuki, Masashi

    2013-03-01

    Moraxella catarrhalis is a Gram-negative aerobic diplococcus that is currently the third most frequent cause of bacterial acute otitis media (AOM) in children. In this study, we developed an experimental murine AOM model by inoculating M. catarrhalis in the middle ear bulla and studied the local response to this inoculation, and modulation of its course by the pili of M. catarrhalis. The pili-positive and pili-negative M. catarrhalis showed differences in bacterial clearance and infiltration of inflammatory cells in the middle ear. Pili-negative M. catarrhalis induced a more delayed and prolonged immune response in the middle ear than that of pili-positive M. catarrhalis. TLR2, -4, -5 and -9 mRNA expression was upregulated in neutrophils that infiltrated the middle ear cavity during AOM caused by both pili-positive and pili-negative bacteria. TLR5 mRNA expression and TLR5 protein in the neutrophils were induced more robustly by pili-positive M. catarrhalis. This immune response is likely to be related to neutrophil function such as toll-like 5-dependent phagocytosis. Our results show that mice may provide a useful AOM model for studying the role of M. catarrhalis. Furthermore, we show that pili play an important role in enhancing M. catarrhalis clearance from the middle ear that is probably mediated through neutrophil-dependent TLR5 signaling.

  14. Central beta-adrenergic receptors play an important role in the enhancing effect of voluntary exercise on learning and memory in rat.

    Science.gov (United States)

    Ebrahimi, Shima; Rashidy-Pour, Ali; Vafaei, Abbas A; Akhavan, Maziar M

    2010-03-17

    The beneficial effects of physical activity and exercise on brain functions such as improvement in learning and memory are well documented. The aim of this study was to examine the role of the beta-adrenergic system in voluntary exercise-induced enhancement of learning and memory in rat. In order to block the beta-adrenergic receptors, the animals were received propranolol (a beta-blocker), or nadolol (a peripherally acting beta-blocker) before each night of five consecutive nights of exercise. Then their learning and memory were tested on the water maze task using a two-trials-per-day for 5 consecutive days. A probe trial was performed 2 days after the last training day. Our results showed that propranolol, but not nadolol reversed the exercise-induced improvement in learning and memory in rat. Our findings indicate that central beta-adrenergic receptors play an important role in mediating the beneficial effects of voluntary exercise on learning and memory.

  15. The importance of physical function to people with osteoporosis.

    Science.gov (United States)

    Kerr, C; Bottomley, C; Shingler, S; Giangregorio, L; de Freitas, H M; Patel, C; Randall, S; Gold, D T

    2017-03-06

    There is increasing need to understand patient outcomes in osteoporosis. This article discusses that fracture in osteoporosis can lead to a cycle of impairment, driven by complex psychosocial factors, having a profound impact on physical function/activity which accumulates over time. More information is required on how treatments impact physical function.

  16. Surface texture and priming play important roles in predator recognition by the red-backed shrike in field experiments.

    Science.gov (United States)

    Němec, Michal; Syrová, Michaela; Dokoupilová, Lenka; Veselý, Petr; Šmilauer, Petr; Landová, Eva; Lišková, Silvie; Fuchs, Roman

    2015-01-01

    We compared the responses of the nesting red-backed shrikes (Lanius collurio) to three dummies of a common nest predator, the Eurasian jay (Garrulus glandarius), each made from a different material (stuffed, plush, and silicone). The shrikes performed defensive behaviour including attacks on all three dummies. Nevertheless, the number of attacks significantly decreased from the stuffed dummy through the plush dummy and finally to the silicone dummy. Our results show that wild birds use not only colours but also other surface features as important cues for recognition and categorization of other bird species. Moreover, the silicone dummy was attacked only when presented after the stuffed or plush dummy. Thus, we concluded that the shrikes recognized the jay only the stuffed (with feathered surface) and plush (with hairy surface) dummies during the first encounter. Recognition of the silicon dummy (with glossy surface) was facilitated by previous encounters with the more accurate model. This process resembles the effect of perceptual priming, which is widely described in the literature on humans.

  17. Attribute-Value Functions as Global Interpretations of Attribute Importance

    NARCIS (Netherlands)

    Ittersum, van K.; Pennings, J.M.E.

    2012-01-01

    In order to better understand decision maker’s perceptions of the importance of attributes, Goldstein (1990) differentiates between global and local interpretations of attribute importance. While the appreciation for the distinction is growing, research on the relationship between measures of global

  18. Pathogenesis of Congenital Rubella Virus Infection in Human Fetuses: Viral Infection in the Ciliary Body Could Play an Important Role in Cataractogenesis

    Directory of Open Access Journals (Sweden)

    Thong Van Nguyen

    2015-01-01

    Interpretation: Our study based on the pathological examination demonstrated that the rubella virus infection occurred via systemic organs of human fetuses. This fact was confirmed by immunohistochemistry and direct detection of viral RNA in multiple organs. To the best of our knowledge, this study is the first report demonstrating that the rubella virus infection occurred via systemic organs of the human body. Importantly, virus infection of the ciliary body could play an important role in cataractogenesis.

  19. GhDET2,a Steroid 5alpha-reductase,Plays an Important Role in Cotton Fiber Cell Initiation and Elongation

    Institute of Scientific and Technical Information of China (English)

    LUO Ming; XIAO Yue-hua; LI Xian-bi; LI De-mou; HOU Lei; HU Ming-yu; PEI Yan

    2008-01-01

    @@ Cotton (Gossypium hirsutum L.) fibers,one of the most important natural raw materials for the textile industry,are highly elongated trichomes from epidermal cells of cotton ovules.Among the longest plant cells ever characterized,cotton fiber is an ideal system for studying plant cell elongation.Brassinosteroids (BRs),a class of steroidal phytohormone,play an important role in plant cell division and elongation.

  20. The importance of the global oils and fats supply and the role that palm oil plays in meeting the demand for oils and fats worldwide.

    Science.gov (United States)

    Fry, James; Fitton, Claire

    2010-06-01

    This article highlights the importance of the role that palm oil plays in meeting the demand for oils and fats worldwide for food. On top of this food demand, the demand for vegetable oils for biofuels, which now absorb over 10% of world oil and fat supplies, has rapidly increased.

  1. Specific Subunits of Heterotrimeric G Proteins Play Important Roles during Nodulation in Soybean1[W][OA

    Science.gov (United States)

    Choudhury, Swarup Roy; Pandey, Sona

    2013-01-01

    Heterotrimeric G proteins comprising Gα, Gβ, and Gγ subunits regulate many fundamental growth and development processes in all eukaryotes. Plants possess a relatively limited number of G-protein components compared with mammalian systems, and their detailed functional characterization has been performed mostly in Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa). However, the presence of single Gα and Gβ proteins in both these species has significantly undermined the complexity and specificity of response regulation in plant G-protein signaling. There is ample pharmacological evidence for the role of G proteins in regulation of legume-specific processes such as nodulation, but the lack of genetic data from a leguminous species has restricted its direct assessment. Our recent identification and characterization of an elaborate G-protein family in soybean (Glycine max) and the availability of appropriate molecular-genetic resources have allowed us to directly evaluate the role of G-protein subunits during nodulation. We demonstrate that all G-protein genes are expressed in nodules and exhibit significant changes in their expression in response to Bradyrhizobium japonicum infection and in representative supernodulating and nonnodulating soybean mutants. RNA interference suppression and overexpression of specific G-protein components results in lower and higher nodule numbers, respectively, validating their roles as positive regulators of nodule formation. Our data further show preferential usage of distinct G-protein subunits in the presence of an additional signal during nodulation. Interestingly, the Gα proteins directly interact with the soybean nodulation factor receptors NFR1α and NFR1β, suggesting that the plant G proteins may couple with receptors other than the canonical heptahelical receptors common in metazoans to modulate signaling. PMID:23569109

  2. Neurospora COP9 signalosome integrity plays major roles for hyphal growth, conidial development, and circadian function.

    Directory of Open Access Journals (Sweden)

    Zhipeng Zhou

    Full Text Available The COP9 signalosome (CSN is a highly conserved multifunctional complex that has two major biochemical roles: cleaving NEDD8 from cullin proteins and maintaining the stability of CRL components. We used mutation analysis to confirm that the JAMM domain of the CSN-5 subunit is responsible for NEDD8 cleavage from cullin proteins in Neurospora crassa. Point mutations of key residues in the metal-binding motif (EX(nHXHX(10D of the CSN-5 JAMM domain disrupted CSN deneddylation activity without interfering with assembly of the CSN complex or interactions between CSN and cullin proteins. Surprisingly, CSN-5 with a mutated JAMM domain partially rescued the phenotypic defects observed in a csn-5 mutant. We found that, even without its deneddylation activity, the CSN can partially maintain the stability of the SCF(FWD-1 complex and partially restore the degradation of the circadian clock protein FREQUENCY (FRQ in vivo. Furthermore, we showed that CSN containing mutant CSN-5 efficiently prevents degradation of the substrate receptors of CRLs. Finally, we found that deletion of the CAND1 ortholog in N. crassa had little effect on the conidiation circadian rhythm. Our results suggest that CSN integrity plays major roles in hyphal growth, conidial development, and circadian function in N. crassa.

  3. RIG-I, MDA5 and TLR3 synergistically play an important role in restriction of dengue virus infection.

    Directory of Open Access Journals (Sweden)

    A M A Nasirudeen

    Full Text Available Dengue virus (DV infection is one of the most common mosquito-borne viral diseases in the world. The innate immune system is important for the early detection of virus and for mounting a cascade of defense measures which include the production of type 1 interferon (IFN. Hence, a thorough understanding of the innate immune response during DV infection would be essential for our understanding of the DV pathogenesis. A recent application of the microarray to dengue virus type 1 (DV1 infected lung carcinoma cells revealed the increased expression of both extracellular and cytoplasmic pattern recognition receptors; retinoic acid inducible gene-I (RIG-I, melanoma differentiation associated gene-5 (MDA-5 and Toll-like receptor-3 (TLR3. These intracellular RNA sensors were previously reported to sense DV infection in different cells. In this study, we show that they are collectively involved in initiating an effective IFN production against DV. Cells silenced for these genes were highly susceptible to DV infection. RIG-I and MDA5 knockdown HUH-7 cells and TLR3 knockout macrophages were highly susceptible to DV infection. When cells were silenced for only RIG-I and MDA5 (but not TLR3, substantial production of IFN-β was observed upon virus infection and vice versa. High susceptibility to virus infection led to ER-stress induced apoptosis in HUH-7 cells. Collectively, our studies demonstrate that the intracellular RNA virus sensors (RIG-I, MDA5 and TLR3 are activated upon DV infection and are essential for host defense against the virus.

  4. A putative mitochondrial iron transporter MrsA in Aspergillus fumigatus plays important roles in azole-, oxidative stress responses and virulence

    Directory of Open Access Journals (Sweden)

    Nanbiao eLong

    2016-05-01

    Full Text Available Iron is an essential nutrient and enzyme co-factor required for a wide range of cellular processes, especially for the function of mitochondria. For the opportunistic fungal pathogen Aspergillus fumigatus, the ability to obtain iron is required for growth and virulence during the infection process. However, knowledge of how mitochondria are involved in iron regulation is still limited. Here, we show that a mitochondrial iron transporter, MrsA, a homolog of yeast Mrs4p, is critical for adaptation to iron-limited or iron-excess conditions in A. fumigatus. Deletion of mrsA leads to disruption of iron homeostasis with a decreased sreA expression, resulted in activated reductive iron assimilation (RIA and siderophore-mediated iron acquisition (SIA. Furthermore, deletion of mrsA induces hypersusceptibility to azole and oxidative stresses. An assay for cellular ROS content in ΔmrsA combined with rescue from the mrsA-defective phenotype by the antioxidant reagent L-ascorbic acid indicates that the increased sensitivity of ΔmrsA to the azole itraconazole and to oxidative stress is mainly the result of abnormal ROS accumulation. Moreover, site-directed mutation experiments verified that three conserved histidine residues related to iron transport in MrsA are required for responses to oxidative and azole stresses. Importantly, ΔmrsA causes significant attenuation of virulence in an immunocompromised murine model of aspergillosis. Collectively, our results show that the putative mitochondrial iron transporter MrsA plays important roles in azole- and oxidative-stress responses and virulence by regulating the balance of cellular iron in A. fumigatus.

  5. A Putative Mitochondrial Iron Transporter MrsA in Aspergillus fumigatus Plays Important Roles in Azole-, Oxidative Stress Responses and Virulence.

    Science.gov (United States)

    Long, Nanbiao; Xu, Xiaoling; Qian, Hui; Zhang, Shizhu; Lu, Ling

    2016-01-01

    Iron is an essential nutrient and enzyme co-factor required for a wide range of cellular processes, especially for the function of mitochondria. For the opportunistic fungal pathogen Aspergillus fumigatus, the ability to obtain iron is required for growth and virulence during the infection process. However, knowledge of how mitochondria are involved in iron regulation is still limited. Here, we show that a mitochondrial iron transporter, MrsA, a homolog of yeast Mrs4p, is critical for adaptation to iron-limited or iron-excess conditions in A. fumigatus. Deletion of mrsA leads to disruption of iron homeostasis with a decreased sreA expression, resulted in activated reductive iron assimilation (RIA) and siderophore-mediated iron acquisition (SIA). Furthermore, deletion of mrsA induces hypersusceptibility to azole and oxidative stresses. An assay for cellular ROS content in ΔmrsA combined with rescue from the mrsA-defective phenotype by the antioxidant reagent L-ascorbic acid indicates that the increased sensitivity of ΔmrsA to the azole itraconazole and to oxidative stress is mainly the result of abnormal ROS accumulation. Moreover, site-directed mutation experiments verified that three conserved histidine residues related to iron transport in MrsA are required for responses to oxidative and azole stresses. Importantly, ΔmrsA causes significant attenuation of virulence in an immunocompromised murine model of aspergillosis. Collectively, our results show that the putative mitochondrial iron transporter MrsA plays important roles in azole- and oxidative-stress responses and virulence by regulating the balance of cellular iron in A. fumigatus.

  6. The heat shock response plays an important role in TDP-43 clearance: evidence for dysfunction in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Chen, Han-Jou; Mitchell, Jacqueline C; Novoselov, Sergey; Miller, Jack; Nishimura, Agnes L; Scotter, Emma L; Vance, Caroline A; Cheetham, Michael E; Shaw, Christopher E

    2016-05-01

    Detergent-resistant, ubiquitinated and hyperphosphorylated Tar DNA binding protein 43 (TDP-43, encoded by TARDBP) neuronal cytoplasmic inclusions are the pathological hallmark in ∼95% of amyotrophic lateral sclerosis and ∼60% of frontotemporal lobar degeneration cases. We sought to explore the role for the heat shock response in the clearance of insoluble TDP-43 in a cellular model of disease and to validate our findings in transgenic mice and human amyotrophic lateral sclerosis tissues. The heat shock response is a stress-responsive protective mechanism regulated by the transcription factor heat shock factor 1 (HSF1), which increases the expression of chaperones that refold damaged misfolded proteins or facilitate their degradation. Here we show that manipulation of the heat shock response by expression of dominant active HSF1 results in a dramatic reduction of insoluble and hyperphosphorylated TDP-43 that enhances cell survival, whereas expression of dominant negative HSF1 leads to enhanced TDP-43 aggregation and hyperphosphorylation. To determine which chaperones were mediating TDP-43 clearance we over-expressed a range of heat shock proteins (HSPs) and identified DNAJB2a (encoded by DNAJB2, and also known as HSJ1a) as a potent anti-aggregation chaperone for TDP-43. DNAJB2a has a J domain, allowing it to interact with HSP70, and ubiquitin interacting motifs, which enable it to engage the degradation of its client proteins. Using functionally deleted DNAJB2a constructs we demonstrated that TDP-43 clearance was J domain-dependent and was not affected by ubiquitin interacting motif deletion or proteasome inhibition. This indicates that TDP-43 is maintained in a soluble state by DNAJB2a, leaving the total levels of TDP-43 unchanged. Additionally, we have demonstrated that the levels of HSF1 and heat shock proteins are significantly reduced in affected neuronal tissues from a TDP-43 transgenic mouse model of amyotrophic lateral sclerosis and patients with

  7. Complement and the alternative pathway play an important role in LPS/D-GalN-induced fulminant hepatic failure.

    Directory of Open Access Journals (Sweden)

    Shihui Sun

    Full Text Available Fulminant hepatic failure (FHF is a clinically severe type of liver injury with an extremely high mortality rate. Although the pathological mechanisms of FHF are not well understood, evidence suggests that the complement system is involved in the pathogenesis of a variety of liver disorders. In the present study, to investigate the role of complement in FHF, we examined groups of mice following intraperitoneal injection of LPS/D-GalN: wild-type C57BL/6 mice, wild-type mice treated with a C3aR antagonist, C5aR monoclonal antibody (C5aRmAb or CR2-Factor H (CR2-fH, an inhibitor of the alternative pathway, and C3 deficient mice (C3⁻/⁻ mice. The animals were euthanized and samples analyzed at specific times after LPS/D-GalN injection. The results show that intraperitoneal administration of LPS/D-GalN activated the complement pathway, as evidenced by the hepatic deposition of C3 and C5b-9 and elevated serum levels of the complement activation product C3a, the level of which was associated with the severity of the liver damage. C3a receptor (C3aR and C5a receptor (C5aR expression was also upregulated. Compared with wild-type mice, C3⁻/⁻ mice survived significantly longer and displayed reduced liver inflammation and attenuated pathological damage following LPS/D-GalN injection. Similar levels of protection were seen in mice treated with C3aR antagonist,C5aRmAb or CR2-fH. These data indicate an important role for the C3a and C5a generated by the alternative pathway in LPS/D-GalN-induced FHF. The data further suggest that complement inhibition may be an effective strategy for the adjunctive treatment of fulminant hepatic failure.

  8. Unit cost of healthcare services at 200-bed public hospitals in Myanmar: what plays an important role of hospital budgeting?

    Science.gov (United States)

    Than, Thet Mon; Saw, Yu Mon; Khaing, Moe; Win, Ei Mon; Cho, Su Myat; Kariya, Tetsuyoshi; Yamamoto, Eiko; Hamajima, Nobuyuki

    2017-09-19

    Cost information is important for efficient allocation of healthcare expenditure, estimating future budget allocation, and setting user fees to start new financing systems. Myanmar is in political transition, and trying to achieve universal health coverage by 2030. This study assessed the unit cost of healthcare services at two public hospitals in the country from the provider perspective. The study also analyzed the cost structure of the hospitals to allocate and manage the budgets appropriately. A hospital-based cross-sectional study was conducted at 200-bed Magway Teaching Hospital (MTH) and Pyinmanar General Hospital (PMN GH), in Myanmar, for the financial year 2015-2016. The step-down costing method was applied to calculate unit cost per inpatient day and per outpatient visit. The costs were calculated by using Microsoft Excel 2010. The unit costs per inpatient day varied largely from unit to unit in both hospitals. At PMN GH, unit cost per inpatient day was 28,374 Kyats (27.60 USD) for pediatric unit and 1,961,806 Kyats (1908.37 USD) for ear, nose, and throat unit. At MTH, the unit costs per inpatient day were 19,704 Kyats (19.17 USD) for medicine unit and 168,835 Kyats (164.24 USD) for eye unit. The unit cost of outpatient visit was 14,882 Kyats (14.48 USD) at PMN GH, while 23,059 Kyats (22.43 USD) at MTH. Regarding cost structure, medicines and medical supplies was the largest component at MTH, and the equipment was the largest component at PMN GH. The surgery unit of MTH and the eye unit of PMN GH consumed most of the total cost of the hospitals. The unit costs were influenced by the utilization of hospital services by the patients, the efficiency of available resources, type of medical services provided, and medical practice of the physicians. The cost structures variation was also found between MTH and PMN GH. The findings provided the basic information regarding the healthcare cost of public hospitals which can apply the efficient utilization of the

  9. The human LIS1 is downregulated in hepatocellular carcinoma and plays a tumor suppressor function

    Energy Technology Data Exchange (ETDEWEB)

    Xing, Zhen; Tang, Xin; Gao, Yuan; Da, Liang; Song, Hai; Wang, Suiquan [State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Tiollais, Pierre [Unite' d' Organisation Nucleaire et Oncogenese, INSERM U.579, Institut Pasteur, Paris (France); Li, Tsaiping [State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Zhao, Mujun, E-mail: mjzhao@sibs.ac.cn [State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China)

    2011-06-03

    Highlights: {yields} LIS1 mRNA and protein levels are decreased in 70% HCC tissues. {yields} Downregulation of LIS1 expression induces oncogenic transformation of QSG7701 and NIH3T3 cells in vitro and in vivo. {yields} LIS1 downregulation leads to mitotic errors including spindle and chromosome defects. {yields} Ectopic expression of LIS1 could significantly inhibit HCC cell proliferation and colony formation. {yields} Our results suggest that LIS1 plays a potential tumor suppressor role in the development and progression of HCC. -- Abstract: The human lissencephaly-1 gene (LIS1) is a disease gene responsible for Miller-Dieker lissencephaly syndrome (MDL). LIS1 gene is located in the region of chromosome 17p13.3 that is frequency deleted in MDL patients and in human liver cancer cells. However, the expression and significance of LIS1 in liver cancer remain unknown. Here, we investigated the expression of LIS1 in hepatocellular carcinoma (HCC) tissues by real-time PCR, Western blot, and immunohistochemistry. The results indicated that the mRNA and protein levels of LIS1 were downregulated in about 70% of HCC tissues, and this downregulation was significantly associated with tumor progression. Functional studies showed that the reduction of LIS1 expression in the normal human liver cell line QSG7701 or the mouse fibroblast cell line NIH3T3 by shRNA resulted in colony formation in soft agar and xenograft tumor formation in nude mice, demonstrating that a decrease in the LIS1 level can promote the oncogenic transformation of cells. We also observed that the phenotypes of LIS1-knockdown cells displayed various defective mitotic structures, suggesting that the mechanism by which reduced LIS1 levels results in tumorigenesis is associated with its role in mitosis. Furthermore, we demonstrated that ectopic expression of LIS1 could significantly inhibit HCC cell proliferation and colony formation. Our results suggest that LIS1 plays a potential tumor suppressor role in the

  10. Extensions of PDZ domains as important structural and functional elements

    OpenAIRE

    Wang, Conan K.; Pan, Lifeng; Chen, Jia; Zhang, Mingjie

    2010-01-01

    ‘Divide and conquer’ has been the guiding strategy for the study of protein structure and function. Proteins are divided into domains with each domain having a canonical structural definition depending on its type. In this review, we push forward with the interesting observation that many domains have regions outside of their canonical definition that affect their structure and function; we call these regions ‘extensions’. We focus on the highly abundant PDZ (PSD-95, DLG1 and ZO-1) domain. Us...

  11. Importance of Fragmentation Functions in Determining Polarized Parton Densities

    CERN Document Server

    Leader, Elliot; Stamenov, Dimiter B

    2012-01-01

    New fragmentation functions (FFs) are extracted from a NLO QCD fit to the preliminary COMPASS data on pion and kaon multiplicities. It is shown that the new kaon FFs are very different from those of De Florian at al. (DSS) and Hirai et al. (HKNS). The sensitivity of the extracted polarized PDFs to the new FFs is discussed.

  12. Quantifying the importance of plant functional diversity for ecosystem functioning and resilience under scenarios of climate change (Invited)

    Science.gov (United States)

    Pavlick, R.; Drewry, D.; Kleidon, A.

    2013-12-01

    Dynamic Global Vegetation Models (DGVMs) typically employ only a small set of Plant Functional Types (PFTs) to represent the vast diversity of observed vegetation forms and functioning. There is growing evidence, however, that this abstraction may not adequately represent the observed variation in plant functional traits, which is thought to play an important role for many ecosystem functions and for ecosystem resilience to environmental change. The geographic distribution of PFTs in these models is also often based on empirical relationships between present-day climate and vegetation patterns. Projections of future climate change, however, point toward the possibility of novel regional climates, which could lead to no-analog vegetation compositions incompatible with the PFT paradigm. Here, we present results from the Jena Diversity-DGVM (JeDi-DGVM), a novel traits-based vegetation model, which simulates a large number of hypothetical plant growth strategies constrained by functional tradeoffs, thereby allowing for a more flexible temporal and spatial representation of the terrestrial biosphere. We run two sets of model experiments forced with the latest bias-corrected climate change scenarios from several different global climate models. In the first set, we simulate a diverse biosphere using a large number of plant growth strategies, allowing the modelled ecosystems to adapt through emergent changes in ecosystem composition. We then aggregate the surviving growth strategies from the first set of diverse simulations to a small number of biome-averaged growth strategies, recreating something akin to PFTs. We use this smaller set of PFT-like growth strategies to represent a sparse or low-diversity biosphere in the second set of model experiments. We quantify the importance of functional diversity by comparing key metrics of ecosystem functioning across the two sets of simulations. The results reveal the implications of using the common PFT vegetation modelling

  13. Pretend play.

    Science.gov (United States)

    Weisberg, Deena Skolnick

    2015-01-01

    Pretend play is a form of playful behavior that involves nonliteral action. Although on the surface this activity appears to be merely for fun, recent research has discovered that children's pretend play has connections to important cognitive and social skills, such as symbolic thinking, theory of mind, and counterfactual reasoning. The current article first defines pretend play and then reviews the arguments and evidence for these three connections. Pretend play has a nonliteral correspondence to reality, hence pretending may provide children with practice with navigating symbolic relationships, which may strengthen their language skills. Pretend play and theory of mind reasoning share a focus on others' mental states in order to correctly interpret their behavior, hence pretending and theory of mind may be mutually supportive in development. Pretend play and counterfactual reasoning both involve representing nonreal states of affairs, hence pretending may facilitate children's counterfactual abilities. These connections make pretend play an important phenomenon in cognitive science: Studying children's pretend play can provide insight into these other abilities and their developmental trajectories, and thereby into human cognitive architecture and its development.

  14. TLR4 plays a crucial role in MSC-induced inhibition of NK cell function

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Ying [No. 307 Hospital of the Chinese People' s Liberation Army, Beijing (China); Liu, Jin; Liu, Yang; Qin, Yaru [Beijing Institute of Radiation Medicine, Beijing (China); Luo, Qun [No. 307 Hospital of the Chinese People' s Liberation Army, Beijing (China); Wang, Quanli, E-mail: 13691110351@163.com [No. 307 Hospital of the Chinese People' s Liberation Army, Beijing (China); Duan, Haifeng, E-mail: duanhf0720@163.com [Beijing Institute of Radiation Medicine, Beijing (China)

    2015-08-21

    Mesenchymal stem cells (MSC) are a kind of stromal cell within the tumor microenvironment. In our research, MSC derived from acute myeloid leukemia patients' bone marrow (AML-MSC) and lung cancer tissues (LC-MSC) as well as normal bone marrow-derived MSC (BM-MSC) cultured in conditioned medium of HeLa cells were found to have higher expressions of Toll-like receptor (TLR4) mRNA compared with BM-MSC. The sorted TLR4-positive MSC (TLR4+ MSC) differed in cytokine (interleukin-6, interleukin-8, and monocyte chemoattractant protein-1) secretion from those of unsorted MSC. MSC was reported to inhibit natural killer (NK) cell proliferation and function. In this research, we confirmed that TLR4+ MSC aggravate this suppression. Furthermore, when TLR4 in the sorted cells were stimulated by LPS or following blocked by antibody, the suppression on NK cell proliferation and cytotoxicity were more intensive or recovered respectively. Compared to unsorted MSC, NKG2D receptor expression on NK cells were also inhibited by TLR4+ MSC. These findings suggest that activation of TLR4 pathway is important for TLR4+ MSC and MSC to obstruct anti-tumor immunity by inhibiting NK cell function, which may provide a potential stroma-targeted tumor therapy. - Highlights: • TLR4+ MSC inhibit NK cell proliferation in vivo and in vitro. • TLR4+ MSC inhibit NKG2D expression on NK cells and NK cell cytotoxicity. • The distinguished cytokine expression of TLR4+ MSC may contribute to the inhibition on NK cell function.

  15. Structured Parent-Child Observations Predict Development of Conduct Problems: the Importance of Parental Negative Attention in Child-Directed Play.

    Science.gov (United States)

    Fleming, Andrew P; McMahon, Robert J; King, Kevin M

    2017-04-01

    Structured observations of parent-child interactions are commonly used in research and clinical settings, but require additional empirical support. The current study examined the capacity of child-directed play, parent-directed play, and parent-directed chore interaction analogs to uniquely predict the development of conduct problems across a 6-year follow-up period. Parent-child observations were collected from 338 families from high-risk neighborhoods during the summer following the child's first-grade year. Participating children were 49.2 % female, 54.4 % white, and 45.6 % black, and had an average age of 7.52 years at the first assessment. Conduct problems were assessed via parent report and teacher report at five assessment points between first grade and seventh grade. Latent growth curve modeling was used to analyze predictors of conduct problem trajectory across this 6-year follow-up period. When race, sex, socioeconomic status, and maternal depressive symptoms were controlled, parental negative attention during child-directed play predicted higher levels of parent-reported conduct problems concurrently and after a 6-year follow-up period. Parental negative attention during child-directed play also predicted higher teacher-reported conduct problems 6 years later. Findings support the use of child-directed play and parent-directed chore analogs in predicting longitudinal development of conduct problems. The presence of parental negative attention during child-directed play appears to be an especially important predictor of greater conduct problems over time and across multiple domains. Additionally, the potential importance of task-incongruent behavior is proposed for further study.

  16. Social-communicative abilities as treatment goals for preschool children with autism spectrum disorder: the importance of imitation, joint attention, and play.

    Science.gov (United States)

    Warreyn, Petra; van der Paelt, Sara; Roeyers, Herbert

    2014-08-01

    Autism spectrum disorder (ASD) is a pervasive developmental disorder with a lifelong impact on multiple domains of functioning. Often, a diagnosis is possible by 3 years of age. Given the benefits of early intervention, it is advisable to start treatment as soon as possible after the diagnosis has been made. Among other factors, early intervention should focus on social-communicative abilities such as imitation, joint attention, and play. In this review, the typical developmental course and functions of these social-communicative abilities are described, and the problems young children with ASD experience in this domain. In addition, different approaches to promoting these abilities are explained. The authors recommend the inclusion of imitation, joint attention, and play as treatment goals in community settings for children with ASD.

  17. Study protocol: effect of playful training on functional abilities of older adults - a randomized controlled trial

    DEFF Research Database (Denmark)

    Jessen, Jari Due; Lund, Henrik Hautop

    2017-01-01

    paired t-test, otherwise using Wilcoxon signed-rank test. "Intention to treat" analysis will be done.Discussion: The trial tests for increased mobility, agility, balancing and general fitness of community-dwelling elderly as a result of playing, in this case on modular interactive tiles. A positive...... of community dwelling elderly as a result of short-term playing with an exergame system in the form of interactive modular tiles. Such playful training may be motivational to perform and viewed by the subjects to offer life-fulfilling quality, while providing improvement in physical abilities, e.g. related...... to prevent fall accidents. The RCT will test for a variety of health parameters of community-dwelling elderly playing on interactive modular tiles.Methods: The study will be a single blinded, randomized controlled trial with 60 community-dwelling adults 70+ years. The trial will consist an intervention group...

  18. N-methyl-D-aspartate receptor-mediated glutamate transmission in nucleus accumbens plays a more important role than that in dorsal striatum in cognitive flexibility

    Directory of Open Access Journals (Sweden)

    Xuekun eDing

    2014-09-01

    Full Text Available Cognitive flexibility is a critical ability for adapting to an ever-changing environment in humans and animals. Deficits in cognitive flexibility are observed in most schizophrenia patients. Previous studies reported that the medial prefrontal cortex-to-ventral striatum and orbital frontal cortex-to-dorsal striatum circuits play important roles in extra- and intra-dimensional strategy switching, respectively. However, the precise function of striatal subregions in flexible behaviors is still unclear. N-methyl-D-aspartate receptors (NMDARs are major glutamate receptors in the striatum that receive glutamatergic projections from the frontal cortex. The membrane insertion of Ca2+-permeable α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors (AMPARs depends on NMDAR activation and is required in learning and memory processes. In the present study, we measured set-shifting and reversal learning performance in operant chambers in rats and assessed the effects of blocking NMDARs and Ca2+-permeable AMPARs in striatal subregions on behavioral flexibility. The blockade of NMDARs in the nucleus accumbens (NAc core by AP5 impaired set-shifting ability by causing a failure to modify prior learning. The suppression of NMDAR-mediated transmission in the NAc shell induced a deficit in set-shifting by disrupting the learning and maintenance of novel strategies. During reversal learning, infusions of AP5 into the NAc shell and core impaired the ability to learn and maintain new strategies. However, behavioral flexibility was not significantly affected by blocking NMDARs in the dorsal striatum. We also found that the blockade of Ca2+-permeable AMPARs by NASPM in any subregion of the striatum did not affect strategy switching. These findings suggest that NMDAR-mediated glutamate transmission in the NAc contributes more to cognitive execution compared with the dorsal striatum.

  19. Two regulators of Vibrio parahaemolyticus play important roles in enterotoxicity by controlling the expression of genes in the Vp-PAI region.

    Directory of Open Access Journals (Sweden)

    Toshio Kodama

    Full Text Available Vibrio parahaemolyticus is an important pathogen causing food-borne disease worldwide. An 80-kb pathogenicity island (Vp-PAI, which contains two tdh (thermostable direct hemolysin genes and a set of genes for the type III secretion system (T3SS2, is closely related to the pathogenicity of this bacterium. However, the regulatory mechanisms of Vp-PAI's gene expression are poorly understood. Here we report that two novel ToxR-like transcriptional regulatory proteins (VtrA and VtrB regulate the expression of the genes encoded within the Vp-PAI region, including those for TDH and T3SS2-related proteins. Expression of vtrB was under control of the VtrA, as vector-expressed vtrB was able to recover a functional protein secretory capacity for T3SS2, independent of VtrA. Moreover, these regulatory proteins were essential for T3SS2-dependent biological activities, such as in vitro cytotoxicity and in vivo enterotoxicity. Enterotoxic activities of vtrA and/or vtrB deletion strains derived from the wild-type strain were almost absent, showing fluid accumulation similar to non-infected control. Whole genome transcriptional profiling of vtrA or vtrB deletion strains revealed that the expression levels of over 60 genes were downregulated significantly in these deletion mutant strains and that such genes were almost exclusively located in the Vp-PAI region. These results strongly suggest that VtrA and VtrB are master regulators for virulence gene expression in the Vp-PAI and play critical roles in the pathogenicity of this bacterium.

  20. Is recreational hunting important for landscape multi-functionality?

    DEFF Research Database (Denmark)

    Lund, Jens Friis; Jensen, Frank Søndergaard

    2017-01-01

    , and preservation of valued and/or threatened animal and plant species. Recreational hunting may thus contribute to preserve and enhance landscape multifunctionality. Yet, little is known about the importance of hunting interests in motivating such landscape management. In this article, we seek to shed light...... on these issues on the basis of data from a nationally representative survey of Danish landowners. Our findings show a mixed picture of the role of recreational hunting in supporting multifunctional landscapes. We observe a broad swathe of landscape changes for multifunctionality cross properties with different...

  1. Executive Functions in Tobacco Dependence: Importance of Inhibitory Capacities.

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    Valentin Flaudias

    Full Text Available Executive functions are linked to tobacco dependence and craving. In this cross-sectional study, we assessed the impact of three executive functions: updating, inhibition and shifting processes on tobacco craving and dependence.134 tobacco consumers were included in this study: 81 moderately (Fagerström score 7. Dependence was assessed with the Fagerström test and craving with the tobacco craving questionnaire (TCQ 12. We used the Stroop test and the Hayling test to measure inhibition, the Trail Making Test to measure shifting processes and the n-back test to measure updating processes. A multivariate logistic model was used to assess which variables explained best the level of nicotine dependence.Inhibition (p = 0.002 and updating (p = 0.014 processes, but not shifting processes, were associated with higher tobacco dependence. Inhibition capacity had a significant effect on the nicotine dependence level independently of age, education, time since last cigarette, intellectual quotient, craving, updating and shifting process.Nicotine dependence level seems better explained by inhibition capacities than by craving and updating effects. The capacity to inhibit our behaviours is a good predictor of the severity of tobacco dependence. Our results suggest a prefrontal cortex dysfunction affecting the inhibitory capacities of heavy tobacco dependent smokers. Further studies are needed to investigate the application of these findings in the treatment of tobacco dependence.

  2. Functional polymorphism of the CK2alpha intronless gene plays oncogenic roles in lung cancer.

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    Ming-Szu Hung

    Full Text Available Protein kinase CK2 is frequently up-regulated in human cancers, although the mechanism of CK2 activation in cancer remains unknown. In this study, we investigated the role of the CK2alpha intronless gene (CSNK2A1P, a presumed CK2alpha pseudogene in the pathogenesis of human cancers. We found evidence of amplification and over-expression of the CSNK2A1P gene in non-small cell lung cancer and leukemia cell lines and 25% of the lung cancer tissues studied. The mRNA expression levels correlated with the copy numbers of the CSNK2A1P gene. We also identified a novel polymorphic variant (398T/C, I133T of the CSNK2A1P gene and showed that the 398T allele is selectively amplified over the 398C allele in 101 non-small cell lung cancer tissue samples compared to those in 48 normal controls (p = 0.013<0.05. We show for the first time CSNK2A1P protein expression in transfected human embryonic kidney 293T and mouse embryonic fibroblast NIH-3T3 cell lines. Both alleles are transforming in these cell lines, and the 398T allele appears to be more transforming than the 398C allele. Moreover, the 398T allele degrades PML tumor suppressor protein more efficiently than the 398C allele and shows a relatively stronger binding to PML. Knockdown of the CSNK2A1P gene expression with specific siRNA increased the PML protein level in lung cancer cells. We report, for the first time, that the CSNK2A1P gene is a functional proto-oncogene in human cancers and its functional polymorphism appears to degrade PML differentially in cancer cells. These results are consistent with an important role for the 398T allele of the CSNK2A1P in human lung cancer susceptibility.

  3. Importance of post-translational modifications on the function of key haemostatic proteins.

    Science.gov (United States)

    Karlaftis, Vasiliki; Perera, Sachin; Monagle, Paul; Ignjatovic, Vera

    2016-01-01

    Post-translational modifications (PTMs) such as glycosylation and phosphorylation play an important role on the function of haemostatic proteins and are critical in the setting of disease. Such secondary level changes to haemostatic proteins have wide ranging effects on their ability to interact with other proteins. This review aimed to summarize the knowledge of the common PTMs associated with haemostatic proteins and the implications of such modifications on protein function. Haemostatic proteins that represent the main focus for studies specific to PTMs are von Willebrand factor, tissue factor, factor VIII, antithrombin and fibrinogen. These proteins are susceptible to PTMs by glycosylation, phosphorylation, sulphation, citrullination and nitration, respectively, with a significant impact on their function. During synthesis, vWF must undergo extensive PTMs, with N-linked glycosylation being the most common. Increased phosphorylation of tissue factor results in increased affinity for platelets to the vessel endothelium. Citrullination of antithrombin leads to an increased anticoagulant function of this protein and therefore an anticoagulant state that inhibits clot formation. On the contrary, nitration of fibrinogen has been shown to result in a prothrombotic state, whilst sulphation is required for the normal function of Factor VIII. From this review, it is evident that PTMs of haemostatic proteins as a change in protein structure at a secondary level greatly influences the behaviour of the protein at a tertiary level.

  4. Sirtuin 3, a new target of PGC-1alpha, plays an important role in the suppression of ROS and mitochondrial biogenesis.

    Directory of Open Access Journals (Sweden)

    Xingxing Kong

    Full Text Available BACKGROUND: Sirtuin 3 (SIRT3 is one of the seven mammalian sirtuins, which are homologs of the yeast Sir2 gene. SIRT3 is the only sirtuin with a reported association with the human life span. Peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha plays important roles in adaptive thermogenesis, gluconeogenesis, mitochondrial biogenesis and respiration. PGC-1alpha induces several key reactive oxygen species (ROS-detoxifying enzymes, but the molecular mechanism underlying this is not well understood. RESULTS: Here we show that PGC-1alpha strongly stimulated mouse Sirt3 gene expression in muscle cells and hepatocytes. Knockdown of PGC-1alpha led to decreased Sirt3 gene expression. PGC-1alpha activated the mouse SIRT3 promoter, which was mediated by an estrogen-related receptor (ERR binding element (ERRE (-407/-399 mapped to the promoter region. Chromatin immunoprecipitation and electrophoretic mobility shift assays confirmed that ERRalpha bound to the identified ERRE and PGC-1alpha co-localized with ERRalpha in the mSirt3 promoter. Knockdown of ERRalpha reduced the induction of Sirt3 by PGC-1alpha in C(2C(12 myotubes. Furthermore, Sirt3 was essential for PGC-1alpha-dependent induction of ROS-detoxifying enzymes and several components of the respiratory chain, including glutathione peroxidase-1, superoxide dismutase 2, ATP synthase 5c, and cytochrome c. Overexpression of SIRT3 or PGC-1alpha in C(2C(12 myotubes decreased basal ROS level. In contrast, knockdown of mSIRT3 increased basal ROS level and blocked the inhibitory effect of PGC-1alpha on cellular ROS production. Finally, SIRT3 stimulated mitochondrial biogenesis, and SIRT3 knockdown decreased the stimulatory effect of PGC-1alpha on mitochondrial biogenesis in C(2C(12 myotubes. CONCLUSION: Our results indicate that Sirt3 functions as a downstream target gene of PGC-1alpha and mediates the PGC-1alpha effects on cellular ROS production and mitochondrial biogenesis. Thus

  5. Role-Play and Its Functions in Oral English Teaching in Universities

    Institute of Scientific and Technical Information of China (English)

    郭思含

    2015-01-01

    Role-play is recommended as a useful method to solve the problem of oral English teaching. It ’s much more than a performance and it can be considered as a way to vary the kinds of spoken interaction that learners can experience in the class⁃room of universities. Through the use of role-play, oral English teaching becomes more interesting and attractive;university stu⁃dents can gain more oral English skills in the mini society atmosphere, and the accuracy and fluency of their oral English will be improved.

  6. Role Played Self-Disclosure as a Function of Liking and Knowing

    Science.gov (United States)

    Critelli, Joseph W.; And Others

    1976-01-01

    Examines the effects of liking and knowing on self-disclosure using both self-report and observational measures, obtains separate measures of personal and impersonal self-disclosure, and assesses the utility of the role-playing paradigm for revealing orderly relationships among self-disclosure variables. (Author/RK)

  7. The association between singing and/or playing a musical instrument and cognitive functions in older adults.

    Science.gov (United States)

    Mansens, D; Deeg, D J H; Comijs, H C

    2017-05-19

    Cognitive decline happens to everyone when aging, but to some more than others. Studies with children, adults, and professional musicians suggest that making music could be associated with better cognitive functioning. In older adults however, this association is less well investigated, which is therefore the aim of this study. In this cross-sectional study data from 1101 participants aged 64 and older from the Longitudinal Aging Study Amsterdam were used. Multivariable linear regression analyses were performed to test the association between making music and cognitive functioning and time spent making music and cognitive functioning. ANCOVA analyses were performed to differentiate between participants who made no music, only sang, only played an instrument or both sang and played an instrument in terms of cognitive functioning. Making music was significantly positively associated with letter fluency, learning and attention/short-term memory. Time spent making music yielded no significant results. The ANCOVA analyses showed higher scores for participants who only played an instrument compared to participants who made no music on learning, working memory and processing speed. For processing speed the instrument only group also had a higher score than participants who only sang. Making music at least once every two weeks and especially playing a musical instrument, is associated with better attention, episodic memory and executive functions. The results suggest that making music might be a potential protective factor for cognitive decline; however, to support this notion a longitudinal study design is needed.

  8. Uterine autonomic nerve innervation plays a crucial role in regulating rat uterine mast cell functions during embryo implantation.

    Science.gov (United States)

    Yuan, Xue-Jun; Huang, Li-Bo; Qiao, Hui-Li; Deng, Ze-Pei; Fa, Jing-Jing

    2009-12-01

    To explore the potential mechanism of how uterine innervations would affect the uterine mast cell (MC) population and functions during the periimplantation. We herein first examined the consequence of uterine neurectomy on embryo implantation events. We observed that amputation of autonomic nerves innervating the uterus led to on-time implantation failure in rats. Exploiting MC culture and ELISA approaches, we then further analyzed the effect of neurectomy on cellular histamine levels and its release from uterine MCs, to elucidate the relation of the autonomic nerves and local cellular immunity in the uterine during early pregnancy. We observed that disconnection of autonomic nerve innervation significantly increased the population of uterine MCs. Most interestingly, these increased number of uterine MCs in neuroectomized rats contained a much reduced cellular level of histamine. Our subsequent challenge experiments revealed that uterine MCs in nerve amputated rats exhibited enhanced histamine releasing rate in response to substance P and antiIgE, suggesting loss of nerve innervation in the uterus not only increases the population of uterine MCs, but also facilitates the release of histamine from MCs, thus subsequently interfere with the normal implantation process. Collectively, our findings provide a new line of evidence supporting the concept that immune-neuro-endocrine network plays important role during pregnancy establishment and maintenance.

  9. Have We Overlooked the Importance of Serine/Threonine Protein Phosphatases in Pancreatic Beta-Cells? Role Played by Protein Phosphatase 2A in Insulin Secretion

    Directory of Open Access Journals (Sweden)

    Esser V

    2005-07-01

    Full Text Available Genetic predisposition and environmental influences insidiously converge to cause glucose intolerance and hyperglycemia. Beta-cell compensates by secreting more insulin and when it fails, overt diabetes mellitus ensues. The need to understand the mechanisms involved in insulin secretion cannot be stressed enough. Phosphorylation of proteins plays an important role in regulating insulin secretion. In order to understand how a particular cellular process is regulated by protein phosphorylation the nature of the protein kinases and protein phosphatases involved and the mechanisms that determine when and where these enzymes are active should be investigated. While the actions of protein kinases have been intensely studied within the beta-cell, less emphasis has been placed on protein phosphatases even though they play an important regulatory role. This review focuses on the importance of protein phosphatase 2A in insulin secretion. Most of the present knowledge on protein phosphatase 2A originates from protein phosphatase inhibitor studies on islets and beta-cell lines. The ability of protein phosphatase 2A to change its activity in the presence of glucose and inhibitors provides clues to its role in regulating insulin secretion. An aggressive approach to elucidate the substrates and mechanisms of action of protein phosphatases is crucial to the understanding of phosphorylation events within the beta-cell. Characterizing protein phosphatase 2A within the beta-cell will certainly help us in understanding the mechanisms involved in insulin secretion and provide valuable information for drug development.

  10. The Role of Make-Believe Play in the Development of Executive Function: Status of Research and Future Directions

    Science.gov (United States)

    Berk, Laura E.; Meyers, Adena B.

    2013-01-01

    The authors discuss the association between make-believe play and the development of executive-function (EF) skills in young children. Some forty years ago, Lev S. Vygotsky first proposed that make-believe fosters the development of symbolic thought and self-regulation. Since then, a small body of research has produced evidence of an association…

  11. Mothers' Reports of Play Dates and Observation of School Playground Behavior of Children Having High-Functioning Autism Spectrum Disorders

    Science.gov (United States)

    Frankel, Frederick D.; Gorospe, Clarissa M.; Chang, Ya-Chih; Sugar, Catherine A.

    2011-01-01

    Background: Children with high-functioning autism spectrum disorders (ASD) are generally included with typically developing peers at school. They have difficulties interacting with peers on the school playground. Previous literature suggests that having play dates in the home may be related to better peer acceptance at school. Methods: This study…

  12. The importance of biodiversity and dominance for multiple ecosystem functions in a human-modified tropical landscape.

    Science.gov (United States)

    Lohbeck, Madelon; Bongers, Frans; Martinez-Ramos, Miguel; Poorter, Lourens

    2016-10-01

    Many studies suggest that biodiversity may be particularly important for ecosystem multifunctionality, because different species with different traits can contribute to different functions. Support, however, comes mostly from experimental studies conducted at small spatial scales in low-diversity systems. Here, we test whether different species contribute to different ecosystem functions that are important for carbon cycling in a high-diversity human-modified tropical forest landscape in Southern Mexico. We quantified aboveground standing biomass, primary productivity, litter production, and wood decomposition at the landscape level, and evaluated the extent to which tree species contribute to these ecosystem functions. We used simulations to tease apart the effects of species richness, species dominance and species functional traits on ecosystem functions. We found that dominance was more important than species traits in determining a species' contribution to ecosystem functions. As a consequence of the high dominance in human-modified landscapes, the same small subset of species mattered across different functions. In human-modified landscapes in the tropics, biodiversity may play a limited role for ecosystem multifunctionality due to the potentially large effect of species dominance on biogeochemical functions. However, given the spatial and temporal turnover in species dominance, biodiversity may be critically important for the maintenance and resilience of ecosystem functions.

  13. Collision avoidance behavior as a function of aging and tennis playing.

    Science.gov (United States)

    Lobjois, Régis; Benguigui, Nicolas; Bertsch, Jean; Broderick, Michael P

    2008-02-01

    Daily living often requires pedestrians and drivers to adapt their behavior to the displacement of other objects in their environment in order to avoid collision. Yet little research has paid attention to the effect of age on the completion of such a challenging task. The purpose of this study was to examine the relationship between age and collision avoidance skill and whether a sporting activity affects this. Three age groups (20-30, 60-70, and 70-80 years) of tennis players and non-players launched a projectile toward a target in order to hit it before it was hit by another "object" (a stimulus represented by apparent motion of lights). If the participant judged that time-to-collision (TTC) of the moving stimulus was not long enough for him/her to launch the projectile in time to arrive before the stimulus, the participant had to inhibit the launching. Results showed that for the non-players the number of errors in the 70-80 year-old group was significantly higher than those of the 20-30 and 60-70 year-old groups, which did not differ from each other. However, this increase was not observed in the 70-80 year-old tennis players, demonstrating a beneficial effect of playing tennis on collision avoidance skill. Results also revealed that the older groups of both tennis players and non-players were subject to the typical age-related increase in response time. Additional analyses indicated that the 70-80 year-old non-players did not adjust their actions to these age-related changes in response time. The older tennis-playing participants, however, were more likely to adjust collision avoidance behavior to their diminished response times.

  14. Executive function plays a role in coordinating different perspectives, particularly when one's own perspective is involved.

    Science.gov (United States)

    Fizke, Ella; Barthel, Dana; Peters, Thomas; Rakoczy, Hannes

    2014-03-01

    While developmental experiments with children and elderly subjects, work with neuropsychological patients and adult experimental studies have consistently found close relations between executive function and theory of mind, the foundation of this relation still remains somewhat unclear. One prominent account holds that executive function is specifically involved in ascribing such mental states, paradigmatically beliefs, that aim at representing the world truly because ascribing such states requires inhibition of normative defaults (beliefs being true) (e.g. Sabbagh, Moses, & Shiverick, 2006). The present studies systematically tested for the role of executive function in different forms of mental state ascription as a function of the type of state ascribed (beliefs or desires) and the first person involvement of the ascriber (whether she herself has an attitude conflicting with one to be ascribed to someone else) in young children. The results reveal that (i) executive function is related not only to belief ascription but equally to desire ascription when both are matched in terms of logical complexity (such that two subjective attitudes have to be ascribed to two agents that are incompatible with each other). (ii) Both for desires and for beliefs, these relations are strongest in such tasks where the ascriber herself is one of the two agents, i.e. has a belief or desire herself that stands in contrast to that to be ascribed to someone else. All in all, these findings suggest that executive function figures in coordinating perspectives more generally, not only epistemic ones, and in particular in coordinating others' and one's own conflicting perspectives. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Insights from Cognitive Neuroscience: The Importance of Executive Function for Early Reading Development and Education

    Science.gov (United States)

    Cartwright, Kelly B.

    2012-01-01

    Research Findings: Executive function begins to develop in infancy and involves an array of processes, such as attention, inhibition, working memory, and cognitive flexibility, which provide the means by which individuals control their own behavior, work toward goals, and manage complex cognitive processes. Thus, executive function plays a…

  16. DJ-1 plays an important role in caffeic acid-mediated protection of the gastrointestinal mucosa against ketoprofen-induced oxidative damage.

    Science.gov (United States)

    Cheng, Yu-Ting; Ho, Cheng-Ying; Jhang, Jhih-Jia; Lu, Chi-Cheng; Yen, Gow-Chin

    2014-10-01

    Ketoprofen is widely used to alleviate pain and inflammation in clinical medicine; however, this drug may cause oxidative stress and lead to gastrointestinal (GI) ulcers. We previously reported that nuclear factor erythroid 2-related factor 2 (Nrf2) plays a crucial role in protecting cells against reactive oxygen species, and it facilitates the prevention of ketoprofen-induced GI mucosal ulcers. Recent reports suggested that Nrf2 becomes unstable in the absence of DJ-1/PARK7, attenuating the activity of Nrf2-regulated downstream antioxidant enzymes. Thus, increasing Nrf2 translocation by DJ-1 may represent a novel means for GI protection. In vitro, caffeic acid increases the nuclear/cytosolic Nrf2 ratio and the mRNA expression of the downstream antioxidant enzymes, ϒ-glutamyl cysteine synthetase, glutathione peroxidase, glutathione reductase, and heme oxygenase-1, by activating the JNK/p38 pathway in Int-407 cells. Moreover, knockdown of DJ-1 also reversed caffeic acid-induced nuclear Nrf2 protein expression in a JNK/p38-dependent manner. Our results also indicated that treatment of Sprague-Dawley rats with caffeic acid prior to the administration of ketoprofen inhibited oxidative damage and reversed the inhibitory effects of ketoprofen on the antioxidant system and DJ-1 protein expression in the GI mucosa. Our observations suggest that DJ-1 plays an important role in caffeic acid-mediated protection against ketoprofen-induced oxidative damage in the GI mucosa.

  17. Playing with cardiac "redox switches": the "HNO way" to modulate cardiac function.

    Science.gov (United States)

    Tocchetti, Carlo G; Stanley, Brian A; Murray, Christopher I; Sivakumaran, Vidhya; Donzelli, Sonia; Mancardi, Daniele; Pagliaro, Pasquale; Gao, Wei Dong; van Eyk, Jennifer; Kass, David A; Wink, David A; Paolocci, Nazareno

    2011-05-01

    The nitric oxide (NO(•)) sibling, nitroxyl or nitrosyl hydride (HNO), is emerging as a molecule whose pharmacological properties include providing functional support to failing hearts. HNO also preconditions myocardial tissue, protecting it against ischemia-reperfusion injury while exerting vascular antiproliferative actions. In this review, HNO's peculiar cardiovascular assets are discussed in light of its unique chemistry that distinguish HNO from NO(•) as well as from reactive oxygen and nitrogen species such as the hydroxyl radical and peroxynitrite. Included here is a discussion of the possible routes of HNO formation in the myocardium and its chemical targets in the heart. HNO has been shown to have positive inotropic/lusitropic effects under normal and congestive heart failure conditions in animal models. The mechanistic intricacies of the beneficial cardiac effects of HNO are examined in cellular models. In contrast to β-receptor/cyclic adenosine monophosphate/protein kinase A-dependent enhancers of myocardial performance, HNO uses its "thiophylic" nature as a vehicle to interact with redox switches such as cysteines, which are located in key components of the cardiac electromechanical machinery ruling myocardial function. Here, we will briefly review new features of HNO's cardiovascular effects that when combined with its positive inotropic/lusitropic action may render HNO donors an attractive addition to the current therapeutic armamentarium for treating patients with acutely decompensated congestive heart failure.

  18. The methyl-CpG binding proteins Mecp2, Mbd2 and Kaiso are dispensable for mouse embryogenesis, but play a redundant function in neural differentiation.

    Directory of Open Access Journals (Sweden)

    Isabel Martín Caballero

    Full Text Available BACKGROUND: The precise molecular changes that occur when a neural stem (NS cell switches from a programme of self-renewal to commit towards a specific lineage are not currently well understood. However it is clear that control of gene expression plays an important role in this process. DNA methylation, a mark of transcriptionally silent chromatin, has similarly been shown to play important roles in neural cell fate commitment in vivo. While DNA methylation is known to play important roles in neural specification during embryonic development, no such role has been shown for any of the methyl-CpG binding proteins (Mecps in mice. METHODOLOGY/PRINCIPAL FINDINGS: To explore the role of DNA methylation in neural cell fate decisions, we have investigated the function of Mecps in mouse development and in neural stem cell derivation, maintenance, and differentiation. In order to test whether the absence of phenotype in singly-mutant animals could be due to functional redundancy between Mecps, we created mice and neural stem cells simultaneously lacking Mecp2, Mbd2 and Zbtb33. No evidence for functional redundancy between these genes in embryonic development or in the derivation or maintenance of neural stem cells in culture was detectable. However evidence for a defect in neuronal commitment of triple knockout NS cells was found. CONCLUSIONS/SIGNIFICANCE: Although DNA methylation is indispensable for mammalian embryonic development, we show that simultaneous deficiency of three methyl-CpG binding proteins genes is compatible with apparently normal mouse embryogenesis. Nevertheless, we provide genetic evidence for redundancy of function between methyl-CpG binding proteins in postnatal mice.

  19. AQP4-dependent water transport plays a functional role in exercise-induced skeletal muscle adaptations.

    Science.gov (United States)

    Basco, Davide; Blaauw, Bert; Pisani, Francesco; Sparaneo, Angelo; Nicchia, Grazia Paola; Mola, Maria Grazia; Reggiani, Carlo; Svelto, Maria; Frigeri, Antonio

    2013-01-01

    In this study we assess the functional role of Aquaporin-4 (AQP4) in the skeletal muscle by analyzing whether physical activity modulates AQP4 expression and whether the absence of AQP4 has an effect on osmotic behavior, muscle contractile properties, and physical activity. To this purpose, rats and mice were trained on the treadmill for 10 (D10) and 30 (D30) days and tested with exercise to exhaustion, and muscles were used for immunoblotting, RT-PCR, and fiber-type distribution analysis. Taking advantage of the AQP4 KO murine model, functional analysis of AQP4 was performed on dissected muscle fibers and sarcolemma vesicles. Moreover, WT and AQP4 KO mice were subjected to both voluntary and forced activity. Rat fast-twitch muscles showed a twofold increase in AQP4 protein in D10 and D30 rats compared to sedentary rats. Such increase positively correlated with the animal performance, since highest level of AQP4 protein was found in high runner rats. Interestingly, no shift in muscle fiber composition nor an increase in AQP4-positive fibers was found. Furthermore, no changes in AQP4 mRNA after exercise were detected, suggesting that post-translational events are likely to be responsible for AQP4 modulation. Experiments performed on AQP4 KO mice revealed a strong impairment in osmotic responses as well as in forced and voluntary activities compared to WT mice, even though force development amplitude and contractile properties were unvaried. Our findings definitively demonstrate the physiological role of AQP4 in supporting muscle contractile activity and metabolic changes that occur in fast-twitch skeletal muscle during prolonged exercise.

  20. AQP4-dependent water transport plays a functional role in exercise-induced skeletal muscle adaptations.

    Directory of Open Access Journals (Sweden)

    Davide Basco

    Full Text Available In this study we assess the functional role of Aquaporin-4 (AQP4 in the skeletal muscle by analyzing whether physical activity modulates AQP4 expression and whether the absence of AQP4 has an effect on osmotic behavior, muscle contractile properties, and physical activity. To this purpose, rats and mice were trained on the treadmill for 10 (D10 and 30 (D30 days and tested with exercise to exhaustion, and muscles were used for immunoblotting, RT-PCR, and fiber-type distribution analysis. Taking advantage of the AQP4 KO murine model, functional analysis of AQP4 was performed on dissected muscle fibers and sarcolemma vesicles. Moreover, WT and AQP4 KO mice were subjected to both voluntary and forced activity. Rat fast-twitch muscles showed a twofold increase in AQP4 protein in D10 and D30 rats compared to sedentary rats. Such increase positively correlated with the animal performance, since highest level of AQP4 protein was found in high runner rats. Interestingly, no shift in muscle fiber composition nor an increase in AQP4-positive fibers was found. Furthermore, no changes in AQP4 mRNA after exercise were detected, suggesting that post-translational events are likely to be responsible for AQP4 modulation. Experiments performed on AQP4 KO mice revealed a strong impairment in osmotic responses as well as in forced and voluntary activities compared to WT mice, even though force development amplitude and contractile properties were unvaried. Our findings definitively demonstrate the physiological role of AQP4 in supporting muscle contractile activity and metabolic changes that occur in fast-twitch skeletal muscle during prolonged exercise.

  1. Receptor for advanced glycation end products plays a more important role in cellular survival than in neurite outgrowth during retinoic acid-induced differentiation of neuroblastoma cells.

    Science.gov (United States)

    Sajithlal, Gangadharan; Huttunen, Henri; Rauvala, Heikki; Munch, Gerald

    2002-03-01

    The receptor for advanced glycation end products (RAGE), a member of the immunoglobulin superfamily, is known to interact with amphoterin. This interaction has been proposed to play a role in neurite outgrowth and process elongation during neurodifferentiation. However, there is as yet no direct evidence of the relevance of this pathway to neurodifferentiation under physiological conditions. In this study we have investigated a possible role of RAGE and amphoterin in the retinoic acid-induced differentiation of neuroblastoma cells. The functional inactivation of RAGE by dominant negative and antisense strategies showed that RAGE is not required for process outgrowth or differentiation, although overexpression of RAGE accelerates the elongation of neuritic processes. Using the antisense strategy, amphoterin was shown to be essential for process outgrowth and differentiation, suggesting that amphoterin may interact with other molecules to exert its effect in this context. Interestingly, the survival of the neuroblastoma cells treated with retinoic acid was partly dependent on the expression of RAGE, and inhibition of RAGE function partially blocked the increase in anti-apoptotic protein Bcl-2 following retinoic acid treatment. Based on these results we propose that a combination therapy using RAGE blockers and retinoic acid may prove as a useful approach for chemotherapy for the treatment of neuroblastoma.

  2. Dispersion quality of amine functionalized multiwall carbon nanotubes plays critical roles in polymerase chain reaction enhancement

    Energy Technology Data Exchange (ETDEWEB)

    Yuce, Meral, E-mail: meralyuce@sabanciuniv.edu; Budak, Hikmet [Sabanci University, Nanotechnology Research and Application Centre (Turkey)

    2014-12-15

    Impact of dispersion quality of NH{sub 2}-MWCNTs (13–18 nm in diameter with a length between 1 and 12 µm, >99 % purity) in the amplification efficiency of a random DNA oligonucleotide library (96 bp) was investigated. Amplification yield in the presence of non-filtered NH{sub 2}-MWCNT dispersion, filtered NH{sub 2}-MWCNT dispersion and surface-attached NH{sub 2}-MWCNTs was explored, and physical interactions between NH{sub 2}-MWCNTs and major PCR reagents including DNA template, wild type Taq DNA polymerase enzyme and primers were determined using high resolution polyacrylamide gel electrophoresis, dynamic light scattering, UV–Vis-NIR spectroscopy and scanning electron microscopy techniques. The results revealed that presence of NH{sub 2}-MWCNT dispersion which was sonicated, centrifuged and filtered, enhanced the total PCR efficiency up to 70 % while the presence of NH{sub 2}-MWCNT only centrifuged after sonication, inhibited the reaction significantly at similar concentrations. Furthermore, the NH{sub 2}-MWCNTs coupled covalently onto magnetic microspheres, contributed for the specificity enhancement whilst decreasing the amplification efficiency by 30 % at the maximum concentration, which suggests a removable enhancement system for sensitive applications. On the other hand, the relative hydrodynamic size distribution measurements displayed a clear difference between the filtered NH{sub 2} and non-filtered NH{sub 2}-MWCNT water dispersions, which justifies the inhibition of the amplification by the non-filtered NH{sub 2}-MWCNTs containing big agglomerates and bundles. Finally, we demonstrated that major PCR components adsorb onto the NH{sub 2}-MWCNTs with diverse affinities, and maintain their functions after adsorption, which provides a good framework to further develop tunable NH{sub 2}-MWCNT-carriers to be utilized in various nanobiotechnology and material science applications.

  3. Deep cerebellar nuclei play an important role in two-tone discrimination on delay eyeblink conditioning in C57BL/6 mice.

    Science.gov (United States)

    Sakamoto, Toshiro; Endo, Shogo

    2013-01-01

    Previous studies have shown that deep cerebellar nuclei (DCN)-lesioned mice develop conditioned responses (CR) on delay eyeblink conditioning when a salient tone conditioned stimulus (CS) is used, which suggests that the cerebellum potentially plays a role in more complicated cognitive functions. In the present study, we examined the role of DCN in tone frequency discrimination in the delay eyeblink-conditioning paradigm. In the first experiment, DCN-lesioned and sham-operated mice were subjected to standard simple eyeblink conditioning under low-frequency tone CS (LCS: 1 kHz, 80 dB) or high-frequency tone CS (HCS: 10 kHz, 70 dB) conditions. DCN-lesioned mice developed CR in both CS conditions as well as sham-operated mice. In the second experiment, DCN-lesioned and sham-operated mice were subjected to two-tone discrimination tasks, with LCS+ (or HCS+) paired with unconditioned stimulus (US), and HCS- (or LCS-) without US. CR% in sham-operated mice increased in LCS+ (or HCS+) trials, regardless of tone frequency of CS, but not in HCS- (or LCS-) trials. The results indicate that sham-operated mice can discriminate between LCS+ and HCS- (or HCS+ and LCS-). In contrast, DCN-lesioned mice showed high CR% in not only LCS+ (or HCS+) trials but also HCS- (or LCS-) trials. The results indicate that DCN lesions impair the discrimination between tone frequency in eyeblink conditioning. Our results suggest that the cerebellum plays a pivotal role in the discrimination of tone frequency.

  4. Deep cerebellar nuclei play an important role in two-tone discrimination on delay eyeblink conditioning in C57BL/6 mice.

    Directory of Open Access Journals (Sweden)

    Toshiro Sakamoto

    Full Text Available Previous studies have shown that deep cerebellar nuclei (DCN-lesioned mice develop conditioned responses (CR on delay eyeblink conditioning when a salient tone conditioned stimulus (CS is used, which suggests that the cerebellum potentially plays a role in more complicated cognitive functions. In the present study, we examined the role of DCN in tone frequency discrimination in the delay eyeblink-conditioning paradigm. In the first experiment, DCN-lesioned and sham-operated mice were subjected to standard simple eyeblink conditioning under low-frequency tone CS (LCS: 1 kHz, 80 dB or high-frequency tone CS (HCS: 10 kHz, 70 dB conditions. DCN-lesioned mice developed CR in both CS conditions as well as sham-operated mice. In the second experiment, DCN-lesioned and sham-operated mice were subjected to two-tone discrimination tasks, with LCS+ (or HCS+ paired with unconditioned stimulus (US, and HCS- (or LCS- without US. CR% in sham-operated mice increased in LCS+ (or HCS+ trials, regardless of tone frequency of CS, but not in HCS- (or LCS- trials. The results indicate that sham-operated mice can discriminate between LCS+ and HCS- (or HCS+ and LCS-. In contrast, DCN-lesioned mice showed high CR% in not only LCS+ (or HCS+ trials but also HCS- (or LCS- trials. The results indicate that DCN lesions impair the discrimination between tone frequency in eyeblink conditioning. Our results suggest that the cerebellum plays a pivotal role in the discrimination of tone frequency.

  5. The importance of rare species: a trait-based assessment of rare species contributions to functional diversity and possible ecosystem function in tall-grass prairies.

    Science.gov (United States)

    Jain, Meha; Flynn, Dan Fb; Prager, Case M; Hart, Georgia M; Devan, Caroline M; Ahrestani, Farshid S; Palmer, Matthew I; Bunker, Daniel E; Knops, Johannes Mh; Jouseau, Claire F; Naeem, Shahid

    2014-01-01

    The majority of species in ecosystems are rare, but the ecosystem consequences of losing rare species are poorly known. To understand how rare species may influence ecosystem functioning, this study quantifies the contribution of species based on their relative level of rarity to community functional diversity using a trait-based approach. Given that rarity can be defined in several different ways, we use four different definitions of rarity: abundance (mean and maximum), geographic range, and habitat specificity. We find that rarer species contribute to functional diversity when rarity is defined by maximum abundance, geographic range, and habitat specificity. However, rarer species are functionally redundant when rarity is defined by mean abundance. Furthermore, when using abundance-weighted analyses, we find that rare species typically contribute significantly less to functional diversity than common species due to their low abundances. These results suggest that rare species have the potential to play an important role in ecosystem functioning, either by offering novel contributions to functional diversity or via functional redundancy depending on how rare species are defined. Yet, these contributions are likely to be greatest if the abundance of rare species increases due to environmental change. We argue that given the paucity of data on rare species, understanding the contribution of rare species to community functional diversity is an important first step to understanding the potential role of rare species in ecosystem functioning.

  6. Glycerol-3-Phosphate Acyltransferase 6 (GPAT6) Is Important for Tapetum Development in Arabidopsis and Plays Multiple Roles in Plant Fertility

    Institute of Scientific and Technical Information of China (English)

    Xiao-Chuan Li; Jun Zhu; Jun Yang; Guo-RuiZhang; Wei-Feng Xing; Sen Zhang; Zhong-NanYang

    2012-01-01

    Glycerol-3-phosphate acyltransferase (GPAT) mediates the initial synthetic step for the formation of glycerolipids,which act as the major components of biological membranes and the principal stored forms of energy.GPAT6 is a member of the Arabidopsis GPAT family,which is crucial for cutin biosynthesis in sepals and petals.In this work,a functional analysis of GPAT6 in anther development and plant fertility was performed.GPAT6 was highly expressed in the tapetum and microspores during anther development.The knockout mutant,gpat6,caused a massive reduction in seed production.This report shows that the ablation of GPAT6 caused defective tapetum development with reduced endoplasmic reticulum (ER) profiles in the tapetum,which largely led to the abortion of pollen grains and defective pollen wall formation.In addition,pollen germination and pollen tube elongation were affected in the mutant plants.Furthermore,the double mutant analysis showed that GPAT6 and GPAT1 make joint effects on the release of microspores from tetrads and stamen filament elongation.This work shows that GPAT6 plays multiple roles in stamen development and fertility in Arabidopsis.

  7. Play Matters

    DEFF Research Database (Denmark)

    Sicart (Vila), Miguel Angel

    , but not necessarily fun. Play can be dangerous, addictive, and destructive. Along the way, Sicart considers playfulness, the capacity to use play outside the context of play; toys, the materialization of play--instruments but also play pals; playgrounds, play spaces that enable all kinds of play; beauty......, the aesthetics of play through action; political play -- from Maradona's goal against England in the 1986 World Cup to the hactivist activities of Anonymous; the political, aesthetic, and moral activity of game design; and why play and computers get along so well....

  8. IGF-1 Signaling Plays an Important Role in the Formation of Three-Dimensional Laminated Neural Retina and Other Ocular Structures From Human Embryonic Stem Cells.

    Science.gov (United States)

    Mellough, Carla B; Collin, Joseph; Khazim, Mahmoud; White, Kathryn; Sernagor, Evelyne; Steel, David H W; Lako, Majlinda

    2015-08-01

    We and others have previously demonstrated that retinal cells can be derived from human embryonic stem cells (hESCs) and induced pluripotent stem cells under defined culture conditions. While both cell types can give rise to retinal derivatives in the absence of inductive cues, this requires extended culture periods and gives lower overall yield. Further understanding of this innate differentiation ability, the identification of key factors that drive the differentiation process, and the development of clinically compatible culture conditions to reproducibly generate functional neural retina is an important goal for clinical cell based therapies. We now report that insulin-like growth factor 1 (IGF-1) can orchestrate the formation of three-dimensional ocular-like structures from hESCs which, in addition to retinal pigmented epithelium and neural retina, also contain primitive lens and corneal-like structures. Inhibition of IGF-1 receptor signaling significantly reduces the formation of optic vesicle and optic cups, while exogenous IGF-1 treatment enhances the formation of correctly laminated retinal tissue composed of multiple retinal phenotypes that is reminiscent of the developing vertebrate retina. Most importantly, hESC-derived photoreceptors exhibit advanced maturation features such as the presence of primitive rod- and cone-like photoreceptor inner and outer segments and phototransduction-related functional responses as early as 6.5 weeks of differentiation, making these derivatives promising candidates for cell replacement studies and in vitro disease modeling.

  9. β3GnT8 plays an important role in CD147 signal transduction as an upstream modulator of MMP production in tumor cells.

    Science.gov (United States)

    Jiang, Zhi; Hu, Shuijun; Hua, Dong; Ni, Jianlong; Xu, Lan; Ge, Yan; Zhou, Yinghui; Cheng, Zhihong; Wu, Shiliang

    2014-09-01

    Aberrant carbohydration by related glycosyl-transferases plays an important role in the progression of cancer. This study focused on the ablity of β-1,3-N-acetyl-glucosaminyltransferase-8 (β3GnT8) to regulate MMP-2 expression through regulation of the CD147 signal transduction pathway in cancer cells. β3GnT8 catalyzes and then extends a polylactosamine chain specifically on β1-6-branched tetraantennary N-glycans. CD147 is a major carrier of β1-6-branched polylactosamine sugars on tumor cells, and the high glycoform of CD147 (HG-CD147) induces matrix metalloproteinase (MMP) production. In the present study, we analyzed β3GnT8 mRNA expression in 6 cancer cell lines (MCF-7, M231, LN229, U87, SGC-7901 and U251). We found that β3GnT8 expression in the LN229, SGC-7901 and U251 cell lines was higher than that in the other cell lines. Therefore, we established β3GnT8-knockdown cell lines derived from the LN229 and SGC-7901 cell lines to examine the level of polylactosamine and CD147 N-glycosylation. In addition, tunicamycin is widely used as an inhibitor of N-linked glycosylation. Hence, various concentrations of tunicamycin were used to treat the cells in order to study its influence on CD147 N-glycosylation and MMP-2 expression. In conclusion, we found that β3GnT8 regulated the level of N-glycans on CD147 and that N-glycosylation of CD147 has an important effect on MMP-2 expression. Our findings suggest that β3GnT8 affects the signal transduction pathway of MMP-2 by altering the N-glycan structure of CD147.

  10. Photorespiration plays an important role in the regulation of photosynthetic electron flow under fluctuating light in tobacco plants grown under full sunlight

    Directory of Open Access Journals (Sweden)

    Wei eHuang

    2015-08-01

    Full Text Available Plants usually experience dynamic fluctuations of light intensities under natural conditions. However, the responses of mesophyll conductance, CO2 assimilation, and photorespiration to light fluctuation are not well understood. To address this question, we measured photosynthetic parameters of gas exchange and chlorophyll fluorescence in tobacco leaves at 2-min intervals while irradiance levels alternated between 100 and 1200 μmol photons m-2 s-1. Compared with leaves exposed to a constant light of 1200 μmol photons m-2 s-1, both stomatal and mesophyll conductances were significantly restricted in leaves treated with fluctuating light condition. Meanwhile, CO2 assimilation rate and electron flow devoted to RuBP carboxylation at 1200 μmol photons m-2 s-1 under fluctuating light were limited by the low chloroplast CO2 concentration. Analysis based on the C3 photosynthesis model indicated that, at 1200 μmol photons m-2 s-1 under fluctuating light, the CO2 assimilation rate was limited by RuBP carboxylation. Electron flow devoted to RuBP oxygenation at 1200 μmol photons m-2 s-1 under fluctuating light remained at nearly the maximum level throughout the experimental period. We conclude that fluctuating light restricts CO2 assimilation by decreasing both stomatal and mesophyll conductances. Under such conditions, photorespiration plays an important role in the regulation of photosynthetic electron flow.

  11. Mast cells and histamine play an important role in edema and leukocyte recruitment induced by Potamotrygon motoro stingray venom in mice.

    Science.gov (United States)

    Kimura, Louise F; Prezotto-Neto, José Pedro; Távora, Bianca C L F; Faquim-Mauro, Eliana L; Pereira, Nicole A; Antoniazzi, Marta M; Jared, Simone G S; Teixeira, Catarina F P; Santoro, Marcelo L; Barbaro, Katia C

    2015-09-01

    This work aimed to investigate mechanisms underlying the inflammatory response caused by Potamotrygon motoro stingray venom (PmV) in mouse paws. Pre-treatment of animals with a mast cell degranulation inhibitor (cromolyn) diminished edema (62% of inhibition) and leukocyte influx into the site of PmV injection. Promethazine (histamine type 1 receptor antagonist) or thioperamide (histamine type 3 and 4 receptor antagonist) also decreased edema (up to 30%) and leukocyte numbers, mainly neutrophils (40-50 %). Cimetidine (histamine type 2 receptor antagonist) had no effect on PmV-induced inflammation. In the RBL-2H3 lineage of mast cells, PmV caused proper cell activation, in a dose-dependent manner, with release of PGD2 and PGE2. In addition, the role of COXs products on PmV inflammatory response was evaluated. Indomethacin (COX-1/COX-2 inhibitor) or etoricoxib (COX-2 inhibitor) partially diminished edema (around 20%) in PmV-injected mice. Indomethacin, but not etoricoxib, modulated neutrophil influx into the site of venom injection. In conclusion, mast cell degranulation and histamine, besides COXs products, play an important role in PmV-induced reaction. Since PmV mechanism of action remains unknown, hindering accurate treatment, clinical studies can be performed to validate the prescription of antihistaminic drugs, besides NSAIDs, to patients injured by freshwater stingrays.

  12. Stabilisation of the fractured fibula plays an important role in the treatment of pilon fractures: a retrospective comparison of fibular fixation methods.

    Science.gov (United States)

    Lee, Yih-Shiunn; Chen, Shu-Wen; Chen, Shih-Hao; Chen, Wen-Chiao; Lau, Ming-Jye; Hsu, Tzu-Liang

    2009-06-01

    Ninety-eight pilon fractures associated with ipsilateral distal fibular fracture were included in this study. The pilon fractures were treated by open reduction and plating. The 98 fractures were divided into three groups based on the treatment method of fractured fibula. Group A was composed of 50 fibular fractures treated by open reduction and plate fixation. Group B was composed of 23 fibular fractures treated by open reduction and pin fixation. Group C was composed of 25 fibular fractures treated conservatively by closed reduction. The radiographs were reviewed for adequacy of fracture reduction and posttraumatic arthrosis. At the end of follow-up, the clinical outcomes were evaluated using a rating scale. The three groups were similar in respect to Ruedi type, open fracture grade, and demographics (all p values >0.25). Group A showed a decreasing trend of malunion and ankle arthrosis compared to group C (p = 0.091 and p = 0.099, respectively). Group A had a better clinical outcome than group C (p = 0.008). In addition, group A showed an increasing trend of satisfactory outcome compared to group B (p = 0.096). In conclusion, for pilon fractures associated with ipsilateral fibular fractures, stabilisation of the fractured fibula plays an important role in the decrease of distal tibial malunion and post-traumatic ankle arthrosis as well as improvement of clinical outcomes.

  13. Photorespiration plays an important role in the regulation of photosynthetic electron flow under fluctuating light in tobacco plants grown under full sunlight.

    Science.gov (United States)

    Huang, Wei; Hu, Hong; Zhang, Shi-Bao

    2015-01-01

    Plants usually experience dynamic fluctuations of light intensities under natural conditions. However, the responses of mesophyll conductance, CO2 assimilation, and photorespiration to light fluctuation are not well understood. To address this question, we measured photosynthetic parameters of gas exchange and chlorophyll fluorescence in tobacco leaves at 2-min intervals while irradiance levels alternated between 100 and 1200 μmol photons m(-2) s(-1). Compared with leaves exposed to a constant light of 1200 μmol photons m(-2) s(-1), both stomatal and mesophyll conductances were significantly restricted in leaves treated with fluctuating light condition. Meanwhile, CO2 assimilation rate and electron flow devoted to RuBP carboxylation at 1200 μmol photons m(-2) s(-1) under fluctuating light were limited by the low chloroplast CO2 concentration. Analysis based on the C3 photosynthesis model indicated that, at 1200 μmol photons m(-2) s(-1) under fluctuating light, the CO2 assimilation rate was limited by RuBP carboxylation. Electron flow devoted to RuBP oxygenation at 1200 μmol photons m(-2) s(-1) under fluctuating light remained at nearly the maximum level throughout the experimental period. We conclude that fluctuating light restricts CO2 assimilation by decreasing both stomatal and mesophyll conductances. Under such conditions, photorespiration plays an important role in the regulation of photosynthetic electron flow.

  14. H2O2 plays an important role in the lifestyle of Colletotrichum gloeosporioides during interaction with cowpea [Vigna unguiculata (L.) Walp].

    Science.gov (United States)

    Eloy, Ygor R G; Vasconcelos, Ilka M; Barreto, Ana L H; Freire-Filho, Francisco R; Oliveira, Jose T A

    2015-08-01

    Plant-fungus interactions usually generate H(2)O(2) in the infected plant tissue. H(2)O(2) has a direct antimicrobial effect and is involved in the cross-linking of cell walls, signaling, induction of gene expression, hypersensitive cell death and induced systemic acquired resistance. This has raised the hypothesis that H(2)O(2) manipulation by pharmacological compounds could alter the lifestyle of Colletotrichum gloeosporioides during interaction with the BR-3-Tracuateua cowpea genotype. The primary leaves of cowpea were excised, infiltrated with salicylic acid (SA), glucose oxidase + glucose (GO/G), catalase (CAT) or diphenyliodonium chloride (DPI), followed by spore inoculation on the adaxial leaf surface. SA or GO/G-treated plantlets showed increased H(2)O(2) accumulation and lipid peroxidation. The fungus used a subcuticular, intramural necrotrophic strategy, and developed secondary hyphae associated with the quick spread and rapid killing of host cells. However, CAT or DPI-treated leaves exhibited decreased H(2)O(2) concentration and lipid peroxidation and the fungus developed intracellular hemibiotrophic infection with vesicles, in addition to primary and secondary hyphal formation. These results suggest that H(2)O(2) plays an important role in the cowpea (C. gloeosporioides) pathosystem given that it affected fungal lifestyle during interaction.

  15. Identification of a disulfide bridge important for transport function of SNAT4 neutral amino acid transporter.

    Directory of Open Access Journals (Sweden)

    Rugmani Padmanabhan Iyer

    Full Text Available SNAT4 is a member of system N/A amino acid transport family that primarily expresses in liver and muscles and mediates the transport of L-alanine. However, little is known about the structure and function of the SNAT family of transporters. In this study, we showed a dose-dependent inhibition in transporter activity of SNAT4 with the treatment of reducing agents, dithiothreitol (DTT and Tris(2-carboxyethylphosphine (TCEP, indicating the possible involvement of disulfide bridge(s. Mutation of residue Cys-232, and the two highly conserved residues Cys-249 and Cys-321, compromised the transport function of SNAT4. However, this reduction was not caused by the decrease of SNAT4 on the cell surface since the cysteine-null mutant generated by replacing all five cysteines with alanine was equally capable of being expressed on the cell surface as wild-type SNAT4. Interestingly, by retaining two cysteine residues, 249 and 321, a significant level of L-alanine uptake was restored, indicating the possible formation of disulfide bond between these two conserved residues. Biotinylation crosslinking of free thiol groups with MTSEA-biotin provided direct evidence for the existence of a disulfide bridge between Cys-249 and Cys-321. Moreover, in the presence of DTT or TCEP, transport activity of the mutant retaining Cys-249 and Cys-321 was reduced in a dose-dependent manner and this reduction is gradually recovered with increased concentration of H2O2. Disruption of the disulfide bridge also decreased the transport of L-arginine, but to a lesser degree than that of L-alanine. Together, these results suggest that cysteine residues 249 and 321 form a disulfide bridge, which plays an important role in substrate transport but has no effect on trafficking of SNAT4 to the cell surface.

  16. 充分发挥博物馆的美育功能%Fully Playing Aesthetic Education Function of Museums

    Institute of Scientific and Technical Information of China (English)

    叶春辉

    2012-01-01

    充分发挥博物馆的美育功能,有利于促进人的德智体美全面发展,促进社会的和谐发展和国家的长治久安,有利于培育创新人才,有利于社会主义新文化的发展。博物馆要采取措施,强化美育功能。%Fully playing the aesthetic education function of museums not only helps to improve the comprehensive quality of citizens,but also leads to harmony of the society and stability of the nation.Moreover,it benefits to cultivate innovative talents and advancement of new socialist culture.Museums should take measures to strengthen aesthetic education function.

  17. The importance of species identity and interactions for multifunctionality depends on how ecosystem functions are valued.

    Science.gov (United States)

    Slade, Eleanor M; Kirwan, Laura; Bell, Thomas; Philipson, Christopher D; Lewis, Owen T; Roslin, Tomas

    2017-10-01

    Studies investigating how biodiversity affects ecosystem functioning increasingly focus on multiple functions measured simultaneously ("multifunctionality"). However, few such studies assess the role of species interactions, particularly under alternative environmental scenarios, despite interactions being key to ecosystem functioning. Here we address five questions of central importance to ecosystem multifunctionality using a terrestrial animal system. (1) Does the contribution of individual species differ for different ecosystem functions? (2) Do inter-species interactions affect the delivery of single functions and multiple functions? (3) Does the community composition that maximizes individual functions also maximize multifunctionality? (4) Is the functional role of individual species, and the effect of interspecific interactions, modified by changing environmental conditions? (5) How do these roles and interactions change under varying scenarios where ecosystem services are weighted to reflect different societal preferences? We manipulated species' relative abundance in dung beetle communities and measured 16 functions contributing to dung decomposition, plant productivity, nutrient recycling, reduction of greenhouse gases, and microbial activity. Using the multivariate diversity-interactions framework, we assessed how changes in species identity, composition, and interspecific interactions affected these functions in combination with an environmental driver (increased precipitation). This allowed us to identify key species and interactions across multiple functions. We then developed a desirability function approach to examine how individual species and species mixtures contribute to a desired state of overall ecosystem functioning. Species contributed unequally to individual functions, and to multifunctionality, and individual functions were maximized by different community compositions. Moreover, the species and interactions important for maintaining

  18. Efflux pump gene hefA of Helicobacter pylori plays an important role in multidrug resistanceZhi-Qiang Liu,Peng-Yuan Zheng,Ping-Chang Yang

    Institute of Scientific and Technical Information of China (English)

    Zhi-Qiang Liu; Peng-Yuan Zheng; Ping-Chang Yang

    2008-01-01

    AIM:To determine whether efflux systems contribute to multidrug resistance of H pylori.METHODS:A chloramphenicol-induced multidrug resistance model of six susceptible H pylori strains(5 isolates and H pylori NCTC11637)was developed.Multidrug-resistant(MDR)strains were selected and the minimal inhibitory concentration(MIC)of erythromycin,metronidazole,penicillin G,tetracycline,and ciprofloxacin in multidrug resistant strains and their parent strains was determined by agar dilution tests.The level of mRNA expression of hefA was assessed by fluorescence real-time quantitative PCR.A H pylori LZ1026 knockout mutant(△H pylori LZ1026)for(putative)efflux protein was constructed by inserting the kanamycin resistance cassette from pEGFP-N2 into hefA,and its susceptibility profiles to 10 antibiotics were evaluated.RESULTS:The MIC of six multidrug-resistant strains(including 5 clinical isolates and H pylori NaCTC11637)increased significantly(≥4-fold)compared with their parent strains.The expression level of herA gene was significantly higher in the MDR strains than in their parent strains(P=0.033).A H pylori LZ1026 mutant was successfully constructed and the △H pylori LZ1026 was more susceptible to four of the 10 antibiotics.All the 20 strains displayed transcripts for hefA that con-firmed the in vitro expression of these genes.CONCLUSION:The efflux pump gene hefA plays an important role in multidrug resistance of H pylori.(C)2008 The WJG Press.All rights reserved.

  19. Neurons in the amygdala play an important role in the neuronal network mediating a clonic form of audiogenic seizures both before and after audiogenic kindling.

    Science.gov (United States)

    Raisinghani, Manish; Faingold, Carl L

    2005-01-25

    Previous studies showed that neuronal network nuclei for behaviorally different forms of audiogenic seizure (AGS) exhibit similarities and important differences. The amygdala is involved differentially in tonic AGS as compared to clonic AGS networks. The role of the lateral amygdala (LAMG) undergoes major changes after AGS repetition (AGS kindling) in tonic forms of AGS. The present study examined the role of LAMG in a clonic form of AGS [genetically epilepsy-prone rats (GEPR-3s)] before and after AGS kindling using bilateral microinjection and chronic neuronal recordings. AGS kindling in GEPR-3s results in facial and forelimb (F&F) clonus, and this behavior could be blocked following bilateral microinjection of a NMDA antagonist (2-amino-7-phosphonoheptanoate) without affecting generalized clonus. Higher AP7 doses blocked both generalized clonus and F&F clonus. LAMG neurons in GEPR-3s exhibited only onset type neuronal responses both before and after AGS kindling, unlike LAMG neurons in normal rats and a tonic form of AGS. A significantly greater LAMG neuronal firing rate occurred after AGS kindling at high acoustic intensities. The latency of LAMG neuronal firing increased significantly after AGS kindling. Burst firing occurred during wild running and generalized clonic behaviors before and after AGS kindling. Burst firing also occurred during F&F clonus after AGS kindling. These findings indicate that LAMG neurons play a critical role in the neuronal network for generalized clonus as well as F&F clonus in GEPR-3s, both before and after AGS kindling, which contrasts markedly with the role of LAMG in tonic AGS.

  20. Transcriptional profiling of Medicago truncatula under salt stress identified a novel CBF transcription factor MtCBF4 that plays an important role in abiotic stress responses

    Directory of Open Access Journals (Sweden)

    Su Zhen

    2011-07-01

    Full Text Available Abstract Background Salt stress hinders the growth of plants and reduces crop production worldwide. However, different plant species might possess different adaptive mechanisms to mitigate salt stress. We conducted a detailed pathway analysis of transcriptional dynamics in the roots of Medicago truncatula seedlings under salt stress and selected a transcription factor gene, MtCBF4, for experimental validation. Results A microarray experiment was conducted using root samples collected 6, 24, and 48 h after application of 180 mM NaCl. Analysis of 11 statistically significant expression profiles revealed different behaviors between primary and secondary metabolism pathways in response to external stress. Secondary metabolism that helps to maintain osmotic balance was induced. One of the highly induced transcription factor genes was successfully cloned, and was named MtCBF4. Phylogenetic analysis revealed that MtCBF4, which belongs to the AP2-EREBP transcription factor family, is a novel member of the CBF transcription factor in M. truncatula. MtCBF4 is shown to be a nuclear-localized protein. Expression of MtCBF4 in M. truncatula was induced by most of the abiotic stresses, including salt, drought, cold, and abscisic acid, suggesting crosstalk between these abiotic stresses. Transgenic Arabidopsis over-expressing MtCBF4 enhanced tolerance to drought and salt stress, and activated expression of downstream genes that contain DRE elements. Over-expression of MtCBF4 in M. truncatula also enhanced salt tolerance and induced expression level of corresponding downstream genes. Conclusion Comprehensive transcriptomic analysis revealed complex mechanisms exist in plants in response to salt stress. The novel transcription factor gene MtCBF4 identified here played an important role in response to abiotic stresses, indicating that it might be a good candidate gene for genetic improvement to produce stress-tolerant plants.

  1. Important role of Granzyme B playing in cardiovascular diseases%颗粒酶B在心血管疾病中的重要作用

    Institute of Scientific and Technical Information of China (English)

    董武松; 杨俊

    2012-01-01

    Apoptosis plays an important role in cardiovascular diseases such as atherosclerosis, ischemic heart disease, congestive heart failure. Previous studies have showed that oxidative stress, physiological stress, and tumor necrosis factor and Fas ligand are involved in apoptosis of cardiovascular system. Recent studies also proved that another apoptosis--elated factor i. e. granzyme B/perforin system is involved in cardiovascular diseases. In this review, we collected the latest survey results show that granzyme B is involved in cardiovascular disease, and inhibiting granzyme B/perforin protein system may become a new therapeutic application.%细胞凋亡在心血管疾病如动脉粥样硬化,缺血性心脏病,充血性心力衰竭中起着重要的作用.以往的研究已经证明氧化应激、生理应激、肿瘤坏死因子和Fas配体参与了心血管系统的细胞凋亡.而最近的研究证明了另一个凋亡相关因子,即颗粒酶B/穿孔蛋白系统也参与了心血管系统的细胞凋亡.在这篇综述中,我们阐述了颗粒酶B在心血管疾病中的作用,并且发现颗粒酶B抑制剂的实验应用可以减轻心血管病的发生发展,从而使抑制颗粒酶B/穿孔蛋白系统治疗心血管疾病成为可能.

  2. Pulmonary vein triggers play an important role in the initiation of atrial flutter: Initial results from the prospective randomized Atrial Fibrillation Ablation in Atrial Flutter (Triple A) trial.

    Science.gov (United States)

    Schneider, Ralph; Lauschke, Joerg; Tischer, Tina; Schneider, Cindy; Voss, Wolfgang; Moehlenkamp, Felix; Glass, Aenne; Diedrich, Doreen; Bänsch, Dietmar

    2015-05-01

    The incidence of atrial fibrillation (AF) after ablation of a cavotricuspid isthmus (CTI)-dependent atrial flutter (AFL) is high. The purpose of this study was to test the hypothesis that AFL and AF may be initiated by pulmonary vein triggers. This prospective randomized trial tested the efficacy of a standalone pulmonary vein isolation (PVI) in patients with AFL but without AF. Patients with AFL but without documented AF were randomly assigned to 1 of 3 treatment groups: (1) antiarrhythmic drugs (AAD), (2) CTI ablation, or (3) circumferential PVI. The primary end-point was defined as any recurrent atrial tachyarrhythmia and the secondary end-point as recurrence of AFL. In case of tachyarrhythmia recurrence in the PVI group, a second PVI was performed to close gaps in the ablation lines. Of the 60 patients, 17 were randomized to AAD, 23 to CTI ablation, and 20 to PVI. During follow-up of 1.42 ± 0.83 years, 14 of 17 patients (82.4%) in the AAD group, 14 of 23 patients (60.9%) in the CTI group, and 2 of 20 patients (10%) in the PVI group reached the primary end-point (P PVI procedures per patient. AFL reoccurred in 9 patients (52.9.%) in the AAD group, in 2 patients (8.7%) in the CTI group, and after a single PVI in 3 patients (15%) in the PVI group (P = .003). After closure of gaps, 1 patient (5%) in the PVI group presented with recurrent AFL. Pulmonary vein triggers play an important role in AFL. PVI can prevent the recurrence of AFL, even without CTI ablation. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  3. RRP41L, a putative core subunit of the exosome, plays an important role in seed germination and early seedling growth in Arabidopsis.

    Science.gov (United States)

    Yang, Min; Zhang, Bangyue; Jia, Jianheng; Yan, Chunxia; Habaike, Ayijiang; Han, Yuzhen

    2013-01-01

    In prokaryotic and eukaryotic cells, the 3'-5'-exonucleolytic decay and processing of RNAs are essential for RNA metabolism. However, the understanding of the mechanism of 3'-5'-exonucleolytic decay in plants is very limited. Here, we report the characterization of an Arabidopsis (Arabidopsis thaliana) transfer DNA insertional mutant that shows severe growth defects in early seedling growth, including delayed germination and cotyledon expansion, thinner yellow/pale-green leaves, and a slower growth rate. High-efficiency thermal asymmetric interlaced polymerase chain reaction analysis showed that the insertional locus was in the sixth exon of AT4G27490, encoding a predicted 3'-5'-exonuclease, that contained a conserved RNase phosphorolytic domain with high similarity to RRP41, designated RRP41L. Interestingly, we detected highly accumulated messenger RNAs (mRNAs) that encode seed storage protein and abscisic acid (ABA) biosynthesis and signaling pathway-related protein during the early growth stage in rrp41l mutants. The mRNA decay kinetics analysis for seed storage proteins, 9-cis-epoxycarotenoid dioxygenases, and ABA INSENSITIVEs revealed that RRP41L catalyzed the decay of these mRNAs in the cytoplasm. Consistent with these results, the rrp41l mutant was more sensitive to ABA in germination and root growth than wild-type plants, whereas overexpression lines of RRP41L were more resistant to ABA in germination and root growth than wild-type plants. RRP41L was localized to both the cytoplasm and nucleus, and RRP41L was preferentially expressed in seedlings. Altogether, our results showed that RRP41L plays an important role in seed germination and early seedling growth by mediating specific cytoplasmic mRNA decay in Arabidopsis.

  4. Group play

    DEFF Research Database (Denmark)

    Tychsen, Anders; Hitchens, Michael; Brolund, Thea

    2008-01-01

    Role-playing games (RPGs) are a well-known game form, existing in a number of formats, including tabletop, live action, and various digital forms. Despite their popularity, empirical studies of these games are relatively rare. In particular there have been few examinations of the effects of the v......Role-playing games (RPGs) are a well-known game form, existing in a number of formats, including tabletop, live action, and various digital forms. Despite their popularity, empirical studies of these games are relatively rare. In particular there have been few examinations of the effects...... of the various formats used by RPGs on the gaming experience. This article presents the results of an empirical study, examining how multi-player tabletop RPGs are affected as they are ported to the digital medium. Issues examined include the use of disposition assessments to predict play experience, the effect...... RPGs, with the first being of greater importance to digital games and the latter to the tabletop version....

  5. Playful Gaming.

    Science.gov (United States)

    Makedon, Alexander

    A philosophical analysis of play and games is undertaken in this paper. Playful gaming, which is shown to be a synthesis of play and games, is utilized as a category for undertaking the examination of play and games. The significance of playful gaming to education is demonstrated through analyses of Plato's, Dewey's, Sartre's, and Marcuse's…

  6. The prognostic importance of lung function in patients admitted with heart failure

    DEFF Research Database (Denmark)

    Iversen, Kasper Karmark; Kjaergaard, Jesper; Akkan, Dilek

    2010-01-01

    The purpose of the present study was to determine the prognostic importance for all-cause mortality of lung function variables obtained by spirometry in an unselected group of patients admitted with heart failure (HF).......The purpose of the present study was to determine the prognostic importance for all-cause mortality of lung function variables obtained by spirometry in an unselected group of patients admitted with heart failure (HF)....

  7. Light-dependent maintenance of hydraulic function in mangrove branches: do xylary chloroplasts play a role in embolism repair?

    Science.gov (United States)

    Schmitz, N; Egerton, J J G; Lovelock, C E; Ball, M C

    2012-07-01

    • To clarify the role of branch photosynthesis in tree functioning, the presence and function of chloroplasts in branch xylem tissue were studied in a diverse range of mangrove species growing in Australia. • The presence of xylary chloroplasts was observed via chlorophyll fluorescence of transverse sections. Paired, attached branches were selected to study the effects of covering branches with aluminium foil on the gas exchange characteristics of leaves and the hydraulic conductivity of branches. • Xylary chloroplasts occurred in all species, but were differently distributed among living cell types in the xylem. Covering stems altered the gas exchange characteristics of leaves, such that water-use efficiency was greater in exposed leaves of covered than of uncovered branches. • Leaf-specific hydraulic conductivity of stems was lower in covered than in uncovered branches, implicating stem photosynthesis in the maintenance of hydraulic function. Given their proximity to xylem vessels, we suggest that xylary chloroplasts may play a role in light-dependent repair of embolized xylem vessels.

  8. The subunit gene Ldα1 of nicotinic acetylcholine receptors plays important roles in the toxicity of imidacloprid and thiamethoxam against Leptinotarsa decemlineata.

    Science.gov (United States)

    Qu, Yang; Chen, Jinhua; Li, Chenge; Wang, Qiang; Guo, Wenchao; Han, Zhaojun; Jiang, Weihua

    2016-02-01

    Nicotinic acetylcholine receptors (nAChRs) are pentameric ACh-gated ion channels. It is believed that nAChRs composed of different subunits may vary in their function and toxicological characteristics. Neonicotinoids are activators of nAChRs and important insecticides that are extensively used for crop protection and resistance has been developed by some pests. They are also major insecticides for the control of Leptinotarsa decemlineata, which is a destructive defoliator pest that invaded the Xinjiang region of China in the 1990s. However, little is known about the constitution or subunits of the target in this pest. In this study, the full-length cDNAs encoding four new nAChR subunits (named Ldα3, Ldα6, Ldα10, and Ldβ1) were cloned from L. decemlineata. These genes encode 822-, 753-, 672-, and 759-amino acid proteins, respectively, which share typical features of insect nAChRs subunits and closely resemble the corresponding subunits of the nAChRs from Tribolium castaneum. Temporal and spatial expression analyses showed that these genes, as well as the previously identified Ldα1, Ldα2, and Ldα8 genes, are widely expressed in all developmental stages, including eggs, larvae of various instars, pupae, and adults. All genes monitored were expressed at higher levels in the head than in the thorax and abdomen, except for Ldα10. Dietary ingestion of double-stranded RNA bacterially expressed for Ldα1 (dsLdα1) significantly reduced the mRNA level of Ldα1 in treated larvae and adults by 48.0% and 78.6%, respectively. Among the non-target genes, Ldα3, Ldα9, and Ldβ1 were significantly up-regulated in larvae. A toxicity bioassay showed that dsLdα1 treatment greatly decreased the sensitivity to imidacloprid and thiamethoxam in adults. The larval susceptibility to thiamethoxam but not to imidacloprid was also reduced because of the lower down-regulation of Ldα1. Thus, our results suggest that Ldα1 encodes a subunit of a functional nAChR that mediates the

  9. Perceived difficulty, importance, and satisfaction with physical function in COPD patients

    Directory of Open Access Journals (Sweden)

    Berry Michael J

    2004-03-01

    Full Text Available Abstract Background Research suggests that patients' satisfaction with their physical functioning (SPF is a critical component of HRQL. This study was designed to examine the extent to which perceptions of physical function and the value placed on physical function are related to satisfaction ratings. The sample consisted of older adults suffering from a progressively debilitating disease, chronic obstructive pulmonary disease (COPD. Methods During baseline assessments, COPD patients participating in a randomized controlled physical activity trial completed measures of SPF, perceived difficulty, and perceived importance. Results An ANCOVA controlling for age and gender indicated that perceived difficulty, perceived importance, and their interaction accounted for 43% of the variance in SPF. Additionally, participants were most satisfied with important tasks that they performed with little difficulty. Participants were least satisfied with important tasks that they perceived as highly difficult. Conclusion The results of the present study indicate that not being able to perform valued tasks produces discontent that is reflected in lower rating of satisfaction with physical functioning. Clearly, the significance of loss in function to individual patients is related to the importance of the functional activities that may be compromised. These data have implications for the scope of patient assessment in clinical care and for the conceptual basis of future research in the area of physical functioning.

  10. Collagenase IV plays an important role in regulating hair cycle by inducing VEGF, IGF-1, and TGF-β expression

    Directory of Open Access Journals (Sweden)

    Hou C

    2015-09-01

    , and TGF-β. The MMPs agonist also significantly increased expression of VEGF, IGF-1, and TGF-β. Meanwhile, SB-3CT treatment significantly suppressed hair growth. Conclusion: All these data suggest that the type IV collagenases, MMP-2 and MMP-9, play important roles in hair cycle, and this could be mediated by induced expression of VEGF, IGF-1, and TGF-β. Keywords: MMP-2, MMP-9, SB-3CT, telogen 

  11. Mig-14 plays an important role in influencing gene expression of Salmonella enterica serovar Typhi, which contributes to cell invasion under hyperosmotic conditions.

    Science.gov (United States)

    Sheng, Xiumei; Zhang, Hong; Xia, Qiufeng; Xu, Shungao; Xu, Huaxi; Huang, Xinxiang

    2013-11-01

    mig-14 is a horizontally acquired host-induced virulence gene in Salmonella enterica serovar Typhi. The molecular function of mig-14 is still unknown; sequence analysis showed that mig-14 shared homology with the helix-loop-helix motif of the AraC family of transcriptional regulatory proteins. In our previous microarray-based studies, mig-14 was upregulated at the early stage of high osmotic stress, indicating a potential role under this condition. Therefore, we compared growth and the global transcriptional difference between wild-type and mig-14 mutant strains to identify the role of Mig-14. The results showed that growth of mig-14 mutant strain was clearly slower than that of the wild-type strain, and 148 genes showed significant differences in expression between these two strains under upshift high osmotic treatment for 30 min. In total, 77 genes and 71 genes in the mig-14 mutant strain were upregulated and downregulated, respectively. Genes involved in invasion, virulence, flagellation, motility and chemotaxis of Salmonella were downregulated. Thus, cell invasion abilities of these two strains were further analyzed. The results confirmed that activities of mig-14 were important for cell invasion.

  12. Aesthetic Play

    DEFF Research Database (Denmark)

    Bang, Jytte Susanne

    2012-01-01

    to the children’s complex life-worlds. Further, this leads to an analysis of music-play activities as play with an art-form (music), which includes aesthetic dimensions and gives the music-play activities its character of being aesthetic play. Following Lev Vygotsky’s insight that art is a way of building life...

  13. Alteration of a single amino acid in the basic domain of Marek's disease virus Meq oncoprotein plays an important role in T-cell transformation

    Science.gov (United States)

    Marek’s disease virus encoded oncoprotein, Meq, has been shown to play a major role in transformation of T-lymphocytes. We have earlier shown that replacement of the meq gene in the very virulent strain Md5 with that of vaccine strain CVI988/Rispens resulted in virus attenuation in chickens. To dete...

  14. Enhancing Playful Teachers' Perception of the Importance of ICT Use in the Classroom: The Role of Risk Taking as a Mediator

    Science.gov (United States)

    Goodwin, A. Lin; Low, Ee Ling; Ng, Pak Tee; Yeung, Alexander S.; Cai, Li

    2015-01-01

    In today's world, teaching and learning processes inevitably involve the application of information and communication technology (ICT). It seems reasonable to expect personal attributes such as cognitive playfulness to be associated with consistent application of ICT. Using survey responses from Singapore students in a teacher education programme…

  15. ATF4 plays a pivotal role in the development of functional hematopoietic stem cells in mouse fetal liver.

    Science.gov (United States)

    Zhao, Yunze; Zhou, Jie; Liu, Dan; Dong, Fang; Cheng, Hui; Wang, Weili; Pang, Yakun; Wang, Yajie; Mu, Xiaohuan; Ni, Yanli; Li, Zhuan; Xu, Huiyu; Hao, Sha; Wang, Xiaochen; Ma, Shihui; Wang, Qian-fei; Xiao, Guozhi; Yuan, Weiping; Liu, Bing; Cheng, Tao

    2015-11-19

    The fetal liver (FL) serves as a predominant site for expansion of functional hematopoietic stem cells (HSCs) during mouse embryogenesis. However, the mechanisms for HSC development in FL remain poorly understood. In this study, we demonstrate that deletion of activating transcription factor 4 (ATF4) significantly impaired hematopoietic development and reduced HSC self-renewal in FL. In contrast, generation of the first HSC population in the aorta-gonad-mesonephros region was not affected. The migration activity of ATF4(-/-) HSCs was moderately reduced. Interestingly, the HSC-supporting ability of both endothelial and stromal cells in FL was significantly compromised in the absence of ATF4. Gene profiling using RNA-seq revealed downregulated expression of a panel of cytokines in ATF4(-/-) stromal cells, including angiopoietin-like protein 3 (Angptl3) and vascular endothelial growth factor A (VEGFA). Addition of Angptl3, but not VEGFA, partially rescued the repopulating defect of ATF4(-/-) HSCs in the culture. Furthermore, chromatin immunoprecipitation assay in conjunction with silencing RNA-mediated silencing and complementary DNA overexpression showed transcriptional control of Angptl3 by ATF4. To summarize, ATF4 plays a pivotal role in functional expansion and repopulating efficiency of HSCs in developing FL, and it acts through upregulating transcription of cytokines such as Angptl3 in the microenvironment.

  16. Transmembrane domain V plays a stabilizing role in the function of human bile acid transporter SLC10A2.

    Science.gov (United States)

    Moore, Robyn H; Chothe, Paresh; Swaan, Peter W

    2013-07-30

    The human apical sodium-dependent bile acid transporter (hASBT, SLC10A2), primarily expressed in the ileum, is involved in both the recycling of bile acids and cholesterol homeostasis. In this study, the structure-function relationship of transmembrane domain 5 (TM5) residues involved in transport is elucidated. Cysteine scanning mutagenesis of each consecutive residue on TM5 resulted in 96% of mutants having a significantly decreased transport activity, although each was expressed at the cell surface. Specifically, G197 and I208 were no longer functional, and G201 and G212 functioned at a level of Conservative alanine mutations of the four residues displayed a higher activity in all but G197A, indicating its functional importance. G197 and G201 form a GxxxG motif, which has been found to be important in helix-helix interactions. According to our model, G197 and G201 face transmembrane domain 4 (TM4) residues G179 and P175, respectively. Similarly, G212 faces G237, which forms part of a GxxxG domain in transmembrane domain 6 (TM6). It is possible that these GxxxG domains and their interacting partners are responsible for maintaining the structure of the helices and their interactions with one another. I205 and I208 are both in positions to anchor the GxxxG domains and direct the change in interaction of TM5 from TM4 to TM6. Combined, the results suggest that residues along TM5 are critical for ASBT function but are not directly involved in substrate translocation.

  17. TaLHY, a 1R-MYB Transcription Factor, Plays an Important Role in Disease Resistance against Stripe Rust Fungus and Ear Heading in Wheat.

    Directory of Open Access Journals (Sweden)

    Zijin Zhang

    Full Text Available LHY (late elongated hypocotyl is an important gene that regulates and controls biological rhythms in plants. Additionally, LHY is highly expressed in the SSH (suppression subtractive hybridization cDNA library-induced stripe rust pathogen (CYR32 in our previous research. To identify the function of the LHY gene in disease resistance against stripe rust, we used RACE-PCR technology to clone TaLHY in the wheat variety Chuannong19. The cDNA of TaLHY is 3085 bp long with an open reading frame of 1947 bp. TaLHY is speculated to encode a 70.3 kDa protein of 648 amino acids , which has one typical plant MYB-DNA binding domain; additionally, phylogenetic tree shows that TaLHY has the highest homology with LHY of Brachypodium distachyon(BdLHY-like. Quantitative fluorescence PCR indicates that TaLHY has higher expression in the leaf, ear and stem of wheat but lower expression in the root. Infestation of CYR32 can result in up-regulated expression of TaLHY, peaking at 72 h. Using VIGS (virus-induced gene silencing technology to disease-resistant wheat in the fourth leaf stage, plants with silenced TaLHY cannot complete their heading stage. Through the compatible interaction with the stripe rust physiological race CYR32, Chuannong 19 loses its immune capability toward the stripe rust pathogen, indicating that TaLHY may regulate and participate in the heading of wheat, as well as the defense responses against stripe rust infection.

  18. Children's Empowerment in Play

    Science.gov (United States)

    Canning, Natalie

    2007-01-01

    This article examines the level of empowerment and autonomy children can create in their play experiences. It examines the play discourses that children build and maintain and considers the importance of play contexts in supporting children's emotional and social development. These aspects of play are often unseen or misunderstood by the adult…

  19. The Importance of Take-Out Food Packaging Attributes: Conjoint Analysis and Quality Function Deployment Approach

    Directory of Open Access Journals (Sweden)

    Widaningrum Dyah Lestari

    2014-03-01

    Full Text Available This research aims to investigate the importance of take-out food packaging attributes, using conjoint analysis and QFD approach among consumers of take-out food products in Jakarta, Indonesia. The conjoint results indicate that perception about packaging material (such as paper, plastic, and polystyrene foam plays the most important role overall in consumer perception. The clustering results that there is strong segmentation in which take-out food packaging material consumer consider most important. Some consumers are mostly oriented toward the colour of packaging, while another segment of customers concerns on packaging shape and packaging information. Segmentation variables based on packaging response can provide very useful information to maximize image of products through the package’s impact. The results of House of Quality development described that Conjoint Analysis – QFD is a useful combination of the two methodologies in product development, market segmentation, and the trade off between customers’ requirements in the early stages of HOQ process

  20. The Importance of Take-Out Food Packaging Attributes: Conjoint Analysis and Quality Function Deployment Approach

    Science.gov (United States)

    Lestari Widaningrum, Dyah

    2014-03-01

    This research aims to investigate the importance of take-out food packaging attributes, using conjoint analysis and QFD approach among consumers of take-out food products in Jakarta, Indonesia. The conjoint results indicate that perception about packaging material (such as paper, plastic, and polystyrene foam) plays the most important role overall in consumer perception. The clustering results that there is strong segmentation in which take-out food packaging material consumer consider most important. Some consumers are mostly oriented toward the colour of packaging, while another segment of customers concerns on packaging shape and packaging information. Segmentation variables based on packaging response can provide very useful information to maximize image of products through the package's impact. The results of House of Quality development described that Conjoint Analysis - QFD is a useful combination of the two methodologies in product development, market segmentation, and the trade off between customers' requirements in the early stages of HOQ process

  1. The importance of emotional expression in the process of playing the piano%钢琴演奏过程中情感表达的重要性

    Institute of Scientific and Technical Information of China (English)

    仙景

    2015-01-01

    现今的社会中,学习钢琴的人越来越多,但是人们往往在钢琴演奏的过程中忽略了情感的表达。在音乐发生的过程中,情感表达却是一个必不可少的因素。因此,在钢琴演奏过程中,只有注重情感的表达才能将乐曲所包含的情感及思想表达得透彻,使听众感受到音乐的美。%In today's society, more and more people to learn to play the piano, but people often ignores the expression of emotion during the course of piano playing .In the process of music, emotional expression is an essential factor. Therefore,in the piano playing procession,only pay attention to the emotional expression can express the contains of music emotions and thoughts,and make the audience feel the beauty of music.

  2. 工会在企业社会责任履行中要发挥重要作用%Labor Unions should Play an Important Role in Fulfilling CSR

    Institute of Scientific and Technical Information of China (English)

    孔龙; 宋天邦

    2015-01-01

    企业社会责任(Corporate Social Responsibility)简称CSR。工会组织保护雇员权益的基本职能与社会责任关注员工权益的层面不谋而合。社会责任的全面、切实履行有利于企业可持续发展。工会应在广义利益相关者群体范畴的企业社会责任的履行中发挥重要作用。根据利益相关者群体类别,可将工会对企业社会责任的作用分为伦理规范作用和非伦理规范作用;根据作用方式的差异,可将非伦理规范作用再分为直接非伦理规范作用和间接非伦理规范作用。要充分发挥工会组织在企业社会责任履行中的作用,一是要完善工会组织参与CSR建设制度;二是要加强工会组织参与CSR的建设管理;三是要发挥政府的管理和引导作用。%Corporate Social Responsibility is abbreviated as CSR. The Labor Union’s primary responsibility of protecting the employees’rights and interests happen to coincide with one of the social responsibilities to focus on employees’rights and interests. The comprehensive and practical fulfillment of social responsibility contributes to the sustainable development of corporations. Labor Union should play an important role in the fulfill-ment of CSR in a general category of stakeholder group. According to categories of stakeholder group, the functions of Labor Union to CSR can be di-vided as ethical norm function and non-ethical norm function. In order to allow full play of Labor Union in fulfillment of CSR, one is to perfect the system of Labor Union participating in building up CSR;the second is to enhance Labor Union’s participation into building-up and management of CSR;the third is to give play of government in managing and guiding.

  3. Aesthetic Play

    DEFF Research Database (Denmark)

    Bang, Jytte Susanne

    2012-01-01

    The present article explores the role of music-related artefacts and technologies in children’s lives. More specifically, it analyzes how four 10- to 11-year old girls use CDs and DVD games in their music-play activities and which developmental themes and potentials may accrue from such activities...... to the children’s complex life-worlds. Further, this leads to an analysis of music-play activities as play with an art-form (music), which includes aesthetic dimensions and gives the music-play activities its character of being aesthetic play. Following Lev Vygotsky’s insight that art is a way of building life...

  4. An importance of the muscular imbalance in the context of functional disorders of the spine

    OpenAIRE

    JOZOVÁ, Kateřina

    2010-01-01

    ABSTRACT A topic of my thesis is an importance of the muscular imbalance in the context of functional disorders of the spine. The topic has been very up-to-date, because a large proportion of the population suffers from vertebral disorders of functional nature, which are just caused by muscular imbalances. A goal of the first part of the thesis was a theoretic analysis of the problem of muscular imbalances and functional disorders of the spine. A content of that chapter is an introduction to ...

  5. Skin Barrier Function and Its Importance at the Start of the Atopic March

    Science.gov (United States)

    Hogan, Mary Beth; Peele, Kathy; Wilson, Nevin W.

    2012-01-01

    Atopic dermatitis can be due to a variety of causes from nonatopic triggers to food allergy. Control of egress of water and protection from ingress of irritants and allergens are key components of cutaneous barrier function. Current research suggests that a degraded barrier function of the skin allows the immune system inappropriate access to environmental allergens. Epidermal aeroallergen exposure may allow sensitization to allergen possibly initiating the atopic march. Further research into connections between epidermal barrier function and possible allergen sensitization will be important to undertake. Future clinical trials focused on skin barrier protection may be of value as a possible intervention in prevention of the initiation of the atopic march. PMID:22619686

  6. Playful Membership

    DEFF Research Database (Denmark)

    Åkerstrøm Andersen, Niels; Pors, Justine Grønbæk

    2014-01-01

    This article studies the implications of current attempts by organizations to adapt to a world of constant change by introducing the notion of playful organizational membership. To this end we conduct a brief semantic history of organizational play and argue that when organizations play, employees...... are expected to engage in playful exploration of alternative selves. Drawing on Niklas Luhmann's theory of time and decision-making and Gregory Bateson's theory of play, the article analyses three empirical examples of how games play with conceptions of time. We explore how games represent an organizational...... desire to reach out - not just to the future - but to futures beyond the future presently imaginable. The article concludes that playful membership is membership through which employees are expected to develop a surplus of potential identities and continuously cross boundaries between real and virtual...

  7. Effective Boolean dynamics analysis to identify functionally important genes in large-scale signaling networks.

    Science.gov (United States)

    Trinh, Hung-Cuong; Kwon, Yung-Keun

    2015-11-01

    Efficiently identifying functionally important genes in order to understand the minimal requirements of normal cellular development is challenging. To this end, a variety of structural measures have been proposed and their effectiveness has been investigated in recent literature; however, few studies have shown the effectiveness of dynamics-based measures. This led us to investigate a dynamic measure to identify functionally important genes, and the effectiveness of which was verified through application on two large-scale human signaling networks. We specifically consider Boolean sensitivity-based dynamics against an update-rule perturbation (BSU) as a dynamic measure. Through investigations on two large-scale human signaling networks, we found that genes with relatively high BSU values show slower evolutionary rate and higher proportions of essential genes and drug targets than other genes. Gene-ontology analysis showed clear differences between the former and latter groups of genes. Furthermore, we compare the identification accuracies of essential genes and drug targets via BSU and five well-known structural measures. Although BSU did not always show the best performance, it effectively identified the putative set of genes, which is significantly different from the results obtained via the structural measures. Most interestingly, BSU showed the highest synergy effect in identifying the functionally important genes in conjunction with other measures. Our results imply that Boolean-sensitive dynamics can be used as a measure to effectively identify functionally important genes in signaling networks.

  8. Estimating the Importance of Differential Item Functioning. Program Statistics Research Technical Report No. 95-3.

    Science.gov (United States)

    Rudas, Tamas; Zwick, Rebecca

    A method is proposed to assess the importance of differential item functioning (DIF) by estimating the largest possible fraction of the population in which DIF does not occur, or equivalently, the smallest possible portion of the population in which DIF may occur. The approach is based on latent class (C. C. Clogg, 1981) or mixture concepts, and…

  9. Functional β-adrenoceptors are important for early muscle regeneration in mice through effects on myoblast proliferation and differentiation.

    Directory of Open Access Journals (Sweden)

    Jarrod E Church

    Full Text Available Muscles can be injured in different ways and the trauma and subsequent loss of function and physical capacity can impact significantly on the lives of patients through physical impairments and compromised quality of life. The relative success of muscle repair after injury will largely determine the extent of functional recovery. Unfortunately, regenerative processes are often slow and incomplete, and so developing novel strategies to enhance muscle regeneration is important. While the capacity to enhance muscle repair by stimulating β2-adrenoceptors (β-ARs using β2-AR agonists (β2-agonists has been demonstrated previously, the exact role β-ARs play in regulating the regenerative process remains unclear. To investigate β-AR-mediated signaling in muscle regeneration after myotoxic damage, we examined the regenerative capacity of tibialis anterior and extensor digitorum longus muscles from mice lacking either β1-AR (β1-KO and/or β2-ARs (β2-KO, testing the hypothesis that muscles from mice lacking the β2-AR would exhibit impaired functional regeneration after damage compared with muscles from β1-KO or β1/β2-AR null (β1/β2-KO KO mice. At 7 days post-injury, regenerating muscles from β1/β2-KO mice produced less force than those of controls but muscles from β1-KO or β2-KO mice did not exhibit any delay in functional restoration. Compared with controls, β1/β2-KO mice exhibited an enhanced inflammatory response to injury, which delayed early muscle regeneration, but an enhanced myoblast proliferation later during regeneration ensured a similar functional recovery (to controls by 14 days post-injury. This apparent redundancy in the β-AR signaling pathway was unexpected and may have important implications for manipulating β-AR signaling to improve the rate, extent and efficacy of muscle regeneration to enhance functional recovery after injury.

  10. Actin polymerization negatively regulates p53 function by impairing its nuclear import in response to DNA damage.

    Directory of Open Access Journals (Sweden)

    Ling Wang

    Full Text Available Actin, one of the most evolutionarily conservative proteins in eukaryotes, is distributed both in the cytoplasm and the nucleus, and its dynamics plays important roles in numerous cellular processes. Previous evidence has shown that actin interacts with p53 and this interaction increases in the process of p53 responding to DNA damage, but the physiological significance of their interaction remains elusive. Here, we show that DNA damage induces both actin polymerization and p53 accumulation. To further understand the implication of actin polymerization in p53 function, cells were treated with actin aggregation agent. We find that the protein level of p53 decrease. The change in p53 is a consequence of the polymeric actin anchoring p53 in the cytoplasm, thus impairing p53 nuclear import. Analysis of phosphorylation and ubiquitination of p53 reveals that actin polymerization promotes the p53 phosphorylation at Ser315 and reduces the stabilization of p53 by recruiting Aurora kinase A. Taken together, our results suggest that the actin polymerization serves as a negative modulator leading to the impairment of nuclear import and destabilization of p53. On the basis of our results, we propose that actin polymerization might be a factor participating in the process of orchestrating p53 function in response to DNA damage.

  11. Phylogenetic Gaussian process model for the inference of functionally important regions in protein tertiary structures.

    Science.gov (United States)

    Huang, Yi-Fei; Golding, G Brian

    2014-01-01

    A critical question in biology is the identification of functionally important amino acid sites in proteins. Because functionally important sites are under stronger purifying selection, site-specific substitution rates tend to be lower than usual at these sites. A large number of phylogenetic models have been developed to estimate site-specific substitution rates in proteins and the extraordinarily low substitution rates have been used as evidence of function. Most of the existing tools, e.g. Rate4Site, assume that site-specific substitution rates are independent across sites. However, site-specific substitution rates may be strongly correlated in the protein tertiary structure, since functionally important sites tend to be clustered together to form functional patches. We have developed a new model, GP4Rate, which incorporates the Gaussian process model with the standard phylogenetic model to identify slowly evolved regions in protein tertiary structures. GP4Rate uses the Gaussian process to define a nonparametric prior distribution of site-specific substitution rates, which naturally captures the spatial correlation of substitution rates. Simulations suggest that GP4Rate can potentially estimate site-specific substitution rates with a much higher accuracy than Rate4Site and tends to report slowly evolved regions rather than individual sites. In addition, GP4Rate can estimate the strength of the spatial correlation of substitution rates from the data. By applying GP4Rate to a set of mammalian B7-1 genes, we found a highly conserved region which coincides with experimental evidence. GP4Rate may be a useful tool for the in silico prediction of functionally important regions in the proteins with known structures.

  12. Automatic determination of important mode-mode correlations in many-mode vibrational wave functions.

    Science.gov (United States)

    König, Carolin; Christiansen, Ove

    2015-04-14

    We introduce new automatic procedures for parameterizing vibrational coupled cluster (VCC) and vibrational configuration interaction wave functions. Importance measures for individual mode combinations in the wave function are derived based on upper bounds to Hamiltonian matrix elements and/or the size of perturbative corrections derived in the framework of VCC. With a threshold, this enables an automatic, system-adapted way of choosing which mode-mode correlations are explicitly parameterized in the many-mode wave function. The effect of different importance measures and thresholds is investigated for zero-point energies and infrared spectra for formaldehyde and furan. Furthermore, the direct link between important mode-mode correlations and coordinates is illustrated employing water clusters as examples: Using optimized coordinates, a larger number of mode combinations can be neglected in the correlated many-mode vibrational wave function than with normal coordinates for the same accuracy. Moreover, the fraction of important mode-mode correlations compared to the total number of correlations decreases with system size. This underlines the potential gain in efficiency when using optimized coordinates in combination with a flexible scheme for choosing the mode-mode correlations included in the parameterization of the correlated many-mode vibrational wave function. All in all, it is found that the introduced schemes for parameterizing correlated many-mode vibrational wave functions lead to at least as systematic and accurate calculations as those using more standard and straightforward excitation level definitions. This new way of defining approximate calculations offers potential for future calculations on larger systems.

  13. Playful Literacy

    DEFF Research Database (Denmark)

    Froes, Isabel

    2017-01-01

    these practices, which compose the taxonomy of tablet play. My contribution lies in identifying and proposing a series of theoretical concepts that complement recent theories related to play and digital literacy studies. The data collected through observations informed some noteworthy aspects, including how...... with tablets’ physical and digital affordances shape children’s digital play. This thesis presents how young children’s current practices when playing with tablets inform digital experiences in Denmark and Japan. Through an interdisciplinary lens and a grounded theory approach, I have identified and mapped...... vocabulary in children’s digital play experiences. These early digital experiences set the rules for the playgrounds and assert digital tablets as twenty-first-century toys, shaping young children’s playful literacy....

  14. Recurrent use of evolutionary importance for functional annotation of proteins based on local structural similarity.

    Science.gov (United States)

    Kristensen, David M; Chen, Brian Y; Fofanov, Viacheslav Y; Ward, R Matthew; Lisewski, Andreas Martin; Kimmel, Marek; Kavraki, Lydia E; Lichtarge, Olivier

    2006-06-01

    The annotation of protein function has not kept pace with the exponential growth of raw sequence and structure data. An emerging solution to this problem is to identify 3D motifs or templates in protein structures that are necessary and sufficient determinants of function. Here, we demonstrate the recurrent use of evolutionary trace information to construct such 3D templates for enzymes, search for them in other structures, and distinguish true from spurious matches. Serine protease templates built from evolutionarily important residues distinguish between proteases and other proteins nearly as well as the classic Ser-His-Asp catalytic triad. In 53 enzymes spanning 33 distinct functions, an automated pipeline identifies functionally related proteins with an average positive predictive power of 62%, including correct matches to proteins with the same function but with low sequence identity (the average identity for some templates is only 17%). Although these template building, searching, and match classification strategies are not yet optimized, their sequential implementation demonstrates a functional annotation pipeline which does not require experimental information, but only local molecular mimicry among a small number of evolutionarily important residues.

  15. Frequency band-importance functions for auditory and auditory-visual speech recognition

    Science.gov (United States)

    Grant, Ken W.

    2005-04-01

    In many everyday listening environments, speech communication involves the integration of both acoustic and visual speech cues. This is especially true in noisy and reverberant environments where the speech signal is highly degraded, or when the listener has a hearing impairment. Understanding the mechanisms involved in auditory-visual integration is a primary interest of this work. Of particular interest is whether listeners are able to allocate their attention to various frequency regions of the speech signal differently under auditory-visual conditions and auditory-alone conditions. For auditory speech recognition, the most important frequency regions tend to be around 1500-3000 Hz, corresponding roughly to important acoustic cues for place of articulation. The purpose of this study is to determine the most important frequency region under auditory-visual speech conditions. Frequency band-importance functions for auditory and auditory-visual conditions were obtained by having subjects identify speech tokens under conditions where the speech-to-noise ratio of different parts of the speech spectrum is independently and randomly varied on every trial. Point biserial correlations were computed for each separate spectral region and the normalized correlations are interpreted as weights indicating the importance of each region. Relations among frequency-importance functions for auditory and auditory-visual conditions will be discussed.

  16. Playful Interaction

    DEFF Research Database (Denmark)

    2003-01-01

    The video Playful Interaction describes a future architectural office, and envisions ideas and concepts for playful interactions between people, materials and appliances in a pervasive and augmented working environment. The video both describes existing developments, technologies and designs...... as well as ideas not yet implemented such as playful modes of interaction with an augmented ball. Playful Interaction has been used as a hybrid of a vision video and a video prototype (1). Externally the video has been used to visualising our new ideas, and internally the video has also worked to inspire...

  17. Mediatized play

    DEFF Research Database (Denmark)

    Johansen, Stine Liv

    Children’s play must nowadays be understood as a mediatized field in society and culture. Media – understood in a very broad sense - holds severe explanatory power in describing and understanding the practice of play, since play happens both with, through and inspired by media of different sorts....... In this presentation the case of ‘playing soccer’ will be outlined through its different mediated manifestations, including soccer games and programs on TV, computer games, magazines, books, YouTube videos and soccer trading cards....

  18. Functions of synapsins in corticothalamic facilitation: important roles of synapsin I.

    Science.gov (United States)

    Nikolaev, Maxim; Heggelund, Paul

    2015-10-01

    The synaptic vesicle associated proteins synapsin I and synapsin II have important functions in synaptic short-term plasticity. We investigated their functions in cortical facilitatory feedback to neurons in dorsal lateral geniculate nucleus (dLGN), feedback that has important functions in state-dependent regulation of thalamic transmission of visual input to cortex. We compared results from normal wild-type (WT) mice and synapsin knockout (KO) mice in several types of synaptic plasticity, and found clear differences between the responses of neurons in the synapsin I KO and the WT, but no significant differences between the synapsin II KO and the WT. These results are in contrast to the important role of synapsin II previously demonstrated in similar types of synaptic plasticity in other brain regions, indicating that the synapsins can have different roles in similar types of STP in different parts of the brain. The synaptic vesicle associated proteins synapsin I (SynI) and synapsin II (SynII) have important functions in several types of synaptic short-term plasticity in the brain, but their separate functions in different types of synapses are not well known. We investigated possible distinct functions of the two synapsins in synaptic short-term plasticity at corticothalamic synapses on relay neurons in the dorsal lateral geniculate nucleus. These synapses provide excitatory feedback from visual cortex to the relay cells, feedback that can facilitate transmission of signals from retina to cortex. We compared results from normal wild-type (WT), SynI knockout (KO) and SynII KO mice, in three types of synaptic plasticity mainly linked to presynaptic mechanism. In SynI KO mice, paired-pulse stimulation elicited increased facilitation at short interpulse intervals compared to the WT. Pulse-train stimulation elicited weaker facilitation than in the WT, and also post-tetanic potentiation was weaker in SynI KO than in the WT. Between SynII KO and the WT we found no

  19. Play practices and play moods

    DEFF Research Database (Denmark)

    Karoff, Helle Skovbjerg

    2013-01-01

    The aim of this article is to develop a view of play as a relation between play practices and play moods based on an empirical study of children's everyday life and by using Bateson's term of ‘framing’ [(1955/2001). In Steps to an ecology of mind (pp. 75–80). Chicago: University of Chicago Press......], Schmidt's notion of ‘commonness’ [(2005). Om respekten. København: Danmarks Pædagogiske Universitets Forlag; (2011). On respect. Copenhagen: Danish School of Education University Press] and Heidegger's term ‘mood’ [(1938/1996). Time and being. Cornwall: Wiley-Blackwell.]. Play mood is a state of being...... in which we are open and ready, both to others and their production of meaning and to new opportunities for producing meaning. This play mood is created when we engage with the world during play practices. The article points out four types of play moods – devotion, intensity, tension and euphorica – which...

  20. Does constructive neutral evolution play an important role in the origin of cellular complexity? Making sense of the origins and uses of biological complexity

    NARCIS (Netherlands)

    D. Speijer

    2011-01-01

    Recently, constructive neutral evolution has been touted as an important concept for the understanding of the emergence of cellular complexity. It has been invoked to help explain the development and retention of, amongst others, RNA splicing, RNA editing and ribosomal and mitochondrial respiratory

  1. GhDET2,a Steroid 5alpha-reductase,Plays an Important Role in Cotton Fiber Cell Initiation and Elongation

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Cotton(Gossypium hirsutum L.) fibers,one of the most important natural raw materials for the textile industry,are highly elongated trichomes from epidermal cells of cotton ovules.Among the longest plant cells ever characterized,cotton fiber is an ideal system for studying plant cell elongation.

  2. Executive function is an important consideration for coping strategy use in people with multiple sclerosis.

    Science.gov (United States)

    Grech, Lisa B; Kiropoulos, Litza A; Kirby, Katherine M; Butler, Ernest; Paine, Mark; Hester, Robert

    2017-10-01

    Executive function deficits are prevalent in people with multiple sclerosis (PwMS), and PwMS use less adaptive coping than healthy controls. This cross-sectional study assessed whether there is a relationship between executive function and coping in PwMS. One hundred and seven participants with relapsing remitting or secondary progressive MS (n = 83 and 24, respectively; age M = 48.8 ± 11.1 years) completed measures of coping and executive function. A positive relationship was found between verbal fluency and use of active, emotional, and instrumental social support coping, and total executive function and substance abuse coping. There was a negative relationship between coping strategies and core (social support, acceptance, religion, restraint, and total coping), higher order (denial and humor), and total executive function indices (acceptance, religion, behavioral disengagement, denial, and total coping). These directional differences provide support for the importance of specific executive functions in coping strategy utilization. Understanding these relationships will assist psychologists and neuropsychologists with patient psychoeducation, adaptive coping strategy intervention and management for PwMS with reduced executive function ability.

  3. Importance of ventricular function in the election of electro heart mode.

    Science.gov (United States)

    Nicolás-Franco, S; Rodríguez-González, F J; Nicolás-Boluda, A; Sánchez-Martos, A

    2015-04-01

    The integration of the ventricular function is essential when making decisions over a patient subjected to cardiac electrostimulation in order to understand the structure followed in the new cardiac stimulation and resynchronising therapy guides. To support the importance of ventricular function in cardiac electrostimulation it is important to know: (i)the deleterious effect of stimulation on the right ventricle apex; (ii)the effect over the left ventricular function produced by complete blockage of the left branch, and (iii)left ventricular disfunction as arrythmogenic substrate. When it comes to decide what type of cardiac electrostimualtion to apply we will know: the percentage of ventricular stimulation needed and its ventricular function. A normal ventricular function will enable electrostimulation from the right ventricle apex or alternative site. On the contrary, if this value is lower than 50% the most recommended electrostimulation is cardiac resynchronisation (CRT-P), which will be accompanied by defibrillation (CRT-D) if FEVI is lower than 35%. Copyright © 2014 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.

  4. Spectral Data Captures Important Variability Between and Among Species and Functional Types

    Science.gov (United States)

    Townsend, P. A.; Serbin, S. P.; Kingdon, C.; Singh, A.; Couture, J. J.; Gamon, J. A.

    2013-12-01

    Narrowband spectral data in the visible, near and shortwave infrared (400-2500 nm) are being used increasingly in plant ecology to characterize the biochemical, physiological and water status of vegetation, as well as community composition. In particular, spectroscopic data have recently received considerable attention for their capacity to discriminate plants according to functional properties or 'optical types.' Such measurements can be acquired from airborne/satellite remote sensing imagery or field spectrometers and are commonly used to directly estimate or infer properties important to photosynthesis, carbon and water fluxes, nutrient dynamics, phenology, and disturbance. Spectral data therefore represent proxies for measurements that are otherwise time consuming or expensive to make, and - more importantly - provide the opportunity to characterize the spatial and temporal variability of taxonomic or functional groups. We have found that spectral variation within species and functional types can in fact exceed the variation between types. As such, we recommend that the traditional quantification of characteristics defining species and/or functional types must be modified to include the range of variability in those properties. We provide four examples of the importance of spectral data for describing within-species/functional type variation. First, within temperate forests, the spectral properties of foliage vary considerably with canopy position. This variability is strongly related to differences in specific leaf area between shade- and sun-lit leaves, and the resulting differences among leaves in strategies for light harvesting, photosynthesis, and leaf longevity. These results point to the need to better characterize leaf optical properties throughout a canopy, rather than basing the characterization of ecosystem functioning on only the sunlit portion of the canopy crown. Second, we show considerable differences in optical properties of foliage from

  5. The Photographic History of Greenland’s Glaciers – and how the historical data plays an important role in today’s glacier research

    DEFF Research Database (Denmark)

    Bjørk, Anders Anker; Kjeldsen, Kristian Kjellerup; Korsgaard, Niels Jákup

    As the Greenland Ice Sheet and Greenland's glaciers are continuing to loss mass at high rates, knowledge of their past response to climatic changes is ever important. By harvesting the archives for images, both terrestrial and airborne, we are able to expand the record of glacier observation...... by several decades, thus supplying crucial knowledge on glacier behavior to important climatic transitions such as the end of the Little Ice Age and the early 20th Century warming. Here we show how a large collection of historical aerial images portray the glacial response to the Little Ice Age deglaciation...... in Greenland and document frontal change throughout the 20th Century. A detailed story of the LIA-deglaciation is told by supplementing with terrestrial photos that capture the onset of retreat and high resolution aerial images that portray geomorphological evidence of the Little Ice Age maximum extent...

  6. The complex and important cellular and metabolic functions of saturated fatty acids.

    Science.gov (United States)

    Legrand, Philippe; Rioux, Vincent

    2010-10-01

    This review summarizes recent findings on the metabolism and biological functions of saturated fatty acids (SFA). Some of these findings show that SFA may have important and specific roles in the cells. Elucidated biochemical mechanisms like protein acylation (N-myristoylation, S-palmitoylation) and regulation of gene transcription are presented. In terms of physiology, SFA are involved for instance in lipogenesis, fat deposition, polyunsaturated fatty acids bioavailability and apoptosis. The variety of their functions demonstrates that SFA should no longer be considered as a single group.

  7. Physical Function Assessment of a Mayan Population Living With Osteoarthritis: The Importance of Considering Different Aspects of Functioning

    Directory of Open Access Journals (Sweden)

    Adalberto Loyola-Sanchez

    2017-06-01

    Full Text Available Objectives: To assess the physical function of people living with osteoarthritis in a Maya-Yucateco rural community from 3 perspectives and explore factors associated with the presence of disability. Design: Physical function and social, physical, psychological, and behavioral factors were evaluated in all adults detected with hand, hip, and/or knee osteoarthritis (n = 144 through a Community-Oriented Program for the Control of Rheumatic Diseases–based census in the Mayan community of Chankom, Yucatán. All cases fulfilled the American College of Rheumatology criteria. Physical function was assessed from 3 perspectives: hypothetical or “what people think they can do” (Health Assessment Questionnaire-Disability Index [HAQ-DI], experimental or “what people could do in standardized conditions” (6-minute walk test [6MWT] + the Functional Dexterity Test and enacted or “what people actually do” (personal care, work, and leisure activities’ self-report. Results: About 80% of participants reported “mild” disability (HAQ-DI ≤ 1 in the hypothetical function perspective, whereas average experimental function scores were low (6MWT: 206 m, Functional Dexterity Test: 64 seconds, and 78% of participants reported problems with enacted function (ie, work. Pain was significantly associated with disability in the hypothetical perspective (odds ratio [OR] = 3 [95% confidence interval [CI]: 1-4]; levels of wealth (β = 5 [95% CI: 1-9] and muscle strength (β = 54 [95% CI: 20-87] were significantly associated with functioning in the experimental perspective; and lower levels of self-efficacy (OR = 12 [95% CI: 6-27] and physical activity (OR = 12 [95% CI: 6-27] were significantly associated with work disability in the enacted function perspective. Conclusions: People living with osteoarthritis in Chankom show important issues when assessing physical function at the experimental and enacted perspectives, which

  8. RSC Chromatin-Remodeling Complex Is Important for Mitochondrial Function in Saccharomyces cerevisiae.

    Science.gov (United States)

    Imamura, Yuko; Yu, Feifei; Nakamura, Misaki; Chihara, Yuhki; Okane, Kyo; Sato, Masahiro; Kanai, Muneyoshi; Hamada, Ryoko; Ueno, Masaru; Yukawa, Masashi; Tsuchiya, Eiko

    2015-01-01

    RSC (Remodel the Structure of Chromatin) is an ATP-dependent chromatin remodeling complex essential for the growth of Saccharomyces cerevisiae. RSC exists as two distinct isoforms that share core subunits including the ATPase subunit Nps1/Sth1 but contain either Rsc1or Rsc2. Using the synthetic genetic array (SGA) of the non-essential null mutation method, we screened for mutations exhibiting synthetic growth defects in combination with the temperature-sensitive mutant, nps1-105, and found connections between mitochondrial function and RSC. rsc mutants, including rsc1Δ, rsc2Δ, and nps1-13, another temperature-sensitive nps1 mutant, exhibited defective respiratory growth; in addition, rsc2Δ and nps1-13 contained aggregated mitochondria. The rsc2Δ phenotypes were relieved by RSC1 overexpression, indicating that the isoforms play a redundant role in respiratory growth. Genome-wide expression analysis in nps1-13 under respiratory conditions suggested that RSC regulates the transcription of some target genes of the HAP complex, a transcriptional activator of respiratory gene expression. Nps1 physically interacted with Hap4, the transcriptional activator moiety of the HAP complex, and overexpression of HAP4 alleviated respiratory defects in nps1-13, suggesting that RSC plays pivotal roles in mitochondrial gene expression and shares a set of target genes with the HAP complex.

  9. Graphene Oxide Catalyzed C-H Bond Activation: The Importance Oxygen Functional Groups for Biaryl Construction

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Yongjun; Tang, Pei; Zhou, Hu; Zhang, Wei; Yang, Hanjun; Yan, Ning; Hu, Gang; Mei, Donghai; Wang, Jianguo; Ma, Ding

    2016-02-24

    A heterogeneous, inexpensive and environment-friendly carbon catalytic system was developed for the C-H bond arylation of benzene resulting in the subsequent formation of biaryl compounds. The oxygen-containing groups on these graphene oxide sheets play an essential role in the observed catalytic activity. The catalytic results of model compounds and DFT calculations show that these functional groups promote this reaction by stabilization and activation of K ions at the same time of facilitating the leaving of I. And further mechanisms studies show that it is the charge induced capabilities of oxygen groups connected to specific carbon skeleton together with the giant π-reaction platform provided by the π-domain of graphene that played the vital roles in the observed excellent catalytic activity. D. Mei acknowledges the support from the US Department of Energy (DOE), Office of Science, Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences & Biosciences. Pacific Northwest National Laboratory (PNNL) is a multiprogram national laboratory operated for DOE by Battelle. Computing time was granted by the grand challenge of computational catalysis of the William R. Wiley Environmental Molecular Sciences Laboratory.

  10. IL-10 plays an important role in the control of inflammation but not in the bacterial burden in S. epidermidis CNS catheter infection.

    Science.gov (United States)

    Gutierrez-Murgas, Yenis M; Skar, Gwenn; Ramirez, Danielle; Beaver, Matthew; Snowden, Jessica N

    2016-10-13

    Shunt infection is a frequent and serious complication in the surgical treatment in hydrocephalus. Previous studies have shown an attenuated immune response to these biofilm-mediated infections. We proposed that IL-10 reduces the inflammatory response to Staphylococcus epidermidis (S. epidermidis) CNS catheter infection. In this study, a murine model of catheter-associated S. epidermidis biofilm infection in the CNS was generated based on a well-established similar model for S. aureus. The catheters were pre-coated with a clinically derived biofilm-forming strain of S. epidermidis (strain 1457) which were then stereotactically implanted into the lateral left ventricle of 8-week-old C57BL/6 and IL-10 knockout (IL-10 knockout) mice. Bacterial titers as well as cytokine and chemokine levels were measured at days 3, 5, 7, and 10 in mice implanted with sterile and S. epidermidis-coated catheters. Cultures demonstrated a catheter-associated and parenchymal infection that persisted through 10 days following infection. Cytokine analysis of the tissue surrounding the catheters revealed greater levels of IL-10, an anti-inflammatory cytokine, in the infected group compared to the sterile. In IL-10 KO mice, we noted no change in bacterial burdens, showing that IL-10 is not needed to control the infection in a CNS catheter infection model. However, IL-10 KO mice had increased levels of pro-inflammatory mediators in the tissues immediately adjacent to the infected catheter, as well as an increase in weight loss. Together our results indicate that IL-10 plays a key role in regulating the inflammatory response to CNS catheter infection but not in control of bacterial burdens. Therefore, IL-10 may be a useful therapeutic target for immune modulation in CNS catheter infection but this should be used in conjunction with antibiotic therapy for bacterial eradication.

  11. Transcription factor σB plays an important role in the production of extracellular membrane-derived vesicles in Listeria monocytogenes.

    Directory of Open Access Journals (Sweden)

    Jung Hwa Lee

    Full Text Available Gram-negative bacteria produce extracellular outer membrane vesicles (OMVs that interact with host cells. Unlike Gram-negative bacteria, less is known about the production and role of extracellular membrane vesicles (MVs in Gram-positive bacteria. The food-borne pathogen Listeria monocytogenes can survive under extreme environmental and energy stress conditions and the transcription factor σ(B is involved in this survival ability. Here, we first determined the production of MVs from L. monocytogenes and evaluated whether general stress transcription factor σ(B affected production of MVs in L. monocytogenes. L. monocytogenes secreted MVs during in vitro broth culture. The wild-type strain actively produced MVs approximately nine times more and also produced more intact shapes of MVs than those of the isogenic ΔsigB mutant. A proteomic analysis showed that 130 and 89 MV proteins were identified in the wild-type and ΔsigB mutant strains, respectively. Wild-type strain-derived MVs contained proteins regulated by σ(B such as transporters (OpuCA and OpuCC, stress response (Kat, metabolism (LacD, translation (InfC, and cell division protein (FtsZ. Gene Ontology (GO enrichment analysis showed that wild-type-derived MV proteins corresponded to several GO terms, including response to stress (heat, acid, and bile resistance and extracellular polysaccharide biosynthetic process, but not the ΔsigB mutant. Internalin B (InlB was almost three times more contained in MVs derived from the wild-type strain than in MVs derived from the ΔsigB mutant. Taken together, these results suggest that σ(B plays a pivotal role in the production of MVs and protein profiles contained in MVs. L. monocytogenes MVs may contribute to host infection and survival ability under various stressful conditions.

  12. Prediction of enzyme function based on 3D templates of evolutionarily important amino acids

    Directory of Open Access Journals (Sweden)

    Chen Brian Y

    2008-01-01

    Full Text Available Abstract Background Structural genomics projects such as the Protein Structure Initiative (PSI yield many new structures, but often these have no known molecular functions. One approach to recover this information is to use 3D templates – structure-function motifs that consist of a few functionally critical amino acids and may suggest functional similarity when geometrically matched to other structures. Since experimentally determined functional sites are not common enough to define 3D templates on a large scale, this work tests a computational strategy to select relevant residues for 3D templates. Results Based on evolutionary information and heuristics, an Evolutionary Trace Annotation (ETA pipeline built templates for 98 enzymes, half taken from the PSI, and sought matches in a non-redundant structure database. On average each template matched 2.7 distinct proteins, of which 2.0 share the first three Enzyme Commission digits as the template's enzyme of origin. In many cases (61% a single most likely function could be predicted as the annotation with the most matches, and in these cases such a plurality vote identified the correct function with 87% accuracy. ETA was also found to be complementary to sequence homology-based annotations. When matches are required to both geometrically match the 3D template and to be sequence homologs found by BLAST or PSI-BLAST, the annotation accuracy is greater than either method alone, especially in the region of lower sequence identity where homology-based annotations are least reliable. Conclusion These data suggest that knowledge of evolutionarily important residues improves functional annotation among distant enzyme homologs. Since, unlike other 3D template approaches, the ETA method bypasses the need for experimental knowledge of the catalytic mechanism, it should prove a useful, large scale, and general adjunct to combine with other methods to decipher protein function in the structural proteome.

  13. Two people playing together: some thoughts on play, playing, and playfulness in psychoanalytic work.

    Science.gov (United States)

    Vliegen, Nicole

    2009-01-01

    Children's play and the playfulness of adolescents and adults are important indicators of personal growth and development. When a child is not able to play, or an adolescent/adult is not able to be playful with thoughts and ideas, psychotherapy can help to find a more playful and creative stance. Elaborating Winnicott's (1968, p. 591) statement that "psychotherapy has to do with two people playing together," three perspectives on play in psychotherapy are discussed. In the first point of view, the child gets in touch with and can work through aspects of his or her inner world, while playing in the presence of the therapist. The power of play is then rooted in the playful communication with the self In a second perspective, in play the child is communicating aspects of his or her inner world to the therapist as a significant other. In a third view, in "playing together" child and therapist are coconstructing new meanings. These three perspectives on play are valid at different moments of a therapy process or for different children, depending on the complex vicissitudes of the child's constitution, life experiences, development, and psychic structure. Concerning these three perspectives, a parallel can be drawn between the therapist's attitude toward the child's play and the way the therapist responds to the verbal play of an adolescent or adult. We illustrate this with the case of Jacob, a late adolescent hardly able to play with ideas.

  14. Toddlers: Learning by Playing

    Science.gov (United States)

    ... Feeding Your 1- to 2-Year-Old Toddlers: Learning by Playing KidsHealth > For Parents > Toddlers: Learning by Playing Print A A A What's in ... child's play, but toddlers are hard at work learning important physical skills as they gain muscle control, ...

  15. Playing against the Game

    Science.gov (United States)

    Remmele, Bernd

    2017-01-01

    The paper first outlines a differentiation of play/game-motivations that include "negative" attitudes against the play/game itself like cheating or spoilsporting. This problem is of particular importance in concern of learning games because they are not "played" for themselves--at least in the first place--but due to an…

  16. Leukaemia-associated Rho guanine nucleotide exchange factor (LARG) plays an agonist specific role in platelet function through RhoA activation.

    Science.gov (United States)

    Zou, Siying; Teixeira, Alexandra M; Yin, Mingzhu; Xiang, Yaozu; Xavier-Ferrucio, Juliana; Zhang, Ping-Xia; Hwa, John; Min, Wang; Krause, Diane S

    2016-08-30

    Leukemia-Associated RhoGEF (LARG) is highly expressed in platelets, which are essential for maintaining normal haemostasis. We studied the function of LARG in murine and human megakaryocytes and platelets with Larg knockout (KO), shRNA-mediated knockdown and small molecule-mediated inhibition. We found that LARG is important for human, but not murine, megakaryocyte maturation. Larg KO mice exhibit macrothrombocytopenia, internal bleeding in the ovaries and prolonged bleeding times. KO platelets have impaired aggregation, α-granule release and integrin α2bβ3 activation in response to thrombin and thromboxane, but not to ADP. The same agonist-specific reductions in platelet aggregation occur in human platelets treated with a LARG inhibitor. Larg KO platelets have reduced RhoA activation and myosin light chain phosphorylation, suggesting that Larg plays an agonist-specific role in platelet signal transduction. Using two different in vivo assays, Larg KO mice are protected from in vivo thrombus formation. Together, these results establish that LARG regulates human megakaryocyte maturation, and is critical for platelet function in both humans and mice.

  17. The complex and important cellular and metabolic functions of saturated fatty acids

    OpenAIRE

    Legrand, Philippe; Rioux, Vincent

    2010-01-01

    This review summarizes recent findings on the metabolism and biological functions of saturated fatty acids (SFA). Some of these findings show that SFA may have important and specific roles in the cells. Elucidated biochemical mechanisms like protein acylation (N-myristoylation, S-palmitoylation) and regulation of gene transcription are presented. In terms of physiology, SFA are involved for instance in lipogenesis, fat deposition, polyunsaturated fatty acids bioavailability and apoptosis. The...

  18. Inulin and Oligofructosis: a review about functional properties, prebiotic effects and importance for food industry

    OpenAIRE

    Maria Celia de Oliveira Hauly; Janaína Andréa Moscatto

    2002-01-01

    Nowadays consumers are more conscious about the relation between food and health. Therefore food industry has been looking for food that has a lot of benefits besides good flavor and appearance. Inulin and oligofructose are fructose polimers, vastly found in plants as storage carbohydrates. They present important functional for the food industry. Both inulin and oligofructose have been used as fiber bulk in food products. Differently from other fibers, they do not add flavor, allowing the foo...

  19. Proteomics of Fusarium oxysporum race 1 and race 4 reveals enzymes involved in carbohydrate metabolism and ion transport that might play important roles in banana Fusarium wilt.

    Science.gov (United States)

    Sun, Yong; Yi, Xiaoping; Peng, Ming; Zeng, Huicai; Wang, Dan; Li, Bo; Tong, Zheng; Chang, Lili; Jin, Xiang; Wang, Xuchu

    2014-01-01

    Banana Fusarium wilt is a soil-spread fungal disease caused by Fusarium oxysporum. In China, the main virulence fungi in banana are F. oxysporum race 1 (F1, weak virulence) and race 4 (F4, strong virulence). To date, no proteomic analyses have compared the two races, but the difference in virulence between F1 and F4 might result from their differentially expressed proteins. Here we report the first comparative proteomics of F1 and F4 cultured under various conditions, and finally identify 99 protein species, which represent 59 unique proteins. These proteins are mainly involved in carbohydrate metabolism, post-translational modification, energy production, and inorganic ion transport. Bioinformatics analysis indicated that among the 46 proteins identified from F4 were several enzymes that might be important for virulence. Reverse transcription PCR analysis of the genes for 15 of the 56 proteins revealed that their transcriptional patterns were similar to their protein expression patterns. Taken together, these data suggest that proteins involved in carbohydrate metabolism and ion transport may be important in the pathogenesis of banana Fusarium wilt. Some enzymes such as catalase-peroxidase, galactosidase and chitinase might contribute to the strong virulence of F4. Overexpression or knockout of the genes for the F4-specific proteins will help us to further understand the molecular mechanism of Fusarium-induced banana wilt.

  20. The Stable Level of Glutamine synthetase 2 Plays an Important Role in Rice Growth and in Carbon-Nitrogen Metabolic Balance.

    Science.gov (United States)

    Bao, Aili; Zhao, Zhuqing; Ding, Guangda; Shi, Lei; Xu, Fangsen; Cai, Hongmei

    2015-06-04

    Glutamine synthetase 2 (GS2) is a key enzyme involved in the ammonium metabolism in plant leaves. In our previous study, we obtained GS2-cosuppressed plants, which displayed a normal growth phenotype at the seedling stage, while at the tillering stage they showed a chlorosis phenotype. In this study, to investigate the chlorosis mechanism, we systematically analyzed the plant growth, carbon-nitrogen metabolism and gene expressions between the GS2-cosuppressed rice and wild-type plants. The results revealed that the GS2-cosuppressed plants exhibited a poor plant growth phenotype and a poor nitrogen transport ability, which led to nitrogen accumulation and a decline in the carbon/nitrogen ratio in the stems. Interestingly, there was a higher concentration of soluble proteins and a lower concentration of carbohydrates in the GS2-cosuppressed plants at the seedling stage, while a contrasting result was displayed at the tillering stage. The analysis of the metabolic profile showed a significant increase of sugars and organic acids. Additionally, gene expression patterns were different in root and leaf of GS2-cosuppressed plants between the seedling and tillering stage. These results indicated the important role of a stable level of GS2 transcription during normal rice development and the importance of the carbon-nitrogen metabolic balance in rice growth.

  1. Objective measures for predicting speech intelligibility in noisy conditions based on new band-importance functions.

    Science.gov (United States)

    Ma, Jianfen; Hu, Yi; Loizou, Philipos C

    2009-05-01

    The articulation index (AI), speech-transmission index (STI), and coherence-based intelligibility metrics have been evaluated primarily in steady-state noisy conditions and have not been tested extensively in fluctuating noise conditions. The aim of the present work is to evaluate the performance of new speech-based STI measures, modified coherence-based measures, and AI-based measures operating on short-term (30 ms) intervals in realistic noisy conditions. Much emphasis is placed on the design of new band-importance weighting functions which can be used in situations wherein speech is corrupted by fluctuating maskers. The proposed measures were evaluated with intelligibility scores obtained by normal-hearing listeners in 72 noisy conditions involving noise-suppressed speech (consonants and sentences) corrupted by four different maskers (car, babble, train, and street interferences). Of all the measures considered, the modified coherence-based measures and speech-based STI measures incorporating signal-specific band-importance functions yielded the highest correlations (r=0.89-0.94). The modified coherence measure, in particular, that only included vowel/consonant transitions and weak consonant information yielded the highest correlation (r=0.94) with sentence recognition scores. The results from this study clearly suggest that the traditional AI and STI indices could benefit from the use of the proposed signal- and segment-dependent band-importance functions.

  2. From L-dopa to dihydroxyphenylacetaldehyde: a toxic biochemical pathway plays a vital physiological function in insects.

    Directory of Open Access Journals (Sweden)

    Christopher Vavricka

    Full Text Available One protein in Aedes aegypti, classified into the aromatic amino acid decarboxylase (AAAD family based on extremely high sequence homology (∼70% with dopa decarboxylase (Ddc, was biochemically investigated. Our data revealed that this predicted AAAD protein use L-dopa as a substrate, as does Ddc, but it catalyzes the production of 3,4-dihydroxylphenylacetaldehyde (DHPAA directly from L-dopa and apparently has nothing to do with the production of any aromatic amine. The protein is therefore named DHPAA synthase. This subsequently led to the identification of the same enzyme in Drosophila melanogaster, Anopheles gambiae and Culex quinquefasciatus by an initial prediction of putative DHPAA synthase based on sequence homology and subsequent verification of DHPAA synthase identity through protein expression and activity assays. DHPAA is highly toxic because its aldehyde group readily reacts with the primary amino groups of proteins, leading to protein crosslinking and inactivation. It has previously been demonstrated by several research groups that Drosophila DHPAA synthase was expressed in tissues that produce cuticle materials and apparent defects in regions of colorless, flexible cuticular structures have been observed in its gene mutants. The presence of free amino groups in proteins, the high reactivity of DHPAA with the free amino groups, and the genetically ascertained function of the Drosophila DHPAA synthase in the formation of colorless, flexible cuticle, when taken together, suggest that mosquito and Drosophila DHPAA synthases are involved in the formation of flexible cuticle through their reactive DHPAA-mediated protein crosslinking reactions. Our data illustrate how a seemingly highly toxic pathway can serve for an important physiological function in insects.

  3. Skin Barrier Function and Its Importance at the Start of the Atopic March

    Directory of Open Access Journals (Sweden)

    Mary Beth Hogan

    2012-01-01

    Full Text Available Atopic dermatitis can be due to a variety of causes from nonatopic triggers to food allergy. Control of egress of water and protection from ingress of irritants and allergens are key components of cutaneous barrier function. Current research suggests that a degraded barrier function of the skin allows the immune system inappropriate access to environmental allergens. Epidermal aeroallergen exposure may allow sensitization to allergen possibly initiating the atopic march. Further research into connections between epidermal barrier function and possible allergen sensitization will be important to undertake. Future clinical trials focused on skin barrier protection may be of value as a possible intervention in prevention of the initiation of the atopic march.

  4. Hippocampal angiotensin II receptors play an important role in mediating the effect of voluntary exercise on learning and memory in rat.

    Science.gov (United States)

    Akhavan, Maziar M; Emami-Abarghoie, Mitra; Sadighi-Moghaddam, Bizhan; Safari, Manouchehr; Yousefi, Yasaman; Rashidy-Pour, Ali

    2008-09-26

    The beneficial effects of physical activity and exercise on brain functions such as improvement in learning and memory are well documented. The aim of this study was to examine the possible role of hippocampal angiotensin II receptors in voluntary exercise-induced enhancement of learning and memory in rat. In order to block the hippocampal angiotension II receptors, the animals received a single injection of latex microbeads for delivery of [Sar1 Thr8]-Angiotensin II into the hippocampus. The animals were exposed to five consecutive nights of exercise and then their learning and memory were tested on the Morris water maze (MWM) task using a two-trial-per-day for five consecutive days. A probe trial was performed 2 days after the last training day. Our results showed that hippocampal angiotensin II receptor blockade reversed the exercise-induced improvement in learning and memory in rat.

  5. Executive function deficits in congenital heart disease: why is intervention important?

    Science.gov (United States)

    Calderon, Johanna; Bellinger, David C

    2015-10-01

    It is widely recognised that children with congenital heart disease (CHD) are at high risk for neurodevelopmental impairments including attention deficit hyperactivity disorder and autism spectrum disorder symptoms. Executive function impairments are one of the most prominent neurodevelopmental features associated with CHD. These deficits can have widespread debilitating repercussions in children's neurocognitive, behavioural, and psycho-social development. There is a crucial gap in research regarding the efficacy of preventive or treatment strategies for these important cognitive morbidities. Executive functions are complex neurocognitive skills highly amenable to improvement. Evidence-based interventions have shown promising results in other paediatric populations, strongly suggesting that they might also benefit the growing population of children with CHD. In this review, we summarise the available data on executive function impairments in children and adolescents with CHD. We underline the important co-morbidity of executive dysfunction with other cognitive and psychiatric issues in CHD, which raises awareness of the crucial need to prevent or at least mitigate these deficits. Finally, we summarise future avenues for research in terms of interventions that may help reduce executive function impairments in youth with CHD.

  6. The Band-Importance Function for the Korean Standard Sentence Lists for Adults

    Science.gov (United States)

    Jin, In-Ki; Lee, Kyoungwon; Kim, Jinsook; Kim, Dongwook; Sohn, Junil; Lee, Kyung-Ju

    2016-01-01

    Background and Objectives The band-importance function (BIF) refers to a value characterizing the relative importance of different frequencies to speech intelligibility. The purpose of this study was to derive the BIF for the Korean standard sentence lists for adults (KS-SL-A). Subjects and Methods In this study, sentences from the KS-SL-A were used as the speech material. Twenty-six normal-hearing Korean listeners participated and intelligibility scores in 8 filters with 3 signal-to-noise ratio conditions were obtained. Based on the intelligibility score percentages, the BIF for the KS-SL-A was derived by using an established protocol. Results Band-importance weights varied across frequency bands. The most important frequency region was around 316 Hz (20.0%), and the importance of the frequency bands below the center frequency (CF) of 1,778 Hz was 59.6%. Therefore, low frequencies below the CF of 1,778 Hz were more important than high frequencies above the CF of 1,778 Hz. Conclusions The BIF for KS-SL-A could be applied towards developing a hearing aid fitting formulae for Korean listeners. PMID:27626080

  7. The importance of hydrology in restoration of bottomland hardwood wetland functions

    Science.gov (United States)

    Hunter, R.G.; Faulkner, S.P.; Gibson, K.A.

    2008-01-01

    Bottomland hardwood (BLH) forests have important biogeochemical functions and it is well known that certain structural components, including pulsed hydrology, hydric soils, and hydrophytic vegetation, enhance these functions. It is unclear, however, how functions of restored BLH wetlands compare to mature, undisturbed wetlands. We measured a suite of structural and functional attributes in replicated natural BLH wetlands (NAT), restored BLH wetlands with hydrology re-established (RWH), and restored BLH wetlands without hydrology re-established (RWOH) in this study. Trees were replanted in all restored wetlands at least four years prior to the study and those wetlands with hydrology re-established had flashboard risers placed in drainage ditches to allow seasonal surface flooding. Vegetation, soils, and selected biogeochemical functions were characterized at each site. There was a marked difference in woody vegetation among the wetlands that was due primarily to site age. There was also a difference in herbaceous vegetation among the restored sites that may have been related to differences in age or hydrology. Water table fluctuations of the RWH wetlands were comparable to those of the NAT wetlands. Thus, placing flashboard risers in existing drainage ditches, along with proper management, can produce a hydroperiod that is similar to that of a relatively undisturbed BLH. Average length of saturation within the upper 15 cm of soils was 37, 104, and 97 days for RWOH, RWH, and NAT, respectively. Soil moisture, denitrification potential, and soluble organic carbon concentrations differed among wetland sites, but soil carbon and nitrogen concentrations, heterotrophic microbial activity, and readily mineralizable carbon concentrations did not. Significant linear relationships were also found between soil moisture and heterotrophic microbial activity, readily mineralizable carbon, and soluble organic carbon. In addition, sedimentation rates were higher in NAT and RWH

  8. Does constructive neutral evolution play an important role in the origin of cellular complexity? Making sense of the origins and uses of biological complexity.

    Science.gov (United States)

    Speijer, Dave

    2011-05-01

    Recently, constructive neutral evolution has been touted as an important concept for the understanding of the emergence of cellular complexity. It has been invoked to help explain the development and retention of, amongst others, RNA splicing, RNA editing and ribosomal and mitochondrial respiratory chain complexity. The theory originated as a welcome explanation of isolated small scale cellular idiosyncrasies and as a reaction to 'overselectionism'. Here I contend, that in its extended form, it has major conceptual problems, can not explain observed patterns of complex processes, is too easily dismissive of alternative selectionist models, underestimates the creative force of complexity as such, and--if seen as a major evolutionary mechanism for all organisms--could stifle further thought regarding the evolution of highly complex biological processes. Copyright © 2011 WILEY Periodicals, Inc.

  9. F1C fimbriae play an important role in biofilm formation and intestinal colonization by the Escherichia coli commensal strain Nissle 1917.

    Science.gov (United States)

    Lasaro, Melissa A; Salinger, Nina; Zhang, Jing; Wang, Yantao; Zhong, Zhengtao; Goulian, Mark; Zhu, Jun

    2009-01-01

    Bacterial biofilm formation is thought to enhance survival in natural environments and during interaction with hosts. A robust colonizer of the human gastrointestinal tract, Escherichia coli Nissle 1917, is widely employed in probiotic therapy. In this study, we performed a genetic screen to identify genes that are involved in Nissle biofilm formation. We found that F1C fimbriae are required for biofilm formation on an inert surface. In addition, these structures are also important for adherence to epithelial cells and persistence in infant mouse colonization. The data suggest a possible connection between Nissle biofilm formation and the survival of this commensal within the host. Further study of the requirements for robust biofilm formation may improve the therapeutic efficacy of Nissle 1917.

  10. F1C Fimbriae Play an Important Role in Biofilm Formation and Intestinal Colonization by the Escherichia coli Commensal Strain Nissle 1917▿

    Science.gov (United States)

    Lasaro, Melissa A.; Salinger, Nina; Zhang, Jing; Wang, Yantao; Zhong, Zhengtao; Goulian, Mark; Zhu, Jun

    2009-01-01

    Bacterial biofilm formation is thought to enhance survival in natural environments and during interaction with hosts. A robust colonizer of the human gastrointestinal tract, Escherichia coli Nissle 1917, is widely employed in probiotic therapy. In this study, we performed a genetic screen to identify genes that are involved in Nissle biofilm formation. We found that F1C fimbriae are required for biofilm formation on an inert surface. In addition, these structures are also important for adherence to epithelial cells and persistence in infant mouse colonization. The data suggest a possible connection between Nissle biofilm formation and the survival of this commensal within the host. Further study of the requirements for robust biofilm formation may improve the therapeutic efficacy of Nissle 1917. PMID:18997018

  11. Playful Organizations

    DEFF Research Database (Denmark)

    Pors, Justine Grønbæk; Åkerstrøm Andersen, Niels

    2015-01-01

    and undecidability. With an empirical point of departure in Danish public school policy and two concrete examples of games utilised in school development, the article analyses how play is a way for organisations to simultaneously decide and also avoid making a decision, thus keeping flexibility and possibilities...... intact. In its final sections, the article discusses what happens to conditions of decision-making when organisations do not just see undecidability as a given condition, but as a limited resource indispensable for change and renewal. The article advances discussions of organisational play by exploring......This article explores how organisational play becomes a managerial tool to increase and benefit from undecidability. The article draws on Niklas Luhmann's concept of decision and on Gregory Bateson's theory of play to create a conceptual framework for analysing the relation between decision...

  12. A pericentrin-related protein homolog in Aspergillus nidulans plays important roles in nucleus positioning and cell polarity by affecting microtubule organization.

    Science.gov (United States)

    Chen, Peiying; Gao, Rongsui; Chen, Shaochun; Pu, Li; Li, Pin; Huang, Ying; Lu, Ling

    2012-12-01

    Pericentrin is a large coiled-coil protein in mammalian centrosomes that serves as a multifunctional scaffold for anchoring numerous proteins. Recent studies have linked numerous human disorders with mutated or elevated levels of pericentrin, suggesting unrecognized contributions of pericentrin-related proteins to the development of these disorders. In this study, we characterized AnPcpA, a putative homolog of pericentrin-related protein in the model filamentous fungus Aspergillus nidulans, and found that it is essential for conidial germination and hyphal development. Compared to the hyphal apex localization pattern of calmodulin (CaM), which has been identified as an interactive partner of the pericentrin homolog, GFP-AnPcpA fluorescence dots are associated mainly with nuclei, while the accumulation of CaM at the hyphal apex depends on the function of AnPcpA. In addition, the depletion of AnPcpA by an inducible alcA promoter repression results in severe growth defects and abnormal nuclear segregation. Most interestingly, in mature hyphal cells, knockdown of pericentrin was able to significantly induce changes in cell shape and cytoskeletal remodeling; it resulted in some enlarged compartments with condensed nuclei and anucleate small compartments as well. Moreover, defects in AnPcpA significantly disrupted the microtubule organization and nucleation, suggesting that AnPcpA may affect nucleus positioning by influencing microtubule organization.

  13. Cross-sectional study showed psychosocial variables, gender and family involvement played an important role in an adolescent weight management programme.

    Science.gov (United States)

    Prioste, Ana; Fonseca, Helena; Sousa, Pedro; Gaspar, Pedro; Machado, Maria do Céu

    2017-01-01

    This study aimed to investigate the psychosocial gains perceived by overweight adolescents attending a 12-week weight management programme and to analyse gender-specific differences. A quantitative cross-sectional study was conducted with a sample of 70 overweight adolescents aged between 12 and 18 (52.9% girls), evaluated at baseline and at week 12 using anthropometric measurements and self-reported questionnaires. We analysed gender-specific differences related to body self-esteem, social life, relationships with their family, physical comfort, health responsibility, perceived benefits of the intervention, self-efficacy and adherence. We further investigated whether the variables at week 12 would predict changes in their body mass index. While weight had a greater impact on the body self-esteem of girls, both at baseline and week 12, boys reported higher self-efficacy and adherence as well as a greater perception of the benefits of the intervention at week 12. The body mass index change was positively associated with body self-esteem, relationships within the family and self-efficacy and adherence. Gender specifics and the role of psychosocial variables must be taken into account during weight management programmes for adolescents, and it is important to include the family throughout the entire process. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  14. Circadian clock gene Per2 plays an important role in cell proliferation, apoptosis and cell cycle progression in human oral squamous cell carcinoma.

    Science.gov (United States)

    Wang, Qingqing; Ao, Yiran; Yang, Kai; Tang, Hong; Chen, Dan

    2016-06-01

    Previous studies have shown that the aberrant expression of period circadian clock 2 (Per2) is closely related to the occurrence and development of cancers, but the specific mechanism remains unclear. In the present study, we used shRNA to downregulate Per2 in oral squamous cell carcinoma (OSCC) Tca8113 cells, and then detected the alterations in cell cycle, cell proliferation and apoptosis by flow cytometric analysis and mRNA expression alterations in all the important genes in the cyclin/cyclin-dependent protein kinase (CDK)/cyclin-dependent kinase inhibitor (CKI) cell cycle network by RT-qPCR. We found that in the Tca8113 cells, after Per2 downregulation, the mRNA expression levels of cyclin A2, B1 and D1, CDK4, CDK6 and E2F1 were significantly increased (Pcycle progression and the balance of cell proliferation and apoptosis by regulation of the cyclin/CDK/CKI cell cycle network. Further research on Per2 may provide a new effective molecular target for cancer treatments.

  15. Rubisco and Rubisco Activase Play an Important Role in the Biochemical Limitations of Photosynthesis in Rice, Wheat, and Maize under High Temperature and Water Deficit

    Science.gov (United States)

    Perdomo, Juan A.; Capó-Bauçà, Sebastià; Carmo-Silva, Elizabete; Galmés, Jeroni

    2017-01-01

    To understand the effect of heat and drought on three major cereal crops, the physiological and biochemical (i.e., metabolic) factors affecting photosynthesis were examined in rice, wheat, and maize plants grown under long-term water deficit (WD), high temperature (HT) and the combination of both stresses (HT-WD). Diffusional limitations to photosynthesis prevailed under WD for the C3 species, rice and wheat. Conversely, biochemical limitations prevailed under WD for the C4 species, maize, under HT for all three species, and under HT-WD in rice and maize. These biochemical limitations to photosynthesis were associated with Rubisco activity that was highly impaired at HT and under HT-WD in the three species. Decreases in Rubisco activation were unrelated to the amount of Rubisco and Rubisco activase (Rca), but were probably caused by inhibition of Rca activity, as suggested by the mutual decrease and positive correlation between Rubisco activation state and the rate of electron transport. Decreased Rubisco activation at HT was associated with biochemical limitation of net CO2 assimilation rate (AN). Overall, the results highlight the importance of Rubisco as a target for improving the photosynthetic performance of these C3 (wheat and rice) and C4 (maize) cereal crops under increasingly variable and warmer climates. PMID:28450871

  16. Cell division and endoreduplication play important roles in stem swelling of tuber mustard (Brassica juncea Coss. var. tumida Tsen et Lee).

    Science.gov (United States)

    Shi, H; Wang, L L; Sun, L T; Dong, L L; Liu, B; Chen, L P

    2012-11-01

    We investigated spatio-temporal variations in cell division and the occurrence of endoreduplication in cells of tuber mustard stems during development. Cells in the stem had 8C nuclei (C represents DNA content of a two haploid genome), since it is an allotetraploid species derived from diploid Brassica rapa (AA) and B. nigra (BB), thus indicating the occurrence of endoreduplication. Additionally, we observed a dynamic change of cell ploidy in different regions of the swollen stems, with a decrease in 4C proportion in P4-1 and a sharp increase in 8C cells that became the dominant cell type (86.33% at most) in the inner pith cells. Furthermore, cDNAs of 14 cell cycle genes and four cell expansion genes were cloned and their spatial transcripts analysed in order to understand their roles in stem development. The expression of most cell cycle genes peaked in regions of the outer pith (P2 or P3), some genes regulating S/G2 and G2/M (BjCDKB1;2, BjCYCB1;1 and BjCYCB1;2) significantly decrease in P5 and P6, while G1/S regulators (BjE2Fa, BjE2Fb and BjE2Fc) showed a relative high expression level in the inner pith (P5) where cells were undergoing endoreduplication. Coincidentally, BjXTH1and BjXTH2 were exclusively expressed in the endoreduplicated cells. Our results suggest that cells of outer pith regions (P2 and P3) mainly divide for cell proliferation, while cells of the inner pith expand through endoreduplication. Endoreduplication could trigger expression of BjXTH1 and BjXTH2 and thus function in cell expansion of the pith tissue. © 2012 German Botanical Society and The Royal Botanical Society of the Netherlands.

  17. Two glycerol 3-phosphate dehydrogenase isogenes from Candida versatilis SN-18 play an important role in glycerol biosynthesis under osmotic stress.

    Science.gov (United States)

    Mizushima, Daiki; Iwata, Hisashi; Ishimaki, Yuki; Ogihara, Jun; Kato, Jun; Kasumi, Takafumi

    2016-05-01

    Two isogenes of glycerol 3-phosphate dehydrogenase (GPD) from Candida versatilis SN-18 were cloned and sequenced. These intronless genes (Cagpd1 and Cagpd2) were both predicted to encode a 378 amino acid polypeptide, and the deduced amino acid sequences mutually showed 76% identity. Interestingly, Cagpd1 and Cagpd2 were located tandemly in a locus of genomic DNA within a 262 bp interval. To our knowledge, this represents a novel instance of isogenic genes relating to glucose metabolism. The stress response element (STRE) was found respectively at -93 to -89 bp upstream of the 5'end of Cagpd1 and -707 to -703 bp upstream of Cagpd2, indicating that these genes are involved in osmotic stress response. In heterologous expression using a gpd1Δgpd2Δ double deletion mutant of Saccharomyces cerevisiae, Cagpd1 and Cagpd2 transformants complemented the function of GPD, with Cagpd2 being much more effective than Cagpd1 in promoting growth and glycerol synthesis. Phylogenetic analysis of the amino acid sequences suggested that Cagpd1p and Cagpd2p are NADP(+)-dependent GPDs (EC 1.1.1.94). However, crude enzyme extract from Cagpd1 and Cagpd2 transformants showed GPD activity with only NAD(+) as cofactor. Hence, both Cagpd1p and Cagpd2p are likely NAD(+)-dependent GPDs (EC 1.1.1.8), similar to GPDs from S. cerevisiae and Candida magnoliae. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  18. A glutathione-independent glyoxalase of the DJ-1 superfamily plays an important role in managing metabolically generated methylglyoxal in Candida albicans.

    Science.gov (United States)

    Hasim, Sahar; Hussin, Nur Ahmad; Alomar, Fadhel; Bidasee, Keshore R; Nickerson, Kenneth W; Wilson, Mark A

    2014-01-17

    Methylglyoxal is a cytotoxic reactive carbonyl compound produced by central metabolism. Dedicated glyoxalases convert methylglyoxal to d-lactate using multiple catalytic strategies. In this study, the DJ-1 superfamily member ORF 19.251/GLX3 from Candida albicans is shown to possess glyoxalase activity, making this the first demonstrated glutathione-independent glyoxalase in fungi. The crystal structure of Glx3p indicates that the protein is a monomer containing the catalytic triad Cys(136)-His(137)-Glu(168). Purified Glx3p has an in vitro methylglyoxalase activity (Km = 5.5 mM and kcat = 7.8 s(-1)) that is significantly greater than that of more distantly related members of the DJ-1 superfamily. A close Glx3p homolog from Saccharomyces cerevisiae (YDR533C/Hsp31) also has glyoxalase activity, suggesting that fungal members of the Hsp31 clade of the DJ-1 superfamily are all probable glutathione-independent glyoxalases. A homozygous glx3 null mutant in C. albicans strain SC5314 displays greater sensitivity to millimolar levels of exogenous methylglyoxal, elevated levels of intracellular methylglyoxal, and carbon source-dependent growth defects, especially when grown on glycerol. These phenotypic defects are complemented by restoration of the wild-type GLX3 locus. The growth defect of Glx3-deficient cells in glycerol is also partially complemented by added inorganic phosphate, which is not observed for wild-type or glucose-grown cells. Therefore, C. albicans Glx3 and its fungal homologs are physiologically relevant glutathione-independent glyoxalases that are not redundant with the previously characterized glutathione-dependent GLO1/GLO2 system. In addition to its role in detoxifying glyoxals, Glx3 and its close homologs may have other important roles in stress response.

  19. Combined transcriptome and metabolite profiling reveals that IiPLR1 plays an important role in lariciresinol accumulation in Isatis indigotica.

    Science.gov (United States)

    Xiao, Ying; Ji, Qian; Gao, Shouhong; Tan, Hexin; Chen, Ruibing; Li, Qing; Chen, Junfeng; Yang, Yingbo; Zhang, Lei; Wang, Zhengtao; Chen, Wansheng; Hu, Zhibi

    2015-10-01

    A lignan, lariciresinol, is an important efficacious compound for the antiviral effect of Isatis indigotica, a widely used herb for the treatment of colds, fever, and influenza. Although some rate-limiting steps of the lariciresinol biosynthetic pathway are well known, the specific roles of gene family members in I. indigotica in regulating lariciresinol production are poorly understood. In the present study, a correlation analysis between the RNA sequencing (RNA-Seq) expression profile and lignan content by using I. indigotica hairy roots treated with methyl jamonate (0.5 μM) at different time points as a source implicated that I. indigotica pinoresinol/lariciresinol reductase 1 (IiPLR1), but not IiPLR2 or IiPLR3, contributed greatly to lariciresinol accumulation. Gene silencing by RNA interference (RNAi) demonstrated that IiPLR1 indeed influenced lariciresinol biosynthesis, whereas suppression of IiPLR2 or IiPLR3 did not change lariciresinol abundance significantly. IiPLR1 was thus further characterized; IiPLR1 was constitutively expressed in roots, stems, leaves, and flowers of I. indigotica, with the highest expression in roots, and it responds to different stress treatments to various degrees. Recombinant IiPLR1 reduces both (±)-pinoresinol and (±)-lariciresinol efficiently, with comparative K cat/K m values. Furthermore, overexpression of IiPLR1 significantly enhanced lariciresinol accumulation in I. indigotica hairy roots, and the best line (ovx-2) produced 353.9 μg g(-1) lariciresinol, which was ~6.3-fold more than the wild type. This study sheds light on how to increase desired metabolites effectively by more accurate or appropriate genetic engineering strategies, and also provides an effective approach for the large-scale commercial production of pharmaceutically valuable lariciresinol by using hairy root culture systems as bioreactors.

  20. Domain III of Bacillus thuringiensis Cry1Ie Toxin Plays an Important Role in Binding to Peritrophic Membrane of Asian Corn Borer

    Science.gov (United States)

    Feng, Dongmei; Chen, Zhen; Wang, Zhiwen; Zhang, Chunlu; He, Kanglai; Guo, Shuyuan

    2015-01-01

    The insecticidal IE648 toxin is a truncated Cry1Ie protein with increased toxicity against Asian corn borer (ACB). Cry toxins are pore-forming toxins that disrupt insect midgut cells to kill the larvae. However, the peritrophic membrane (PM) is an important barrier that Cry toxins must cross before binding to midgut cells. Previously, it was shown that Cry toxins are able to bind and accumulate in the PM of several lepidopteran insects. Binding of IE648 toxin to PM of ACB was previously reported and the goal of the current work was the identification of the binding region between Cry1Ie and the PM of ACB. Homologous competition binding assays showed that this interaction was specific. Heterologous competition binding assays performed with different fragments corresponding to domain I, domain II and domain III allowed us to identify that domain III participates in the interaction of IE648 with the PM. Specifically, peptide D3-L8 (corresponding to Cry1Ie toxin residues 607 to 616), located in an exposed loop region of domain III is probably involved in this interaction. Ligand blot assays show that IE648 interact with chitin and PM proteins with sizes of 30, 32 and 80 kDa. The fact that domain III interacts with proteins of similar molecular masses supports that this region of the toxin might be involved in PM interaction. These data provide for the first time the identification of domain III as a putative binding region between PM and 3D-Cry toxin. PMID:26295704

  1. Domain III of Bacillus thuringiensis Cry1Ie Toxin Plays an Important Role in Binding to Peritrophic Membrane of Asian Corn Borer.

    Directory of Open Access Journals (Sweden)

    Dongmei Feng

    Full Text Available The insecticidal IE648 toxin is a truncated Cry1Ie protein with increased toxicity against Asian corn borer (ACB. Cry toxins are pore-forming toxins that disrupt insect midgut cells to kill the larvae. However, the peritrophic membrane (PM is an important barrier that Cry toxins must cross before binding to midgut cells. Previously, it was shown that Cry toxins are able to bind and accumulate in the PM of several lepidopteran insects. Binding of IE648 toxin to PM of ACB was previously reported and the goal of the current work was the identification of the binding region between Cry1Ie and the PM of ACB. Homologous competition binding assays showed that this interaction was specific. Heterologous competition binding assays performed with different fragments corresponding to domain I, domain II and domain III allowed us to identify that domain III participates in the interaction of IE648 with the PM. Specifically, peptide D3-L8 (corresponding to Cry1Ie toxin residues 607 to 616, located in an exposed loop region of domain III is probably involved in this interaction. Ligand blot assays show that IE648 interact with chitin and PM proteins with sizes of 30, 32 and 80 kDa. The fact that domain III interacts with proteins of similar molecular masses supports that this region of the toxin might be involved in PM interaction. These data provide for the first time the identification of domain III as a putative binding region between PM and 3D-Cry toxin.

  2. MicroRNA 145 may play an important role in uveal melanoma cell growth by potentially targeting insulin receptor substrate-1

    Institute of Scientific and Technical Information of China (English)

    Li Yang; Huang Qiming; Shi Xuehui; Jin Xiang; Shen Li; Xu Xiaolin; Wei Wenbin

    2014-01-01

    Background MicroRNAs (miRNAs) contribute to tumorigenesis by acting as either oncogenes or tumor suppressor genes.In this study,we investigated the role of miR-145 in the pathogenesis of uveal melanoma.Methods Expression profiles of miRNAs in uveal melanoma were performed using Agilent miRNA array.Quantitative real-time polymerase chain reaction was used to screen the expression levels of miR-145 in normal uveal tissue,uveal melanoma tissue,and uveal melanoma cell lines.Lenti-virus expression system was used to construct MUM-2B and OCM-1 cell lines with stable overexpression of miR-145.Cell proliferation,cell cycle,and cell apoptosis of these miR-145 overexpression cell lines were examined by MTT assay and flow cytometry respectively.The target genes of miR-145 were predicted by bioinformatics and confirmed using a luciferase reporter assay.The expression of insulin-like growth factor-1 receptor (IGF-1R),insulin receptor substrate-1 (IRS-1) proteins was determined by Western blotting analysis.IRS-1 was knocked down in OCM-1 cells.TUNEL,BrdU,and flow cytometry assay were performed in IRS-1 knocked down OCM-1 cell lines to analyze its function.Results Forty-seven miRNAs were up regulated in uveal melanoma and 61 were down regulated.miR-145 expression was significantly lower in uveal melanoma sample and the cell lines were compared with normal uveal sample.Overexpression of miR-145 suppressed cell proliferation by blocking the G1 phase entering S phase in uveal melanoma cells,and promoted uveal melanoma cell apoptosis.IRS-1 was identified as a potential target of miR-145 by dual luciferase reporter assay.Knocking down of IRS-1 had similar effect as overexpression of miR-145.Conclusion miR-145 might act as a tumor suppressor in uveal melanoma,and downregulation of the target IRS-1 might be a potential mechanism.

  3. The important role of stratum corneum lipids for the cutaneous barrier function.

    Science.gov (United States)

    van Smeden, J; Janssens, M; Gooris, G S; Bouwstra, J A

    2014-03-01

    The skin protects the body from unwanted influences from the environment as well as excessive water loss. The barrier function of the skin is located in the stratum corneum (SC). The SC consists of corneocytes embedded in a lipid matrix. This lipid matrix is crucial for the lipid skin barrier function. This paper provides an overview of the reported SC lipid composition and organization mainly focusing on healthy and diseased human skin. In addition, an overview is provided on the data describing the relation between lipid modulations and the impaired skin barrier function. Finally, the use of in vitro lipid models for a better understanding of the relation between the lipid composition, lipid organization and skin lipid barrier is discussed. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias.

  4. Group play

    DEFF Research Database (Denmark)

    Tychsen, Anders; Hitchens, Michael; Brolund, Thea

    2008-01-01

    of group dynamics, the influence of the fictional game characters and the comparative play experience between the two formats. The results indicate that group dynamics and the relationship between the players and their digital characters, are integral to the quality of the gaming experience in multiplayer......Role-playing games (RPGs) are a well-known game form, existing in a number of formats, including tabletop, live action, and various digital forms. Despite their popularity, empirical studies of these games are relatively rare. In particular there have been few examinations of the effects...... of the various formats used by RPGs on the gaming experience. This article presents the results of an empirical study, examining how multi-player tabletop RPGs are affected as they are ported to the digital medium. Issues examined include the use of disposition assessments to predict play experience, the effect...

  5. Postphenomenological Play

    DEFF Research Database (Denmark)

    Hammar, Emil

    This paper aims to identify an understanding of digital games in virtual environments by using Don Ihde’s (1990) postphenomenological approach to how technology mediates the world to human beings in conjunction with Hans-Georg Gadamer’s (1993) notion of play . Through this tentatively proposed...... amalgamation of theories I point towards an alternative understanding of the relationship between play and game as not only dialectic, but also as socially and ethically relevant qua the design and implementation of the game as technology....

  6. Importance of Beta Cell Function for the Treatment of Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Yoshifumi Saisho

    2014-08-01

    Full Text Available Type 2 diabetes (T2DM is characterized by insulin resistance and beta cell dysfunction. Recent evidence has emerged that beta cell dysfunction is a common pathogenetic feature of both type 1 and type 2 diabetes, and T2DM never develops without beta cell dysfunction. Therefore, treatment of T2DM should aim to restore beta cell function. Although the treatment of T2DM has greatly improved over the past few decades, remaining issues in the current treatment of T2DM include (1 hypoglycemia; (2 body weight gain; (3 peripheral hyperinsulinemia and (4 postprandial hyperglycemia, which are all associated with inappropriate insulin supplementation, again underpinning the important role of endogenous and physiological insulin secretion in the management of T2DM. This review summarizes the current knowledge on beta cell function in T2DM and discusses the treatment strategy for T2DM in relation to beta cell dysfunction.

  7. Determining importance weighting functions for Contributon theory eigenvalue sensitivity coefficient methodologies

    Energy Technology Data Exchange (ETDEWEB)

    Perfetti, C.; Martin, W. [Univ. of Michigan, Dept. of Nuclear Engineering and Radiological Sciences, 2355 Bonisteel Boulevard, Ann Arbor, MI 48109-2104 (United States); Rearden, B.; Williams, M. [Oak Ridge National Laboratory, Reactor and Nuclear Systems Div., Bldg. 5700, P.O. Box 2008, Oak Ridge, TN 37831-6170 (United States)

    2012-07-01

    This study introduced two new approaches for calculating the F*(r) importance weighting function for Contributon and CLUTCH eigenvalue sensitivity coefficient calculations, and compared them in terms of accuracy and applicability. The necessary levels of F*(r) mesh refinement and mesh convergence for obtaining accurate eigenvalue sensitivity coefficients were determined for two preliminary problems through two parametric studies, and the results of these studies suggest that a sufficiently accurate F*(r) mesh for calculating eigenvalue sensitivity coefficients can be obtained for these problems with only a small increase in problem runtime. (authors)

  8. Determining Importance Weighting Functions for Contributon Theory Eigenvalue Sensitivity Coefficient Methodologies

    Energy Technology Data Exchange (ETDEWEB)

    Perfetti, Christopher M [ORNL; Martin, William R [University of Michigan; Rearden, Bradley T [ORNL; Williams, Mark L [ORNL

    2012-01-01

    This study introduced three approaches for calculating the importance weighting function for Contributon and CLUTCH eigenvalue sensitivity coefficient calculations, and compared them in terms of accuracy and applicability. The necessary levels of mesh refinement and mesh convergence for obtaining accurate eigenvalue sensitivity coefficients were determined through two parametric studies, and the results of these studies suggest that a sufficiently-accurate mesh for calculating eigenvalue sensitivity coefficients can be obtained for the Contributon and CLUTCH methods with only a small increase in problem runtime.

  9. Play at Work

    DEFF Research Database (Denmark)

    Meier Sørensen, Bent; Spoelstra, Sverre

    2012-01-01

    for business and the other insists that work and play are largely indistinguishable in the postindustrial organization. Our field study of a design and communications company in Denmark shows that organizational play can be much more than just functional to the organization. We identify three ways in which......The interest in organizational play is growing, both in popular business discourse and organization studies. As the presumption that play is dysfunctional for organizations is increasingly discarded, the existing positions may be divided into two camps; one proposes ‘serious play’ as an engine...... workplaces engage in play: play as a (serious) continuation of work, play as a (critical) intervention into work and play as an (uninvited) usurpation of work....

  10. Clay Play

    Science.gov (United States)

    Rogers, Liz; Steffan, Dana

    2009-01-01

    This article describes how to use clay as a potential material for young children to explore. As teachers, the authors find that their dialogue about the potential of clay as a learning medium raises many questions: (1) What makes clay so enticing? (2) Why are teachers noticing different play and conversation around the clay table as compared to…

  11. Cryptic biodiversity effects: importance of functional redundancy revealed through addition of food web complexity.

    Science.gov (United States)

    Philpott, Stacy M; Pardee, Gabriella L; Gonthier, David J

    2012-05-01

    Interactions between predators and the degree of functional redundancy among multiple predator species may determine whether herbivores experience increased or decreased predation risk. Specialist parasites can modify predator behavior, yet rarely have cascading effects on multiple predator species and prey been evaluated. We examined influences of specialist phorid parasites (Pseudacteon spp.) on three predatory ant species and herbivores in a coffee agroecosystem. Specifically, we examined whether changes in ant richness affected fruit damage by the coffee berry borer (Hypothenemus hampei) and whether phorids altered multi-predator effects. Each ant species reduced borer damage, and without phorids, increasing predator richness did not further decrease borer damage. However, with phorids, activity of one ant species was reduced, indicating that the presence of multiple ant species was necessary to limit borer damage. In addition, phorid presence revealed synergistic effects of multiple ant species, not observed without the presence of this parasite. Thus, a trait-mediated cascade resulting from a parasite-induced predator behavioral change revealed the importance of functional redundancy, predator diversity, and food web complexity for control of this important pest.

  12. Importance of NPA motifs in the expression and function of water channel aquaporin-1

    Institute of Scientific and Technical Information of China (English)

    JIANG Yong; MA TongHui

    2007-01-01

    The asparagine-proline-alanine sequences (NPA motifs) are highly conserved in aquaporin water channel family. Crystallographic studies of AQP1 structure demonstrated that the two NPA motifs are in the narrow central constriction of the channel, serving to bind water molecules for selective and efficient water passage. To investigate the importance of the two NPA motifs in the structure, function and biogenesis of aquaporin water channels, we generated AQP1 mutations with NPA1 deletion, NPA2 deletion and NPA1,2 double deletion. The coding sequences of the three mutated cDNAs were subcloned into the mammalian expression vector pcDNA3.1 to form expression plasmids. We established stably transfected CHO cell lines expressing these AQP1 mutants. Immunofluorescence indicated that all the three mutated AQP1 proteins are expressed normally on the plasma membrane of stably transfected CHO cells, suggesting that deletion of NPA motifs does not influence the expression and intracellular processing of AQP1. Functional analysis demonstrated that NPA1 or NPA2 deletion reduced AQP1 water permeability by 49.6% and 46.7%, respectively, while NPA1,2 double deletion had little effect on AQP1 water permeability. These results provide evidence that NPA motifs are important for water per-meation but not essential for the expression, intracellular processing and the basic structure of AQP1 water channel.

  13. Competitive versus Cooperative Exergame Play for African American Adolescents' Executive Function Skills: Short-Term Effects in a Long-Term Training Intervention

    Science.gov (United States)

    Staiano, Amanda E.; Abraham, Anisha A.; Calvert, Sandra L.

    2012-01-01

    Exergames are videogames that require gross motor activity, thereby combining gaming with physical activity. This study examined the role of competitive versus cooperative exergame play on short-term changes in executive function skills, following a 10-week exergame training intervention. Fifty-four low-income overweight and obese African American…

  14. The Importance of Playing Devil's Advocate.

    Science.gov (United States)

    Schwenk, Charles; Cosier, Richard

    1990-01-01

    A "devil's advocacy" approach is proposed for the management of higher education conflict and ultimate improvement in the quality of decisions. Research supporting the value of active questioning of a preferred plan or strategy is summarized and its application is described. (DB)

  15. Limits of Science and the Importance of Epistemological Functions of Religion

    Directory of Open Access Journals (Sweden)

    Qodratullah Qorbani

    2012-12-01

    Full Text Available Human is encountered by many metaphysical, scientific, religious and other fundamentalquestions which Science, and its potentials, can answer some of them, specially in the material realm.In fact, empirical science is limited to the material world, and it can’t answer human’s fundamentalquestions of his/her living. Then human can’t provide all his/her epistemological requirements byempirical science. In addition, contemporary human’s scientism caused many problems for him/her.Human tried to make empirical science as a worldview which caused some important andfundamental crisis. So he/she needs metaphysical, religious and other sources to know aboutsupernatural facts. Fulfilling this, he/she has to use religious teachings, because religions, in particulardivine ones, have many basic functions. They can make man aware about immaterial realms andexistents including God, origin and resurrection of man, the world system etc. They can give areasonable explanation of the origin and resurrection of human’s life and the meaning of human’sevolution in the mundane universe, and the philosophy of living by explaining the nature of Goodnessand Evil. Religions give some ethical and religious laws to manage and control his/her individual andsocial treatments. In fact, through religious teachings,man can take a suitable framework to managehis/her living, for example, by them man can determine functional results of his/her scientific andtechnological activities. In addition, religions can draw the spiritual future of human’s mundaneliving, and give a good motivation to get mundane and spiritual happiness. In the other word, man,only by the help of religious teachings, can take his/her fundamental requirements. Then, byconsidering the contemporary human epistemological crisis and important limits of human’sknowledge and science, there is the only way to refer to divine religions teachings. In this paper, it istried to explain religion functions in

  16. Cardiac Alpha1-Adrenergic Receptors: Novel Aspects of Expression, Signaling Mechanisms, Physiologic Function, and Clinical Importance

    Science.gov (United States)

    O’Connell, Timothy D.; Jensen, Brian C.; Baker, Anthony J.

    2014-01-01

    Adrenergic receptors (AR) are G-protein-coupled receptors (GPCRs) that have a crucial role in cardiac physiology in health and disease. Alpha1-ARs signal through Gαq, and signaling through Gq, for example, by endothelin and angiotensin receptors, is thought to be detrimental to the heart. In contrast, cardiac alpha1-ARs mediate important protective and adaptive functions in the heart, although alpha1-ARs are only a minor fraction of total cardiac ARs. Cardiac alpha1-ARs activate pleiotropic downstream signaling to prevent pathologic remodeling in heart failure. Mechanisms defined in animal and cell models include activation of adaptive hypertrophy, prevention of cardiac myocyte death, augmentation of contractility, and induction of ischemic preconditioning. Surprisingly, at the molecular level, alpha1-ARs localize to and signal at the nucleus in cardiac myocytes, and, unlike most GPCRs, activate “inside-out” signaling to cause cardioprotection. Contrary to past opinion, human cardiac alpha1-AR expression is similar to that in the mouse, where alpha1-AR effects are seen most convincingly in knockout models. Human clinical studies show that alpha1-blockade worsens heart failure in hypertension and does not improve outcomes in heart failure, implying a cardioprotective role for human alpha1-ARs. In summary, these findings identify novel functional and mechanistic aspects of cardiac alpha1-AR function and suggest that activation of cardiac alpha1-AR might be a viable therapeutic strategy in heart failure. PMID:24368739

  17. Functional importance of motif I of pseudouridine synthases: mutagenesis of aligned lysine and proline residues.

    Science.gov (United States)

    Spedaliere, C J; Hamilton, C S; Mueller, E G

    2000-08-01

    On the basis of sequence alignments, the pseudouridine synthases were grouped into four families that share no statistically significant global sequence similarity, though some common sequence motifs were discovered [Koonin, E. V. (1996) Nucleic Acids. Res. 24, 2411-2415; Gustafsson, C., Reid, R., Greene, P. J., and Santi, D. V. (1996) Nucleic Acids Res. 24, 3756-3762]. We have investigated the functional significance of these alignments by substituting the nearly invariant lysine and proline residues in Motif I of RluA and TruB, pseudouridine synthases belonging to different families. Contrary to our expectations, the altered enzymes display only very mild kinetic impairment. Substitution of the aligned lysine and proline residues does, however, reduce structural stability, consistent with a temperature sensitive phenotype that results from substitution of the cognate proline residue in Cbf5p, a yeast homologue of TruB [Zerbarjadian, Y., King, T., Fournier, M. J., Clarke, L., and Carbon, J. (1999) Mol. Cell. Biol. 19, 7461-7472]. Together, our data support a functional role for Motif I, as predicted by sequence alignments, though the effect of substituting the highly conserved residues was milder than we anticipated. By extrapolation, our findings also support the assignment of pseudouridine synthase function to certain physiologically important eukaryotic proteins that contain Motif I, including the human protein dyskerin, alteration of which leads to the disease dyskeratosis congenita.

  18. Perifoveal function in patients with North Carolina macular dystrophy: the importance of accounting for fixation locus.

    Science.gov (United States)

    Seiple, William; Szlyk, Janet P; Paliga, Jennifer; Rabb, Maurice F

    2006-04-01

    To quantify the extent of visual function losses in patients with North Carolina Macular Dystrophy (NCMD) and to demonstrate the importance of accounting for eccentric fixation when making comparisons with normal data. Five patients with NCMD who were from a single family were examined. Multifocal electroretinograms (mfERGs) and psychophysical assessments of acuity and luminance visual field sensitivities were measured throughout the central retina. Comparisons of responses from equivalent retinal areas were accomplished by shifting normal templates to be centered at the locus of fixation for each patient. Losses of psychophysically measured visual function in patients with NCMD extend to areas adjacent to the locations of visible lesions. The multifocal ERG amplitude was reduced only within the area of visible lesion. Multifocal ERG implicit times were delayed throughout the entire central retinal area assessed. ERG timing is a sensitive assay of retinal function, and our results indicate that NCMD has a widespread effect at the level of the mid and outer retina. The findings also demonstrated that it is necessary to account for fixation locus and to ensure that equivalent retinal areas are compared when testing patients with macular disease who have eccentric fixation.

  19. Formation and function of vacancies in Si/Ge Clathrates: The importance of broken symmetries

    Science.gov (United States)

    Bhattacharya, Amrita; Carbogno, Christian; Scheffler, Matthias; Dr. Matthias Scheffler Team, Prof.

    2015-03-01

    One promising material class for improved thermoelectrics are the clathrates, i.e., semiconducting host lattices encapsulating guest atom. Even in simple clathrates, such as, Si46 and Ge46, the introduction of guests can result in important but not yet understood effects: In Si hosts, the addition of K (or Ba) results in defect-free K8Si46 (Ba8Si46) phases. In spite of their structural and electronic similitude, Ge hosts behave fundamentally different upon filling, where, the spontaneously formed framework vacancies completely (or partially) balance the electron donated by K (or Ba) guests leading to K8Ge44(orBa8Ge43) clathrates. In this work, we use density-functional theory, carefully validating the exchange correlation functional, to compute the formation energies of vacancies and vacancy complexes in Si- and Ge-hosts as function of the filling of guests. By taking into account of the structural disorder, geometric relaxations, and vibrational entropies, we verify the experimentally found vacancy concentration and the thermodynamic stabilities of these compounds. We can trace back the contrasting behaviour of Si/Ge clathrates upon filling to a curious, charged vacancy induced break in symmetry that occurs in Si but not in Ge hosts.

  20. Performance evaluation of the short-time objective intelligibility measure with different band importance functions

    DEFF Research Database (Denmark)

    Heidemann Andersen, Asger; de Haan, Jan Mark; Tan, Zheng-Hua

    2017-01-01

    , is that all frequency bands are equally weighted in the final measure. This is in contrast to classical methods such as the speech intelligibility index (SII) which employs empirically determined band importance functions (BIFs), specifying the relative contribution of each frequency band to intelligibility....... In this study we investigated the use of BIFs in the STOI measure. BIFs were fitted to several datasets of measured intelligibility. This was done such as to minimize the root-mean-squared prediction error. We then performed a cross-evaluation of the obtained BIFs on all datasets, using three different...... performance measures: root-mean-squared-error, Pearson correlation, and Kendall rank correlation. The results show substantially improved performance when fitting and evaluating on the same dataset. However, this advantage does not necessarily subsist when fitting and evaluating on different datasets. When...

  1. Particle filter with importance density function generated by updated system equation

    Institute of Scientific and Technical Information of China (English)

    左军毅; 贾颖娜; 张炜; 高全学

    2013-01-01

    The current measurement was exploited in a more efficient way. Firstly, the system equation was updated by introducing a correction term, which depends on the current measurement and can be obtained by running a suboptimal filter. Then, a new importance density function(IDF) was defined by the updated system equation. Particles drawn from the new IDF are more likely to be in the significant region of state space and the estimation accuracy can be improved. By using different suboptimal filter, different particle filters(PFs) can be developed in this framework. Extensions of this idea were also proposed by iteratively updating the system equation using particle filter itself, resulting in the iterated particle filter. Simulation results demonstrate the effectiveness of the proposed IDF.

  2. Rapid high-resolution characterization of functionally important monoclonal antibody N-glycans by capillary electrophoresis.

    Science.gov (United States)

    Szabo, Zoltan; Guttman, András; Bones, Jonathan; Karger, Barry L

    2011-07-01

    Characterization of the N-glycosylation present in the Fc region of therapeutic monoclonal antibodies requires rapid, high-resolution separation methods to guarantee product safety and efficacy during all stages of process development. Determination of fucosylated oligosaccharides is particularly important during clone selection, product characterization, and lot release as fucose has been shown to adversely affect the ability of mAbs to induce antibody dependent cellular cytotoxicity (ADCC). Here, we apply a general capillary electrophoresis optimization strategy to separate functionally relevant fucosylated and afucosylated glycans on mononclonal antibody products in the presence of several high mannose oligosaccharides. The N-glycans chosen represent those most commonly reported on CHO cell derived therapeutic antibodies. A rapid (processing for automated 96 well plate-based glycosylation analyses of two nonproprietary therapeutic monoclonal antibodies, demonstrating ruggedness and suitability for high-throughput process and product monitoring applications.

  3. New aspects of the role of histamine in cardiovascular function: identification, characterization, and potential pathophysiological importance of H3 receptors.

    Science.gov (United States)

    Göthert, M; Garbarg, M; Hey, J A; Schlicker, E; Schwartz, J C; Levi, R

    1995-05-01

    As a result of intensive research during several decades, the distribution, function, and pathophysiological role of cardiovascular H1 and H2 receptors are well known, whereas reports on the occurrence and function of H3 receptors in blood vessels and the heart have not become available before the last 7 years (i.e., 4 years after the first description of these receptors in the central nervous system in 1983). The development of selective and potent H3 receptor agonists and antagonists was a prerequisite for convenient investigations of cardiovascular H3 receptors, which like H1 and H2 receptors are G-protein coupled but unlike them have not yet been cloned. Both in blood vessels and the heart, H3 receptors are located on noradrenergic nerve endings and upon stimulation mediate an inhibition of noradrenaline release. Whereas it remains to be clarified under which conditions the vascular H3 receptors may be stimulated by endogenous histamine, those in the heart become activated in the early phases of myocardial ischemia characterized by an increased histamine spillover. The H3 receptors in the central nervous system also appear to be of importance for the control of vascular function. Inhibitory presynaptic H3 receptors occur on trigeminal sensory C fibres supplying blood vessels in the dura mater. Release of neuropeptides from these fibres induces a neurogenic inflammation, which has been suggested to be involved in the pathogenesis of migraine. An interaction, involving presynaptic H3 receptors, between sensory C fibres and mast cells in close apposition to these fibres plays a role in the control of histamine synthesis in the dura mater.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Impaired social cognition 30 years after hemispherectomy for intractable epilepsy: the importance of the right hemisphere in complex social functioning.

    Science.gov (United States)

    Fournier, N M; Calverley, K L; Wagner, J P; Poock, J L; Crossley, M

    2008-04-01

    Clinical research with individuals following hemispherectomy typically quantifies the success of surgical outcomes by focusing primarily on the achievement of seizure control and the preservation of general brain functions, such as movement, sensation, language, and memory. In addition to these outcomes, careful study of individuals following hemispherectomy also has the potential to contribute to our understanding of functional brain asymmetries involving other complex cognitive behaviors. In this study, we report preliminary evidence for the lateralization of social perception. We administered a series of neuropsychological tests that were developed to assess emotional recognition and the formation of social inferences and advanced social cognitive judgments, as they occur in everyday situations, to two adult participants who underwent complete anatomic left- or right-sided hemispherectomy. Our results show that despite a 30-year postsurgical period of recovery and consistent and high levels of family support and social engagement, distinct cognitive profiles are still evident between our right- and left-sided participants. In particular, participant S.M., who underwent an anatomic right hemispherectomy, showed the most severe impairments in identifying negative emotional expressions and conversational exchanges involving lies and sarcasm and in "mentalizing" the intent of others. In contrast, participant J.H., who underwent an anatomic left hemispherectomy was highly skilled interpersonally, despite evident language-related limitations, and showed only mild difficulties when asked to identify emotional expressions involving disgust and anger. These results suggest that the right hemisphere plays a particularly important role in social cognitive functioning and reasoning. Further examination of the extent of social perceptual difficulties prior to and following surgical intervention for epilepsy may guide the development of effective social skills training

  5. Myosin VIIA, important for human auditory function, is necessary for Drosophila auditory organ development.

    Directory of Open Access Journals (Sweden)

    Sokol V Todi

    Full Text Available BACKGROUND: Myosin VIIA (MyoVIIA is an unconventional myosin necessary for vertebrate audition [1]-[5]. Human auditory transduction occurs in sensory hair cells with a staircase-like arrangement of apical protrusions called stereocilia. In these hair cells, MyoVIIA maintains stereocilia organization [6]. Severe mutations in the Drosophila MyoVIIA orthologue, crinkled (ck, are semi-lethal [7] and lead to deafness by disrupting antennal auditory organ (Johnston's Organ, JO organization [8]. ck/MyoVIIA mutations result in apical detachment of auditory transduction units (scolopidia from the cuticle that transmits antennal vibrations as mechanical stimuli to JO. PRINCIPAL FINDINGS: Using flies expressing GFP-tagged NompA, a protein required for auditory organ organization in Drosophila, we examined the role of ck/MyoVIIA in JO development and maintenance through confocal microscopy and extracellular electrophysiology. Here we show that ck/MyoVIIA is necessary early in the developing antenna for initial apical attachment of the scolopidia to the articulating joint. ck/MyoVIIA is also necessary to maintain scolopidial attachment throughout adulthood. Moreover, in the adult JO, ck/MyoVIIA genetically interacts with the non-muscle myosin II (through its regulatory light chain protein and the myosin binding subunit of myosin II phosphatase. Such genetic interactions have not previously been observed in scolopidia. These factors are therefore candidates for modulating MyoVIIA activity in vertebrates. CONCLUSIONS: Our findings indicate that MyoVIIA plays evolutionarily conserved roles in auditory organ development and maintenance in invertebrates and vertebrates, enhancing our understanding of auditory organ development and function, as well as providing significant clues for future research.

  6. Playing Possum

    Directory of Open Access Journals (Sweden)

    Enrico Euli

    2016-07-01

    Full Text Available Our society is drenched in the catastrophe; where the growth of financial crisis, environmental cataclysm and militarization represents its gaudiest and mortifying phenomena. Humans struggle with depression, sense of impotence, anguish towards a future considered a threat.  A possibility to keep us alive can be represented by the enhancement of our ability in ‘playing Possum’, an exercise of desisting and renitence: to firmly say ‘no’. To say no to a world that proposes just one way of being and living free, that imposes as the only unavoidable possible destiny.

  7. Playful Technology

    DEFF Research Database (Denmark)

    Johansen, Stine Liv; Eriksson, Eva

    2013-01-01

    In this paper, the design of future services for children in Danish public libraries is discussed, in the light of new challenges and opportunities in relation to new media and technologies. The Danish government has over the last few years initiated and described a range of initiatives regarding...... in the library, the changing role of the librarians and the library space. We argue that intertwining traditional library services with new media forms and engaging play is the core challenge for future design in physical public libraries, but also that it is through new media and technology that new...

  8. Playful Technology

    DEFF Research Database (Denmark)

    Johansen, Stine Liv; Eriksson, Eva

    2013-01-01

    in the library, the changing role of the librarians and the library space. We argue that intertwining traditional library services with new media forms and engaging play is the core challenge for future design in physical public libraries, but also that it is through new media and technology that new......In this paper, the design of future services for children in Danish public libraries is discussed, in the light of new challenges and opportunities in relation to new media and technologies. The Danish government has over the last few years initiated and described a range of initiatives regarding...

  9. Functional hoarseness in children: short-term play therapy with family dynamic counseling as therapy of choice.

    Science.gov (United States)

    Kollbrunner, Jürg; Seifert, Eberhard

    2013-09-01

    Children with nonorganic voice disorders (NVDs) are treated mainly using direct voice therapy techniques such as the accent method or glottal attack changes and indirect methods such as vocal hygiene and voice education. However, both approaches tackle only the symptoms and not etiological factors in the family dynamics and therefore often enjoy little success. The aim of the "Bernese Brief Dynamic Intervention" (BBDI) for children with NVD was to extend the effectiveness of pediatric voice therapies with a psychosomatic concept combining short-term play therapy with the child and family dynamic counseling of the parents. This study compares the therapeutic changes in three groups where different procedures were used, before intervention and 1 year afterward: counseling of parents (one to two consultations; n = 24), Brief Dynamic Intervention on the lines of the BBDI (three to five play therapy sessions with the child plus two to four sessions with the parents; n = 20), and traditional voice therapy (n = 22). A Voice Questionnaire for Parents developed by us with 59 questions to be answered on a four-point Likert scale was used to measure the change. According to the parents' assessment, a significant improvement in voice quality was achieved in all three methods. Counseling of parents (A) appears to have led parents to give their child more latitude, for example, they stopped nagging the child or demanding that he/she should behave strictly by the rules. After BBDI (B), the mothers were more responsive to their children's wishes and the children were more relaxed and their speech became livelier. At home, they called out to them less often at a distance, which probably improved parent-child dialog. Traditional voice therapy (C) seems to have had a positive effect on the children's social competence. BBDI seems to have the deepest, widest, and therefore probably the most enduring therapeutic effect on children with NVD.

  10. Long-term importance of right ventricular outflow tract patch function in patients with pulmonary regurgitation.

    Science.gov (United States)

    Puranik, Rajesh; Tsang, Victor; Lurz, Philip; Muthurangu, Vivek; Offen, Sophie; Frigiola, Alessandra; Norman, Wendy; Walker, Fiona; Bonhoeffer, Philip; Taylor, Andrew M

    2012-05-01

    Chronic pulmonary regurgitation (PR) has deleterious effects on right ventricular (RV) function in repaired tetralogy of Fallot (ToF). However, there are little data regarding right ventricular outflow tract (RVOT) contractile dysfunction in response to chronic PR and on both RV and LV volumes and function. We retrospectively identified consecutive patients with PR who were referred for magnetic resonance imaging quantification of "free PR" detected on echocardiography between 2003 and 2008. Patients had ToF and a transannular patch procedure (n = 30, 25.1 ± 1.2 years) or PR resulting from valvar pulmonary stenosis treated with surgical or percutaneous valvotomy (n = 30, 26.6 ± 1.8 years). The ToF and the PS groups were well matched for age at scan, age at repair surgery in ToF or initial valvotomy in PS, duration of exposure to PR, body surface area, heart rate, PR fraction, net forward pulmonary artery flow, and main and branch pulmonary artery dimensions. Severe PR fractions were identified in both groups (ToF: 40% ± 1% vs PS: 37% ± 2%, P = .2). Indexed RV and LV end-diastolic volumes were similar for both ToF and PS groups (RV end-diastolic volume index: 137 ± 6 mL/m(2) vs 128 ± 5 mL/m(2), P = .2, and LV end-diastolic volume index: 72 ± 2 mL/m(2) vs 67 ± 2 mL/m(2), P = .1, respectively). RV mass was also similar between groups (95 ± 5 g vs 81 ± 6 g, respectively, P = .08). However, indexed RV and LV end-systolic volumes were consistently higher in ToF when compared with PS (RV end-systolic volume index: 70 ± 5 mL/m(2) vs 54 ± 3 mL/m(2), P function in patients with ToF when compared with PS (RV ejection fraction: 52% ± 1.5% vs 59% ± 1%, P function were similar when only patients with contractile RV outflow tracts were compared. RV outflow tract patch dysfunction in repaired ToF is responsible for higher end-systolic volumes and thus lower global measures of ventricular systolic function. These findings were not evident in cases of PS treated with

  11. 5′ isomiR variation is of functional and evolutionary importance

    Science.gov (United States)

    Tan, Geok Chin; Chan, Elcie; Molnar, Attila; Sarkar, Rupa; Alexieva, Diana; Isa, Ihsan Mad; Robinson, Sophie; Zhang, Shuchen; Ellis, Peter; Langford, Cordelia F.; Guillot, Pascale V.; Chandrashekran, Anil; Fisk, Nick M.; Castellano, Leandro; Meister, Gunter; Winston, Robert M.; Cui, Wei; Baulcombe, David; Dibb, Nick J.

    2014-01-01

    We have sequenced miRNA libraries from human embryonic, neural and foetal mesenchymal stem cells. We report that the majority of miRNA genes encode mature isomers that vary in size by one or more bases at the 3′ and/or 5′ end of the miRNA. Northern blotting for individual miRNAs showed that the proportions of isomiRs expressed by a single miRNA gene often differ between cell and tissue types. IsomiRs were readily co-immunoprecipitated with Argonaute proteins in vivo and were active in luciferase assays, indicating that they are functional. Bioinformatics analysis predicts substantial differences in targeting between miRNAs with minor 5′ differences and in support of this we report that a 5′ isomiR-9–1 gained the ability to inhibit the expression of DNMT3B and NCAM2 but lost the ability to inhibit CDH1 in vitro. This result was confirmed by the use of isomiR-specific sponges. Our analysis of the miRGator database indicates that a small percentage of human miRNA genes express isomiRs as the dominant transcript in certain cell types and analysis of miRBase shows that 5′ isomiRs have replaced canonical miRNAs many times during evolution. This strongly indicates that isomiRs are of functional importance and have contributed to the evolution of miRNA genes. PMID:25056318

  12. 5' isomiR variation is of functional and evolutionary importance.

    Science.gov (United States)

    Tan, Geok Chin; Chan, Elcie; Molnar, Attila; Sarkar, Rupa; Alexieva, Diana; Isa, Ihsan Mad; Robinson, Sophie; Zhang, Shuchen; Ellis, Peter; Langford, Cordelia F; Guillot, Pascale V; Chandrashekran, Anil; Fisk, Nick M; Castellano, Leandro; Meister, Gunter; Winston, Robert M; Cui, Wei; Baulcombe, David; Dibb, Nick J

    2014-08-01

    We have sequenced miRNA libraries from human embryonic, neural and foetal mesenchymal stem cells. We report that the majority of miRNA genes encode mature isomers that vary in size by one or more bases at the 3' and/or 5' end of the miRNA. Northern blotting for individual miRNAs showed that the proportions of isomiRs expressed by a single miRNA gene often differ between cell and tissue types. IsomiRs were readily co-immunoprecipitated with Argonaute proteins in vivo and were active in luciferase assays, indicating that they are functional. Bioinformatics analysis predicts substantial differences in targeting between miRNAs with minor 5' differences and in support of this we report that a 5' isomiR-9-1 gained the ability to inhibit the expression of DNMT3B and NCAM2 but lost the ability to inhibit CDH1 in vitro. This result was confirmed by the use of isomiR-specific sponges. Our analysis of the miRGator database indicates that a small percentage of human miRNA genes express isomiRs as the dominant transcript in certain cell types and analysis of miRBase shows that 5' isomiRs have replaced canonical miRNAs many times during evolution. This strongly indicates that isomiRs are of functional importance and have contributed to the evolution of miRNA genes.

  13. Prognostic Importance of Pretransplant Functional Capacity After Allogeneic Hematopoietic Cell Transplantation

    Science.gov (United States)

    Devlin, Sean M.; Maloy, Molly A.; Wood, William A.; Tuohy, Sharlynn; Espiritu, Noel; Aquino, Jennifer; Kendig, Tiffany; Michalski, Meghan G.; Gyurkocza, Boglarka; Schaffer, Wendy L.; Ali, Benzar; Giralt, Sergio; Jakubowski, Ann A.

    2015-01-01

    Background. The purpose of this study was to investigate the prognostic importance of functional capacity in patients undergoing allogeneic hematopoietic cell transplantation (HCT) for hematological malignancies. Patients and Methods. Using a retrospective design, 407 patients completed a 6-minute walk distance (6MWD) test to assess functional capacity before HCT; 193 (47%) completed a 6MWD test after hospital discharge. Cox proportional hazards regression was used to estimate the risk of nonrelapse mortality (NRM) and overall survival (OS) according to the 6MWD category ( .05 for all). Patients presenting with a pre-HCT 6MWD of <400 m and experiencing a decline in 6MWD had the highest risk of NRM. Conclusion. The 6MWD is a significant univariate predictor of clinical outcomes but did not provide prognostic information beyond that of traditional prognostic markers in HCT. Implications for Practice: The pretransplant 6-minute walk test is a significant univariate predictor of clinical outcomes in hematological patients beyond age but not beyond that of performance status. On this basis, 6-minute walk distance testing should not be considered part of the standard battery of assessments for risk stratification before hematopoietic cell transplantation. PMID:26446235

  14. Playing cards.

    Science.gov (United States)

    1977-01-01

    Mrs. Zahia Marzouk, vice-president of the Alexandria Family Planning Association and a living legend of Egyptian family planning, does not believe in talking about problems. She is far too busy learning from people and teaching them. Her latest brainstorm is a set of playing cards designed to help girls and women to read and learn about family planning at the same time. The 5 packs of cards, representing familiar words and sounds, and each with a family planning joker, took Mrs. Marzouk 6 months to design and paint by hand. They have now been printed, packed into packets provided by UNICEF, and distributed to some 2000 literacy groups in factories and family planning clinics. Each woman who succeeds in learning to read is encouraged to teach 4 others. They then go to the family planning clinic to be examined and gain a certificate. For the teacher who has made them proficient there is a special prize. Girls at El Brinth village outside Alexandria are pictured playing cards at the family planning center where they are learning various skills including how to read.

  15. Identification of functionally important TonB-ExbD periplasmic domain interactions in vivo.

    Science.gov (United States)

    Ollis, Anne A; Postle, Kathleen

    2012-06-01

    In gram-negative bacteria, the cytoplasmic membrane proton-motive force energizes the active transport of TonB-dependent ligands through outer membrane TonB-gated transporters. In Escherichia coli, cytoplasmic membrane proteins ExbB and ExbD couple the proton-motive force to conformational changes in TonB, which are hypothesized to form the basis of energy transduction through direct contact with the transporters. While the role of ExbB is not well understood, contact between periplasmic domains of TonB and ExbD is required, with the conformational response of TonB to presence or absence of proton motive force being modulated through ExbD. A region (residues 92 to 121) within the ExbD periplasmic domain was previously identified as being important for TonB interaction. Here, the specific sites of periplasmic domain interactions between that region and the TonB carboxy terminus were identified by examining 270 combinations of 45 TonB and 6 ExbD individual cysteine substitutions for disulfide-linked heterodimer formation. ExbD residues A92C, K97C, and T109C interacted with multiple TonB substitutions in four regions of the TonB carboxy terminus. Two regions were on each side of the TonB residues known to interact with the TonB box of TonB-gated transporters, suggesting that ExbD positions TonB for correct interaction at that site. A third region contained a functionally important glycine residue, and the fourth region involved a highly conserved predicted amphipathic helix. Three ExbD substitutions, F103C, L115C, and T121C, were nonreactive with any TonB cysteine substitutions. ExbD D25, a candidate to be on a proton translocation pathway, was important to support efficient TonB-ExbD heterodimerization at these specific regions.

  16. Play as Experience

    Science.gov (United States)

    Henricks, Thomas S.

    2015-01-01

    The author investigates what he believes one of the more important aspects of play--the experience it generates in its participants. He considers the quality of this experience in relation to five ways of viewing play--as action, interaction, activity, disposition, and within a context. He treats broadly the different forms of affect, including…

  17. Thinking to Promote Employment Function Play an Unemployment Insurance%对发挥失业保险促进就业功能的思考

    Institute of Scientific and Technical Information of China (English)

    韩慧

    2013-01-01

      失业保险是国家通过立法强制实行的,由社会集中建立基金,对非因本人原因失去工作、中断收入的劳动者提供限定时期的物质帮助,并同时获得再就业服务、提高再就业竞争能力的一种社会保障制度。目前,国内外社会保险理论界和实践部门都已经认识到失业保险具有社会保障和促进就业双重目标。我国的失业保险制度自建立以来,在促进企业改革和维护社会稳定方面发挥了积极的作用。但是,现行的失业保险制度以救济为主,对失业人员提供生活保障起到了缓冲作用,促进再就业的作用却十分有限,影响了失业保险制度整体功能的发挥。因此,努力探索失业保险促进再就业的方式方法就显得尤为迫切和重要。文章就失业保险,促进就业的功能提出了一些思考。%Unemployment insurance is the adoption of national legislation imposed by the community to focus on the establishment of the Fund, have lost their jobs due to personal reasons on non-interrupt income workers a limited period of material assistance, and access to re-employment services to improve the competitiveness of the re-employment asocial security system.At present, domestic and foreign social insurance theorists and practice departments have recognized the unemployment insurance social security and promote the dual goals of em⁃ployment. China's unemployment insurance system since its establishment, has played an active role in the promotion of enterprise reform and the maintenance of social stability.However, the current unemployment insurance system mainly relief, play a buffer role to safeguard the live⁃lihood of the unemployed, to promote the re-employment is very limited role, affecting the overall function of the unemployment insurance sys⁃tem to play.Therefore, unemployment insurance, and strive to explore the ways and means to promote the re-employment is particularly

  18. Does the inferior frontal sulcus play a functional role in deception? A neuronavigated theta-burst transcranial magnetic stimulation study

    NARCIS (Netherlands)

    B. Verschuere; T. Schuhmann; A.T. Sack

    2012-01-01

    By definition, lying involves withholding the truth. Response inhibition may therefore be the cognitive function at the heart of deception. Neuroimaging research has shown that the same brain region that is activated during response inhibition tasks, namely the inferior frontal region, is also activ

  19. Role-Playing and Problem-Based Learning: The Use of Cross-Functional Student Teams in Business Application Development

    Science.gov (United States)

    Pike, Jacqueline C.; Spangler, William; Williams, Valerie; Kollar, Robert

    2017-01-01

    To create a learning experience which replicates the process by which consultants, systems developers and business end users collaborate to design and implement a business application, a cross-functional student team project was developed and is described. The overall learning experience was distinguished by specific components and characteristics…

  20. Mammalian Exo1 encodes both structural and catalytic functions that play distinct roles in essential biological processes.

    Science.gov (United States)

    Schaetzlein, Sonja; Chahwan, Richard; Avdievich, Elena; Roa, Sergio; Wei, Kaichun; Eoff, Robert L; Sellers, Rani S; Clark, Alan B; Kunkel, Thomas A; Scharff, Matthew D; Edelmann, Winfried

    2013-07-02

    Mammalian Exonuclease 1 (EXO1) is an evolutionarily conserved, multifunctional exonuclease involved in DNA damage repair, replication, immunoglobulin diversity, meiosis, and telomere maintenance. It has been assumed that EXO1 participates in these processes primarily through its exonuclease activity, but recent studies also suggest that EXO1 has a structural function in the assembly of higher-order protein complexes. To dissect the enzymatic and nonenzymatic roles of EXO1 in the different biological processes in vivo, we generated an EXO1-E109K knockin (Exo1(EK)) mouse expressing a stable exonuclease-deficient protein and, for comparison, a fully EXO1-deficient (Exo1(null)) mouse. In contrast to Exo1(null/null) mice, Exo1(EK/EK) mice retained mismatch repair activity and displayed normal class switch recombination and meiosis. However, both Exo1-mutant lines showed defects in DNA damage response including DNA double-strand break repair (DSBR) through DNA end resection, chromosomal stability, and tumor suppression, indicating that the enzymatic function is required for those processes. On a transformation-related protein 53 (Trp53)-null background, the DSBR defect caused by the E109K mutation altered the tumor spectrum but did not affect the overall survival as compared with p53-Exo1(null) mice, whose defects in both DSBR and mismatch repair also compromised survival. The separation of these functions demonstrates the differential requirement for the structural function and nuclease activity of mammalian EXO1 in distinct DNA repair processes and tumorigenesis in vivo.

  1. Enhancing Social Skills in Adolescents with High Functioning Autism using Motor-based Role-play Intervention

    Directory of Open Access Journals (Sweden)

    Sharon A. Gutman PhD, OTR, FAOTA

    2012-11-01

    Full Text Available The purpose of this pilot study was to collect pilot data evaluating whether a motor-based role-play intervention using a canine animal assistant can enhance social skill use in two adolescents with HFA. A single subject ABA design across two participants was used. The intervention consisted of four 1-hour sessions over 4 weeks. The quality of social interaction was measured by the Evaluation of Social Interaction (ESIadministered at baseline and the 3-month probe. Frequency of targeted social skill use was measured duringbaseline, intervention, and probe phases. Participant 1 experienced statistically significant increases in both ESI scores (p = .012, t = -5.488 from baseline to the 3-month probe. Participant 2 also experienced a statistically significant increase in ESI scores from baseline to probe (p = .002, t = -10.167, but he was unable to fully maintain these gains at the 3-month probe. This pilot study’s findings suggest that the intervention produced positive effects in both participants and warrant further investigation.

  2. HealthPaths: Using functional health trajectories to quantify the relative importance of selected health determinants

    Directory of Open Access Journals (Sweden)

    Michael Wolfson

    2014-10-01

    Full Text Available Background: It is widely known that that there is a significant dispersion in health status, as well as a strong correlation between health status and socio-economic status. But considerable uncertainty remains as to the quantitative importance of the various explanatory factors typically cited in this context. As health status is intrinsically a reflection of co-evolving dynamic processes, it is important to take a lifetime perspective when seeking to understand its determinants. The "bottom line" measure of overall population health is, though, health-adjusted life expectancy (HALE, which is an aggregation of individuals' health-adjusted life lengths (HALLs. Objective: In an exploratory mode, we intend to provide a realistic assessment of the relative importance of selected health determinants of HALE. Methods: This paper first draws on very detailed estimates of the covariates of vector-valued functional health trajectories, using the National Population Health Survey (Statistics Canada. We then use longitudinal microsimulation to draw out their implications by synthesising first a realistic base case -- specifically, a representative longitudinal population sample -- and then a series of exploratory counterfactual populations. Comparisons between and among counterfactuals and the base case are then used to estimate the quantitative importance of various factors in accounting for HALE. Results: Several surprising results emerged. Of the four risk factors explicitly examined, obesity had the smallest impacts on HALE: moving from the fifth to the 95th percentiles of BMI increased HALE 1.5 and 2.5 years for men and women, respectively. Eliminating smoking increased HALE by five and four years, while moving from the lowest to the highest levels of education had similar effects of about five years for both men and women. Perhaps surprisingly, moving from the fifth to the 95th percentiles of the psycho-social factor, Antonovsky's sense of coherence

  3. Effects of short-term active video game play on community adults:under International Classification of Functioning, Disability and Health consideration

    Institute of Scientific and Technical Information of China (English)

    Wei-Che Tseng; Ru-Lan Hsieh

    2013-01-01

    Background The effects of active video game play on healthy individuals remain uncertain.A person's functional health status constitutes a dynamic interaction between components identified in the International Classification of Functioning,Disability,and Health (ICF).The aim of this study was to investigate the short-term effects of active video game play on community adults using the ICF.Methods Sixty community adults with an average age of 59.3 years and without physical disabilities were recruited.Over 2 weeks,each adult participated in six sessions of active video game play lasting 20 minutes each.Participants were assessed before and af~er the intervention.Variables were collected using sources related to the ICF components,including the Hospital Anxiety and Depression Scale,Multidimensional Fatigue Inventory,Biodex Stability System,chairrising time,Frenchay Activity Index,Rivermead Mobility Index,Chronic Pain Grade Questionnaire,Work Ability Index,and World Health Organization Quality of Life-Brief Version.Results Compared to baseline data,significantly reduced risk of a fall measured by Biodex Stability System and improvements in disability scores measured by the Chronic Pain Grade Questionnaire were noted.There was no significant change in the other variables measured.Conclusion Short-term,active video game play reduces fall risks and ameliorates disabilities in community adults.

  4. Identification of genes important for cutaneous function revealed by a large scale reverse genetic screen in the mouse.

    Science.gov (United States)

    DiTommaso, Tia; Jones, Lynelle K; Cottle, Denny L; Gerdin, Anna-Karin; Vancollie, Valerie E; Watt, Fiona M; Ramirez-Solis, Ramiro; Bradley, Allan; Steel, Karen P; Sundberg, John P; White, Jacqueline K; Smyth, Ian M

    2014-10-01

    The skin is a highly regenerative organ which plays critical roles in protecting the body and sensing its environment. Consequently, morbidity and mortality associated with skin defects represent a significant health issue. To identify genes important in skin development and homeostasis, we have applied a high throughput, multi-parameter phenotype screen to the conditional targeted mutant mice generated by the Wellcome Trust Sanger Institute's Mouse Genetics Project (Sanger-MGP). A total of 562 different mouse lines were subjected to a variety of tests assessing cutaneous expression, macroscopic clinical disease, histological change, hair follicle cycling, and aberrant marker expression. Cutaneous lesions were associated with mutations in 23 different genes. Many of these were not previously associated with skin disease in the organ (Mysm1, Vangl1, Trpc4ap, Nom1, Sparc, Farp2, and Prkab1), while others were ascribed new cutaneous functions on the basis of the screening approach (Krt76, Lrig1, Myo5a, Nsun2, and Nf1). The integration of these skin specific screening protocols into the Sanger-MGP primary phenotyping pipelines marks the largest reported reverse genetic screen undertaken in any organ and defines approaches to maximise the productivity of future projects of this nature, while flagging genes for further characterisation.

  5. Identification of genes important for cutaneous function revealed by a large scale reverse genetic screen in the mouse.

    Directory of Open Access Journals (Sweden)

    Tia DiTommaso

    2014-10-01

    Full Text Available The skin is a highly regenerative organ which plays critical roles in protecting the body and sensing its environment. Consequently, morbidity and mortality associated with skin defects represent a significant health issue. To identify genes important in skin development and homeostasis, we have applied a high throughput, multi-parameter phenotype screen to the conditional targeted mutant mice generated by the Wellcome Trust Sanger Institute's Mouse Genetics Project (Sanger-MGP. A total of 562 different mouse lines were subjected to a variety of tests assessing cutaneous expression, macroscopic clinical disease, histological change, hair follicle cycling, and aberrant marker expression. Cutaneous lesions were associated with mutations in 23 different genes. Many of these were not previously associated with skin disease in the organ (Mysm1, Vangl1, Trpc4ap, Nom1, Sparc, Farp2, and Prkab1, while others were ascribed new cutaneous functions on the basis of the screening approach (Krt76, Lrig1, Myo5a, Nsun2, and Nf1. The integration of these skin specific screening protocols into the Sanger-MGP primary phenotyping pipelines marks the largest reported reverse genetic screen undertaken in any organ and defines approaches to maximise the productivity of future projects of this nature, while flagging genes for further characterisation.

  6. Kub5-Hera, the human Rtt103 homolog, plays dual functional roles in transcription termination and DNA repair.

    Science.gov (United States)

    Morales, Julio C; Richard, Patricia; Rommel, Amy; Fattah, Farjana J; Motea, Edward A; Patidar, Praveen L; Xiao, Ling; Leskov, Konstantin; Wu, Shwu-Yuan; Hittelman, Walter N; Chiang, Cheng-Ming; Manley, James L; Boothman, David A

    2014-04-01

    Functions of Kub5-Hera (In Greek Mythology Hera controlled Artemis) (K-H), the human homolog of the yeast transcription termination factor Rtt103, remain undefined. Here, we show that K-H has functions in both transcription termination and DNA double-strand break (DSB) repair. K-H forms distinct protein complexes with factors that repair DSBs (e.g. Ku70, Ku86, Artemis) and terminate transcription (e.g. RNA polymerase II). K-H loss resulted in increased basal R-loop levels, DSBs, activated DNA-damage responses and enhanced genomic instability. Significantly lowered Artemis protein levels were detected in K-H knockdown cells, which were restored with specific K-H cDNA re-expression. K-H deficient cells were hypersensitive to cytotoxic agents that induce DSBs, unable to reseal complex DSB ends, and showed significantly delayed γ-H2AX and 53BP1 repair-related foci regression. Artemis re-expression in K-H-deficient cells restored DNA-repair function and resistance to DSB-inducing agents. However, R loops persisted consistent with dual roles of K-H in transcription termination and DSB repair.

  7. Play, dreams, and creativity.

    Science.gov (United States)

    Oremland, J D

    1998-01-01

    Viewed ontogenetically, creating, dreaming, and playing are a variant of object relatedness. It is suggested that in recapitulating the ontogenetic sequence, creating, dreaming, and playing each as a process initiates by de-differentiation to primal union, evolves into transitional functioning, and consummates in tertiary cognitive discourse. The products of the triad--the created object, the dream, and play--are viewed as synergistic psychodynamic composites of topical, personal, and arche-typical imperatives. Creating, dreaming, and playing are easily overburdened by events, becoming stereotypical and repetitious. Nowhere is this more clearly seen than in the play of chronically ill, hospitalized children. It is suggested that with development generally, playing is replaced by formalized games; only dreaming continues as the vestige of early creative abilities.

  8. Arthropod Diversity and Functional Importance in Old-Growth Forests of North America

    Directory of Open Access Journals (Sweden)

    Timothy Schowalter

    2017-03-01

    Full Text Available Old-growth forests have become rare in North America but provide habitat for unique assemblages of species that often are rare in younger forests. Insects and related arthropods reach their highest diversity in old-growth forests because of their stable moderate temperature and relative humidity and the rich variety of resources represented by high plant species richness and structural complexity. Old-growth arthropod assemblages typically are distinct from those in younger, managed forests. Major subcommunities include the arboreal community that is composed of a rich assemblage of herbivores, fungivores, and their associated predators and parasitoids that function to regulate primary production and nutrient fluxes, the stem zone community that includes bark- and wood-boring species and their associated predators and parasitoids that initiate the decomposition of coarse woody debris, and the forest floor community composed of a variety of detritivores, fungivores, burrowers, and their associated predators and parasitoids that are instrumental in litter decomposition. Insect outbreaks are relatively rare in old-growth forests, where the diversity of resources and predators limit population growth. In turn, insects contribute to plant diversity and limit primary production of host plant species, thereby promoting development of old-growth forest characteristics. Arthropods also provide important functions in decomposition and nutrient cycling that may be lost in younger, managed forests with limited provision of coarse woody debris and accumulated litter. Protection of remnant old-growth forests within the forest matrix may be particularly valuable for maintaining the diversity of plant and arthropod predators that can minimize outbreaks, thereby contributing to resilience to changing environmental conditions.

  9. Aspartic acid 413 is important for the normal allosteric functioning of ADP-glucose pyrophosphorylase

    Energy Technology Data Exchange (ETDEWEB)

    Greene, T.W.; Woodbury, R.L.; Okita, T.W. [Washington State Univ., Pullman, WA (United States)

    1996-11-01

    As part of a structure-function analysis of the higher-plant ADP-glucose pyrophosphorylase (AGP), we used a random mutagenesis approach in combination with a novel bacterial complementation system to isolate over 100 mutants that were defective in glycogen production. One mutant of the large subunit M27 was identified by its capacity to only partially complement a mutation in the structural gene for the bacterial AGP (glg C), as determined by its light-staining phenotype when cells were exposed to I{sub 2} vapors. Enzyme-linked immunosorbent assay and enzymatic pyrophosphorylysis assays of M27 cell extracts showed that the level of expression and AGP activity was comparable to those of cells that expressed the wildtype recombinant enzyme. Kinetic analysis indicated that the M27 AGP displays normal Michaelis constant values for the substrates glucose-1-phosphate and ATP but requires 6- to 10-fold greater levels of 3-phosphoglycerate (3-PGA) than the wild-type recombinant enzyme for maximum activation. DNA sequence analysis showed that M27 contains a single point mutation that resulted in the replacement of aspartic acid 413 to alanine. Substitution of a lysine residue at this site almost completely abolished activation by 3-PGA. Aspartic acid 413 is adjacent to a lysine residue that was previously identified by chemical modification studies to be important in the binding of 3-PGA. The kinetic properties of M27 corroborate the importance of this region in the allosteric regulation of a higher-plant AGP. 28 refs., 3 figs., 1 tab.

  10. Aspartic acid 413 is important for the normal allosteric functioning of ADP-glucose pyrophosphorylase.

    Science.gov (United States)

    Greene, T W; Woodbury, R L; Okita, T W

    1996-01-01

    As part of a structure-function analysis of the higher-plant ADP-glucose pyrophosphorylase (AGP), we used a random mutagenesis approach in combination with a novel bacterial complementation system to isolate over 100 mutants that were defective in glycogen production (T.W. Greene, S.E. Chantler, M.L. Khan, G.F. Barry, J. Preiss, T.W. Okita [1996] Proc Natl Acad Sci USA 93: 1509-1513). One mutant of the large subunit M27 was identified by its capacity to only partially complement a mutation in the structural gene for the bacterial AGP (glg C), as determined by its light-staining phenotype when cells were exposed to l3 vapors. Enzyme-linked immunosorbent assay and enzymatic pyrophosphorylysis assays of M27 cell extracts showed that the level of expression and AGP activity was comparable to those of cells that expressed the wild-type recombinant enzyme. Kinetic analysis indicated that the M27 AGP displays normal Michaelis constant values for the substrates glucose-1-phosphate and ATP but requires 6- to 10-fold greater levels of 3-phosphoglycerate (3-PGA) than the wild-type recombinant enzyme for maximum activation. DNA sequence analysis showed that M27 contains a single point mutation that resulted in the replacement of aspartic acid 413 to alanine. Substitution of a lysine residue at this site almost completely abolished activation by 3-PGA. Aspartic acid 413 is adjacent to a lysine residue that was previously identified by chemical modification studies to be important in the binding of 3-PGA (K. Ball, J. Preiss [1994] J Biol Chem 269: 24706-24711). The kinetic properties of M27 corroborate the importance of this region in the allosteric regulation of a higher-plant AGP. PMID:8938421

  11. The importance of sexual self-disclosure to sexual satisfaction and functioning in committed relationships.

    Science.gov (United States)

    Rehman, Uzma S; Rellini, Alessandra H; Fallis, Erin

    2011-11-01

    Past research indicates that sexual self-disclosure, or the degree to which an individual is open with his or her partner about sexual preferences, is a key aspect of sexual satisfaction and that partner's lack of knowledge about one's sexual preferences is associated with persistent sexual dysfunction. To replicate and extend past research by examining (i) how one's own levels of sexual self-disclosure are related to one's own sexual health (after controlling for partner's levels of sexual self-disclosure); (ii) how one's partner's levels of sexual self-disclosure are associated with one's own sexual health (after controlling for one's own levels of sexual self-disclosure); and (iii) whether gender moderates the associations between sexual self-disclosure and sexual health. Scores from the Golombok Rust Inventory of Sexual Satisfaction and the Sexual Communication Satisfaction Scale. A cross-sectional dyadic study using a convenience sample of 91 heterosexual couples in long-term committed relationships. Data were analyzed using the Actor-Partner Interdependence Model. One's own level of sexual self-disclosure is positively associated with one's own sexual satisfaction, β = -0.24, t(172.85) = -3.50, P self-disclosure is associated with men's sexual satisfaction but not with women's sexual satisfaction, β = -0.45, t(86.81) = -4.06, P self-disclosure and sexual problems is stronger for women as compared with men, β = -0.72, t(87.00) = -6.31, P self-disclosure is significantly associated with sexual satisfaction and functioning for both men and women, albeit in different ways. Our findings underscore the importance of sexual self-disclosure and highlight the importance of the interpersonal level of analysis in understanding human sexuality. © 2011 International Society for Sexual Medicine.

  12. The Effectiveness of Singing or Playing a Wind Instrument in Improving Respiratory Function in Patients with Long-Term Neurological Conditions: A Systematic Review.

    Science.gov (United States)

    Ang, Kexin; Maddocks, Matthew; Xu, Huiying; Higginson, Irene J

    2017-03-01

    Many long-term neurological conditions adversely affect respiratory function. Singing and playing wind instruments are relatively inexpensive interventions with potential for improving respiratory function; however, synthesis of current evidence is needed to inform research and clinical use of music in respiratory care. To critically appraise, analyze, and synthesize published evidence on the effectiveness of singing or playing a wind instrument to improve respiratory function in people with long-term neurological conditions. Systematic review of published randomized controlled trials and observational studies examining singing or playing wind instruments to improve respiratory function in individuals with long-term neurological conditions. Articles meeting specified inclusion criteria were identified through a search of the Medline, Embase, PsycINFO, Cochrane Library, CINAHL, Web of Science, CAIRSS for Music, WHO International Clinical Trials Registry Platform Search Portal, and AMED databases as early as 1806 through March 2015. Information on study design, clinical populations, interventions, and outcome measures was extracted and summarized using an electronic standardized coding form. Methodological quality was assessed and summarized across studies descriptively. From screening 584 references, 68 full texts were reviewed and five studies included. These concerned 109 participants. The studies were deemed of low quality, due to evidence of bias, in part due to intervention complexity. No adverse effects were reported. Overall, there was a trend toward improved respiratory function, but only one study on Parkinson's disease had significant between-group differences. The positive trend in respiratory function in people with long-term neurological conditions following singing or wind instrument therapy is of interest, and warrants further investigation.

  13. Late Modern Play Culture

    DEFF Research Database (Denmark)

    Skovbjerg-Karoff, Helle

    2008-01-01

    Children's play and culture have changed over the recent years, and it is possible to understand the changes as a result of a more general change in society. We witness a large degree of changes connected to demographical aspects of children's lives. First of all it is a fact that large groups....... They are changing play arenas in order to find the identity, which suits them. In order to play children must know and be conscious of the cultural heritage, which contains knowledge of the way to organize in the playing session, the aesthetics, the techniques of playing, and this is something that is handed down...... from one generation to the next. Because older children are no longer present as younger children grow up, the traditional "cultural leaders" are gone. They have taken with them much of the inspiration for play as well as important knowledge about how to organise a game. In that sense we can say...

  14. DOES THE INFERIOR FRONTAL SULCUS PLAY A FUNCTIONAL ROLE IN DECEPTION? A NEURONAVIGATED THETA-BURST TRANSCRANIAL MAGNETIC STIMULATION STUDY

    Directory of Open Access Journals (Sweden)

    Bruno eVerschuere

    2012-10-01

    Full Text Available Background. By definition, lying involves withholding the truth. Response inhibition may therefore be the cognitive function at the heart of deception. Neuroimaging research has shown that the same brain region that is activated during response inhibition tasks, namely the inferior frontal region, is also activated during deception paradigms. This led to the hypothesis that the inferior frontal region is the neural substrate critically involved in withholding the truth. Objective. We critically examine the functional necessity of the inferior frontal region in withholding the truth during deception. Method. We experimentally manipulated the neural activity level in right inferior frontal sulcus (IFS by means of neuronavigated continuous theta burst stimulation (cTBS. Individual structural magnetic resonance brain images (MRI were used to allow precise stimulation in each participant. Twenty-six participants answered autobiographical questions truthfully or deceptively before and after sham and real cTBS. Results. Deception was reliably associated with more errors, longer and more variable response times than truth telling. Despite the potential role of IFS in deception as suggested by neuroimaging data, the cTBS-induced disruption of right IFS did not affect response times or error rates, when compared to sham stimulation. Conclusions. The present findings do not support the hypothesis that the right inferior frontal sulcus is critically involved in deception.

  15. How the choice of safety performance function affects the identification of important crash prediction variables.

    Science.gov (United States)

    Wang, Ketong; Simandl, Jenna K; Porter, Michael D; Graettinger, Andrew J; Smith, Randy K

    2016-03-01

    Across the nation, researchers and transportation engineers are developing safety performance functions (SPFs) to predict crash rates and develop crash modification factors to improve traffic safety at roadway segments and intersections. Generalized linear models (GLMs), such as Poisson or negative binomial regression, are most commonly used to develop SPFs with annual average daily traffic as the primary roadway characteristic to predict crashes. However, while more complex to interpret, data mining models such as boosted regression trees have improved upon GLMs crash prediction performance due to their ability to handle more data characteristics, accommodate non-linearities, and include interaction effects between the characteristics. An intersection data inventory of 36 safety relevant parameters for three- and four-legged non-signalized intersections along state routes in Alabama was used to study the importance of intersection characteristics on crash rate and the interaction effects between key characteristics. Four different SPFs were investigated and compared: Poisson regression, negative binomial regression, regularized generalized linear model, and boosted regression trees. The models did not agree on which intersection characteristics were most related to the crash rate. The boosted regression tree model significantly outperformed the other models and identified several intersection characteristics as having strong interaction effects.

  16. Inulin and Oligofructosis: a review about functional properties, prebiotic effects and importance for food industry

    Directory of Open Access Journals (Sweden)

    Maria Celia de Oliveira Hauly

    2002-01-01

    Full Text Available Nowadays consumers are more conscious about the relation between food and health. Therefore food industry has been looking for food that has a lot of benefits besides good flavor and appearance. Inulin and oligofructose are fructose polimers, vastly found in plants as storage carbohydrates. They present important functional for the food industry. Both inulin and oligofructose have been used as fiber bulk in food products. Differently from other fibers, they do not add flavor, allowing the food to be improved without changing its viscosity. Inulin and oligofructose have similar nutritional properties. Inulin is more indicated for obtaining products with a low fat content such as ice cream, cake and soup, while oligofructose is indicated for yogurt with a low caloric value and in order to mask the residual flavor from high intensity sweeteners used in food preparation. Research has shown that inulin and oligofructose have prebiotic effects because they are not digestible and they can develop bifidogenic effects, improving the intestinal microflora. The simultaneous use of inulin and oligofructose with probiotic agents in food is recommended for symbiotic effects.

  17. Prognostic importance of weight change on short-term functional outcome in acute ischemic stroke.

    Science.gov (United States)

    Kim, Yerim; Kim, Chi Kyung; Jung, Seunguk; Ko, Sang-Bae; Lee, Seung-Hoon; Yoon, Byung-Woo

    2015-10-01

    Controversy exists regarding the question of whether weight change decreases or increases the risk of mortality. The aim of this study was to evaluate the prognostic importance of weight change on short-term outcomes in acute ischemic stroke patients. A total of 654 patients with acute ischemic stroke were enrolled in this study from March 2010 to May 2013. We assessed the weight change of each participant between admission and discharge from the Department of Neurology. Weight change was defined as change ≥0·05 kg/baseline body mass index unit. We evaluated the short-term outcomes using a modified Rankin Scale at three-months after the onset of a stroke. Among the 654 patients, 35·2% were included in the weight-change group. Weight loss occurred in 24·6% of the participants during the hospital stay following the stroke, which lasted an average of nine-days. Compared with the weight-stable group, the pronounced weight-loss group had a higher risk of unfavorable outcomes (odds ratio 2·43; 95% confidence interval 1·12-5·25). Short-term weight loss after stroke appears to be more common than we expected, and our results suggest that it is associated with unfavorable functional outcomes. Therefore, clinical nutrition should be considered as a component of medical treatment and weight loss should be monitored as an indicator of malnutrition. © 2015 World Stroke Organization.

  18. Particle filter based on iterated importance density function and parallel resampling

    Institute of Scientific and Technical Information of China (English)

    武勇; 王俊; 曹运合

    2015-01-01

    The design, analysis and parallel implementation of particle filter (PF) were investigated. Firstly, to tackle the particle degeneracy problem in the PF, an iterated importance density function (IIDF) was proposed, where a new term associating with the current measurement information (CMI) was introduced into the expression of the sampled particles. Through the repeated use of the least squares estimate, the CMI can be integrated into the sampling stage in an iterative manner, conducing to the greatly improved sampling quality. By running the IIDF, an iterated PF (IPF) can be obtained. Subsequently, a parallel resampling (PR) was proposed for the purpose of parallel implementation of IPF, whose main idea was the same as systematic resampling (SR) but performed differently. The PR directly used the integral part of the product of the particle weight and particle number as the number of times that a particle was replicated, and it simultaneously eliminated the particles with the smallest weights, which are the two key differences from the SR. The detailed implementation procedures on the graphics processing unit of IPF based on the PR were presented at last. The performance of the IPF, PR and their parallel implementations are illustrated via one-dimensional numerical simulation and practical application of passive radar target tracking.

  19. Why do Dolphins Play?

    Directory of Open Access Journals (Sweden)

    Stan A. Kuczaj

    2014-05-01

    Full Text Available Play is an important aspect of dolphin life, perhaps even an essential one. Play provides opportunities for dolphin calves to practice and perfect locomotor skills, including those involved in foraging and mating strategies and behaviors. Play also allows dolphin calves to learn important social skills and acquire information about the characteristics and predispositions of members of their social group, particularly their peers. In addition to helping dolphin calves learn how to behave, play also provides valuable opportunities for them to learn how to think. The ability to create and control play contexts enables dolphins to create novel experiences for themselves and their playmates under relatively safe conditions. The behavioral variability and individual creativity that characterize dolphin play yield ample opportunities for individual cognitive development as well as social learning, and sometimes result in innovations that are reproduced by other members of the group. Although adults sometimes produce innovative play, calves are the primary source of such innovations. Calves are also more likely to imitate novel play behaviors than are adults, and so calves contribute significantly to both the creation and transmission of novel play behaviors within a group. Not unexpectedly, then, the complexity of dolphin play increases with the involvement of peers. As a result, the opportunity to observe and/or interact with other dolphin calves enhances the effects of play on the acquisition and maintenance of flexible problem solving skills, the emergence and strengthening of social and communicative competencies, and the establishment of social relationships. It seems that play may have evolved to help young dolphins learn to adapt to novel situations in both their physical and social worlds, the beneficial result being a set of abilities that increases the likelihood that an individual survives and reproduces.

  20. N-Glycosylation Is Important for Proper Haloferax volcanii S-Layer Stability and Function.

    Science.gov (United States)

    Tamir, Adi; Eichler, Jerry

    2017-03-15

    N-Glycosylation, the covalent linkage of glycans to select Asn residues of target proteins, is an almost universal posttranslational modification in archaea. However, whereas roles for N-glycosylation have been defined in eukarya and bacteria, the function of archaeal N-glycosylation remains unclear. Here, the impact of perturbed N-glycosylation on the structure and physiology of the haloarchaeon Haloferax volcanii was considered. Cryo-electron microscopy was used to examine right-side-out membrane vesicles prepared from cells of a parent strain and from strains lacking genes encoding glycosyltransferases involved in assembling the N-linked pentasaccharide decorating the surface layer (S-layer) glycoprotein, the sole component of the S-layer surrounding H. volcanii cells. Whereas a regularly repeating S-layer covered the entire surface of vesicles prepared from parent strain cells, vesicles from the mutant cells were only partially covered. To determine whether such N-glycosylation-related effects on S-layer assembly also affected cell function, the secretion of a reporter protein was addressed in the parent and N-glycosylation mutant strains. Compromised S-layer glycoprotein N-glycosylation resulted in impaired transfer of the reporter past the S-layer and into the growth medium. Finally, an assessment of S-layer glycoprotein susceptibility to added proteases in the mutants revealed that in cells lacking AglD, which is involved in adding the final pentasaccharide sugar, a distinct S-layer glycoprotein conformation was assumed in which the N-terminal region was readily degraded. Perturbed N-glycosylation thus affects S-layer glycoprotein folding. These findings suggest that H. volcanii could adapt to changes in its surroundings by modulating N-glycosylation so as to affect S-layer architecture and function.IMPORTANCE Long held to be a process unique to eukaryotes, it is now accepted that bacteria and archaea also perform N-glycosylation, namely, the covalent

  1. The disequilibrium of nucleosomes distribution along chromosomes plays a functional and evolutionarily role in regulating gene expression.

    Directory of Open Access Journals (Sweden)

    Peng Cui

    Full Text Available To further understand the relationship between nucleosome-space occupancy (NO and global transcriptional activity in mammals, we acquired a set of genome-wide nucleosome distribution and transcriptome data from the mouse cerebrum and testis based on ChIP (H3-seq and RNA-seq, respectively. We identified a nearly consistent NO patterns among three mouse tissues--cerebrum, testis, and ESCs--and found, through clustering analysis for transcriptional activation, that the NO variations among chromosomes are closely associated with distinct expression levels between house-keeping (HK genes and tissue-specific (TS genes. Both TS and HK genes form clusters albeit the obvious majority. This feature implies that NO patterns, i.e. nucleosome binding and clustering, are coupled with gene clustering that may be functionally and evolutionarily conserved in regulating gene expression among different cell types.

  2. The disequilibrium of nucleosomes distribution along chromosomes plays a functional and evolutionarily role in regulating gene expression

    KAUST Repository

    Cui, Peng

    2011-08-19

    To further understand the relationship between nucleosome-space occupancy (NO) and global transcriptional activity in mammals, we acquired a set of genome-wide nucleosome distribution and transcriptome data from the mouse cerebrum and testis based on ChIP (H3)-seq and RNA-seq, respectively. We identified a nearly consistent NO patterns among three mouse tissues-cerebrum, testis, and ESCs-and found, through clustering analysis for transcriptional activation, that the NO variations among chromosomes are closely associated with distinct expression levels between house-keeping (HK) genes and tissue-specific (TS) genes. Both TS and HK genes form clusters albeit the obvious majority. This feature implies that NO patterns, i.e. nucleosome binding and clustering, are coupled with gene clustering that may be functionally and evolutionarily conserved in regulating gene expression among different cell types. © 2011 Cui et al.

  3. Members of the Penicillium chrysogenum velvet complex play functionally opposing roles in the regulation of penicillin biosynthesis and conidiation.

    Science.gov (United States)

    Kopke, Katarina; Hoff, Birgit; Bloemendal, Sandra; Katschorowski, Alexandra; Kamerewerd, Jens; Kück, Ulrich

    2013-02-01

    A velvet multisubunit complex was recently detected in the filamentous fungus Penicillium chrysogenum, the major industrial producer of the β-lactam antibiotic penicillin. Core components of this complex are P. chrysogenum VelA (PcVelA) and PcLaeA, which regulate secondary metabolite production, hyphal morphology, conidiation, and pellet formation. Here we describe the characterization of PcVelB, PcVelC, and PcVosA as novel subunits of this velvet complex. Using yeast two-hybrid analysis and bimolecular fluorescence complementation (BiFC), we demonstrate that all velvet proteins are part of an interaction network. Functional analyses using single- and double-knockout strains clearly indicate that velvet subunits have opposing roles in the regulation of penicillin biosynthesis and light-dependent conidiation. PcVelC, together with PcVelA and PcLaeA, activates penicillin biosynthesis, while PcVelB represses this process. In contrast, PcVelB and PcVosA promote conidiation, while PcVelC has an inhibitory effect. Our genetic analyses further show that light-dependent spore formation depends not only on PcVelA but also on PcVelB and PcVosA. The results provided here contribute to our fundamental understanding of the function of velvet subunits as part of a regulatory network mediating signals responsible for morphology and secondary metabolism and will be instrumental in generating mutants with newly derived properties that are relevant to strain improvement programs.

  4. Autoinducer-2 plays a crucial role in gut colonization and probiotic functionality of Bifidobacterium breve UCC2003.

    Directory of Open Access Journals (Sweden)

    Steven E A Christiaen

    Full Text Available In the present study we show that luxS of Bifidobacterium breve UCC2003 is involved in the production of the interspecies signaling molecule autoinducer-2 (AI-2, and that this gene is essential for gastrointestinal colonization of a murine host, while it is also involved in providing protection against Salmonella infection in Caenorhabditis elegans. We demonstrate that a B. breve luxS-insertion mutant is significantly more susceptible to iron chelators than the WT strain and that this sensitivity can be partially reverted in the presence of the AI-2 precursor DPD. Furthermore, we show that several genes of an iron starvation-induced gene cluster, which are downregulated in the luxS-insertion mutant and which encodes a presumed iron-uptake system, are transcriptionally upregulated under in vivo conditions. Mutation of two genes of this cluster in B. breve UCC2003 renders the derived mutant strains sensitive to iron chelators while deficient in their ability to confer gut pathogen protection to Salmonella-infected nematodes. Since a functional luxS gene is present in all tested members of the genus Bifidobacterium, we conclude that bifidobacteria operate a LuxS-mediated system for gut colonization and pathogen protection that is correlated with iron acquisition.

  5. The Countermeasure Research on Playing the Important Role of Counselors in Vocational Education%发挥辅导员在高职教育教学中重要作用的对策研究

    Institute of Scientific and Technical Information of China (English)

    黄志勇; 李散绵

    2012-01-01

    文章从高职院校教育的特点和辅导员工作的特殊性出发,结合高职教育教学工作要求,提出发挥辅导员在高职教育教学中重要作用的对策。%This article from the characteristic of higher vocational education and the particularity of the counselor work,combined with higher vocational education teaching job requirements,develop the strategy of playing the important role of counselors in the teaching of higher vocational education.

  6. Linking functional traits and demographic rates in a subtropical tree community: the importance of size dependency

    National Research Council Canada - National Science Library

    Iida, Yoshiko; Kohyama, Takashi S; Swenson, Nathan G; Su, Sheng‐Hsin; Chen, Chien‐Teh; Chiang, Jyh‐Min; Sun, I‐Fang; Zuidema, Pieter

    2014-01-01

    .... Several functional traits have been shown to correlate with growth and mortality rates in trees, but less is known about how the relationships between functional traits and demographic rates change with tree size...

  7. Prognostic importance of systolic and diastolic function after acute myocardial infarction

    DEFF Research Database (Denmark)

    Møller, Jacob E; Egstrup, Kenneth; Køber, Lars

    2003-01-01

    BACKGROUND: Although risk stratification after acute myocardial infarction (AMI) often is focused on systolic left ventricular (LV) function, it appears that a more complete study of ventricular function including assessment of LV filling would be useful. Doppler echocardiography allows assessment...

  8. Automatic variance reduction for Monte Carlo simulations via the local importance function transform

    Energy Technology Data Exchange (ETDEWEB)

    Turner, S.A.

    1996-02-01

    The author derives a transformed transport problem that can be solved theoretically by analog Monte Carlo with zero variance. However, the Monte Carlo simulation of this transformed problem cannot be implemented in practice, so he develops a method for approximating it. The approximation to the zero variance method consists of replacing the continuous adjoint transport solution in the transformed transport problem by a piecewise continuous approximation containing local biasing parameters obtained from a deterministic calculation. He uses the transport and collision processes of the transformed problem to bias distance-to-collision and selection of post-collision energy groups and trajectories in a traditional Monte Carlo simulation of ``real`` particles. He refers to the resulting variance reduction method as the Local Importance Function Transform (LIFI) method. He demonstrates the efficiency of the LIFT method for several 3-D, linearly anisotropic scattering, one-group, and multigroup problems. In these problems the LIFT method is shown to be more efficient than the AVATAR scheme, which is one of the best variance reduction techniques currently available in a state-of-the-art Monte Carlo code. For most of the problems considered, the LIFT method produces higher figures of merit than AVATAR, even when the LIFT method is used as a ``black box``. There are some problems that cause trouble for most variance reduction techniques, and the LIFT method is no exception. For example, the author demonstrates that problems with voids, or low density regions, can cause a reduction in the efficiency of the LIFT method. However, the LIFT method still performs better than survival biasing and AVATAR in these difficult cases.

  9. Automatic variance reduction for Monte Carlo simulations via the local importance function transform

    Energy Technology Data Exchange (ETDEWEB)

    Turner, S.A.

    1996-02-01

    The author derives a transformed transport problem that can be solved theoretically by analog Monte Carlo with zero variance. However, the Monte Carlo simulation of this transformed problem cannot be implemented in practice, so he develops a method for approximating it. The approximation to the zero variance method consists of replacing the continuous adjoint transport solution in the transformed transport problem by a piecewise continuous approximation containing local biasing parameters obtained from a deterministic calculation. He uses the transport and collision processes of the transformed problem to bias distance-to-collision and selection of post-collision energy groups and trajectories in a traditional Monte Carlo simulation of ``real`` particles. He refers to the resulting variance reduction method as the Local Importance Function Transform (LIFI) method. He demonstrates the efficiency of the LIFT method for several 3-D, linearly anisotropic scattering, one-group, and multigroup problems. In these problems the LIFT method is shown to be more efficient than the AVATAR scheme, which is one of the best variance reduction techniques currently available in a state-of-the-art Monte Carlo code. For most of the problems considered, the LIFT method produces higher figures of merit than AVATAR, even when the LIFT method is used as a ``black box``. There are some problems that cause trouble for most variance reduction techniques, and the LIFT method is no exception. For example, the author demonstrates that problems with voids, or low density regions, can cause a reduction in the efficiency of the LIFT method. However, the LIFT method still performs better than survival biasing and AVATAR in these difficult cases.

  10. Ferritin has an important immune function in the ark shell Scapharca broughtonii.

    Science.gov (United States)

    Zheng, Libing; Liu, Zhihong; Wu, Biao; Dong, Yinghui; Zhou, Liqing; Tian, Jiteng; Sun, Xiujun; Yang, Aiguo

    2016-06-01

    Ferritin, the principle cytosolic iron storage protein in the majority of living organisms, has important roles during immune process in invertebrates. Detailed information about ferritin in the ark shell Scapharca broughtonii, however, has been very limited. In this study, full-length ferritin (termed SbFer) was cloned by the rapid amplication of cDNA ends (RACE) method based upon the sequence from the transcriptome library. The cDNA contained a 182 bp 5'-untranslated region, a 519 bp open reading frame encoding a polypeptide of 172 amino acids, a 229 bp 3'-untranslated region, and three introns (902, 373 and 402 bp) embedded in four exons. There was an iron response element (IRE) in the 5'-untranslated region. The deduced amino acid sequence of SbFer possessed many characteristics of vertebrate H type ferritin, shared 63%-91% identity with mollusks and greater identity with vertebrate H type ferritin compared to the L type. The SbFer gene expression pattern examined by quantitative real-time PCR showed ferritin mRNA was expressed in all ark shell tissues examined. The highest levels of expression were found in hemocytes with decreasing levels of expression in foot, mantle, gill, adductor muscle and hepatopancreas. A challenge with Vibrio anguillarum resulted in time-dependent significant upregulation of SbFer mRNA, indicating SbFer participated actively in the bacterial defense process. Further analysis of the antibacterial activity indicated recombinant SbFer could function as an immune antibacterial agent to both Gram-positive and Gram-negative bacteria. Taken together, these results suggested strongly that ferritin of the ark shell is involved in immune defense against microbial infection and it is a constitutive and inducible acute-phase protein.

  11. Play and Positive Group Dynamics

    Science.gov (United States)

    Thompson, Pam; White, Samantha

    2010-01-01

    Play is an important part of a child's life and essential to learning and development (Vygotsky, 1978). It is vital that students participate in play and that play be conducted in a restorative manner. Play allows a variety of group dynamics to emerge. Irvin Yalom (1995) identifies 11 curative factors of the group experience. These factors include…

  12. Type conversion of secretomes in a 3D TAM2 and HCC cell co-culture system and functional importance of CXCL2 in HCC

    Science.gov (United States)

    Lu, Yu; Li, Shan; Ma, Liping; Li, Yan; Zhang, Xiaolian; Peng, Qiliu; Mo, Cuiju; Huang, Li; Qin, Xue; Liu, Yinkun

    2016-01-01

    Macrophages play important roles in the tumor microenvironment, driving cancer progression and metastasis, particularly in hepatocellular carcinoma (HCC). However, few studies have assessed the exact secretome composition in HCC. In the present study, the impact of different phenotype of macrophages on HCC cells was investigated. Alternatively activated macrophages (M2) were found to significantly increase the proliferation, migration, and invasion abilities of SMMC7721 cells (all P 1.3-fold) and 96 down-regulated (<0.7-fold). CXCL2 was confirmed to have higher expression in the co-culture system and HCC tissues, and was selected for further investigation. Functional effects data suggested that recombinant human CXCL2 significantly enhanced the migration, invasion ability of SMMC7721 cells, and weakened adhesion ability. While CXCL2 neutralization and CXCR2 blockage significantly inhibited the effects of CXCL2 on SMMC7721 cells, indicating that CXCL2 may play pivotal role in HCC metastasis. PMID:27117207

  13. Identifying faecal impaction is important for ensuring the timely diagnosis of childhood functional constipation

    DEFF Research Database (Denmark)

    Modin, Line; Walsted, Anne-Mette; Jakobsen, Marianne Skytte

    2015-01-01

    AIM: Most research on functional constipation has been carried out at a tertiary level. We focused this study on a secondary-level hospital outpatients' department, assessing the distribution of diagnostic criteria for childhood functional constipation and evaluating the consequences of current...... diagnostic practice based on current guidelines. METHODS: We enrolled 235 children, aged two to 16 years of age, with functional constipation according to the Rome III criteria and assessed them using medical histories and physical examinations, including rectal examinations and ultrasound measurements...... the timely diagnosis of childhood functional constipation at the secondary care level. Ultrasound examination proved a reliable alternative to rectal examination or abdominal radiography when identifying faecal impaction....

  14. TO STUDY THE EFFECT OF PLAY THERAPY AND CHILD FRIENDLY CONSTRAINT INDUCED MOMEMENT THERAPY TO IMPROVE HAND FUNCTION IN SPASTIC HEMIPLEGIC CEREBRAL PALSY CHILDREN: A COMPARATIVE STUDY

    Directory of Open Access Journals (Sweden)

    Anjuman Nahar

    2015-12-01

    Full Text Available Background: Cerebral Palsy (CP is a neurodevelopmental disorder caused by nonprogressive lesion in the developing brain. The early central nervous system (CNS damage results in chronic physical disabilities and often includes sensory impairments. In addition CP is often associated with epilepsy and abnormalities of speech, vision, and intellect; it is the selective vulnerability of the brains motor systems that defines the disorder. Child friendly CIMT involves intensive targeted practice with the involved extremity coordination above and beyond their unilateral impairments. Ply Therapy is designed for active involvement of child in performing various tasks. The aim of the study is to evaluate the effectiveness of constraint induced movement therapy and play therapy to improve hand function in spastic hemiplegic cerebral palsy children. Methods: A sample of 30 patients was divided in two groups, each group having 15 children. Convenient sampling was done on the basis of base line assessment and diagnosis of their condition. Duration of the study was 3 months and data collection started at day 0 and at the end of 90 days. Children in group A wore a bivalve plaster cast on the non-involved upper extremity from shoulder to finger tips for the entire time during the session lasting for 2 hours and the plaster cast was removed at the end of the session. B group consists of 15 subjects who received play therapy. The treatment program was conducted individually and adjusted to current needs and abilities of each of the patients. Outcomes: Box and Block test, QOM scale and AOU scale. Results: It was found that there is an improvement in the hand function on application of child friendly CIMT in the patients with spastic hemiplegic cerebral palsy which was found significant using the Mann-Whitney U test (p≤0.005. Conclusion: In this study it has been found that the use of Child friendly CIMT and PLAY THERAPY produces significant improvement in hand

  15. Nitrate removal in a restored riparian groundwater system: functioning and importance of individual riparian zones

    Directory of Open Access Journals (Sweden)

    S. Peter

    2012-11-01

    Full Text Available For the design and the assessment of river restoration projects, it is important to know to what extent the elimination of reactive nitrogen (N can be improved in the riparian groundwater. We investigated the effectiveness of different riparian zones, characterized by a riparian vegetation succession, for nitrate (NO3 removal from infiltrating river water in a restored and a still channelized section of the river Thur, Switzerland. Functional genes of denitrification (nirS and nosZ were relatively abundant in groundwater from willow bush and mixed forest dominated zones, where oxygen concentrations remained low compared to the main channel and other riparian zones. After flood events, a substantial decline in NO3 concentration (> 50% was observed in the willow bush zone but not in the other riparian zones closer to the river. In addition, the characteristic enrichment of 15N and 18O in the residual NO3 pool (by up to 22‰ for δ15N and up to 12‰ for δ18O provides qualitative evidence that the willow bush and forest zones were sites of active denitrification and, to a lesser extent, NO3 removal by plant uptake. Particularly in the willow bush zone during a period of water table elevation after a flooding event, substantial input of organic carbon into the groundwater occurred, thereby fostering post-flood denitrification activity that reduced NO3 concentration with a rate of ~21 μmol N l−1 d−1. Nitrogen removal in the forest zone was not sensitive to flood pulses, and overall NO3 removal rates were lower (~6 μmol l−1 d−1. Hence, discharge-modulated vegetation–soil–groundwater coupling was found to be a key driver for riparian NO3 removal. We estimated that

  16. Nitrate removal in a restored riparian groundwater system: functioning and importance of individual riparian zones

    Science.gov (United States)

    Peter, S.; Rechsteiner, R.; Lehmann, M. F.; Brankatschk, R.; Vogt, T.; Diem, S.; Wehrli, B.; Tockner, K.; Durisch-Kaiser, E.

    2012-11-01

    For the design and the assessment of river restoration projects, it is important to know to what extent the elimination of reactive nitrogen (N) can be improved in the riparian groundwater. We investigated the effectiveness of different riparian zones, characterized by a riparian vegetation succession, for nitrate (NO3-) removal from infiltrating river water in a restored and a still channelized section of the river Thur, Switzerland. Functional genes of denitrification (nirS and nosZ) were relatively abundant in groundwater from willow bush and mixed forest dominated zones, where oxygen concentrations remained low compared to the main channel and other riparian zones. After flood events, a substantial decline in NO3- concentration (> 50%) was observed in the willow bush zone but not in the other riparian zones closer to the river. In addition, the characteristic enrichment of 15N and 18O in the residual NO3- pool (by up to 22‰ for δ15N and up to 12‰ for δ18O) provides qualitative evidence that the willow bush and forest zones were sites of active denitrification and, to a lesser extent, NO3- removal by plant uptake. Particularly in the willow bush zone during a period of water table elevation after a flooding event, substantial input of organic carbon into the groundwater occurred, thereby fostering post-flood denitrification activity that reduced NO3- concentration with a rate of ~21 μmol N l-1 d-1. Nitrogen removal in the forest zone was not sensitive to flood pulses, and overall NO3- removal rates were lower (~6 μmol l-1 d-1). Hence, discharge-modulated vegetation-soil-groundwater coupling was found to be a key driver for riparian NO3- removal. We estimated that, despite higher rates in the fairly constrained willow bush hot spot, total NO3- removal from the groundwater is lower than in the extended forest area. Overall, the aquifer in the restored section was more effective and removed ~20% more NO3- than the channelized section.

  17. Functional outcomes of child and adolescent mental disorders. Current disorder most important but psychiatric history matters as well

    NARCIS (Netherlands)

    Ormel, J; Oerlemans, A M; Raven, D; Laceulle, O M; Hartman, C A; Veenstra, R.; Verhulst, F C; Vollebergh, W; Rosmalen, J G M; Reijneveld, S A; Oldehinkel, A J

    Background. Various sources indicate that mental disorders are the leading contributor to the burden of disease among youth. An important determinant of functioning is current mental health status. This study investigated whether psychiatric history has additional predictive power when predicting

  18. The 101st Canton Fair,Import Functions Added, Eyes New Market,New Trade Partners

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ The 101st Session of Canton Fair will be held in Canton city,Guangdong province from April 15 to 30, 2007. The fair, used to be named as China Export Commodities Fair for 100 sessions, is to be rebranded as China Import and Export Fair. By changing the name, a new service as import will be added, so as to encourage more import to meet the capacious market demand in China market, pursuing a more balanced and healthier international trade development.

  19. The importance of current contributions to shielding constants in density-functional theory.

    Science.gov (United States)

    Reimann, Sarah; Ekström, Ulf; Stopkowicz, Stella; Teale, Andrew M; Borgoo, Alex; Helgaker, Trygve

    2015-07-28

    The sources of error in the calculation of nuclear-magnetic-resonance shielding constants determined by density-functional theory are examined. Highly accurate Kohn-Sham wave functions are obtained from coupled-cluster electron density functions and used to define accurate-but current independent-density-functional shielding constants. These new reference values, in tandem with high-accuracy coupled-cluster shielding constants, provide a benchmark for the assessment of errors in common density-functional approximations. In particular the role of errors arising in the diamagnetic and paramagnetic terms is investigated, with particular emphasis on the role of current-dependence in the latter. For carbon and nitrogen the current correction is found to be, in some cases, larger than 10 ppm. This indicates that the absence of this correction in general purpose exchange-correlation functionals is one of the main sources of error in shielding calculations using density functional theory. It is shown that the current correction improves the shielding performance of many popular approximate DFT functionals.

  20. Pretend Play and Creative Processes

    Science.gov (United States)

    Russ, Sandra W.; Wallace, Claire E.

    2013-01-01

    The authors contend that many cognitive abilities and affective processes important in creativity also occur in pretend play and that pretend play in childhood affects the development of creativity in adulthood. They discuss a variety of theories and observations that attempt to explain the importance of pretend play to creativity. They argue that…

  1. Interpersonal Attraction Toward a Black Person as a Function of Value Importance.

    Science.gov (United States)

    Penner, Louis A.

    The purpose of this study was to test two hypotheses derived from Rokeach's (1968) theory of values and value change. These were: (1) that interpersonal attraction toward a black person will be correlated with the importance of the value, "equality," and (2) that changes in the importance of the value, "equality," will be…

  2. Cortisol secretion and functional disabilities in old age: importance of using adaptive control strategies.

    Science.gov (United States)

    Wrosch, Carsten; Miller, Gregory E; Schulz, Richard

    2009-11-01

    To examine whether the use of health-related control strategies moderates the association between elevated diurnal cortisol secretion and increases in older adults' functional disabilities. Functional disabilities of 164 older adults were assessed over 4 years by measuring participants' problems with performing activities of daily living. The main predictors included baseline levels of diurnal cortisol secretion and control strategies used to manage physical health threats. A large increase in functional disabilities was observed among participants who secreted elevated baseline levels of cortisol and did not use health-related control strategies. By contrast, high cortisol level was not associated with increases in functional disabilities among participants who reported using these control strategies. Among participants with low cortisol level, there was a relatively smaller increase in functional disabilities over time, and the use of control strategies was not significantly associated with changes in functional disabilities. The findings suggest that high cortisol level is associated with an increase in older adults' functional disabilities, but only if older adults do not engage in adaptive control strategies.

  3. Evaluating the Importance of Plant Functional Traits: the Subalpine and Alpine

    Science.gov (United States)

    Sanchez, A.; Smith, W. K.

    2011-12-01

    Over the past several decades, researchers have attempted to characterize plant groups according to traits that are considered functional, i.e. contributing significantly to fitness. Due to the complexity of measuring fitness, the capability for photosynthetic carbon gain is often used as a proxy. Thus, this approach correlates structural differences to photosynthetic performance, especially those differences that are known to be associated with photosynthesis, are easily measured and inexpensive. At the often sharp boundary between the subalpine forest and alpine community (treeline ecotone), plant structural traits change dramatically, i.e. tall evergreen trees give way abruptly to low-stature shrubs, grasses, forbs, and herbs. Yet, the differences in functional traits, so abundant in the literature for a variety of species and communities, have not been compared contiguous communities such as the subalpine forest and alpine. Can differences in functional traits already identified in the literature also be used to characterize species of these two contrasting communities? Or are there other traits that are most functional and/or, possibly, unique to each community and not the most popular traits reported so far in the literature. Also, does the community structure itself help determine functional traits? For example, the top ten most frequently studied traits (145 total papers from approximately 63 different refereed journals) considered functional include the following (% of the 145 publications): specific leaf area or mass (SLA or SLM 39%), plant height (36%), leaf nitrogen content (34%), leaf size (19%), leaf area (16%), leaf photosynthetic performance (15%), leaf dry matter content (LDMC 15%), leaf mass per unit leaf area (LMA 15%), leaf thickness (15%), and seed mass (14%). In addition, another 120 traits were mentioned as functional, although all fell below a 14% citation rate. Particular focus was placed on this group due to the possibility that they might

  4. Variable importance of macrofaunal functional biodiversity for biogeochemical cycling in temperate coastal sediments

    OpenAIRE

    Braeckman, U.; Yazdani Foshtomi, M.; Van Gansbeke, D.; Meysman, F.; Soetaert, K.; Vincx, M.; Vanaverbeke, J.

    2014-01-01

    Coastal marine systems are currently subject to a variety of anthropogenic and climate-change-induced pressures. An important challenge is to predict how marine sediment communities and benthic biogeochemical cycling will be affected by these ongoing changes. To this end, it is of paramount importance to first better understand the natural variability in coastal benthic biogeochemical cycling and how this is influenced by local environmental conditions and faunal biodiversity. Here, we studie...

  5. Murine Herc6 Plays a Critical Role in Protein ISGylation In Vivo and Has an ISGylation-Independent Function in Seminal Vesicles.

    Science.gov (United States)

    Arimoto, Kei-ichiro; Hishiki, Takayuki; Kiyonari, Hiroshi; Abe, Takaya; Cheng, Chuyi; Yan, Ming; Fan, Jun-Bao; Futakuchi, Mitsuru; Tsuda, Hiroyuki; Murakami, Yoshiki; Suzuki, Hideyuki; Zhang, Dong-Er; Shimotohno, Kunitada

    2015-05-01

    ISG15 conjugation (ISGylation) to proteins is a multistep process involving interferon (IFN)-inducible UBE1L (E1), UbcH8 (E2), and ISG15 E3 ligases (E3s). Studies performed over the past several years have shown that ISGylation plays a pivotal role in the host antiviral response against certain viruses. Recent in vitro studies revealed that human Herc5 and mouse Herc6 are major ISG15 E3 ligases, respectively. However, the global function of Herc5/6 proteins in vivo still remains unclear. Here, we report generation and initial characterization of Herc6 knockout mice. Substantial reductions of ISGylation were observed in Herc6-deficient cells after polyinosinic-polycytidylic acid double-stranded RNA injection of mice or IFN treatment of cells. On the other hand, Herc6-deficient cells and wild-type (WT) cells had similar responses to IFN stimulation, Sendai virus (Z strain) infection, and vesicular stomatitis virus infection. These results indicate that Herc6 does not play a critical role in antiviral defense of these viral infections in mice. Interestingly, male Herc6-deficient mice showed seminal vesicle hypertrophy. No such problem was detected in WT and ISG15 activating enzyme Ube1L-deficient mice. These results suggest that in addition to promoting protein ISGylation, Herc6 has a novel and protein ISGylation-independent function in the male reproductive system.

  6. Importance of the Kinetic Energy Density for Band Gap Calculations in Solids with Density Functional Theory.

    Science.gov (United States)

    Tran, Fabien; Blaha, Peter

    2017-05-04

    Recently, exchange-correlation potentials in density functional theory were developed with the goal of providing improved band gaps in solids. Among them, the semilocal potentials are particularly interesting for large systems since they lead to calculations that are much faster than with hybrid functionals or methods like GW. We present an exhaustive comparison of semilocal exchange-correlation potentials for band gap calculations on a large test set of solids, and particular attention is paid to the potential HLE16 proposed by Verma and Truhlar. It is shown that the most accurate potential is the modified Becke-Johnson potential, which, most noticeably, is much more accurate than all other semilocal potentials for strongly correlated systems. This can be attributed to its additional dependence on the kinetic energy density. It is also shown that the modified Becke-Johnson potential is at least as accurate as the hybrid functionals and more reliable for solids with large band gaps.

  7. Importance of local exact exchange potential in hybrid functionals for accurate excited states

    CERN Document Server

    Kim, Jaewook; Hwang, Sang-Yeon; Ryu, Seongok; Choi, Sunghwan; Kim, Woo Youn

    2016-01-01

    Density functional theory has been an essential analysis tool for both theoretical and experimental chemists since accurate hybrid functionals were developed. Here we propose a local hybrid method derived from the optimized effective potential (OEP) method and compare its distinct features with conventional nonlocal ones from the Hartree-Fock (HF) exchange operator. Both are formally exact for ground states and thus show similar accuracy for atomization energies and reaction barrier heights. For excited states, the local version yields virtual orbitals with N-electron character, while those of the nonlocal version have mixed characters between N- and (N+1)-electron orbitals. As a result, the orbital energy gaps from the former well approximate excitation energies with a small mean absolute error (MAE = 0.40 eV) for the Caricato benchmark set. The correction from time-dependent density functional theory with a simple local density approximation kernel further improves its accuracy by incorporating multi-config...

  8. The structure, function, and importance of ceramides in skin and their use as therapeutic agents in skin-care products.

    Science.gov (United States)

    Meckfessel, Matthew H; Brandt, Staci

    2014-07-01

    Ceramides (CERs) are epidermal lipids that are important for skin barrier function. Much research has been devoted to identifying the numerous CERs found in human skin and their function. Alterations in CER content are associated with a number of skin diseases such as atopic dermatitis. Newer formulations of skin-care products have incorporated CERs into their formulations with the goal of exogenously applying CERs to help skin barrier function. CERs are a complex class of molecules and because of their growing ubiquity in skin-care products, a clear understanding of their role in skin and use in skin-care products is essential for clinicians treating patients with skin diseases. This review provides an overview of the structure, function, and importance of skin CERs in diseased skin and how CERs are being used in skin-care products to improve or restore skin barrier function. Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  9. Play and Power

    DEFF Research Database (Denmark)

    The power of play, so central to psychoanalytic theory and practice, is conjoined to the social psychological or socio-politically coloured concept of power, giving rise to many fruitful discussions of how these concepts manifest themselves in clinical work with children, groups and adults....... The inspiration for this book was the 3-section EFPP conference in Copenhagen in May 2007 with the main theme "Play and Power". At the conference and in the book, this theme is presented both inside and outside the therapeutic space. It is amply illustrated in clinical cases from individual psychotherapies....... Play and power are also explored in the broader context of the community, however. In relation to society at large, psychoanalytic psychotherapy has important contributions to offer society, and we need playful creativity and power to bring forward our knowledge about it....

  10. The transmembrane tyrosines Y56, Y91 and Y167 play important roles in determining the affinity and transport rate of the rabbit proton-coupled peptide transporter PepT1.

    Science.gov (United States)

    Pieri, Myrtani; Gan, Christine; Bailey, Patrick; Meredith, David

    2009-11-01

    The mammalian proton-coupled peptide transporter PepT1 is widely accepted as the major route of uptake for dietary nitrogen, as well as being responsible for the oral absorption of a number of classes of drugs, including beta-lactam antibiotics and angiotensin-converting enzyme (ACE) inhibitors. Using site-directed mutagenesis and zero-trans transport assays, we investigated the role of conserved tyrosines in the transmembrane domains (TMDs) of rabbit PepT1 as predicted by hydropathy plots. All the individual TMD tyrosines were substituted with phenylalanine and shown to retain the ability to traffic to the plasma membrane of Xenopus laevis oocytes. These single substitutions of TMD tyrosines by phenylalanine residues did not affect the proton dependence of peptide uptake, with all retaining wild-type PepT1-like pH dependence. Individual mutations of four of the nine TMD residue tyrosines (Y64, Y287, Y345 and Y587) were without measurable effect on PepT1 function, whereas the other five (Y12, Y56, Y91, Y167 and Y345) were shown to result in altered transport function compared to the wild-type PepT1. Intriguingly, the affinity of Y56F-PepT1 was found to be dramatically increased (approximately 100-fold) in comparison to that of the wild-type rabbit PepT1. Y91 mutations also affected the substrate affinity of the transporter, which increased in line with the hydrophilicity of the substituted amino acid (F>Y>Q>R). Y167 was demonstrated to play a pivotal role in rabbit PepT1 function since Y167F, Y167R and Y167Q demonstrated very little transport function. These results are discussed with regard to a proposed mechanism for PepT1 substrate binding.

  11. How Language Learners Can Improve Their Emotional Functioning: Important Psychological and Psychospiritual Theories

    Science.gov (United States)

    Oxford, Rebecca L.

    2015-01-01

    Emotion is "the primary human motive" (MacIntyre, 2002, p. 61). The human brain is an emotional brain, creating relationships among thought, emotion, and motivation in a complex dynamic system (Dörnyei, 2009). Emotion "functions as an amplifier, providing the intensity, urgency, and energy to propel our behavior" in…

  12. How Language Learners Can Improve Their Emotional Functioning: Important Psychological and Psychospiritual Theories

    Science.gov (United States)

    Oxford, Rebecca L.

    2015-01-01

    Emotion is "the primary human motive" (MacIntyre, 2002, p. 61). The human brain is an emotional brain, creating relationships among thought, emotion, and motivation in a complex dynamic system (Dörnyei, 2009). Emotion "functions as an amplifier, providing the intensity, urgency, and energy to propel our behavior" in…

  13. IMPORTANCE OF ACTIVATED CARBON'S OXYGEN SURFACE FUNCTIONAL GROUPS ON ELEMENTAL MERCURY ADSORPTION

    Science.gov (United States)

    The effect of varying physical and chemical properties of activated carbons on adsorption of elemental mercury [Hg(0)] was studied by treating two activated carbons to modify their surface functional groups and pore structures. Heat treatment (1200 K) in nitrogen (N2), air oxidat...

  14. Self-Monitoring Interventions for At-Risk Middle School Students: The Importance of Considering Function

    Science.gov (United States)

    Briere, Donald E., III; Simonsen, Brandi

    2011-01-01

    Self-monitoring is a popular, efficient, and effective intervention that is associated with improved academic and social behavior for students across age and ability levels. To date, this is the first study to directly compare the outcomes of self-monitoring functionally relevant and non-relevant replacement behaviors. Specifically, we used an…

  15. New functions of the chloroplast Preprotein and Amino acid Transporter (PRAT) family members in protein import.

    Science.gov (United States)

    Rossig, Claudia; Reinbothe, Christiane; Gray, John; Valdes, Oscar; von Wettstein, Diter; Reinbothe, Steffen

    2014-01-01

    Plant cells contain distinct compartments such as the nucleus, the endomembrane system comprising the endoplasmic reticulum and Golgi apparatus, peroxisomes, vacuoles, as well as mitochondria and chloroplasts. All of these compartments are surrounded by 1 or 2 limiting membranes and need to import proteins from the cytosol. Previous work led to the conclusion that mitochondria and chloroplasts use structurally different protein import machineries in their outer and inner membranes for the uptake of cytosolic precursor proteins. Our most recent data show that there is some unexpected overlap. Three members of the family of preprotein and amino acid transporters, PRAT, were identified in chloroplasts that mediate the uptake of transit sequence-less proteins into the inner plastid envelope membrane. By analogy, mitochondria contain with TIM22 a related PRAT protein that is involved in the import of transit sequence-less proteins into the inner mitochondrial membrane. Both mitochondria and chloroplasts thus make use of similar import mechanisms to deliver some of their proteins to their final place. Because single homologs of HP20- and HP30-like proteins are present in algae such as Chlamydomonas, Ostreococcus, and Volvox, which diverged from land plants approximately 1 billion years ago, it is likely that the discovered PRAT-mediated mechanism of protein translocation evolved concomitantly with the secondary endosymbiotic event that gave rise to green plants.

  16. Heterologous expression of a membrane-spanning auxin importer: implications for functional analyses of auxin transporters.

    Science.gov (United States)

    Carrier, David John; Abu Bakar, Norliza Tendot; Lawler, Karen; Dorrian, James Matthew; Haider, Ameena; Bennett, Malcolm John; Kerr, Ian Derek

    2009-01-01

    Biochemical studies of plant auxin transporters in vivo are made difficult by the presence of multiple auxin transporters and auxin-interacting proteins. Furthermore, the expression level of most such transporters in plants is likely to be too low for purification and downstream functional analysis. Heterologous expression systems should address both of these issues. We have examined a number of such systems for their efficiency in expressing AUX1 from Arabidopsis thaliana. We find that a eukaryotic system based upon infection of insect cells with recombinant baculovirus provides a high level, easily scalable expression system capable of delivering a functional assay for AUX1. Furthermore, a transient transfection system in mammalian cells enables localization of AUX1 and AUX1-mediated transport of auxin to be investigated. In contrast, we were unable to utilise P. pastoris or L. lactis expression systems to reliably express AUX1.

  17. Importance of N-Glycosylation on CD147 for Its Biological Functions

    Directory of Open Access Journals (Sweden)

    Yang Bai

    2014-04-01

    Full Text Available Glycosylation of glycoproteins is one of many molecular changes that accompany malignant transformation. Post-translational modifications of proteins are closely associated with the adhesion, invasion, and metastasis of tumor cells. CD147, a tumor-associated antigen that is highly expressed on the cell surface of various tumors, is a potential target for cancer diagnosis and therapy. A significant biochemical property of CD147 is its high level of glycosylation. Studies on the structure and function of CD147 glycosylation provide valuable clues to the development of targeted therapies for cancer. Here, we review current understanding of the glycosylation characteristics of CD147 and the glycosyltransferases involved in the biosynthesis of CD147 N-glycans. Finally, we discuss proteins regulating CD147 glycosylation and the biological functions of CD147 glycosylation.

  18. Emotion perception and functional outcome in schizophrenia: the importance of negative valence and fear.

    Science.gov (United States)

    Brittain, Philip J; Ffytche, Dominic H; Surguladze, Simon A

    2012-12-30

    A substantial body of work has demonstrated that persons with schizophrenia have a deficit in the perception of emotional stimuli. More recently this deficit has been linked to poor functional outcomes (FO) in this group. The current research investigated the perception of emotional stimuli in a group of 64 schizophrenia patients and 65 matched healthy controls. In the patient group, across two different emotion perception tasks and a social perception task, small deficits were found in the perception of negative, positive and neutrally valenced stimuli. Only the ability to perceive negative and neutrally valenced stimuli significantly correlated with a set of FO measures in the patients, with one task indicating these associations were strongest for the perception of fear. Subsequent regression modelling, controlling for the effects of symptomatology, demonstrated that for each of the three tasks, the measure of negative valence perception accounted for a similar but small amount (4%) of the variance seen in the functional status of the patients.

  19. Importance of N-glycosylation on CD147 for its biological functions.

    Science.gov (United States)

    Bai, Yang; Huang, Wan; Ma, Li-Tian; Jiang, Jian-Li; Chen, Zhi-Nan

    2014-04-15

    Glycosylation of glycoproteins is one of many molecular changes that accompany malignant transformation. Post-translational modifications of proteins are closely associated with the adhesion, invasion, and metastasis of tumor cells. CD147, a tumor-associated antigen that is highly expressed on the cell surface of various tumors, is a potential target for cancer diagnosis and therapy. A significant biochemical property of CD147 is its high level of glycosylation. Studies on the structure and function of CD147 glycosylation provide valuable clues to the development of targeted therapies for cancer. Here, we review current understanding of the glycosylation characteristics of CD147 and the glycosyltransferases involved in the biosynthesis of CD147 N-glycans. Finally, we discuss proteins regulating CD147 glycosylation and the biological functions of CD147 glycosylation.

  20. Cherubism Gene Sh3bp2 is Important for Optimal Bone Formation, Osteoblast Differentiation and Function

    Science.gov (United States)

    Mukherjee, Padma M.; Wang, Chiachien J.; Chen, I-Ping; Jafarov, Toghrul; Olsen, Bjorn R.; Ueki, Yasuyoshi; Reichenberger, Ernst J.

    2012-01-01

    Introduction Cherubism is a human genetic disorder that causes bilateral symmetrical enlargement of the maxilla and mandible in children. It is caused by mutations in SH3BP2. The exact pathogenesis of the disorder is an area of active research. Sh3bp2 knock-in mice were developed by introducing a Pro416Arg mutation (Pro418Arg in humans) in the mouse genome. The osteoclast phenotype of this mouse model was recently described. Methods We examined the bone phenotype of the cherubism mouse model, the role of Sh3bp2 during bone formation, osteoblast differentiation and osteoblast function. Results We observed delays in early postnatal development of homozygous Sh3bp2KI/KI mice. Sh3bp2KI/KI mice exhibit increased growth plate thickness and significantly decreased trabecular bone thickness and reduced bone mineral density. Histomorphometric and μ-CT analyses reveal bone loss in cranial and appendicular skeleton. Sh3bp2KI/KI mice also exhibit a significant decrease in osteoid formation that indicates a defect in osteoblast function. Calvarial osteoblast cell cultures exhibit a decrease in alkaline phosphatase expression and mineralization suggesting reduced differentiation potential. Gene expression of osteoblast differentiation markers like collagen type-I, alkaline phosphatase and osteocalcin are decreased in osteoblast cultures from Sh3bp2KI/KI mice. Conclusions These data suggest that Sh3bp2 function regulates bone homeostasis not only through osteoclast-specific effects but also through effects on osteoblast differentiation and function. PMID:20691350

  1. Hippocampal volumes are important predictors for memory function in elderly women

    Directory of Open Access Journals (Sweden)

    Adolfsdottir Steinunn

    2009-08-01

    Full Text Available Abstract Background Normal aging involves a decline in cognitive function that has been shown to correlate with volumetric change in the hippocampus, and with genetic variability in the APOE-gene. In the present study we utilize 3D MR imaging, genetic analysis and assessment of verbal memory function to investigate relationships between these factors in a sample of 170 healthy volunteers (age range 46–77 years. Methods Brain morphometric analysis was performed with the automated segmentation work-flow implemented in FreeSurfer. Genetic analysis of the APOE genotype was determined with polymerase chain reaction (PCR on DNA from whole-blood. All individuals were subjected to extensive neuropsychological testing, including the California Verbal Learning Test-II (CVLT. To obtain robust and easily interpretable relationships between explanatory variables and verbal memory function we applied the recent method of conditional inference trees in addition to scatterplot matrices and simple pairwise linear least-squares regression analysis. Results APOE genotype had no significant impact on the CVLT results (scores on long delay free recall, CVLT-LD or the ICV-normalized hippocampal volumes. Hippocampal volumes were found to decrease with age and a right-larger-than-left hippocampal asymmetry was also found. These findings are in accordance with previous studies. CVLT-LD score was shown to correlate with hippocampal volume. Multivariate conditional inference analysis showed that gender and left hippocampal volume largely dominated predictive values for CVLT-LD scores in our sample. Left hippocampal volume dominated predictive values for females but not for males. APOE genotype did not alter the model significantly, and age was only partly influencing the results. Conclusion Gender and left hippocampal volumes are main predictors for verbal memory function in normal aging. APOE genotype did not affect the results in any part of our analysis.

  2. Structure-Function of CD36 and Importance of Fatty Acid Signal Transduction in Fat Metabolism

    OpenAIRE

    Pepino, Marta Yanina; Kuda, Ondrej; Samovski, Dmitri; Abumrad, Nada A.

    2014-01-01

    CD36 is a scavenger receptor that functions in high affinity tissue uptake of long chain fatty acids (FA) and contributes under excessive fat supply to lipid accumulation and metabolic dysfunction. This review describes recent evidence regarding the CD36 FA binding site and a potential mechanism for FA transfer. It also presents the view that CD36 and FA signaling coordinate fat utilization based on newly identified CD36 actions that involve oral fat perception, intestinal fat absorption, sec...

  3. Distribution dynamics and functional importance of NHERF1 in regulation of Mrp-2 trafficking in hepatocytes.

    Science.gov (United States)

    Karvar, Serhan; Suda, Jo; Zhu, Lixin; Rockey, Don C

    2014-10-15

    Na(+)/H(+) exchanger regulatory factor 1 (NHERF1) is a multifunctional scaffolding protein that interacts with receptors and ion transporters in its PDZ domains and with the ezrin-radixin-moesin (ERM) family of proteins in its COOH terminus. The role of NHERF1 in hepatocyte function remains largely unknown. We examine the distribution and physiological significance of NHERF1 and multidrug resistance-associated protein 2 (Mrp-2) in hepatocytes. A WT radixin binding site mutant (F355R) and NHERF1 PDZ1 and PDZ2 domain adenoviral mutant constructs were tagged with yellow fluorescent protein and expressed in polarized hepatocytes to study localization and function of NHERF1. Cellular distribution of NHERF1 and radixin was visualized by fluorescence microscopy. A 5-chloromethylfluorescein diacetate (CMFDA) assay was used to characterize Mrp-2 function. Similar to Mrp-2, WT NHERF1 and the NHERF1 PDZ2 deletion mutant were localized to the canalicular membrane. In contrast, the radixin binding site mutant (F355R) and the NHERF1 PDZ1 deletion mutant, which interacts poorly with Mrp-2, were rarely associated with the canalicular membrane. Knockdown of NHERF1 led to dramatically impaired CMFDA secretory response. Use of CMFDA showed that the NHERF1 PDZ1 and F355R mutants were devoid of a secretory response, while WT NHERF1-infected cells exhibited increased secretion of glutathione-methylfluorescein. The data indicate that NHERF1 interacts with Mrp-2 via the PDZ1 domain of NHERF1 and, furthermore, that NHERF1 is essential for maintaining the localization and function of Mrp-2.

  4. Importance of Being Nernst: Synaptic Activity and Functional Relevance in Stem Cell-derived Neurons

    Science.gov (United States)

    2015-07-26

    derived from totipotent cells collected from the inner cell mass of embryos at the blastocyst stage[115]. Mouse ESC are frequently differentiated to...neurons derived from fetal NSCs have also found that long- term integration and transplanted neurons conferred resistance to PD in mouse models[208... Transplantation increases regeneration and functional recovery after ischemic stroke in neonatal rats. Stem Cells 2014; 32: 3075-3087 [PMID: 25132189 DOI

  5. IMPORTANCE OF ILIOPSOAS AND ERECTOR SPINAE MUSCLES IN PREDICTING THE FUNCTIONAL COMPETENCE OF TRANSFEMORAL AMPUTEES

    Directory of Open Access Journals (Sweden)

    Lajja K Rishi

    2014-10-01

    Full Text Available Purpose: Muscle imbalance in transfemoral amputees impair physical mobility and activities of daily living. Aim of this study was to correlate the muscle imbalance with functional competence in transfemoral amputees. Methods: Thirty amputees were evaluated under inclusion criteria and randomly allocated into 2 groups. Group A received stretching(1 week followed by strengthening(3 weeks and in group B strengthening(3 weeks were followed by stretching(1 week . Phase I includes values after 1 week stretching program in group A and 3 weeks strengthening program in group B. Data were recorded at baseline, after phase I completion and end of treatment. Physical mobility was assessed by “Timed up and go” test. Results: Muscle imbalance and physical mobility improved significantly in both groups at the end of treatment. The correlation values of “Timed up and go” test with Iliopsoas and Erector spinae muscle showed significant improvement in both groups. Conclusion: Baseline measurements showed that Iliopsoas and Erector spinae muscles were tight whereas Gluteus maximus and Abdominal muscles were weak in transfemoral amputees. Functional mobility improved after correction of muscle imbalance. Stretching followed by strengthening gave more significant results than vice versa. Good posture in transfemoral amputee prevents muscle dysfunction and improves functional mobility.

  6. [Obesity in old age and its importance for functionality and frailty].

    Science.gov (United States)

    Wojzischke, Julia; Diekmann, Rebecca; Bauer, Jürgen M

    2016-10-01

    In later life a high body mass index (BMI) is associated with the lowest age-related mortality rate. The BMI range used by the World Health Organization (WHO) to classify overweight, a BMI of 25-30 kg/m(2), can be regarded as normal weight in old age; nevertheless, obesity is associated with an increased risk of disability and of a deterioration in physical functionality, particularly among older age groups. This relationship to obesity has also been established for frailty. For this reason, a reduction in weight may be appropriate under functional aspects if BMI values exceed 30 kg/m(2); however, such a decision cannot be made on the basis of an individual BMI alone. The functional status, body composition, comorbidities and, in particular the life perspectives of the patient should also be taken into consideration. If weight loss is intended, it must always be performed under strict medical supervision involving optimized protein intake, a carefully calculated moderate reduction in calories and adequate physical training. In the case of chronically ill elderly patients, weight reduction is not usually appropriate. Restrictive diets of any kind should principally be critically viewed in old age because even temporary inadequate energy intake may lead to accelerated deterioration of muscle and bone structure.

  7. On the function and importance of research design in existential-phenomenological qualitative research

    DEFF Research Database (Denmark)

    Feilberg, Casper

    inquiry. This is very different from the research traditions within the social sciences, which traditionally emphasizes the importance of research design and a controlled inquiry, even with respect to qualitative research. Social research is traditionally divided into three phases: planning, execution...... and reporting. Both De Vaus (2001, Research Design in Social Research) and Blaikie (2009, Designing Social Research) highlight the preparatory phase stressing the importance of designing an inquiry in a way, that brings empirical material forth that makes it possible to answer the research question...... the argument that there would be a fruitful contribution to much phenomenological research from a greater emphasis on research design and controlled inquiry. But is it possible to combine these social science research principles with a phenomenological and hermeneutical approach to qualitative research...

  8. The importance of incorporating functional habitats into conservation planning for highly mobile species in dynamic systems.

    Science.gov (United States)

    Webb, Matthew H; Terauds, Aleks; Tulloch, Ayesha; Bell, Phil; Stojanovic, Dejan; Heinsohn, Robert

    2017-10-01

    The distribution of mobile species in dynamic systems can vary greatly over time and space. Estimating their population size and geographic range can be problematic and affect the accuracy of conservation assessments. Scarce data on mobile species and the resources they need can also limit the type of analytical approaches available to derive such estimates. We quantified change in availability and use of key ecological resources required for breeding for a critically endangered nomadic habitat specialist, the Swift Parrot (Lathamus discolor). We compared estimates of occupied habitat derived from dynamic presence-background (i.e., presence-only data) climatic models with estimates derived from dynamic occupancy models that included a direct measure of food availability. We then compared estimates that incorporate fine-resolution spatial data on the availability of key ecological resources (i.e., functional habitats) with more common approaches that focus on broader climatic suitability or vegetation cover (due to the absence of fine-resolution data). The occupancy models produced significantly (P < 0.001) smaller (up to an order of magnitude) and more spatially discrete estimates of the total occupied area than climate-based models. The spatial location and extent of the total area occupied with the occupancy models was highly variable between years (131 and 1498 km(2) ). Estimates accounting for the area of functional habitats were significantly smaller (2-58% [SD 16]) than estimates based only on the total area occupied. An increase or decrease in the area of one functional habitat (foraging or nesting) did not necessarily correspond to an increase or decrease in the other. Thus, an increase in the extent of occupied area may not equate to improved habitat quality or function. We argue these patterns are typical for mobile resource specialists but often go unnoticed because of limited data over relevant spatial and temporal scales and lack of spatial data on the

  9. Methanosarcina Play an Important Role in Anaerobic Co-Digestion of the Seaweed Ulva lactuca: Taxonomy and Predicted Metabolism of Functional Microbial Communities

    Science.gov (United States)

    FitzGerald, Jamie A.; Allen, Eoin; Wall, David M.; Jackson, Stephen A.; Murphy, Jerry D.; Dobson, Alan D. W.

    2015-01-01

    Macro-algae represent an ideal resource of third generation biofuels, but their use necessitates a refinement of commonly used anaerobic digestion processes. In a previous study, contrasting mixes of dairy slurry and the macro-alga Ulva lactuca were anaerobically digested in mesophilic continuously stirred tank reactors for 40 weeks. Higher proportions of U. lactuca in the feedstock led to inhibited digestion and rapid accumulation of volatile fatty acids, requiring a reduced organic loading rate. In this study, 16S pyrosequencing was employed to characterise the microbial communities of both the weakest (R1) and strongest (R6) performing reactors from the previous work as they developed over a 39 and 27-week period respectively. Comparing the reactor communities revealed clear differences in taxonomy, predicted metabolic orientation and mechanisms of inhibition, while constrained canonical analysis (CCA) showed ammonia and biogas yield to be the strongest factors differentiating the two reactor communities. Significant biomarker taxa and predicted metabolic activities were identified for viable and failing anaerobic digestion of U. lactuca. Acetoclastic methanogens were inhibited early in R1 operation, followed by a gradual decline of hydrogenotrophic methanogens. Near-total loss of methanogens led to an accumulation of acetic acid that reduced performance of R1, while a slow decline in biogas yield in R6 could be attributed to inhibition of acetogenic rather than methanogenic activity. The improved performance of R6 is likely to have been as a result of the large Methanosarcina population, which enabled rapid removal of acetic acid, providing favourable conditions for substrate degradation. PMID:26555136

  10. Methanosarcina Play an Important Role in Anaerobic Co-Digestion of the Seaweed Ulva lactuca: Taxonomy and Predicted Metabolism of Functional Microbial Communities.

    Directory of Open Access Journals (Sweden)

    Jamie A FitzGerald

    Full Text Available Macro-algae represent an ideal resource of third generation biofuels, but their use necessitates a refinement of commonly used anaerobic digestion processes. In a previous study, contrasting mixes of dairy slurry and the macro-alga Ulva lactuca were anaerobically digested in mesophilic continuously stirred tank reactors for 40 weeks. Higher proportions of U. lactuca in the feedstock led to inhibited digestion and rapid accumulation of volatile fatty acids, requiring a reduced organic loading rate. In this study, 16S pyrosequencing was employed to characterise the microbial communities of both the weakest (R1 and strongest (R6 performing reactors from the previous work as they developed over a 39 and 27-week period respectively. Comparing the reactor communities revealed clear differences in taxonomy, predicted metabolic orientation and mechanisms of inhibition, while constrained canonical analysis (CCA showed ammonia and biogas yield to be the strongest factors differentiating the two reactor communities. Significant biomarker taxa and predicted metabolic activities were identified for viable and failing anaerobic digestion of U. lactuca. Acetoclastic methanogens were inhibited early in R1 operation, followed by a gradual decline of hydrogenotrophic methanogens. Near-total loss of methanogens led to an accumulation of acetic acid that reduced performance of R1, while a slow decline in biogas yield in R6 could be attributed to inhibition of acetogenic rather than methanogenic activity. The improved performance of R6 is likely to have been as a result of the large Methanosarcina population, which enabled rapid removal of acetic acid, providing favourable conditions for substrate degradation.

  11. Overuse wrist injuries in young athletes: What do sports physicians consider important signals and functional limitations?

    Science.gov (United States)

    Kox, Laura S; Kuijer, P Paul F M; Opperman, Jip; Kerkhoffs, Gino M M J; Maas, Mario; Frings-Dresen, Monique H W

    2017-02-21

    This study's objective was to collect items from experienced sports physicians, relating to the presence and severity of overuse wrist injuries in young athletes, for developing a measurement instrument for signals of overuse wrist injury. Seven Dutch elite sports physicians involved in guidance and treatment of young athletes in wrist-loading sports (gymnastics, tennis, judo, field hockey, volleyball and rowing) participated in a focus group. They discussed signals and limitations related to overuse wrist injuries in young athletes. Data were coded and categorised into signals and limitations with subcategories, using an inductive approach. Of the resulting 61 signals and limitations in nineteen (sub)categories, 20 were considered important, forming a comprehensive item set for identifying overuse wrist injury in young athletes. Signals such as pain, "click", crepitations, swelling and limited range of motion were marked useful for early identification of overuse wrist injury. Limitations in movement and performance were considered indicative of severe overuse injury but less relevant for initial injury identification. The focus group provided 17 important signals and 3 important limitations indicative of overuse wrist injury. These provide the basis for a valid measurement instrument for identifying overuse wrist injury in young athletes, with equal emphasis on pain and on other symptoms.

  12. Importance of orthodontic movement in interdisciplinary treatment for restoring esthetics and functional occlusion

    Directory of Open Access Journals (Sweden)

    Carlos Henrique Guimarães

    2015-01-01

    Full Text Available This article describes interdisciplinary treatment conducted in adult patients, 49-year-old, with periodontal problems, losses and dental inclination, occlusal trauma, localized bone loss, and necessity of rehabilitation with dental implants. Alignment and leveling of the teeth, the molars uprighting with cantilever, and space closure were performed the treatment was facilitated by periodic periodontal control. The resultant occlusion was stable throughout a 5-year retention period. In conclusion, interdisciplinary treatment combined with periodontics, orthodontics, implantodontist, and restorative dentistry was useful for improving the patient′s oral health, function, and esthetics.

  13. TECHNOLOGICAL AND FUNCTIONAL PROPERTIES OF LACTIC ACID BACTERIA: THE IMPORTANCE OF THESE MICROORGANISMS FOR FOOD

    Directory of Open Access Journals (Sweden)

    Amanda de Souza Motta

    2015-12-01

    Full Text Available Eacters of coccus or rods Gram-positive, catalase negative, non-sporulating, which produce lactic acid as the major end product during the fermentation of carbohydrates. When applied on food, provides beneficial effects to consumers through its functional and technological properties. With this the present review article, explore the potential application of lactic acid bacteria in food. The following genera are considered the principal lactic acid bacteria: Aerococcus, Carnobacterium, Enterococcus, Lactobacillus, Lactococcus, Leuconostoc, Oenococcus, Pediococcus, Streptococcus, Tetragenococcus, Vagococcus and Weissella. These cultures have been used as starter or adjunct cultures for the fermentation of foods and beverages due to their contributions to the sensorial characteristics of these products and by microbiological stability. Their probiotic properties have also been investigated. More recent studies by indigenous cultures have received increased attention in light of the search for isolated cultures of a given raw material and a certain region. These microorganisms are being investigated for its functional and technological potential that may be applied in product development with its own characteristics and designation of origin. Those properties will be discussed in the present review in order to highlight the performance of these bacteria and the high degree of control over the fermentation process and standardization of the final product. The use of autochthonous cultures will be considered due the increase of studies of new cultures of lactic acid bacteria isolated of milk and meat of distinct products.

  14. Importance of oestrogen receptors to preserve functional β-cell mass in diabetes.

    Science.gov (United States)

    Tiano, Joseph P; Mauvais-Jarvis, Franck

    2012-02-14

    Protecting the functional mass of insulin-producing β cells of the pancreas is a major therapeutic challenge in patients with type 1 (T1DM) or type 2 diabetes mellitus (T2DM). The gonadal hormone 17β-oestradiol (E2) is involved in reproductive, bone, cardiovascular and neuronal physiology. In rodent models of T1DM and T2DM, treatment with E2 protects pancreatic β cells against oxidative stress, amyloid polypeptide toxicity, lipotoxicity and apoptosis. Three oestrogen receptors (ERs)--ERα, ERβ and the G protein-coupled ER (GPER)--have been identified in rodent and human β cells. Whereas activation of ERα enhances glucose-stimulated insulin biosynthesis, reduces islet toxic lipid accumulation and promotes β-cell survival from proapoptotic stimuli, activation of ERβ increases glucose-stimulated insulin secretion. However, activation of GPER protects β cells from apoptosis, raises glucose-stimulated insulin secretion and lipid homeostasis without affecting insulin biosynthesis. Oestrogens are also improving islet engraftment in rodent models of pancreatic islet transplantation. This Review describes developments in the role of ERs in islet insulin biosynthesis and secretion, lipid homeostasis and survival. Moreover, we discuss why and how enhancing ER action in β cells without the undesirable effect of general oestrogen therapy is a therapeutic avenue to preserve functional β-cell mass in patients with diabetes mellitus.

  15. Playing the Function of Teaching Department and Im-proving the Quality of Teaching%发挥教研室功能提高教学质量

    Institute of Scientific and Technical Information of China (English)

    张宁

    2015-01-01

    教学质量的提高是每个教师的基本教学目标,是学生得益于知识最直接的方式,教学质量的高低与教研室的功能发挥密不可分。本文通过对杭电工商管理专业教研室活动的归纳总结,针对现阶段慕课等教学模式改革,提出了在专业紧跟市场的前提下,充分发挥教研室的组织功能,运用网络化、信息化技术、组织小组专题讲座、学生角色扮演及情景模拟等实验性教学,提高学生的实践和组织管理能力。%The improvement of the quality of teaching is each teacher's basic teaching objective, and students can benefit knowledge from the way directly. Teaching quality is closely re-lated to the function of teaching department. Based on the busi-ness management major in Hangzhou Dianzi University, the arti-cle sums up the department teaching activity, and in view of the present "MOOC" class reformation, puts forward the suggestion about the premise of majors following the market, in order to fully play the function of the teaching department, adopting network and information techniques, organizing themed lectures, students' role play and situation simulation, which will improve students' ability of practice and management.

  16. The Importance of REST for Development and Function of Beta Cells

    DEFF Research Database (Denmark)

    Martin, David; Grapin-Botton, Anne

    2017-01-01

    these, the transcriptional repressor RE-1 Silencing Transcription factor (REST) is expressed in most cells of the body, excluding most populations of neurons, as well as pancreatic beta and alpha cells. In the cell types where it is expressed, REST represses the expression of hundreds of genes...... that are crucial for both neuronal and pancreatic endocrine function, through the recruitment of multiple transcriptional and epigenetic co-regulators. REST targets include genes encoding transcription factors, proteins involved in exocytosis, synaptic transmission or ion channeling, and non-coding RNAs. REST...... is expressed in the progenitors of both neurons and beta cells during development, but it is down-regulated as the cells differentiate. Although REST mutations and deregulation have yet to be connected to diabetes in humans, REST activation during both development and in adult beta cells leads to diabetes...

  17. Recovery of important physiological functions in 3D culture of immortal hepatocytes

    DEFF Research Database (Denmark)

    Wrzesinski, Krzysztof; Fey, S. J.

    2011-01-01

    hepatocytes using the classical approaches (in “2D”) and using a system which leads to the generation of spheroids of cells held in suspension (“3D”). Both approaches gave rise to cultures where the large majority of cells were viable, produced similar amounts of ATP, incorporated similar amounts......It is widely expected that cells grown in 3D environments (in suspension, on scaffolds etc.) will be superior to growing cells in classical 2D culture flasks. These expectations include the belief that cells grown in 3D culture will possess physiological characteristics that resemble more closely...... to grow human liver cells in ‘3 dimensional’ cultures so that they behave very similar to the liver in our bodies. By growing the immortal hepatocytes in specially designed bioreactors they form small pieces of ‘pseudotissue’ which exhibit several of the functions seen in the adult liver. We have grown...

  18. The importance of benthic-pelagic coupling for marine ecosystem functioning in a changing world

    DEFF Research Database (Denmark)

    Griffiths, Jennifer R.; Kadin, Martina; Nascimento, Francisco J. A.

    2017-01-01

    and function is strongly affected by anthropogenic pressures, however there are large gaps in our understanding of the responses of inorganic nutrient and organic matter fluxes between benthic habitats and the water column. We illustrate the varied nature of physical and biological benthic-pelagic coupling...... processes and their potential sensitivity to three anthropogenic pressures - climate change, nutrient loading, and fishing - using the Baltic Sea as a case study, and summarize current knowledge on the exchange of inorganic nutrients and organic material between habitats. Traditionally measured benthic......-pelagic coupling processes (e.g. nutrient exchange and sedimentation of organic material) are to some extent quantifiable but the magnitude and variability of biological processes are rarely assessed, preventing quantitative comparisons. Changing oxygen conditions will continue to have widespread effects...

  19. Molecular evolution and functional characterisation of haplotypes of an important rubber biosynthesis gene in Hevea brasiliensis.

    Science.gov (United States)

    Uthup, T K; Rajamani, A; Ravindran, M; Saha, T

    2016-07-01

    Hydroxy-methylglutaryl coenzyme-A synthase (HMGS) is a rate-limiting enzyme in the cytoplasmic isoprenoid biosynthesis pathway leading to natural rubber production in Hevea brasiliensis (rubber). Analysis of the structural variants of this gene is imperative to understand their functional significance in rubber biosynthesis so that they can be properly utilised for ongoing crop improvement programmes in Hevea. We report here allele richness and diversity of the HMGS gene in selected popular rubber clones. Haplotypes consisting of single nucleotide polymorphisms (SNPs) from the coding and non-coding regions with a high degree of heterozygosity were identified. Segregation and linkage disequilibrium analysis confirmed that recombination is the major contributor to the generation of allelic diversity, rather than point mutations. The evolutionarily conserved nature of some SNPs was identified by comparative DNA sequence analysis of HMGS orthologues from diverse taxa, demonstrating the molecular evolution of rubber biosynthesis genes in general. In silico three-dimensional structural studies highlighting the structural positioning of non-synonymous SNPs from different HMGS haplotypes revealed that the ligand-binding site on the enzyme remains impervious to the reported sequence variations. In contrast, gene expression results indicated the possibility of association between specific haplotypes and HMGS expression in Hevea clones, which may have a downstream impact up to the level of rubber production. Moreover, haplotype diversity of the HMGS gene and its putative association with gene expression can be the basis for further genetic association studies in rubber. Furthermore, the data also show the role of SNPs in the evolution of candidate genes coding for functional traits in plants.

  20. Functional importance of T-type voltage-gated calcium channels in the cardiovascular and renal system

    DEFF Research Database (Denmark)

    Hansen, Pernille B L

    2015-01-01

    , the lack of highly specific blockers cast doubt on the conclusions. As new T-type channel antagonists are being designed, the roles of T-type channels in cardiovascular and renal pathology need to be elucidated before T-type blockers can be clinically useful. Two types of T-type channels, Cav3.1 and Cav3...... suggested to affect constriction. The Cav3.1 channel is also involved in neointima formation following vascular damage. In the kidney, Cav3.1 regulates plasma flow and Cav3.2 plays a role setting glomerular filtration rate. In conclusion, Cav3.1 and Cav3.2 are new therapeutic targets in several......Over the years, it has been discussed whether T-type calcium channels Cav3 play a role in the cardiovascular and renal system. T-type channels have been reported to play an important role in renal hemodynamics, contractility of resistance vessels, and pacemaker activity in the heart. However...

  1. Function and importance of p63 in normal oral mucosa and squamous cell carcinoma of the head and neck

    DEFF Research Database (Denmark)

    Thurfjell, Niklas; Coates, Philip J; Boldrup, Linda

    2005-01-01

    53, whilst others have functions that oppose p53. METHODS: To understand the function and importance of p63 in oral mucosa and tumour development we have studied protein as well as mRNA expression in normal oral mucosa and tumours. RESULTS/CONCLUSION: Expression of p63 proteins differs between...... and amplification of chromosome 3q21-29, where the p63 gene is located. This gene encodes 6 proteins and is crucial for formation of the oral mucosa, teeth, salivary glands and skin. Each of the 6 different p63 proteins has different characteristics and functions, where some resemble the tumour suppressor protein p...

  2. Function and importance of p63 in normal oral mucosa and squamous cell carcinoma of the head and neck

    DEFF Research Database (Denmark)

    Thurfjell, Niklas; Coates, Philip J; Boldrup, Linda

    2005-01-01

    and amplification of chromosome 3q21-29, where the p63 gene is located. This gene encodes 6 proteins and is crucial for formation of the oral mucosa, teeth, salivary glands and skin. Each of the 6 different p63 proteins has different characteristics and functions, where some resemble the tumour suppressor protein p......53, whilst others have functions that oppose p53. METHODS: To understand the function and importance of p63 in oral mucosa and tumour development we have studied protein as well as mRNA expression in normal oral mucosa and tumours. RESULTS/CONCLUSION: Expression of p63 proteins differs between...

  3. FKBP51 plays an important role in high fat diet-induced obesity%共伴侣蛋白 FKBP51在高脂诱导肥胖中的作用

    Institute of Scientific and Technical Information of China (English)

    张曼; 邱彬; 曹勇; 徐玉雪; 邓然; 杨志伟; 雍伟东

    2015-01-01

    stained with the Oil red-O to detect the lipid accumulation and the expression of metabolic genes.In addition, induction of adipocyte differentiation of immortalized MEF cells from WT and FKBP51 KO mice were used to observe the effect of FKBP51 gene on lipogenesis.Results Compared to WT mice, FKBP51 KO mice has less weight increment, and less lipid accumulation in the liver, but with no difference on food consumption during high-fat diet fed.Moreover, FKBP51 KO mice exhibited more O2 consumption, CO2 production and heated production under both RD and HF diet conditions.The PEPCK, G6Pase and UCP-1 genes up-regulation.In addition, lipid content was reduced in FKBP51 gene deficient MEF cells after adipocyte differentiation.Conclusions The FKBP51 gene plays an important role in high fat diet-induced obesity through the energy metabolism enhancement and lipogenesis inhibition.

  4. The Importance of Saccular Function to Motor Development in Children with Hearing Impairments

    Directory of Open Access Journals (Sweden)

    Mary S. Shall

    2009-01-01

    Full Text Available Children with hearing deficits frequently have delayed motor development. The purpose of this study was to evaluate saccular function in children with hearing impairments using the Vestibular Evoked Myogenic Potential (VEMP. The impact of the saccular hypofunction on the timely maturation of normal balance strategies was examined using the Movement Assessment Battery for Children (Movement ABC. Thirty-three children with bilateral severe/profound hearing impairment between 4 and 7 years of age were recruited from a three-state area. Approximately half of the sample had one or bilateral cochlear implants, one used bilateral hearing aids, and the rest used no amplification. Parents reported whether the hearing impairment was diagnosed within the first year or after 2 years of age. No VEMP was evoked in two thirds of the hearing impaired (HI children in response to the bone-conducted stimulus. Children who were reportedly hearing impaired since birth had significantly poorer scores when tested with the Movement ABC.

  5. Dual Sensory Loss and Depressive Symptoms: The Importance of Hearing, Daily Functioning and Activity Engagement

    Directory of Open Access Journals (Sweden)

    Kim Matthew Kiely

    2013-12-01

    Full Text Available Background: The association between dual sensory loss (DSL and mental health has been well established. However, most studies have relied on self-report data and lacked measures that would enable researchers to examine causal pathways between DSL and depression. This study seeks to extend this research by examining the effects of DSL on mental health, and identify factors that explain the longitudinal associations between sensory loss and depressive symptoms. Methods: Piecewise linear-mixed models were used to analyse 16-years of longitudinal data collected on up to five occasions from 1611 adults (51% men aged between 65 and 103 years. Depressive symptoms were assessed by the Centre for Epidemiological Studies Depression (CES-D. Vision loss (VL was defined by corrected visual acuity greater than 0.3 logMAR in the better eye, blindness or glaucoma. Hearing loss (HL was defined by pure tone average (PTA greater than 25 dB in the better hearing ear. Analyses were adjusted for socio-demographics, medical conditions, lifestyle behaviours, Activities of Daily Living (ADLs, cognitive function, and social engagement. Results: Unadjusted models indicated that higher levels of depressive symptoms were associated with HL (B=1.16, SE=0.33 and DSL (B=2.15, SE=0.39 but not VL. Greater rates of change in depressive symptoms were also evident after the onset of HL (B=0.16, SE=0.06, p

  6. Relative importance of energy dependent diffuseness parameter and barrier position in the analysis of fusion excitation function data

    Directory of Open Access Journals (Sweden)

    Kharab Rajesh

    2014-03-01

    Full Text Available We have investigated the relative importance of the energy dependence of diffuseness parameter and barrier position in the description of the fusion excitation function data of some heavy ion systems in near barrier energy region. The effects of the energy dependent diffuseness parameter are found to be much more prominent in comparison to those of barrier position.

  7. A whole-path importance-sampling scheme for Feynman path integral calculations of absolute partition functions and free energies.

    Science.gov (United States)

    Mielke, Steven L; Truhlar, Donald G

    2016-01-21

    Using Feynman path integrals, a molecular partition function can be written as a double integral with the inner integral involving all closed paths centered at a given molecular configuration, and the outer integral involving all possible molecular configurations. In previous work employing Monte Carlo methods to evaluate such partition functions, we presented schemes for importance sampling and stratification in the molecular configurations that constitute the path centroids, but we relied on free-particle paths for sampling the path integrals. At low temperatures, the path sampling is expensive because the paths can travel far from the centroid configuration. We now present a scheme for importance sampling of whole Feynman paths based on harmonic information from an instantaneous normal mode calculation at the centroid configuration, which we refer to as harmonically guided whole-path importance sampling (WPIS). We obtain paths conforming to our chosen importance function by rejection sampling from a distribution of free-particle paths. Sample calculations on CH4 demonstrate that at a temperature of 200 K, about 99.9% of the free-particle paths can be rejected without integration, and at 300 K, about 98% can be rejected. We also show that it is typically possible to reduce the overhead associated with the WPIS scheme by sampling the paths using a significantly lower-order path discretization than that which is needed to converge the partition function.

  8. Optimization of Functioning of the Klintsovsky State Nature Reserve of Regional Importance in the Bryansk Region

    Directory of Open Access Journals (Sweden)

    Moskalenko Igor Vladimirovich

    2015-09-01

    Full Text Available The paper provides information on the current status of specially protected natural territories of the Bryansk region – namely, the Klintsovsky state nature reserve of regional importance located on the territory of the Bryansk region. The authors touch upon the problems of global biodiversity and conservation of rare and endangered plant species. The species composition is specified, and the habitats of rare plant species are revealed. The purpose of the research is to develop policies and programs aimed at the conservation of biodiversity and restoration of rare and endangered species of plants growing in the region, including in the Klintsovsky reserve of the Bryansk region. The authors have developed the methods on preservation and restorations of rare and endangered plants species populations growing in the reserve. For successful implementation of a number of issues on environmental trends, the authors identified the feasibility of establishing an interregional introduction center. The task of introduction center for issues related to the identification and involvement of economically valuable species of plants, including rare and endangered species in the center. The article also deals with the organization of research on their biology and ecology, modeling optimal conditions for mass breeding and cultivation of planting material and the development of programs for the implementation of these species in natural habitats in order to restore the size and population density.

  9. Extreme evolutionary conservation of functionally important regions in H1N1 influenza proteome.

    Directory of Open Access Journals (Sweden)

    Samantha Warren

    Full Text Available The H1N1 subtype of influenza A virus has caused two of the four documented pandemics and is responsible for seasonal epidemic outbreaks, presenting a continuous threat to public health. Co-circulating antigenically divergent influenza strains significantly complicates vaccine development and use. Here, by combining evolutionary, structural, functional, and population information about the H1N1 proteome, we seek to answer two questions: (1 do residues on the protein surfaces evolve faster than the protein core residues consistently across all proteins that constitute the influenza proteome? and (2 in spite of the rapid evolution of surface residues in influenza proteins, are there any protein regions on the protein surface that do not evolve? To answer these questions, we first built phylogenetically-aware models of the patterns of surface and interior substitutions. Employing these models, we found a single coherent pattern of faster evolution on the protein surfaces that characterizes all influenza proteins. The pattern is consistent with the events of inter-species reassortment, the worldwide introduction of the flu vaccine in the early 80's, as well as the differences caused by the geographic origins of the virus. Next, we developed an automated computational pipeline to comprehensively detect regions of the protein surface residues that were 100% conserved over multiple years and in multiple host species. We identified conserved regions on the surface of 10 influenza proteins spread across all avian, swine, and human strains; with the exception of a small group of isolated strains that affected the conservation of three proteins. Surprisingly, these regions were also unaffected by genetic variation in the pandemic 2009 H1N1 viral population data obtained from deep sequencing experiments. Finally, the conserved regions were intrinsically related to the intra-viral macromolecular interaction interfaces. Our study may provide further insights

  10. Effect of halloysite nanotubes on the structure and function of important multiple blood components.

    Science.gov (United States)

    Wu, Keke; Feng, Ru; Jiao, Yanpeng; Zhou, Changren

    2017-06-01

    Many researchers have investigated the application of halloysite nanotubes (HNTs) in biomedicine, because of their special nanoscale hollow tubular structure. Although the cytocompatibility of HNTs has been studied, their blood compatibility has not been systematically investigated. In this work, the effect of HNTs on the structure and function of different blood components has been studied, including the morphology and hemolysis of red blood cells (RBCs). Based on scanning electron microscopy (SEM) observations, optical density test and flow cytometry analysis, we found that HNTs can affect the morphology and membrane integrity of RBCs in phosphate buffered saline (PBS) in a content-dependent way. In particular, based on UV-vis absorption spectra, fluorescence spectra and circular dichroism (CD) spectra, HNTs can alter the secondary structure and conformation of human fibrinogen and γ-globulins. In addition, the detection of biomarker molecules C3a and C5a in plasma suggests that HNTs can trigger complement activation. In the blood clotting assay, HNTs were found to significantly prolong the activated partial thromboplastin time (APTT), shorten the prothrombin time (PT) of platelet-poor plasma (PPP), and change the thromboelastography (TEG) parameters of whole blood coagulation. Furthermore, confocal laser scanning microscopy and flow cytometry analysis were used to test intracellular uptake by macrophages, and the cellular uptake of HNTs in the RAW 264.7 was found to be content-dependent, but not time-dependent. These findings provide insight for the potential use of HNTs as biofriendly nanocontainers for biomaterials in vivo. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Playing and gaming

    DEFF Research Database (Denmark)

    Karoff, Helle Skovbjerg; Ejsing-Duun, Stine; Hanghøj, Thorkild

    2013-01-01

    The paper develops an approach of playing and gaming activities through the perspective of both activities as mood activities . The point of departure is that a game - is a tool with which we, through our practices, achieve different moods. This based on an empirical study of children's everyday...... lives, where the differences emerge through actual practices, i.e. through the creation of meaning in the specific situations. The overall argument is that it is not that important whether it is a playing or a gaming activity - it is however crucial to be aware of how moods occur and what their optimal...... dimensions: practices and moods. Practice is the concept of all the doing in the activities. Moods are the particular concept of sense and feeling of being, which is what we are drawn to when we are playing or gaming....

  12. Playing and gaming

    DEFF Research Database (Denmark)

    Karoff, Helle Skovbjerg; Ejsing-Duun, Stine; Hanghøj, Thorkild

    2013-01-01

    The paper develops an approach of playing and gaming activities through the perspective of both activities as mood activities . The point of departure is that a game - is a tool with which we, through our practices, achieve different moods. This based on an empirical study of children's everyday...... lives, where the differences emerge through actual practices, i.e. through the creation of meaning in the specific situations. The overall argument is that it is not that important whether it is a playing or a gaming activity - it is however crucial to be aware of how moods occur and what their optimal...... dimensions: practices and moods. Practice is the concept of all the doing in the activities. Moods are the particular concept of sense and feeling of being, which is what we are drawn to when we are playing or gaming....

  13. Salt effects on functional traits in model and in economically important Lotus species.

    Science.gov (United States)

    Uchiya, P; Escaray, F J; Bilenca, D; Pieckenstain, F; Ruiz, O A; Menéndez, A B

    2016-07-01

    A common stress on plants is NaCl-derived soil salinity. Genus Lotus comprises model and economically important species, which have been studied regarding physiological responses to salinity. Leaf area ratio (LAR), root length ratio (RLR) and their components, specific leaf area (SLA) and leaf mass fraction (LMF) and specific root length (SRL) and root mass fraction (RMF) might be affected by high soil salinity. We characterised L. tenuis, L. corniculatus, L. filicaulis, L. creticus, L. burtii and L. japonicus grown under different salt concentrations (0, 50, 100 and 150 mm NaCl) on the basis of SLA, LMF, SRL and RMF using PCA. We also assessed effects of different salt concentrations on LAR and RLR in each species, and explored whether changes in these traits provide fitness benefit. Salinity (150 mm NaCl) increased LAR in L. burtii and L. corniculatus, but not in the remaining species. The highest salt concentration caused a decrease of RLR in L. japonicus Gifu, but not in the remaining species. Changes in LAR and RLR would not be adaptive, according to adaptiveness analysis, with the exception of SLA changes in L. corniculatus. PCA revealed that under favourable conditions plants optimise surfaces for light and nutrient acquisition (SLA and SRL), whereas at higher salt concentrations they favour carbon allocation to leaves and roots (LMF and RMF) in detriment to their surfaces. PCA also showed that L. creticus subjected to saline treatment was distinguished from the remaining Lotus species. We suggest that augmented carbon partitioning to leaves and roots could constitute a salt-alleviating mechanism through toxic ion dilution.

  14. Functional Importance of Deletion Mutant Genotypes in an Insect Nucleopolyhedrovirus Population

    Science.gov (United States)

    Simón, Oihane; Williams, Trevor; López-Ferber, Miguel; Caballero, Primitivo

    2005-01-01

    A Nicaraguan isolate of a nucleopolyhedrovirus (SfNIC) that attacks the fall armyworm, Spodoptera frugiperda, survives as a mixture of nine genotypes (SfNIC A to I) that all present genomic deletions, except variant B (complete genotype). Sequencing of cloned restriction fragments revealed that genotypic variants lack between 5 and 16 of the open reading frames present in a contiguous sequence of 18 kb of the SfNIC genome. The absence of oral infectivity of SfNIC-C and -D variants is related to the deletion of the pif and/or pif-2 gene, while that of SfNIC-G remains unexplained. The presence of open reading frame 10, homolog of Se030, also appeared to influence pathogenicity in certain variants. Previous studies demonstrated a significant positive interaction between genotypes B and C. We compared the median lethal concentration of single genotypes (A, B, C, D, and F) and co-occluded genotype mixtures (B+A, B+D, B+F, A+C, and F+C in a 3:1 ratio). Mixtures B+A and B+D showed increased pathogenicity, although only B+D restored the activity of the mixture to that of the natural population. Mixtures of two deletion variants (A+C and F+C) did not show interactions in pathogenicity. We conclude that minority genotypes have an important influence on the overall pathogenicity of the population. These results clearly demonstrate the value of retaining genotypic diversity in virus-based bioinsecticides. PMID:16085811

  15. A highly conserved sequence in the 3'-untranslated region of the drosophila Adh gene plays a functional role in Adh expression.

    Science.gov (United States)

    Parsch, J; Stephan, W; Tanda, S

    1999-01-01

    Phylogenetic analysis identified a highly conserved eight-base sequence (AAGGCTGA) within the 3'-untranslated region (UTR) of the Drosophila alcohol dehydrogenase gene, Adh. To examine the functional significance of this conserved motif, we performed in vitro deletion mutagenesis on the D. melanogaster Adh gene followed by P-element-mediated germline transformation. Deletion of all or part of the eight-base sequence leads to a twofold increase in in vivo ADH enzymatic activity. The increase in activity is temporally and spatially general and is the result of an underlying increase in Adh transcript. These results indicate that the conserved 3'-UTR motif plays a functional role in the negative regulation of Adh gene expression. The evolutionary significance of our results may be understood in the context of the amino acid change that produces the ADH-F allele and also leads to a twofold increase in ADH activity. While there is compelling evidence that the amino acid replacement has been a target of positive selection, the conservation of the 3'-UTR sequence suggests that it is under strong purifying selection. The selective difference between these two sequence changes, which have similar effects on ADH activity, may be explained by different metabolic costs associated with the increase in activity. PMID:9927459

  16. The β and γ subunits play distinct functional roles in the α2βγ heterotetramer of human NAD-dependent isocitrate dehydrogenase

    Science.gov (United States)

    Ma, Tengfei; Peng, Yingjie; Huang, Wei; Liu, Yabing; Ding, Jianping

    2017-01-01

    Human NAD-dependent isocitrate dehydrogenase existing as the α2βγ heterotetramer, catalyzes the decarboxylation of isocitrate into α-ketoglutarate in the Krebs cycle, and is allosterically regulated by citrate, ADP and ATP. To explore the functional roles of the regulatory β and γ subunits, we systematically characterized the enzymatic properties of the holoenzyme and the composing αβ and αγ heterodimers in the absence and presence of regulators. The biochemical and mutagenesis data show that αβ and αγ alone have considerable basal activity but the full activity of α2βγ requires the assembly and cooperative function of both heterodimers. α2βγ and αγ can be activated by citrate or/and ADP, whereas αβ cannot. The binding of citrate or/and ADP decreases the S0.5,isocitrate and thus enhances the catalytic efficiencies of the enzymes, and the two activators can act independently or synergistically. Moreover, ATP can activate α2βγ and αγ at low concentration and inhibit the enzymes at high concentration, but has only inhibitory effect on αβ. Furthermore, the allosteric activation of α2βγ is through the γ subunit not the β subunit. These results demonstrate that the γ subunit plays regulatory role to activate the holoenzyme, and the β subunit the structural role to facilitate the assembly of the holoenzyme.

  17. The lumen-facing domain is important for the biological function and organelle-to-organelle movement of bZIP28 during ER stress in Arabidopsis.

    Science.gov (United States)

    Sun, Le; Lu, Sun-Jie; Zhang, Shuang-Shuang; Zhou, Shun-Fan; Sun, Ling; Liu, Jian-Xiang

    2013-09-01

    The membrane-associated transcription factor, bZIP28, is relocated from the endoplasmic reticulum (ER) to the Golgi and proteolytically released from the membrane mediated by two proteases, S1P and S2P, in response to ER stress in Arabidopsis. The activated N-terminal domain recruits nuclear factor Y (NF-Y) subunits in the nucleus to regulate ER stress downstream genes. Little is known about the functions of the bZIP28 C-terminal lumen-facing domain. Here, we provide novel insights into how the ER lumen-facing domain affects the biological function and organelle-to-organelle movement of bZIP28 in the ER stress response. First, we demonstrated the functional redundancy of bZIP28 and bZIP60 by generation and analysis of the bZIP28 and bZIP60 double mutant zip28zip60. Subsequent genetic complementation experiments in zip28zip60 background with deletions on bZIP28 lumen-facing domain highlighted the importance of lumen-facing domain for its in vivo function of bZIP28 in the ER stress response. The protein subcellular localization and Western blotting results further revealed that the bZIP28 lumen-facing domain contains ER retention signal which is important for the proteolytic activation of bZIP28. Thus, the bZIP28 lumen-facing C-terminus plays important roles in the ER-to-Golgi movement of bZIP28, which may contribute to the sensing of the ER stress.

  18. Functional importance of T-type voltage-gated calcium channels in the cardiovascular and renal system: news from the world of knockout mice.

    Science.gov (United States)

    Hansen, Pernille B L

    2015-02-15

    Over the years, it has been discussed whether T-type calcium channels Cav3 play a role in the cardiovascular and renal system. T-type channels have been reported to play an important role in renal hemodynamics, contractility of resistance vessels, and pacemaker activity in the heart. However, the lack of highly specific blockers cast doubt on the conclusions. As new T-type channel antagonists are being designed, the roles of T-type channels in cardiovascular and renal pathology need to be elucidated before T-type blockers can be clinically useful. Two types of T-type channels, Cav3.1 and Cav3.2, are expressed in blood vessels, the kidney, and the heart. Studies with gene-deficient mice have provided a way to investigate the Cav3.1 and Cav3.2 channels and their role in the cardiovascular system. This review discusses the results from these knockout mice. Evaluation of the literature leads to the conclusion that Cav3.1 and Cav3.2 channels have important, but different, functions in mice. T-type Cav3.1 channels affect heart rate, whereas Cav3.2 channels are involved in cardiac hypertrophy. In the vascular system, Cav3.2 activation leads to dilation of blood vessels, whereas Cav3.1 channels are mainly suggested to affect constriction. The Cav3.1 channel is also involved in neointima formation following vascular damage. In the kidney, Cav3.1 regulates plasma flow and Cav3.2 plays a role setting glomerular filtration rate. In conclusion, Cav3.1 and Cav3.2 are new therapeutic targets in several cardiovascular pathologies, but the use of T-type blockers should be specifically directed to the disease and to the channel subtype.

  19. Patients with autosomal dominant spinocerebellar ataxia have more risk of falls, important balance impairment, and decreased ability to function

    Directory of Open Access Journals (Sweden)

    Carolina Yuri P. Aizawa

    2013-08-01

    Full Text Available OBJECTIVES: To assess balance and ability to function in patients with spinocerebellar ataxia. METHODS: A total of 44 patients with different spinocerebellar ataxia types 1, 2, 3, and 6 were evaluated using the Tinetti balance and gait assessment and the functional independence measure. The scale for the assessment and rating of ataxia and the international cooperative ataxia rating scale were used to evaluate disease severity. RESULTS: Most patients showed significant risk of falls. The balance scores were significantly different in spinocerebellar ataxia types. A significant positive correlation between balance and disease severity was found. CONCLUSION: Patients with spinocerebellar ataxia have important balance impairment and risk of falls that influence the ability to function such as self-care, transfers, and locomotion. Furthermore, the more severe ataxia is, the more compromised are postural balance, risk of falls, and ability to function.

  20. ENU-induced mutation in the DNA-binding domain of KLF3 reveals important roles for KLF3 in cardiovascular development and function in mice.

    Directory of Open Access Journals (Sweden)

    Lois Kelsey

    Full Text Available KLF3 is a Krüppel family zinc finger transcription factor with widespread tissue expression and no previously known role in heart development. In a screen for dominant mutations affecting cardiovascular function in N-ethyl-N-nitrosourea (ENU mutagenized mice, we identified a missense mutation in the Klf3 gene that caused aortic valvular stenosis and partially penetrant perinatal lethality in heterozygotes. All homozygotes died as embryos. In the first of three zinc fingers, a point mutation changed a highly conserved histidine at amino acid 275 to arginine (Klf3(H275R . This change impaired binding of the mutant protein to KLF3's canonical DNA binding sequence. Heterozygous Klf3(H275R mutants that died as neonates had marked biventricular cardiac hypertrophy with diminished cardiac chambers. Adult survivors exhibited hypotension, cardiac hypertrophy with enlarged cardiac chambers, and aortic valvular stenosis. A dominant negative effect on protein function was inferred by the similarity in phenotype between heterozygous Klf3(H275R mutants and homozygous Klf3 null mice. However, the existence of divergent traits suggested the involvement of additional interactions. We conclude that KLF3 plays diverse and important roles in cardiovascular development and function in mice, and that amino acid 275 is critical for normal KLF3 protein function. Future exploration of the KLF3 pathway provides a new avenue for investigating causative factors contributing to cardiovascular disorders in humans.

  1. Creativity and Playfulness

    DEFF Research Database (Denmark)

    Ejsing-Duun, Stine; Skovbjerg, Helle Marie

    2015-01-01

    Abstract: This article explores how student behavior and interactions change when teachers use “producing games” as a primary pedagogical strategy (Papert, 1980; Ejsing-Duun and Karoff, 2014). Based on student and teacher actions and responses, as well as on students' production—observed during f...... fieldwork—this paper emphasizes the importance of understanding how students explore creativity and playfulness while producing in learning situations....

  2. Creativity and Playfulness

    DEFF Research Database (Denmark)

    Ejsing-Duun, Stine; Skovbjerg, Helle Marie

    2015-01-01

    Abstract: This article explores how student behavior and interactions change when teachers use “producing games” as a primary pedagogical strategy (Papert, 1980; Ejsing-Duun and Karoff, 2014). Based on student and teacher actions and responses, as well as on students' production—observed during f...... fieldwork—this paper emphasizes the importance of understanding how students explore creativity and playfulness while producing in learning situations....

  3. Participation bias in postal surveys among older adults: the role played by self-reported health, physical functional decline and frailty.

    Science.gov (United States)

    Barreto, Philipe de Souto

    2012-01-01

    Postal survey is a simple and efficient way to collect information in large study samples. The purpose of this study was to find out differences between older adults who responded to a postal survey on health outcomes and those who did not, and to examine the importance of frailty, physical functional decline and poor self-reported health in determining non-response. We mailed out a questionnaire on general health twice at a year's interval to 1000 individuals ≥60 years, and members of the medical insurance scheme of the French national education system. At Year1, 535 persons responded to the questionnaire (65% women, 70.9 ± 8.4 years). A year later (Year2), we obtained 384 responses (63.3% women, 70.5 ± 7.8 years). Compared to respondents, non-respondents at Year2 were more frequently categorized as frail, reported more often to be in bad health, and had more physical functional declines. Frailty, physical functional decline and poor self-reported health increased the likelihood of not responding to Year2 questionnaire, with poor self-reported health weakening the association of physical functional decline and non-response. Respondents of this postal survey are fitter and healthier than non-respondents. This participation bias precludes the generalization of postal surveys results.

  4. Plasmacytoid Dendritic Cells Producing Interferon-α (IFN-α) and Inducing Mx1 Play an Important Role for CD4(+) Cells and CD8(+) Cells in Necrotizing Lymphadenitis.

    Science.gov (United States)

    Sato, Hiroko; Asano, Shigeyuki; Mori, Kikuo; Yamazaki, Kazuki; Wakasa, Haruki

    2015-01-01

    We confirmed the characteristic clinical features of necrotizing lymphadenitis (NEL) in 66 cases (23 male, 43 female) in Japan, which included high fever (38-40°), painful cervical lymphadenopathy (62/66, 93.9%), and leukopenia (under 4,000/mm(3)) (25/53, 47.2%), without seasonal occurrence, in a clinicopathological, immunohistochemical, electron microscopic serological study. Patient age varied from 3-55 years, and 72.7% (44/66) of patients were younger than 30 years. Histopathology of NEL was characterized by the presence of CD8(+) immunoblasts, CD123(+) cells (plasmacytoid dendritic cells; PDCs), histiocytes and macrophages phagocytizing CD4(+) apoptotic lymphocytes, but no granulocytes or bacteria. The number of PDCs and CD8(+) cells in lesions tended to increase with time, and PDCs tended to be larger and irregular in the lesions compared with the non-lesion tissue of the lymph nodes. In addition, PDCs showed no temporal morphological change in the lymph nodes. The number of CD4(+) cells in the lymph node lesions sharply decreased from the 2nd to the 4th week, and then tended to increase; however, CD4(+) cells gradually decreased with time in non-lesion tissue. PDCs may produce interferon-α (IFN-α), which induces Mx1 expression. Strong Mx1 immunoreactivity is indicative of IFN-α production. IFN-α induces transformation of CD8(+) cells into immunoblasts, as well as phagocytosis of apoptotic cells derived from CD4(+) cells by macrophages. Thus, PDCs may play an important role with immune cells, including CD8(+) and CD4(+) cells, in necrotizing lymphadenitis.

  5. Expression and Purification of Functional Human Vascular Endothelial Growth Factor-A121; the Most Important Angiogenesis Factor

    Directory of Open Access Journals (Sweden)

    Fatemeh Kazemi-Lomedasht

    2014-12-01

    Full Text Available Purpose: Angiogenesis or formation of new blood vessels is an essential process for tumor growth, invasion and metastasis. Vascular Endothelial Growth Factor (VEGF and its receptors play an important role in angiogenesis-dependent tumors. VEGF-A is the most important factor in angiogenesis process. Human VEGF-A gene consists of eight exons that undergoes alternative exon splicing and produce five different proteins consisting of 121, 145, 165, 189 and 206 amino acids (named VEGF121, VEGF145, VEGF165, VEGF189, and VEGF206. Methods: In this study, VEGF121 gene synthesized and cloned into the pET-26b plasmid. The recombinant plasmid was transferred into appropriate expression strain of BL-21. Expression of VEGF121 induced by IPTG (Isopropyl β-D-1-thiogalactopyranoside and confirmed by SDS-PAGE and Western-Blotting. Recombinant VEGF121 was purified by nickel affinity chromatography. HUVECs (Human Umbilical Vein Endothelia Cells cells were isolated from umbilical vein and the effect of VEGF121 on tube formation of endothelial cells was investigated. Results: SDS-PAGE and Western-Blotting results verified the purification of VEGF121. The final yield of recombinant protein was about 5mg per liter. Endothelial cell tube formation assay results showed that VEGF121 leads to tube formation of endothelial cell on matrix and induces angiogenesis in vitro. Conclusion: Recombinant VEGF121 is important factor in tube formation of endothelial cell, so it could be used in different cancer researches and angiogenesis assay.

  6. Functional Roles of microRNAs in Agronomically Important Plants-Potential as Targets for Crop Improvement and Protection.

    Science.gov (United States)

    Djami-Tchatchou, Arnaud T; Sanan-Mishra, Neeti; Ntushelo, Khayalethu; Dubery, Ian A

    2017-01-01

    MicroRNAs (miRNAs) are a class of small non-coding RNAs that have recently emerged as important regulators of gene expression, mainly through cleavage and/or translation inhibition of the target mRNAs during or after transcription. miRNAs play important roles by regulating a multitude of biological processes in plants which include maintenance of genome integrity, development, metabolism, and adaptive responses toward environmental stresses. The increasing population of the world and their food demands requires focused efforts for the improvement of crop plants to ensure sustainable food production. Manipulation of mRNA transcript abundance via miRNA control provides a unique strategy for modulating differential plant gene expression and miRNAs are thus emerging as the next generation targets for genetic engineering for improvement of the agronomic properties of crops. However, a deeper understanding of its potential and the mechanisms involved will facilitate the design of suitable strategies to obtain the desirable traits with minimum trade-offs in the modified crops. In this regard, this review highlights the diverse roles of conserved and newly identified miRNAs in various food and industrial crops and recent advances made in the uses of miRNAs to improve plants of agronomically importance so as to significantly enhance crop yields and increase tolerance to various environmental stress agents of biotic-or abiotic origin.

  7. Functional Exercise and Physical Fitness Post Stroke: The Importance of Exercise Maintenance for Motor Control and Physical Fitness after Stroke

    Directory of Open Access Journals (Sweden)

    Birgitta Langhammer

    2012-01-01

    Full Text Available It is argued that all stroke patients, indifferent of disability, have the same possibility to improve with training. The aim of the study was to follow and register functional improvements in two groups with different functional capacities at baseline for a period of 36 months. Stroke patients were recruited and divided into groups related to their functional status at baseline. During the acute rehabilitation, both groups received functional task-oriented training, followed by regular self- or therapeutic driven training the first year after stroke and varied exercise patterns the following 24 months. The participants were tested on admission, and at three, six, twelve, and thirty-six months after the onset of stroke. Both groups improved functional activity up to six months which then stabilized up to twelve months to decline somewhat at thirty-six months after stroke. Change scores indicate a greater potential for rehabilitation in the MAS ≤35 in relation to group MAS >35 although the functional capacity was higher in the latter. This indicates the importance of maintaining exercise and training for all persons after stroke.

  8. Androgen action via testicular arteriole smooth muscle cells is important for Leydig cell function, vasomotion and testicular fluid dynamics.

    Directory of Open Access Journals (Sweden)

    Michelle Welsh

    Full Text Available Regulation of blood flow through the testicular microvasculature by vasomotion is thought to be important for normal testis function as it regulates interstitial fluid (IF dynamics which is an important intra-testicular transport medium. Androgens control vasomotion, but how they exert these effects remains unclear. One possibility is by signalling via androgen receptors (AR expressed in testicular arteriole smooth muscle cells. To investigate this and determine the overall importance of this mechanism in testis function, we generated a blood vessel smooth muscle cell-specific AR knockout mouse (SMARKO. Gross reproductive development was normal in SMARKO mice but testis weight was reduced in adulthood compared to control littermates; this reduction was not due to any changes in germ cell volume or to deficits in testosterone, LH or FSH concentrations and did not cause infertility. However, seminiferous tubule lumen volume was reduced in adult SMARKO males while interstitial volume was increased, perhaps indicating altered fluid dynamics; this was associated with compensated Leydig cell failure. Vasomotion was impaired in adult SMARKO males, though overall testis blood flow was normal and there was an increase in the overall blood vessel volume per testis in adult SMARKOs. In conclusion, these results indicate that ablating arteriole smooth muscle AR does not grossly alter spermatogenesis or affect male fertility but does subtly impair Leydig cell function and testicular fluid exchange, possibly by locally regulating microvascular blood flow within the testis.

  9. Regions within the N-terminal domain of human topoisomerase I exert important functions during strand rotation and DNA binding

    DEFF Research Database (Denmark)

    Hougaard, Rikke Frølich; Andersen, Félicie Faucon; Westergaard, Ole

    2004-01-01

    The human topoisomerase I N-terminal domain is the only part of the enzyme still not crystallized and the function of this domain remains enigmatical. In the present study, we have addressed the specific functions of individual N-terminal regions of topoisomerase I by characterizing mutants lacking...... amino acid residues 1–202 or 191–206 or having tryptophane-205 substituted by glycine in a broad variety of in vitro activity assays. As a result of these investigations we find that mutants altered in the region 191–206 distinguished themselves from the wild-type enzyme by a faster strand rotation step...... support a model according to which tryptophane-205 and possibly other residues located between position 191–206 coordinates the restriction of free strand rotation during the topoisomerization step of catalysis. Moreover, tryptophane-205 appears important for the function of the bulk part of the N...

  10. Pesquisa qualitativa em Educação Matemática a distância: aspectos importantes do uso do Role Playing Game como procedimento metodológico de pesquisa Qualitative research in distance Mathematics Education: important aspects of the Role Playing Game as research methodological procedure

    Directory of Open Access Journals (Sweden)

    Maurício Rosa

    2012-09-01

    Full Text Available Este artigo evidencia aspectos do Role Playing Game (RPG, jogo de representação de personagens, que o tornam um importante procedimento de investigação em termos de Pesquisa Qualitativa em Educação (no caso, Educação Matemática a Distância. Esse jogo foi adotado em uma pesquisa (ROSA, 2008 que estudou as relações estabelecidas entre a construção de identidades online e o ensino e a aprendizagem do conceito de Integral Definida (conceito do Cálculo Diferencial e Integral em um curso a distância. Assim, a partir dessa investigação que utilizou o RPG jogado a distância, via chat, como procedimento de coleta de dados, discutimos a inserção desse jogo como procedimento metodológico de pesquisa em Educação Matemática a Distância e caracterizamos como esse processo liga-se a questões referentes à Pesquisa Qualitativa nesse novo cenário: o ciberespaço. Logo, assumimos que adotar o RPG como procedimento de pesquisa favorece tanto o pesquisador, quanto os sujeitos investigados, em termos de mostrarem-se como "diferentes" mesmo sendo "os mesmos" (ROSA, 2008 e isso potencializa a produção do conhecimento matemático, bem como a análise das ações e possibilidades educacionais vislumbradas pelo ser online que se apresenta no ambiente natural apresentado. Também apontamos a adoção do RPG como fator que impele e amplia a concepção pós-estruturalista de Educação que, em ambientes virtuais, cada vez mais, vem destacando e estabelecendo uma amplitude de investigação que transforma esse espaço imaginativo e surpreendente em um ambiente natural de pesquisa.This article highlights aspects of the Role Playing Game (RPG, which make an important procedure in terms of research on Qualitative Research in Distance Education (in this case, Mathematics Education. This game was used in a research (ROSA, 2008 that studied the relations between the construction of online identities and teaching and learning of the concept of

  11. FROM ACUTE ACHILLES TENDON RUPTURE TO RETURN TO PLAY – A CASE REPORT EVALUATING RECOVERY OF TENDON STRUCTURE, MECHANICAL PROPERTIES, CLINICAL AND FUNCTIONAL OUTCOMES

    Science.gov (United States)

    Zellers, Jennifer A.; Cortes, Daniel H.

    2016-01-01

    outlines comprehensive outcomes assessment in an athletic individual following non-surgically managed Achilles tendon rupture using a wide variety of tools that capture different aspects of tendon health. Interestingly, the course of recovery of patient symptoms, functional performance, and tendon structure do not occur in the same time frame. Therefore, it is important to assess patient outcomes using multiple outcome measures encompassing different aspects of patient performance to ensure the patient is progressing steadily with rehabilitation. Level of Evidence Level 4. PMID:27999728

  12. Differences in alpha 2u-globulins increased in male rat kidneys following treatment with several alpha 2u-globulin accumulating agents: cystein protease(s) play(s) an important role in production of kidney-type-alpha 2u-globulin.

    Science.gov (United States)

    Saito, K; Kaneko, H; Isobe, N; Nakatsuka, I; Yoshitake, A; Yamada, H

    1992-11-30

    Effects of alpha 2u-globulin accumulating agents on alpha 2u-globulins in rat kidneys were examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting analysis. Treatment of male animals with decalin (150 mg/kg), 2,2,4-trimethylpentane (50 mg/kg), isophorone (150 mg/kg), d-limonene (150 mg/kg) or 1,4-dichlorobenzene (150 mg/kg) by gavage for 14 consecutive days in each case resulted in a marked intensification of a protein band corresponding to kidney-type-alpha 2u-globulin, with a molecular mass calculated to be approximately 16 kDa. However, intraperitoneal treatment with leupeptin and E-64 (two times 0.07 mmol/kg, for each), well known cystein protease inhibitors, while only slightly increasing this kidney-type-alpha 2u-globulin band, caused the intensification of a approximately 19-kDa molecular mass protein band which was revealed to be a native-type-alpha 2u-globulin by SDS-PAGE and immunoblotting. These results indicated that at least two types of alpha 2u-globulin can be increased in male rat kidney by chemical treatment. Moreover, cystein protease(s) appear(s) to play an important role in the degradation of alpha 2u-globulin and particularly in the conversion of native-type-alpha 2u-globulin to kidney-type-alpha 2u-globulin in rat kidneys.

  13. Cloning and functional characterization of 3-hydroxy-3-methylglutaryl coenzyme A reductase gene from Withania somnifera: an important medicinal plant.

    Science.gov (United States)

    Akhtar, Nehal; Gupta, Parul; Sangwan, Neelam Singh; Sangwan, Rajender Singh; Trivedi, Prabodh Kumar

    2013-04-01

    Withania somnifera (L.) Dunal is one of the most valuable medicinal plants synthesizing a large number of pharmacologically active secondary metabolites known as withanolides, the C28-steroidal lactones derived from triterpenoids. Though the plant has been well characterized in terms of phytochemical profiles as well as pharmaceutical activities, not much is known about the biosynthetic pathway and genes responsible for biosynthesis of these compounds. In this study, we have characterized the gene encoding 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR; EC 1.1.1.34) catalyzing the key regulatory step of the isoprenoid biosynthesis. The 1,728-bp full-length cDNA of Withania HMGR (WsHMGR) encodes a polypeptide of 575 amino acids. The amino acid sequence homology and phylogenetic analysis suggest that WsHMGR has typical structural features of other known plant HMGRs. The relative expression analysis suggests that WsHMGR expression varies in different tissues as well as chemotypes and is significantly elevated in response to exposure to salicylic acid, methyl jasmonate, and mechanical injury. The functional color assay in Escherichia coli showed that WsHMGR could accelerate the biosynthesis of carotenoids, establishing that WsHMGR encoded a functional protein and may play a catalytic role by its positive influence in isoprenoid biosynthesis.

  14. HBcAg-specific CD8 T cells play an important role in virus suppression, and acute flare-up is associated with the expansion of activated memory T cells.

    Science.gov (United States)

    Shimada, Noriaki; Yamamoto, Kazuhide; Kuroda, Marcelo J; Terada, Ryo; Hakoda, Tomomi; Shimomura, Hiroyuki; Hata, Hidenori; Nakayama, Eiichi; Shiratori, Yasushi

    2003-05-01

    We analyzed the prevalence and longitudinal fluctuation of hepatitis B virus (HBV)-specific CD8 T cells in chronic HBV infection using an HLA-A2-HBc18-27 tetramer. Thirty-five HLA-A2-positive patients with chronic HBV infection were divided into 17 HBe antigen (HBeAg)-positive and 18 anti-HBe antibody (anti-HBe)-positive patients. Five HLA-A2-positive normal subjects, five HLA-A2-negative patients with chronic HBV infection, and two HLA-A2-positive patients with acute HBV infection were included as controls. HBc18-27-specific CD8 T cells (c18-27-CD8Ts) were detected at a significantly higher prevalence in patients with anti-HBe (6/18) than in those with HBeAg (1/17), and their frequency reached 0.28% of the total CD8 T cells. The prevalence was significantly higher in patients with HBV DNA below 4.0 log genome equivalents (LGE)/ml (5/12) than in those with HBV DNA above 4.0 LGE/ml (2/23). The frequency of c18-27-CD8Ts was consistently higher in liver-infiltrating lymphocytes, ranging from 0.18 to 1.28%, than in autologous peripheral blood lymphocytes. Longitudinal analysis of patients with acute flare-up demonstrated that the elevation of alanine aminotransferase (ALT) was intimately associated with the expansion of c18-27-CD8Ts. Phenotypic analysis revealed that most c18-27-CD8Ts during acute flare-up expressed HLA-DR and CCR5, while those during low-ALT periods showed low expression. Furthermore, most liver-infiltrating c18-27-CD8Ts were positive for HLA-DR and CCR5, suggesting selective recruitment of activated c18-27-CD8Ts into the liver. In conclusion. HBV-specific CD8 T cells play an important role in the suppression of virus replication, and acute flare-up is associated with the expansion and activation of HBV-specific memory cells.

  15. Haemophilus ducreyi RpoE and CpxRA appear to play distinct yet complementary roles in regulation of envelope-related functions.

    Science.gov (United States)

    Gangaiah, Dharanesh; Zhang, Xinjun; Baker, Beth; Fortney, Kate R; Liu, Yunlong; Munson, Robert S; Spinola, Stanley M

    2014-12-01

    Haemophilus ducreyi causes the sexually transmitted disease chancroid and a chronic limb ulceration syndrome in children. In humans, H. ducreyi is found in an abscess and overcomes a hostile environment to establish infection. To sense and respond to membrane stress, bacteria utilize two-component systems (TCSs) and extracytoplasmic function (ECF) sigma factors. We previously showed that activation of CpxRA, the only intact TCS in H. ducreyi, does not regulate homologues of envelope protein folding factors but does downregulate genes encoding envelope-localized proteins, including many virulence determinants. H. ducreyi also harbors a homologue of RpoE, which is the only ECF sigma factor in the organism. To potentially understand how H. ducreyi responds to membrane stress, here we defined RpoE-dependent genes using transcriptome sequencing (RNA-Seq). We identified 180 RpoE-dependent genes, of which 98% were upregulated; a major set of these genes encodes homologues of envelope maintenance and repair factors. We also identified and validated a putative RpoE promoter consensus sequence, which was enriched in the majority of RpoE-dependent targets. Comparison of RpoE-dependent genes to those controlled by CpxR showed that each transcription factor regulated a distinct set of genes. Given that RpoE activated a large number of genes encoding envelope maintenance and repair factors and that CpxRA represses genes encoding envelope-localized proteins, these data suggest that RpoE and CpxRA appear to play distinct yet complementary roles in regulating envelope homeostasis in H. ducreyi.

  16. The Fractal Self at Play

    Science.gov (United States)

    Marks-Tarlow, Terry

    2010-01-01

    In this article, the author draws on contemporary science to illuminate the relationship between early play experiences, processes of self-development, and the later emergence of the fractal self. She argues that orientation within social space is a primary function of early play and developmentally a two-step process. With other people and with…

  17. Empowering Groups that Enable Play

    Science.gov (United States)

    Wilson, David Sloan; Marshall, Danielle; Iserhott, Hindi

    2011-01-01

    Creating play environments for children usually requires groups of adults working together. An extensive scientific literature describes how groups function to achieve shared goals in general terms, and groups attempting to empower play may find this literature useful. Design principles for managing natural resources, identified by Elinor Ostrom…

  18. Functional Importance of L- and P/Q-Type Voltage-Gated Calcium Channels in Human Renal Vasculature

    DEFF Research Database (Denmark)

    Hansen, Pernille B; Poulsen, Christian B; Walter, Steen

    2011-01-01

    in kidney function. It was hypothesized that human renal vascular excitation-contraction coupling involves different subtypes of channels. In human renal artery and dissected intrarenal blood vessels from nephrectomies, PCR analysis showed expression of L-type (Ca(v) 1.2), P/Q-type (Ca(v) 2.1), and T-type......, and L- and P/Q-type channels are of functional importance for the depolarization-induced vasoconstriction. The contribution of P/Q-type channels to contraction in the human vasculature is a novel mechanism for the regulation of renal blood flow and suggests that clinical treatment with calcium blockers......Calcium channel blockers are widely used for treatment of hypertension, because they decrease peripheral vascular resistance through inhibition of voltage-gated calcium channels. Animal studies of renal vasculature have shown expression of several types of calcium channels that are involved...

  19. Pre-implant right ventricular function might be an important predictor of the response to cardiac resynchronization therapy

    Directory of Open Access Journals (Sweden)

    Ring Margareta

    2011-10-01

    Full Text Available Abstract Objective Cardiac resynchronization therapy is proven efficacious in patients with heart failure (HF. Presence of biventricular HF is associated with a worse prognosis than having only left ventricular (LV HF and pacing might deteriorate heart function. The aim of the study was to assess a possible significance of right ventricular (RV pre-implant systolic function to predict response to CRT. Design We studied 22 HF-patients aged 72 ± 11 years, QRS-duration 155 ± 20 ms and with an LV ejection fraction (EF of 26 ± 6% before and four weeks after receiving a CRT-device. Results There were no changes in LV diameters or end systolic volume (ESV during the study. However, end diastolic volume (EDV decreased from 226 ± 71 to 211 ± 64 ml (p = 0.02 and systolic maximal velocities (SMV increased from 2.2 ± 0.4 to 2.6 ± 0.9 cm/s (p = 0.04. Pre-implant RV-SMV (6.2 ± 2.6 cm/s predicted postoperative increase in LV contractility, p = 0.032. Conclusions Pre-implant decreased RV systolic function might be an important way to predict a poor response to CRT implicating that other treatments should be considered. Furthermore we found that 3D- echocardiography and Tissue Doppler Imaging were feasible to detect short-term changes in LV function.

  20. Human CD45RA(-) FoxP3(hi) Memory-Type Regulatory T Cells Show Distinct TCR Repertoires With Conventional T Cells and Play an Important Role in Controlling Early Immune Activation.

    Science.gov (United States)

    Lei, H; Kuchenbecker, L; Streitz, M; Sawitzki, B; Vogt, K; Landwehr-Kenzel, S; Millward, J; Juelke, K; Babel, N; Neumann, A; Reinke, P; Volk, H-D

    2015-10-01

    Adoptive immunotherapy with regulatory T cells (Treg) is a new option to promote immune tolerance following solid organ transplantation (SOT). However, Treg from elderly patients awaiting transplantation are dominated by the CD45RA(-) CD62L(+) central memory type Treg subset (TregCM), and the yield of well-characterized and stable naïve Treg (TregN) is low. It is, therefore, important to determine whether these TregCM are derived from the thymus and express high stability, suppressive capacity and a broad antigen repertoire like TregN. In this study, we showed that TregCM use a different T cell receptor (TCR) repertoire from conventional T cells (Tconv), using next-generation sequencing of all 24 Vβ families, with an average depth of 534 677 sequences. This showed almost no contamination with induced Treg. Furthermore, TregCM showed enhanced suppressive activity on Tconv at early checkpoints of immune activation controlling activation markers expression and cytokine secretion, but comparable inhibition of proliferation. Following in vitro expansion under mTOR inhibition, TregCM expanded equally as well as TregN without losing their function. Despite relatively limited TCR repertoire, TregCM also showed specific alloresponse, although slightly reduced compared to TregN. These results support the therapeutic usefulness of manufacturing Treg products from CD45RA(-) CD62L(+) Treg-enriched starting material to be applied for adoptive Treg therapy. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  1. The Right Supramarginal Gyrus Is Important for Proprioception in Healthy and Stroke-Affected Participants: A Functional MRI Study

    Science.gov (United States)

    Ben-Shabat, Ettie; Matyas, Thomas A.; Pell, Gaby S.; Brodtmann, Amy; Carey, Leeanne M.

    2015-01-01

    Human proprioception is essential for motor control, yet its central processing is still debated. Previous studies of passive movements and illusory vibration have reported inconsistent activation patterns related to proprioception, particularly in high-order sensorimotor cortices. We investigated brain activation specific to proprioception, its laterality, and changes following stroke. Twelve healthy and three stroke-affected individuals with proprioceptive deficits participated. Proprioception was assessed clinically with the Wrist Position Sense Test, and participants underwent functional magnetic resonance imaging scanning. An event-related study design was used, where each proprioceptive stimulus of passive wrist movement was followed by a motor response of mirror ­copying with the other wrist. Left (LWP) and right (RWP) wrist proprioception were tested separately. Laterality indices (LIs) were calculated for the main cortical regions activated during proprioception. We found proprioception-related brain activation in high-order sensorimotor cortices in healthy participants especially in the supramarginal gyrus (SMG LWP z = 4.51, RWP z = 4.24) and the dorsal premotor cortex (PMd LWP z = 4.10, RWP z = 3.93). Right hemispheric dominance was observed in the SMG (LI LWP mean 0.41, SD 0.22; RWP 0.29, SD 0.20), and to a lesser degree in the PMd (LI LWP 0.34, SD 0.17; RWP 0.13, SD 0.25). In stroke-affected participants, the main difference in proprioception-related brain activation was reduced laterality in the right SMG. Our findings indicate that the SMG and PMd play a key role in proprioception probably due to their role in spatial processing and motor control, respectively. The findings from stroke-­affected individuals suggest that decreased right SMG function may be associated with decreased proprioception. We recommend that clinicians pay particular attention to the assessment and rehabilitation of proprioception following right hemispheric

  2. Hematopoietic lineage cell specific protein 1 (HS1) is a functionally important signaling molecule in platelet activation.

    Science.gov (United States)

    Kahner, Bryan N; Dorsam, Robert T; Mada, Sripal R; Kim, Soochong; Stalker, Timothy J; Brass, Lawrence F; Daniel, James L; Kitamura, Daisuke; Kunapuli, Satya P

    2007-10-01

    Collagen activates platelets through an intracellular signaling cascade downstream of glycoprotein VI (GPVI). We have investigated the contribution of hematopoietic lineage cell-specific protein 1 (HS1) downstream of GPVI in platelet activation. Stimulation of GPVI leads to tyrosine phosphorylation of HS1, which is blocked by Src-family kinase inhibitors. Coimmunoprecipitation experiments revealed that HS1 associates with Syk and phosphatidylinositol 3-kinases. HS1-null mice displayed increased bleeding times and increased time to occlusion in the FeCl(3) in vivo thrombosis model compared with their wild-type littermates. In addition, aggregation and secretion responses were diminished in HS1-null mouse platelets after stimulation of GPVI and protease-activated receptor 4 (PAR-4) agonists compared with wild-type littermate mouse platelets. Finally, Akt phosphorylation was diminished after GPVI or PAR-4 stimulation in platelets from HS1-null mice compared with their wild-type littermates. These results demonstrate that phosphorylation of the HS1 protein occurs downstream of GPVI stimulation and that HS1 plays a significant functional role in platelet activation downstream of GPVI and PARs.

  3. Energies of the adsorption of functional groups to calcium carbonate polymorphs: the importance of -OH and -COOH groups.

    Science.gov (United States)

    Okhrimenko, D V; Nissenbaum, J; Andersson, M P; Olsson, M H M; Stipp, S L S

    2013-09-01

    The adsorption behavior of calcium carbonate is an important factor in many processes in nature, industry, and biological systems. We determined and compared the adsorption energies for a series of small molecules of different sizes and polarities (i.e., water, several alcohols, and acetic acid) on three synthetic CaCO3 polymorphs (calcite, aragonite, and vaterite). We measured isosteric heats of adsorption from vapor adsorption isotherms for 273 < T < 293 K, and we used XRD and SEM to confirm that samples did not change phase during the experiments. Density functional calculations and molecular dynamics simulations complemented the experimental results and aided interpretation. Alcohols with molecular mass greater than that of methanol bind more strongly to the calcium carbonate polymorphs than water and acetic acid. The adsorption energies for the alcohols are typical of chemisorption and indicate alcohol displacement of water from calcium carbonate surfaces. This explains why organisms favor biomolecules that contain alcohol functional groups (-OH) to control which polymorph they use, the crystal face and orientation, and the particle shape and size in biomineralization processes. This new insight is also very useful in understanding organic molecule adsorption mechanisms in soils, sediments, and rocks, which is important for predicting the behavior of mineral-fluid interactions when the challenge is to remediate contaminated groundwater aquifers or to produce oil and gas from reservoirs.

  4. Experimental coccidiosis influences the expression of the ABCB1 gene, a physiological important functional marker of intestinal integrity in chickens.

    Science.gov (United States)

    Haritova, Aneliya; Koinarski, Vencislav; Stanilova, Spaska

    2013-01-01

    Efflux transporters belonging to the family of ABC transporters have an important functional role in the maintenance of the intestinal barrier. As efflux transporters they prevent the absorption of toxic substances from feed, while at the same time facilitating the excretion of metabolic waste products as well as drugs from the circulation into the intestinal lumen. As Eimeria tenella infection significantly affects the integrity of caecum, the effects of experimental E. tenella infection on the levels of expression of ABCB1 mRNAs in the intestines and livers of broilers were evaluated. ABCB1 mRNA expression was quantified by qRT-PCR. Its expression levels were significantly down-regulated in the caecum of infected animals. The levels of ABCB1 mRNA were not changed in the duodenum and the liver. After treatment of the animals with sulfapyrazine for three days, not only a significant improvement of the clinical appearance but also a normalization of the P-gp expression was noticed. Although the current study cannot distinguish between the direct effect of the drug on the host and the drug action on the parasite, these results suggest that the treatment of coccidiosis with sulfachlorpyrazine also restored the expression of the investigated efflux transporter in the caecum. This is of clinical significance as P-glycoproteins contribute to the integrity of intestines and their function as important biological barriers, protecting poultry from pathogens and toxic compounds in animal feeds.

  5. Generation, functional annotation and comparative analysis of black spruce (Picea mariana) ESTs: an important conifer genomic resource.

    Science.gov (United States)

    Mann, Ishminder K; Wegrzyn, Jill L; Rajora, Om P

    2013-10-11

    EST (expressed sequence tag) sequences and their annotation provide a highly valuable resource for gene discovery, genome sequence annotation, and other genomics studies that can be applied in genetics, breeding and conservation programs for non-model organisms. Conifers are long-lived plants that are ecologically and economically important globally, and have a large genome size. Black spruce (Picea mariana), is a transcontinental species of the North American boreal and temperate forests. However, there are limited transcriptomic and genomic resources for this species. The primary objective of our study was to develop a black spruce transcriptomic resource to facilitate on-going functional genomics projects related to growth and adaptation to climate change. We conducted bidirectional sequencing of cDNA clones from a standard cDNA library constructed from black spruce needle tissues. We obtained 4,594 high quality (2,455 5' end and 2,139 3' end) sequence reads, with an average read-length of 532 bp. Clustering and assembly of ESTs resulted in 2,731 unique sequences, consisting of 2,234 singletons and 497 contigs. Approximately two-thirds (63%) of unique sequences were functionally annotated. Genes involved in 36 molecular functions and 90 biological processes were discovered, including 24 putative transcription factors and 232 genes involved in photosynthesis. Most abundantly expressed transcripts were associated with photosynthesis, growth factors, stress and disease response, and transcription factors. A total of 216 full-length genes were identified. About 18% (493) of the transcripts were novel, representing an important addition to the Genbank EST database (dbEST). Fifty-seven di-, tri-, tetra- and penta-nucleotide simple sequence repeats were identified. We have developed the first high quality EST resource for black spruce and identified 493 novel transcripts, which may be species-specific related to life history and ecological traits. We have also

  6. Understanding sex differences in form and function of bird song: The importance of studying song learning processes

    Directory of Open Access Journals (Sweden)

    Katharina eRiebel

    2016-06-01

    Full Text Available Birdsong is a culturally transmitted mating signal. Due to historical and geographical biases, song (learning has been predominantly studied in the temperate zones, where female song is rare. Consequently, mechanisms and function of song learning have been almost exclusively studied in male birds and under the premise that inter- and intrasexual selection favoured larger repertoires and complex songs in males. However, female song is not rare outside the temperate zones and song in both sexes probably is the ancestral state in songbirds. Some song dimorphisms seen today might therefore be manifestations of secondary losses of female song. What selection pressures have favoured such losses and other sexual dimorphisms in song? Combined mapping of phylogenetic and ecological correlates of sex differences in song structure and function might provide important clues to the evolution of male and female song. This requires parameterization of the degree of sexual dimorphism. Simple comparison of male-female song might not provide enough resolution, because the same magnitude of difference (e.g. repertoire overlap could result from different processes: the sexes could differ in how well they learn (‘copying fidelity’ or from whom they learn (‘model selection’. Different learning mechanisms might provide important pointers towards different selection pressures. Investigating sex-specific learning could therefore help to identify the social and ecological selection pressures contributing to sex differences in adult song. The study of female song learning in particular could be crucial to our understanding of i song function in males and females and ii the evolution of sex-specific song.

  7. Syndecan-3: a cell-surface heparan sulfate proteoglycan important for chondrocyte proliferation and function during limb skeletogenesis.

    Science.gov (United States)

    Pacifici, Maurizio; Shimo, Tsuyoshi; Gentili, Chiara; Kirsch, Thorsten; Freeman, Theresa A; Enomoto-Iwamoto, Motomi; Iwamoto, Masahiro; Koyama, Eiki

    2005-01-01

    Syndecans are single-pass integral membrane components that serve as co-receptors for growth factors and cytokines and can elicit signal transduction via their cytoplasmic tails. We review here previous studies from our groups on syndecan-3 biology and function in the growth plates of developing long bones in chick and mouse embryos. Gain- and loss-of-function data indicate that syndecan-3 has important roles in restricting mitotic activity to the proliferative zone of growth plate and may do so in close cooperation and interaction with the signaling molecule Indian hedgehog (IHH). Biochemical and protein-modeling data suggest a dimeric/oligomeric syndecan-3 configuration on the chondrocyte's cell surface. Analyses of embryos misexpressing syndecan-3 or lacking IHH provide further clues on syndecan-3/IHH interdependence and interrelationships. The data and the conclusions reached provide insights into mechanisms fine-tuning chondrocyte proliferation, maturation, and function in the developing and growing skeleton and into how abnormalities in these fundamental mechanisms may subtend human congenital pathologies, including osteochondromas in hereditary multiple exostoses syndrome.

  8. SIRT1 Functions as an Important Regulator of Estrogen-Mediated Cardiomyocyte Protection in Angiotensin II-Induced Heart Hypertrophy

    Directory of Open Access Journals (Sweden)

    Tao Shen

    2014-01-01

    Full Text Available Background. Sirtuin 1 (SIRT1 is a member of the sirtuin family, which could activate cell survival machinery and has been shown to be protective in regulation of heart function. Here, we determined the mechanism by which SIRT1 regulates Angiotensin II- (AngII- induced cardiac hypertrophy and injury in vivo and in vitro. Methods. We analyzed SIRT1 expression in the hearts of control and AngII-induced mouse hypertrophy. Female C57BL/6 mice were ovariectomized and pretreated with 17β-estradiol to measure SIRT1 expression. Protein synthesis, cardiomyocyte surface area analysis, qRT-PCR, TUNEL staining, and Western blot were performed on AngII-induced mouse heart hypertrophy samples and cultured neonatal rat ventricular myocytes (NRVMs to investigate the function of SIRT1. Results. SIRT1 expression was slightly upregulated in AngII-induced mouse heart hypertrophy in vivo and in vitro, accompanied by elevated cardiomyocyte apoptosis. SIRT1 overexpression relieves AngII-induced cardiomyocyte hypertrophy and apoptosis. 17β-Estradiol was able to protect cardiomyocytes from AngII-induced injury with a profound upregulation of SIRT1 and activation of AMPK. Moreover, estrogen receptor inhibitor ICI 182,780 and SIRT1 inhibitor niacinamide could block SIRT1’s protective effect. Conclusions. These results indicate that SIRT1 functions as an important regulator of estrogen-mediated cardiomyocyte protection during AngII-induced heart hypertrophy and injury.

  9. Relative importance of modularity and other morphological attributes on different types of lithic point weapons: assessing functional variations.

    Science.gov (United States)

    González-José, Rolando; Charlin, Judith

    2012-01-01

    The specific using of different prehistoric weapons is mainly determined by its physical properties, which provide a relative advantage or disadvantage to perform a given, particular function. Since these physical properties are integrated to accomplish that function, examining design variables and their pattern of integration or modularity is of interest to estimate the past function of a point. Here we analyze a composite sample of lithic points from southern Patagonia likely formed by arrows, thrown spears and hand-held points to test if they can be viewed as a two-module system formed by the blade and the stem, and to evaluate the degree in which shape, size, asymmetry, blade: stem length ratio, and tip angle explain the observed variance and differentiation among points supposedly aimed to accomplish different functions. To do so we performed a geometric morphometric analysis on 118 lithic points, departing from 24 two-dimensional landmark and semi landmarks placed on the point's contour. Klingenberg's covariational modularity tests were used to evaluate different modularity hypotheses, and a composite PCA including shape, size, asymmetry, blade: stem length ratio, and tip angle was used to estimate the importance of each attribute to explaining variation patterns. Results show that the blade and the stem can be seen as "near decomposable units" in the points integrating the studied sample. However, this modular pattern changes after removing the effects of reduction. Indeed, a resharpened point tends to show a tip/rest of the point modular pattern. The composite PCA analyses evidenced three different patterns of morphometric attributes compatible with arrows, thrown spears, and hand-held tools. Interestingly, when analyzed independently, these groups show differences in their modular organization. Our results indicate that stone tools can be approached as flexible designs, characterized by a composite set of interacting morphometric attributes, and evolving

  10. Relative importance of modularity and other morphological attributes on different types of lithic point weapons: assessing functional variations.

    Directory of Open Access Journals (Sweden)

    Rolando González-José

    Full Text Available The specific using of different prehistoric weapons is mainly determined by its physical properties, which provide a relative advantage or disadvantage to perform a given, particular function. Since these physical properties are integrated to accomplish that function, examining design variables and their pattern of integration or modularity is of interest to estimate the past function of a point. Here we analyze a composite sample of lithic points from southern Patagonia likely formed by arrows, thrown spears and hand-held points to test if they can be viewed as a two-module system formed by the blade and the stem, and to evaluate the degree in which shape, size, asymmetry, blade: stem length ratio, and tip angle explain the observed variance and differentiation among points supposedly aimed to accomplish different functions. To do so we performed a geometric morphometric analysis on 118 lithic points, departing from 24 two-dimensional landmark and semi landmarks placed on the point's contour. Klingenberg's covariational modularity tests were used to evaluate different modularity hypotheses, and a composite PCA including shape, size, asymmetry, blade: stem length ratio, and tip angle was used to estimate the importance of each attribute to explaining variation patterns. Results show that the blade and the stem can be seen as "near decomposable units" in the points integrating the studied sample. However, this modular pattern changes after removing the effects of reduction. Indeed, a resharpened point tends to show a tip/rest of the point modular pattern. The composite PCA analyses evidenced three different patterns of morphometric attributes compatible with arrows, thrown spears, and hand-held tools. Interestingly, when analyzed independently, these groups show differences in their modular organization. Our results indicate that stone tools can be approached as flexible designs, characterized by a composite set of interacting morphometric

  11. Relative Importance of Modularity and Other Morphological Attributes on Different Types of Lithic Point Weapons: Assessing Functional Variations

    Science.gov (United States)

    González-José, Rolando; Charlin, Judith

    2012-01-01

    The specific using of different prehistoric weapons is mainly determined by its physical properties, which provide a relative advantage or disadvantage to perform a given, particular function. Since these physical properties are integrated to accomplish that function, examining design variables and their pattern of integration or modularity is of interest to estimate the past function of a point. Here we analyze a composite sample of lithic points from southern Patagonia likely formed by arrows, thrown spears and hand-held points to test if they can be viewed as a two-module system formed by the blade and the stem, and to evaluate the degree in which shape, size, asymmetry, blade: stem length ratio, and tip angle explain the observed variance and differentiation among points supposedly aimed to accomplish different functions. To do so we performed a geometric morphometric analysis on 118 lithic points, departing from 24 two-dimensional landmark and semi landmarks placed on the point's contour. Klingenberg's covariational modularity tests were used to evaluate different modularity hypotheses, and a composite PCA including shape, size, asymmetry, blade: stem length ratio, and tip angle was used to estimate the importance of each attribute to explaining variation patterns. Results show that the blade and the stem can be seen as “near decomposable units” in the points integrating the studied sample. However, this modular pattern changes after removing the effects of reduction. Indeed, a resharpened point tends to show a tip/rest of the point modular pattern. The composite PCA analyses evidenced three different patterns of morphometric attributes compatible with arrows, thrown spears, and hand-held tools. Interestingly, when analyzed independently, these groups show differences in their modular organization. Our results indicate that stone tools can be approached as flexible designs, characterized by a composite set of interacting morphometric attributes, and

  12. Cognitive and functional impairment in patients suffering from stroke: the importance of cognitive assessment for Occupational Therapy intervention

    Directory of Open Access Journals (Sweden)

    Andressa de Oliveira Ferro

    2013-12-01

    Full Text Available Abstract: Introduction: Stroke (CVA can generate motor, sensory and cognitive development deficits, affecting the individual’s performance in daily activities. Changes in any cognitive area can affect the individual’s occupational engagement. Objective: To evaluate the cognitive and functional capacity in patients suffering from stroke, showing the importance of cognitive assessment for occupational therapy intervention. Method: A comparative study with cross-sectional sampling of 44 subjects aged 30-80 years, both sexes. The subjects were divided in three groups: Adult: 11 individuals affected by stroke, 30-59 years old; Elderly: 10 individuals affected by stroke, 60-80 years old; Control: 23 normal subjects, 30-80 years old. Tests applied: MMSE, Clock Test, Test of tracks A and B, and functional capacity (BOMFAQ. Results: Cognitive changes were identified in the Adult and Elderly groups. The Adult group showed poorer performance on the Clock test (visuospatial and executive functions compared with the Control group. The Adult and Elderly groups presented worse performance in the Track A test (attention compared with the Control group. In the Track B test (visual attention, graphomotor skills, and mental flexibility, applied with absolute numbers, no significant differences were observed between the Adult and Elderly groups and the Control group, but cognitive impairment was perceived when the test was applied with categories. The Adult group showed higher prevalence of moderate/severe impairment in the carrying out of daily activities. Conclusion: As a rule, individuals suffering from stroke, in addition to having impaired functional capacity, present cognitive impairments that can negatively impact the performance of daily tasks, whether they are occupational, leisure or self-care activities. Accordingly, we observed the need to evaluate cognitive rehabilitation for better targeting and quality of life improvement.

  13. Modelling the decadal trend of ecosystem carbon fluxes demonstrates the important role of functional changes in a temperate deciduous forest

    DEFF Research Database (Denmark)

    Wu, Jian; Jansson, P.E.; van der Linden, Leon;

    2013-01-01

    Temperate forests are globally important carbon sinks and stocks. Trends in net ecosystem exchange have been observed in a Danish beech forest and this trend cannot be entirely attributed to changing climatic drivers. This study sought to clarify the mechanisms responsible for the observed trend......, the latent and sensible heat fluxes and the CO2 fluxes decreased the parameter uncertainty considerably compared to using CO2 fluxes as validation data alone. The fitted model was able to simulate the observed carbon fluxes well (R2=0.8, mean error=0.1gCm−2d−1) but did not reproduce the decadal (1997......–2009) trend in carbon uptake when global parameter estimates were used. Annual parameter estimates were able to reproduce the decadal scale trend; the yearly fitted posterior parameters (e.g. the light use efficiency) indicated a role for changes in the ecosystem functional properties. A possible role...

  14. Serum amyloid A: an ozone-induced circulating factor with potentially important functions in the lung-brain axis.

    Science.gov (United States)

    Erickson, Michelle A; Jude, Joseph; Zhao, Hengjiang; Rhea, Elizabeth M; Salameh, Therese S; Jester, William; Pu, Shelley; Harrowitz, Jenna; Nguyen, Ngan; Banks, William A; Panettieri, Reynold A; Jordan-Sciutto, Kelly L

    2017-09-01

    Accumulating evidence suggests that O3 exposure may contribute to CNS dysfunction. Here, we posit that inflammatory and acute-phase proteins in the circulation increase after O3 exposure and systemically convey signals of O3 exposure to the CNS. To model acute O3 exposure, female Balb/c mice were exposed to 3 ppm O3 or forced air for 2 h and were studied after 6 or 24 h. Of 23 cytokines and chemokines, only KC/CXCL1 was increased in blood 6 h after O3 exposure. The acute-phase protein serum amyloid A (A-SAA) was significantly increased by 24 h, whereas C-reactive protein was unchanged. A-SAA in blood correlated with total leukocytes, macrophages, and neutrophils in bronchoalveolar lavage from O3-exposed mice. A-SAA mRNA and protein were increased in the liver. We found that both isoforms of A-SAA completely crossed the intact blood-brain barrier, although the rate of SAA2.1 influx was approximately 5 times faster than that of SAA1.1. Finally, A-SAA protein, but not mRNA, was increased in the CNS 24 h post-O3 exposure. Our findings suggest that A-SAA is functionally linked to pulmonary inflammation in our O3 exposure model and that A-SAA could be an important systemic signal of O3 exposure to the CNS.-Erickson, M. A., Jude, J., Zhao, H., Rhea, E. M., Salameh, T. S., Jester, W., Pu, S., Harrowitz, J., Nguyen, N., Banks, W. A., Panettieri, R. A., Jr., Jordan-Sciutto, K. L. Serum amyloid A: an ozone-induced circulating factor with potentially important functions in the lung-brain axis. © FASEB.

  15. Cyclophilin A is an important mediator of platelet function by regulating integrin αIIbβ3 bidirectional signalling.

    Science.gov (United States)

    Wang, Lian; Soe, Nwe Nwe; Sowden, Mark; Xu, Yingqian; Modjeski, Kristina; Baskaran, Padmamalini; Kim, Yeonghwan; Smolock, Elaine M; Morrell, Craig N; Berk, Bradford C

    2014-05-05

    Cyclophilin A (CyPA) is an important mediator in cardiovascular diseases. It possesses peptidyl-prolyl cis-trans isomerase activity (PPIase) and chaperone functions, which regulate protein folding, intracellular trafficking and reactive oxygen species (ROS) production. Platelet glycoprotein receptor αIIbβ3 integrin activation is the common pathway for platelet activation. It was our objective to understand the mechanism by which CyPA-regulates αIIbβ3 activation in platelets. Mice deficient for CyPA (CyPA-/-) had prolonged tail bleeding time compared to wild-type (WT) controls despite equivalent platelet numbers. In vitro studies revealed that CyPA-/- platelets exhibited dramatically decreased thrombin-induced platelet aggregation. In vivo, formation of occlusive thrombi following FeCl3 injury was also significantly impaired in CyPA-/- mice compared with WT-controls. Furthermore, CyPA deficiency inhibited flow-induced thrombus formation in vitro. Flow cytometry demonstrated that thrombin-induced ROS production and αIIbβ3 activation were reduced in CyPA-/- platelets. Coimmunoprecipitation studies showed ROS-dependent increased association of CyPA and αIIbβ3. This association was dependent upon the PPIase activity of CyPA. Significantly, fibrinogen-platelet binding, platelet spreading and cytoskeleton reorganisation were also altered in CyPA-/- platelets. Moreover, CyPA deficiency prevented thrombin-induced αIIbβ3 and cytoskeleton association. In conclusion, CyPA is an important mediator in platelet function by regulation of αIIbβ3 bidirectionalsignalling through increased ROS production and facilitating interaction between αIIbβ3 and the cell cytoskeleton.

  16. The importance of object geometric properties for trajectory modeling of functional reach-to-grasp robotic therapy tasks - biomed 2009.

    Science.gov (United States)

    Nathan, Dominic; Jeutter, Dean C

    2009-01-01

    Reaching-to-grasp is essential for the performance of activities of daily living. Pathologies such as stroke, spinal cord injury, cerebral palsy, etc. limit individuals from being able to perform meaningful upper extremity movements, leading to a reduced quality of life. Robotic aided therapy is gaining prevalence as a rehabilitation tool because it can provide consistent and quantitative therapy. Such systems are dependent upon models to generate trajectories that dictate their movements. Time scaled polynomial techniques have been extensively used for robotic model development and trajectory generation. However, this approach is limited because it cannot support functional therapy tasks. This is largely due to the influence of cognitive complexity not completely considered with regards to the activity performed. We examine the influence of task cognitive complexity as manifested through the geometric properties of each object on the movement trajectories and kinematic dependent variables tasks through a motion analysis study using healthy subjects (N=8). We then compare the predicted results from several robotic trajectory models with the actual motion analysis data. Our results show that there are differences present, between the trajectory data and kinematic properties for each task, that are specific to the geometric properties of each object. In addition, the predicted results from the robotic trajectory models do not fully correlate with the actual movement information. This study is important as it will help provide some insight with regards to factors that need to be considered during the development of future robotic trajectory models and controllers for upper extremity functional rehabilitation tasks.

  17. The Play of Psychotherapy

    Science.gov (United States)

    Marks-Tarlow, Terry

    2012-01-01

    The author reviews the role of play within psychotherapy. She does not discuss the formal play therapy especially popular for young children, nor play from the Jungian perspective that encourages the use of the sand tray with adults. Instead, she focuses on the informal use of play during psychotherapy as it is orchestrated intuitively. Because…

  18. Applying Play to Therapy.

    Science.gov (United States)

    Ritter, Patricia S.; Fokes, Joann

    The objectives of this paper are (1) to present the relationship of play to language and cognition, (2) to describe the stages of play and discuss recent literature about the characteristics of play, and (3) to describe the use of play with the multifaceted goals of cognition, pragmatics, semantics, syntax, and morphology as an intervention…

  19. Quantifying the importance of orbital over spin correlations in delta-Pu within density-functional theory

    Energy Technology Data Exchange (ETDEWEB)

    Soderlind, P; Wolfer, W

    2007-07-27

    Spin and orbital and electron correlations are known to be important when treating the high-temperature {delta} phase of plutonium within the framework of density-functional theory (DFT). One of the more successful attempts to model {delta}-Pu within this approach has included condensed-matter generalizations of Hund's three rules for atoms, i.e., spin polarization, orbital polarization, and spin-orbit coupling. Here they perform a quantitative analysis of these interactions relative rank for the bonding and electronic structure in {delta}-Pu within the DFT model. The result is somewhat surprising in that spin-orbit coupling and orbital polarization are far more important than spin polarization for a realistic description of {delta}-Pu. They show that these orbital correlations on their own, without any formation of magnetic spin moments, can account for the low atomic density of the {delta} phase with a reasonable equation-of-state. In addition, this unambiguously non-magnetic (NM) treatment produces a one-electron spectra with resonances close to the Fermi level consistent with experimental valence band photoemission spectra.

  20. Playing The Lobby

    DEFF Research Database (Denmark)

    2014-01-01

    Playing a game can be defined as, in a fun way, to reach a goal by means of helpers and challenged by obstacles and opponents. In this workshop we will gain a new understanding of the lobby by making it into a game. The lobby of the museum can be understood as a game in which the players (the....... The object is surprisingly not to play the games, but to design them. Through the design process we are forced to discuss: What are the challenges of a particular lobby (e.g. ticketing, queueing, other visitors, guards, getting lost)? Which properties do the players have (e.g. patience, expectations, need...... of a toilet)? what boosters may they obtain in the lobby (e.g. coffee, help, souvenirs, signs)? And how can we make this an enjoyable experience? The object of the games is to understand the lobby in a new way to identify problems, and think of ways to improve the functions, flow, and services of the lobby....

  1. Functional importance of GGXG sequence motifs in putative reentrant loops of 2HCT and ESS transport proteins.

    Science.gov (United States)

    Dobrowolski, Adam; Lolkema, Juke S

    2009-08-11

    The 2HCT and ESS families are two families of secondary transporters. Members of the two families are unrelated in amino acid sequence but share similar hydropathy profiles, which suggest a similar folding of the proteins in membranes. Structural models show two homologous domains containing five transmembrane segments (TMSs) each, with a reentrant or pore loop between the fourth and fifth TMSs in each domain. Here we show that GGXG sequence motifs present in the putative reentrant loops are important for the activity of the transporters. Mutation of the conserved Gly residues to Cys in the motifs of the Na(+)-citrate transporter CitS in the 2HCT family and the Na(+)-glutamate transporter GltS in the ESS family resulted in strongly reduced transport activity. Similarly, mutation of the variable residue "X" to Cys in the N-terminal half of GltS essentially inactivated the transporter. The corresponding mutations in the N- and C-terminal halves of CitS reduced transport activity to 60 and 25% of that of the wild type, respectively. Residual activity of any of the mutants could be further reduced by treatment with the membrane permeable thiol reagent N-ethylmaleimide (NEM). The X to Cys mutation (S405C) in the cytoplasmic loop in the C-terminal half of CitS rendered the protein sensitive to the bulky, membrane impermeable thiol reagent 4-acetamido-4'-maleimidylstilbene-2,2'-disulfonic acid (AmdiS) added at the periplasmic side of the membrane, providing further evidence that this part of the loop is positioned between the transmembrane segments. The putative reentrant loop in the C-terminal half of the ESS family does not contain the GGXG motif, but a conserved stretch rich in Gly residues. Cysteine-scanning mutagenesis of a stretch of 18 residues in the GltS protein revealed two residues important for function. Mutant N356C was completely inactivated by treatment with NEM, and mutant P351C appeared to be the counterpart of mutant S405C of CitS; the mutant was

  2. Strategies for Family Facilitation of Play Dates

    Science.gov (United States)

    Chambers, Cynthia R.; Horn, Eva M.

    2010-01-01

    Play dates can serve several functions for young children, including children with social difficulties, such as developmental delays, behavioral disorders, autism spectrum disorders, and shyness. Play dates provide children with additional opportunities to be around peers and to practice skills associated with peer play interactions. Play dates…

  3. Importance of congestive heart failure and interaction of congestive heart failure and left ventricular systolic function on prognosis in patients with acute myocardial infarction

    DEFF Research Database (Denmark)

    Køber, L; Torp-Pedersen, C; Pedersen, O D;

    1996-01-01

    Left ventricular (LV) systolic function and congestive heart failure (CHF) are important predictors of long-term mortality after acute myocardial infarction. The importance of transient CHF and the interaction of CHF and LV function on prognosis has not been studied in detail previously...

  4. The play grid

    DEFF Research Database (Denmark)

    Fogh, Rune; Johansen, Asger

    2013-01-01

    In this paper we propose The Play Grid, a model for systemizing different play types. The approach is psychological by nature and the actual Play Grid is based, therefore, on two pairs of fundamental and widely acknowledged distinguishing characteristics of the ego, namely: extraversion vs...... at the Play Grid. Thus, the model has four quadrants, each of them describing one of four play types: the Assembler, the Director, the Explorer, and the Improviser. It is our hope that the Play Grid can be a useful design tool for making entertainment products for children....

  5. Agrobacterium-mediated genetic transformation of yam (Dioscorea rotundata: an important tool for functional study of genes and crop improvement

    Directory of Open Access Journals (Sweden)

    Evans eNyaboga

    2014-09-01

    Full Text Available Although genetic transformation of clonally propagated crops has been widely studied as a tool for crop improvement and as a vital part of the development of functional genomics resources, there has been no report of any existing Agrobacterium-mediated transformation of yam (Dioscorea spp. with evidence of stable integration of T-DNA. Yam is an important crop in the tropics and subtropics providing food security and income to over 300 million people. However, yam production remains constrained by increasing levels of field and storage pests and diseases. A major constraint to the development of biotechnological approaches for yam improvement has been the lack of an efficient and robust transformation and regeneration system. In this study, we developed an Agrobacterium-mediated transformation of Dioscorea rotundata using axillary buds as explants. Two cultivars of D. rotundata were transformed using Agrobacterium tumefaciens harboring the binary vectors containing selectable marker and reporter genes. After selection with appropriate concentrations of antibiotic, shoots were developed on shoot induction and elongation medium. The elongated antibiotic-resistant shoots were subsequently rooted on medium supplemented with selection agent. Successful transformation was confirmed by PCR, Southern blot analysis and reporter genes assay. Expression of gusA gene in transgenic plants was also verified by RT-PCR analysis. Transformation efficiency varied from 9.4% to 18.2% depending on the cultivars, selectable marker genes and the Agrobacterium strain used for transformation. It took 3–4 months from Agro-infection to regeneration of complete transgenic plant. Here we report an efficient, fast and reproducible protocol for Agrobacterium-mediated transformation of D. rotundata using axillary buds as explants, which provides a useful platform for future genetic engineering studies in this economically important crop.

  6. Identification and characterization of functionally important elements in the multidrug resistance protein 1 COOH-terminal region.

    Science.gov (United States)

    Westlake, Christopher J; Payen, Lea; Gao, Mian; Cole, Susan P C; Deeley, Roger G

    2004-12-17

    The ATP binding cassette (ABC) transporter, multidrug resistance protein 1 (MRP1/ABCC1), transports a broad spectrum of conjugated and unconjugated compounds, including natural product chemotherapeutic agents. In this study, we have investigated the importance of the COOH-terminal region of MRP1 for transport activity and basolateral plasma membrane trafficking. The COOH-terminal regions of some ABCC proteins have been implicated in protein trafficking, but the function of this region of MRP1 has not been defined. In contrast to results obtained with other ABCC proteins, we found that the COOH-proximal 30 amino acids of MRP1 can be removed without affecting trafficking to basolateral membranes. However, the truncated protein is inactive. Furthermore, removal of as few as 4 COOH-terminal amino acids profoundly decreases transport activity. Although amino acid sequence conservation of the COOH-terminal regions of ABC proteins is low, secondary structure predictions indicate that they consist of a broadly conserved helix-sheet-sheet-helix-helix structure. Consistent with a conservation of secondary and tertiary structure, MRP1 hybrids containing the COOH-terminal regions of either the homologous MRP2 or the distantly related P-glycoprotein were fully active and trafficked normally. Using mutated proteins, we have identified structural elements containing five conserved hydrophobic amino acids that are required for activity. We show that these are important for binding and hydrolysis of ATP by nucleotide binding domain 2. Based on crystal structures of several ABC proteins, we suggest that the conserved amino acids may stabilize a helical bundle formed by the COOH-terminal three helices and may contribute to interactions between the COOH-terminal region and the protein's two nucleotide binding domains.

  7. Agrobacterium-mediated genetic transformation of yam (Dioscorea rotundata): an important tool for functional study of genes and crop improvement.

    Science.gov (United States)

    Nyaboga, Evans; Tripathi, Jaindra N; Manoharan, Rajesh; Tripathi, Leena

    2014-01-01

    Although genetic transformation of clonally propagated crops has been widely studied as a tool for crop improvement and as a vital part of the development of functional genomics resources, there has been no report of any existing Agrobacterium-mediated transformation of yam (Dioscorea spp.) with evidence of stable integration of T-DNA. Yam is an important crop in the tropics and subtropics providing food security and income to over 300 million people. However, yam production remains constrained by increasing levels of field and storage pests and diseases. A major constraint to the development of biotechnological approaches for yam improvement has been the lack of an efficient and robust transformation and regeneration system. In this study, we developed an Agrobacterium-mediated transformation of Dioscorea rotundata using axillary buds as explants. Two cultivars of D. rotundata were transformed using Agrobacterium tumefaciens harboring the binary vectors containing selectable marker and reporter genes. After selection with appropriate concentrations of antibiotic, shoots were developed on shoot induction and elongation medium. The elongated antibiotic-resistant shoots were subsequently rooted on medium supplemented with selection agent. Successful transformation was confirmed by polymerase chain reaction, Southern blot analysis, and reporter genes assay. Expression of gusA gene in transgenic plants was also verified by reverse transcription polymerase chain reaction analysis. Transformation efficiency varied from 9.4 to 18.2% depending on the cultivars, selectable marker genes, and the Agrobacterium strain used for transformation. It took 3-4 months from Agro-infection to regeneration of complete transgenic plant. Here we report an efficient, fast and reproducible protocol for Agrobacterium-mediated transformation of D. rotundata using axillary buds as explants, which provides a useful platform for future genetic engineering studies in this economically important

  8. EVALUATION OF THE POSSIBLE THREAT OF NAFTA ON U.S. CATFISH INDUSTRY USING A TRADITIONAL IMPORT DEMAND FUNCTION

    OpenAIRE

    Carel LIGEON; Jolly, Curtis M.; Jackson, John D.

    1996-01-01

    The effects of increased exports from NAFTA member countries on the U.S. domestic catfish industry were evaluated. Results showed that the quantity of catfish imported will fall if the domestic price of catfish falls relative to the import price. Past imports have no effect on present imports. The income elasticity was negative indicating that imported catfish may be an inferior good. Doubling present levels of imports from NAFTA member countries is not a threat to the U.S. catfish industry.

  9. Comparative analysis of the noncollagenous NC1 domain of type IV collagen: identification of structural features important for assembly, function, and pathogenesis.

    Science.gov (United States)

    Netzer, K O; Suzuki, K; Itoh, Y; Hudson, B G; Khalifah, R G

    1998-06-01

    Type IV collagen alpha1-alpha6 chains have important roles in the assembly of basement membranes and are implicated in the pathogenesis of Goodpasture syndrome, an autoimmune disorder, and Alport syndrome, a hereditary renal disease. We report comparative sequence analyses and structural predictions of the noncollagenous C-terminal globular NC1 domain (28 sequences). The inferred tree verified that type IV collagen sequences fall into two groups, alpha1-like and alpha2-like, and suggested that vertebrate alpha3/alpha4 sequences evolved before alpha1/alpha2 and alpha5/alpha6. About one fifth of NC1 residues were identified to confer either the alpha1 or alpha2 group-specificity. These residues accumulate opposite charge in subdomain B of alpha1 (positive) and alpha2 (negative) sequences and may play a role in the stoichiometric chain selection upon type IV collagen assembly. Neural network secondary structure prediction on multiple aligned sequences revealed a subdomain core structure consisting of six hydrophobic beta-strands and one short alpha-helix with a significant hydrophobic moment. The existence of opposite charges in the alpha-helices may carry implications for intersubdomain interactions. The results provide a rationale for defining the epitope that binds Goodpasture autoantibodies and a framework for understanding how certain NC1 mutations may lead to Alport syndrome. A search algorithm, based entirely on amino acid properties, yielded a possible similarity of NC1 to tissue inhibitor of metalloproteinases (TIMP) and prompted an investigation of a possible functional relationship. The results indicate that NC1 preparations decrease the activity of matrix metalloproteinases 2 and 3 (MMP-2, MMP-3) toward a peptide substrate, though not to [14C]-gelatin. We suggest that an ancestral NC1 may have been incorporated into type IV collagen as an evolutionarily mobile domain carrying proteinase inhibitor function.

  10. Factors of importance for the functional outcome in orthognathic surgery patients: a prospective study of 118 patients

    DEFF Research Database (Denmark)

    Øland, Jesper; Jensen, John; Melsen, Birte

    2010-01-01

    The aim of this study was to assess the influence of orthognathic surgery on patients' stomatognathic function and, further, to evaluate how post-treatment function relates to satisfaction.......The aim of this study was to assess the influence of orthognathic surgery on patients' stomatognathic function and, further, to evaluate how post-treatment function relates to satisfaction....

  11. The importance of grasslands for animal production and other functions: a review on management and methodological progress in the tropics.

    Science.gov (United States)

    Boval, M; Dixon, R M

    2012-05-01

    The global importance of grasslands is indicated by their extent; they comprise some 26% of total land area and 80% of agriculturally productive land. The majority of grasslands are located in tropical developing countries where they are particularly important to the livelihoods of some one billion poor peoples. Grasslands clearly provide the feed base for grazing livestock and thus numerous high-quality foods, but such livestock also provide products such as fertilizer, transport, traction, fibre and leather. In addition, grasslands provide important services and roles including as water catchments, biodiversity reserves, for cultural and recreational needs, and potentially a carbon sink to alleviate greenhouse gas emissions. Inevitably, such functions may conflict with management for production of livestock products. Much of the increasing global demand for meat and milk, particularly from developing countries, will have to be supplied from grassland ecosystems, and this will provide difficult challenges. Increased production of meat and milk generally requires increased intake of metabolizable energy, and thus increased voluntary intake and/or digestibility of diets selected by grazing animals. These will require more widespread and effective application of improved management. Strategies to improve productivity include fertilizer application, grazing management, greater use of crop by-products, legumes and supplements and manipulation of stocking rate and herbage allowance. However, it is often difficult to predict the efficiency and cost-effectiveness of such strategies, particularly in tropical developing country production systems. Evaluation and on-going adjustment of grazing systems require appropriate and reliable assessment criteria, but these are often lacking. A number of emerging technologies may contribute to timely low-cost acquisition of quantitative information to better understand the soil-pasture-animal interactions and animal management in