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Sample records for factors key regulators

  1. Key factors regulating the mass delivery of macromolecules to model cell membranes

    DEFF Research Database (Denmark)

    Campbell, Richard A.; Watkins, Erik B.; Jagalski, Vivien

    2014-01-01

    We show that both gravity and electrostatics are key factors regulating interactions between model cell membranes and self-assembled liquid crystalline aggregates of dendrimers and phospholipids. The system is a proxy for the trafficking of reservoirs of therapeutic drugs to cell membranes for slow...... diffusion and continuous delivery. Neutron reflectometry measurements were carried out on supported lipid bilayers of varying charge and on hydrophilic silica surfaces. Translocation of the macromolecule across the membrane and adsorption of the lamellar aggregates occur only when the membrane (1...... of the aggregates to activate endocytosis pathways on specific cell types is discussed in the context of targeted drug delivery applications....

  2. Proliferating cell nuclear antigen (PCNA): a key factor in DNA replication and cell cycle regulation.

    Science.gov (United States)

    Strzalka, Wojciech; Ziemienowicz, Alicja

    2011-05-01

    PCNA (proliferating cell nuclear antigen) has been found in the nuclei of yeast, plant and animal cells that undergo cell division, suggesting a function in cell cycle regulation and/or DNA replication. It subsequently became clear that PCNA also played a role in other processes involving the cell genome. This review discusses eukaryotic PCNA, with an emphasis on plant PCNA, in terms of the protein structure and its biochemical properties as well as gene structure, organization, expression and function. PCNA exerts a tripartite function by operating as (1) a sliding clamp during DNA synthesis, (2) a polymerase switch factor and (3) a recruitment factor. Most of its functions are mediated by its interactions with various proteins involved in DNA synthesis, repair and recombination as well as in regulation of the cell cycle and chromatid cohesion. Moreover, post-translational modifications of PCNA play a key role in regulation of its functions. Finally, a phylogenetic comparison of PCNA genes suggests that the multi-functionality observed in most species is a product of evolution. Most plant PCNAs exhibit features similar to those found for PCNAs of other eukaryotes. Similarities include: (1) a trimeric ring structure of the PCNA sliding clamp, (2) the involvement of PCNA in DNA replication and repair, (3) the ability to stimulate the activity of DNA polymerase δ and (4) the ability to interact with p21, a regulator of the cell cycle. However, many plant genomes seem to contain the second, probably functional, copy of the PCNA gene, in contrast to PCNA pseudogenes that are found in mammalian genomes.

  3. Sox2, a key factor in the regulation of pluripotency and neural differentiation

    Institute of Scientific and Technical Information of China (English)

    Shuchen; Zhang; Wei; Cui

    2014-01-01

    Sex determining region Y-box 2(Sox2), a member of the SoxB1 transcription factor family, is an important transcriptional regulator in pluripotent stem cells(PSCs). Together with octamer-binding transcription factor 4 and Nanog, they co-operatively control gene expression in PSCs and maintain their pluripotency. Furthermore, Sox2 plays an essential role in somatic cell reprogram-ming, reversing the epigenetic configuration of differ-entiated cells back to a pluripotent embryonic state. In addition to its role in regulation of pluripotency, Sox2 is also a critical factor for directing the differentiation of PSCs to neural progenitors and for maintaining the properties of neural progenitor stem cells. Here, we review recent findings concerning the involvement of Sox2 in pluripotency, somatic cell reprogramming and neural differentiation as well as the molecular mecha-nisms underlying these roles.

  4. Key role of the kidney in the regulation of fibroblast growth factor 23

    DEFF Research Database (Denmark)

    Mace, Maria L; Gravesen, Eva; Hofman-Bang, Jacob

    2015-01-01

    High circulating levels of fibroblast growth factor 23 (FGF23) have been demonstrated in kidney failure, but mechanisms of this are not well understood. Here we examined the impact of the kidney on the early regulation of intact FGF23 in acute uremia as induced by bilateral or unilateral...... nephrectomy (BNX and UNX, respectively) in the rat. BNX induced a significant increase in plasma intact FGF23 levels from 112 to 267 pg/ml within 15 min, which remained stable thereafter. UNX generated intact FGF23 levels between that seen in BNX and sham-operated rats. The intact to C-terminal FGF23 ratio...... was significantly increased in BNX rats. The rapid rise in FGF23 after BNX was independent of parathyroid hormone or FGF receptor signaling. No evidence of early stimulation of FGF23 gene expression in the bone was found. Furthermore, acute severe hyperphosphatemia or hypercalcemia had no impact on intact FGF23...

  5. The polyadenylation factor subunit CLEAVAGE AND POLYADENYLATION SPECIFICITY FACTOR30: A key factor of programmed cell death and a regulator of immunity in arabidopsis

    KAUST Repository

    Bruggeman, Quentin

    2014-04-04

    Programmed cell death (PCD) is essential for several aspects of plant life, including development and stress responses. Indeed, incompatible plant-pathogen interactions are well known to induce the hypersensitive response, a localized cell death. Mutational analyses have identified several key PCD components, and we recently identified the mips1 mutant of Arabidopsis (Arabidopsis thaliana), which is deficient for the key enzyme catalyzing the limiting step of myoinositol synthesis. One of the most striking features of mips1 is the light-dependent formation of lesions on leaves due to salicylic acid (SA)-dependent PCD, revealing roles for myoinositol or inositol derivatives in the regulation of PCD. Here, we identified a regulator of plant PCD by screening for mutants that display transcriptomic profiles opposing that of the mips1 mutant. Our screen identified the oxt6 mutant, which has been described previously as being tolerant to oxidative stress. In the oxt6 mutant, a transfer DNA is inserted in the CLEAVAGE AND POLYADENYLATION SPECIFICITY FACTOR30 (CPSF30) gene, which encodes a polyadenylation factor subunit homolog. We show that CPSF30 is required for lesion formation in mips1 via SA-dependent signaling, that the prodeath function of CPSF30 is not mediated by changes in the glutathione status, and that CPSF30 activity is required for Pseudomonas syringae resistance. We also show that the oxt6 mutation suppresses cell death in other lesion-mimic mutants, including lesion-simulating disease1, mitogen-activated protein kinase4, constitutive expressor of pathogenesis-related genes5, and catalase2, suggesting that CPSF30 and, thus, the control of messenger RNA 3′ end processing, through the regulation of SA production, is a key component of plant immune responses. © 2014 American Society of Plant Biologists. All rights reserved.

  6. Exercise-induced regulation of key factors in substrate choice and gluconeogenesis in mouse liver

    DEFF Research Database (Denmark)

    Knudsen, Jakob Grunnet; Biensø, Rasmus Sjørup; Hassing, Helle Adser;

    2015-01-01

    As the demand for hepatic glucose production increases during exercise, regulation of liver substrate choice and gluconeogenic activity becomes essential. The aim of the present study was to investigate the effect of a single exercise bout on gluconeogenic protein content and regulation of enzymes...... involved in substrate utilization in the liver. Mice were subjected to 1 h of treadmill exercise, and livers were removed immediately, 4 or 10 h after exercise. Glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxylase (PEPCK) mRNA contents in the liver increased immediately after exercise, while...... immediately after exercise and at 10 h of recovery, respectively. These findings suggest that acute changes in PEPCK and G6Pase protein contents do not contribute to the regulation of gluconeogenic enzyme activity during 1 h of non-exhaustive exercise. In addition, the observation that PDH-E1α, AMPK, and ACC...

  7. Oxygen, a key factor regulating cell behaviour during neurogenesis and cerebral diseases

    Directory of Open Access Journals (Sweden)

    Kuan eZhang

    2011-04-01

    Full Text Available Oxygen is vital to maintain the normal functions of alomost all the organs, especially for brain which is one of the heaviest oxygen consumers in the body. The important roles of oxygen on the brain are not only reflected in the development, but also showed in the pathological processes of many cerebral diseases. In the current review, we summarized the oxygen levels in brain tissues tested by real-time measurements during the embryonic and adult neurogenesis, the cerebral diseases or in the hyperbaric/hypobaric oxygen environment. Oxygen concentration is low in fetal brain (0.01%- 1% and in adult brain (1.5%-7%, decreased during stroke, and increased in hyperbaric oxygen environment. In addition, we reviewed the effects of oxygen tensions on the behaviors of neural stem cells (NSCs in vitro cultures at different oxygen concentration (2%-20% and in vivo niche during different pathological states and in hyperbaric/hypobaric oxygen environment. Moderate hypoxia (3%-10% is known can promote the proliferation of NSCs and enhance the differentiation of NSCs into the TH-positive neurons. Next, we briefly presented the oxygen-sensitive molecular mechanisms regulating NSCs proliferation and differentiation recently found including the Notch, BMP and Wnt pathways. Finally, the future perspectives about the roles of oxygen on brain and NSCs were given.

  8. Regulation of Transcriptional Networks by PKC Isozymes: Identification of c-Rel as a Key Transcription Factor for PKC-Regulated Genes.

    Directory of Open Access Journals (Sweden)

    Rachana Garg

    Full Text Available Activation of protein kinase C (PKC, a family of serine-threonine kinases widely implicated in cancer progression, has major impact on gene expression. In a recent genome-wide analysis of prostate cancer cells we identified distinctive gene expression profiles controlled by individual PKC isozymes and highlighted a prominent role for PKCδ in transcriptional activation.Here we carried out a thorough bioinformatics analysis to dissect transcriptional networks controlled by PKCα, PKCδ, and PKCε, the main diacylglycerol/phorbol ester PKCs expressed in prostate cancer cells. Despite the remarkable differences in the patterns of transcriptional responsive elements (REs regulated by each PKC, we found that c-Rel represents the most frequent RE in promoters regulated by all three PKCs. In addition, promoters of PKCδ-regulated genes were particularly enriched with REs for CREB, NF-E2, RREB, SRF, Oct-1, Evi-1, and NF-κB. Most notably, by using transcription factor-specific RNAi we were able to identify subsets of PKCδ-regulated genes modulated by c-Rel and CREB. Furthermore, PKCδ-regulated genes condensed under the c-Rel transcriptional regulation display significant functional interconnections with biological processes such as angiogenesis, inflammatory response, and cell motility.Our study identified candidate transcription factors in the promoters of PKC regulated genes, in particular c-Rel was found as a key transcription factor in the control of PKCδ-regulated genes. The deconvolution of PKC-regulated transcriptional networks and their nodes may greatly help in the identification of PKC effectors and have significant therapeutics implications.

  9. Screening active components from Yu-ping-feng-san for regulating initiative key factors in allergic sensitization.

    Science.gov (United States)

    Shen, Dandan; Xie, Xuejian; Zhu, Zhijie; Yu, Xi; Liu, Hailiang; Wang, Huizhu; Fan, Hongwei; Wang, Dawei; Jiang, Guorong; Hong, Min

    2014-01-01

    Yu-ping-feng-san (YPFS) is a Chinese medical formula that is used clinically for allergic diseases and characterized by reducing allergy relapse. Our previous studies demonstrated that YPFS efficiently inhibited T helper 2 cytokines in allergic inflammation. The underlying mechanisms of action of YPFS and its effective components remain unclear. In this study, it was shown that YPFS significantly inhibited production of thymic stromal lymphopoietin (TSLP), an epithelial cell-derived initiative factor in allergic inflammation, in vitro and in vivo. A method of human bronchial epithelial cell (16HBE) binding combined with HPLC-MS (named 16HBE-HPLC-MS) was established to explore potential active components of YPFS. The following five components bound to 16HBE cells: calycosin-7-glucoside, ononin, claycosin, sec-o-glucosylhamaudol and formononetin. Serum from YPFS-treated mice was analyzed and three major components were detected claycosin, formononetin and cimifugin. Among these, claycosin and formononetin were detected by 16HBE-HPLC-MS and in the serum of YPFS-treated mice. Claycosin and formononetin decreased the level of TSLP markedly at the initial stage of allergic inflammation in vivo. Nuclear factor (NF)-κB, a key transcription factor in TSLP production, was also inhibited by claycosin and formononetin, either in terms of transcriptional activation or its nuclear translocation in vitro. Allergic inflammation was reduced by claycosin and formononetin when they are administered only at the initial stage in a murine model of atopic contact dermatitis. Thus, epithelial cell binding combined with HPLC-MS is a valid method for screening active components from complex mixtures of Chinese medicine. It was demonstrated that the compounds screened from YPFS significantly attenuated allergic inflammation probably by reducing TSLP production via regulating NF-κB activation.

  10. Regulation of Neph3 gene in podocytes - key roles of transcription factors NF-kappaB and Sp1

    LENUS (Irish Health Repository)

    Ristola, Mervi

    2009-08-24

    Abstract Background Neph3 (filtrin) is expressed in the glomerular podocytes where it localizes at the specialized cell adhesion structures of the foot processes called slit diaphragms which form the outermost layer of the glomerular filtration barrier. Neph3 protein shows homology and structural similarity to Neph1, Neph2 and nephrin, which all are crucial for maintaining the normal glomerular ultrafiltration function. The exact function of Neph3 in the kidney is not known but we have previously shown that the level of Neph3 mRNA is decreased in proteinuric diseases. This suggests that Neph3 may play a role in the pathogenesis of kidney damage, and emphasizes the need to analyze the regulatory mechanisms of Neph3 gene. In this study we investigated the transcriptional regulation of Neph3 gene by identifying transcription factors that control Neph3 expression. Results We cloned and characterized approximately 5 kb fragment upstream of the Neph3 gene. Neph3 proximal promoter near the transcription start site was found to be devoid of TATA and CAAT boxes, but to contain a highly GC-rich area. Using promoter reporter gene constructs, we localized the main activating regulatory region of Neph3 gene in its proximal promoter region from -105 to -57. Within this region, putative transcription factor binding sites for NF-κB and Sp1 were found by computational analysis. Mutational screening indicated that NF-κB and Sp1 response elements are essential for the basal transcriptional activity of the Neph3 promoter. Co-transfection studies further showed that NF-κB and Sp1 regulate Neph3 promoter activity. In addition, overexpression of NF-κB increased endogenous Neph3 gene expression. Chromatin immunoprecipitation assay using cultured human podocytes demonstrated that both NF-κB and Sp1 interact with the Neph3 promoter. Conclusion Our results show that NF-κB and Sp1 are key regulators of Neph3 expression at the basal level in podocytes, therefore providing new insight

  11. Hyperosmotic stress regulates the distribution and stability of myocardin-related transcription factor, a key modulator of the cytoskeleton

    DEFF Research Database (Denmark)

    Ly, Donald L.; Waheed, Faiza; Lodyga, Monika;

    2013-01-01

    through the cis-element CArG box. Silencing or pharmacological inhibition of MRTF prevents the osmotic stimulation of CArG-dependent transcription and renders the cells susceptible to osmotic shock-induced structural damage. Interestingly, strong hyperosmolarity promotes proteasomal degradation of MRTF......, concomitant with apoptosis. Thus, MRTF is an osmosensitive and osmoprotective transcription factor, whose intracellular distribution is regulated by the GEF-H1/RhoA/ROK and p38 pathways. However, strong osmotic stress destabilizes MRTF, concomitant with apoptosis, implying that hyperosmotically induced cell...

  12. Convective moisture adjustment time scale as a key factor in regulating model amplitude of the Madden-Julian Oscillation

    Science.gov (United States)

    Jiang, Xianan; Zhao, Ming; Maloney, Eric D.; Waliser, Duane E.

    2016-10-01

    Despite its pronounced impacts on weather extremes worldwide, the Madden-Julian Oscillation (MJO) remains poorly represented in climate models. Here we present findings that point to some necessary ingredients to produce a strong MJO amplitude in a large set of model simulations from a recent model intercomparison project. While surface flux and radiative heating anomalies are considered important for amplifying the MJO, their strength per unit MJO precipitation anomaly is found to be negatively correlated to MJO amplitude across these multimodel simulations. However, model MJO amplitude is found to be closely tied to a model's convective moisture adjustment time scale, a measure of how rapidly precipitation must increase to remove excess column water vapor, or alternately the efficiency of surface precipitation generation per unit column water vapor anomaly. These findings provide critical insights into key model processes for the MJO and pinpoint a direction for improved model representation of the MJO.

  13. Cortistatin Is a Key Factor Regulating the Sex-Dependent Response of the GH and Stress Axes to Fasting in Mice.

    Science.gov (United States)

    Cordoba-Chacón, José; Gahete, Manuel D; Pozo-Salas, Ana I; de Lecea, Luis; Castaño, Justo P; Luque, Raúl M

    2016-07-01

    Cortistatin (CORT) shares high structural and functional similarities with somatostatin (SST) but displays unique sex-dependent pituitary actions. Indeed, although female CORT-knockout (CORT-KO) mice exhibit enhanced GH expression/secretion, Proopiomelanocortin expression, and circulating ACTH/corticosterone/ghrelin levels, male CORT-KO mice only display increased plasma GH/corticosterone levels. Changes in peripheral ghrelin and SST (rather than hypothalamic levels) seem to regulate GH/ACTH axes in CORT-KOs under fed conditions. Because changes in GH/ACTH axes during fasting provide important adaptive mechanisms, we sought to determine whether CORT absence influences GH/ACTH axes during fasting. Accordingly, fed and fasted male/female CORT-KO were compared with littermate controls. Fasting increased circulating GH levels in male/female controls but not in CORT-KO, suggesting that CORT can be a relevant regulator of GH secretion during fasting. However, GH levels were already higher in CORT-KO than in controls in fed state, which might preclude a further elevation in GH levels. Interestingly, although fasting-induced pituitary GH expression was elevated in both male/female controls, GH expression only increased in fasted female CORT-KOs, likely owing to specific changes observed in key factors controlling somatotrope responsiveness (ie, circulating ghrelin and IGF-1, and pituitary GHRH and ghrelin receptor expression). Fasting increased corticosterone levels in control and, most prominently, in CORT-KO mice, which might be associated with a desensitization to SST signaling and to an augmentation in CRH and ghrelin-signaling regulating corticotrope function. Altogether, these results provide compelling evidence that CORT plays a key, sex-dependent role in the regulation of the GH/ACTH axes in response to fasting.

  14. SUPPLY CHAIN MANAGEMENT – KEY FACTORS

    OpenAIRE

    Magdalena Daniela DINU

    2014-01-01

    This paper exposes Supply Chain Management by its key factors. Briefly, where the Supply Chain Management is treated as strategic part of a company then maintaining both control and influence throughout the entire supply chain are key factors and critical to success. On the other hand, finding the right partner to manage the non-strategic Supply Chains would be another key factor too. To define the most important key factors within Supply Chain Management means a deeply understanding of bot...

  15. Ikaros: a key regulator of haematopoiesis.

    Science.gov (United States)

    Westman, Belinda J; Mackay, Joel P; Gell, David

    2002-10-01

    Ikaros is an essential transcription factor for normal lymphocyte development. Because of its interaction with a number of closely related factors, Ikaros is required for correct regulation of differentiation and cell proliferation in T- and B-cell lineages. Interestingly, Ikaros appears to function both as a transcriptional repressor and as an activator through its ability to bind a large number of nuclear factors, including components of both histone deacetylase and ATP-dependent chromatin remodelling complexes. In addition, nuclear localisation is important for Ikaros function--unlike most transcription factors, Ikaros is localised to discrete nuclear foci in lymphoid cells, suggesting it employs novel mechanisms to regulate transcription.

  16. Aging, microglia and cytoskeletal regulation are key factors in the pathological evolution of the APP23 mouse model for Alzheimer's disease

    NARCIS (Netherlands)

    Janssen, Leen; Dubbelaar, Marissa L.; Holtman, Inge R.; de Boer-Bergsma, Jelkje; Eggen, Bart J. L.; Boddeke, Hendrikus W. G. M.; De Deyn, Peter P.; Dam, van Debby

    Aging is the key risk factor for Alzheimer's disease (AD). In addition, the amyloid-beta (A beta) peptide is considered a critical neurotoxic agent in AD pathology. However, the connection between these factors is unclear. We aimed to provide an extensive characterization of the gene expression

  17. Comprehensive Profiling of Ethylene Response Factor Expression Identifies Ripening-Associated ERF Genes and Their Link to Key Regulators of Fruit Ripening in Tomato.

    Science.gov (United States)

    Liu, Mingchun; Gomes, Bruna Lima; Mila, Isabelle; Purgatto, Eduardo; Peres, Lázaro E P; Frasse, Pierre; Maza, Elie; Zouine, Mohamed; Roustan, Jean-Paul; Bouzayen, Mondher; Pirrello, Julien

    2016-03-01

    Our knowledge of the factors mediating ethylene-dependent ripening of climacteric fruit remains limited. The transcription of ethylene-regulated genes is mediated by ethylene response factors (ERFs), but mutants providing information on the specific role of the ERFs in fruit ripening are still lacking, likely due to functional redundancy among this large multigene family of transcription factors. We present here a comprehensive expression profiling of tomato (Solanum lycopersicum) ERFs in wild-type and tomato ripening-impaired tomato mutants (Never-ripe [Nr], ripening-inhibitor [rin], and non-ripening [nor]), indicating that out of the 77 ERFs present in the tomato genome, 27 show enhanced expression at the onset of ripening while 28 display a ripening-associated decrease in expression, suggesting that different ERFs may have contrasting roles in fruit ripening. Among the 19 ERFs exhibiting the most consistent up-regulation during ripening, the expression of 11 ERFs is strongly down-regulated in rin, nor, and Nr tomato ripening mutants, while only three are consistently up-regulated. Members of subclass E, SlERF.E1, SlERF.E2, and SlERF.E4, show dramatic down-regulation in the ripening mutants, suggesting that their expression might be instrumental in fruit ripening. This study illustrates the high complexity of the regulatory network connecting RIN and ERFs and identifies subclass E members as the most active ERFs in ethylene- and RIN/NOR-dependent ripening.

  18. SUPPLY CHAIN MANAGEMENT – KEY FACTORS

    Directory of Open Access Journals (Sweden)

    Magdalena Daniela DINU

    2014-06-01

    Full Text Available This paper exposes Supply Chain Management by its key factors. Briefly, where the Supply Chain Management is treated as strategic part of a company then maintaining both control and influence throughout the entire supply chain are key factors and critical to success. On the other hand, finding the right partner to manage the non-strategic Supply Chains would be another key factor too. To define the most important key factors within Supply Chain Management means a deeply understanding of both Supply Chain’ s components, procedures, workflow, processes and the importance of Supply Chain Management into maximizing company's value. SCORE model able to provide solid information about measuring performance and identifying priorities within Supply Chain Management will help us to understand the key factors by analyzing its elements: Plan, Source, Make, Deliver,Return, Enable. These elements covers all the challenging areas from first to third tier of Supply Chain Management.

  19. Key Impact Factors to Success of Forest Certification

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    Forest certification has developed very quickly across the world as one of the most important market initiative to promote sustainable forest management (SFM). Its success and effectiveness are influenced by some key factors, including credibility, cost effectiveness, certification standard, effectiveness, equitableness, government's role and laws/regulations framework. The paper analyzed these key factors to the success of forest certification and put forward relevant suggestions and advices for China to d...

  20. The transcription factor PDR-1 is a multi-functional regulator and key component of pectin deconstruction and catabolism in Neurospora crassa.

    Science.gov (United States)

    Thieme, Nils; Wu, Vincent W; Dietschmann, Axel; Salamov, Asaf A; Wang, Mei; Johnson, Jenifer; Singan, Vasanth R; Grigoriev, Igor V; Glass, N Louise; Somerville, Chris R; Benz, J Philipp

    2017-01-01

    Pectin is an abundant component in many fruit and vegetable wastes and could therefore be an excellent resource for biorefinery, but is currently underutilized. Fungal pectinases already play a crucial role for industrial purposes, such as for foodstuff processing. However, the regulation of pectinase gene expression is still poorly understood. For an optimal utilization of plant biomass for biorefinery and biofuel production, a detailed analysis of the underlying regulatory mechanisms is warranted. In this study, we applied the genetic resources of the filamentous ascomycete species Neurospora crassa to screen for transcription factors that play a major role in pectinase induction. The pectin degradation regulator-1 (PDR-1) was identified through a transcription factor mutant screen in N. crassa. The Δpdr-1 mutant exhibited a severe growth defect on pectin and all tested pectin-related poly- and monosaccharides. Biochemical as well as transcriptional analyses of WT and the Δpdr-1 mutant revealed that while PDR-1-mediated gene induction was dependent on the presence of l-rhamnose, it also strongly affected the degradation of the homogalacturonan backbone. The expression of the endo-polygalacturonase gh28-1 was greatly reduced in the Δpdr-1 mutant, while the expression levels of all pectate lyase genes increased. Moreover, a pdr-1 overexpression strain displayed substantially increased pectinase production. Promoter analysis of the PDR-1 regulon allowed refinement of the putative PDR-1 DNA-binding motif. PDR-1 is highly conserved in filamentous ascomycete fungi and is present in many pathogenic and industrially important fungi. Our data demonstrate that the function of PDR-1 in N. crassa combines features of two recently described transcription factors in Aspergillus niger (RhaR) and Botrytis cinerea (GaaR). The results presented in this study contribute to a broader understanding of how pectin degradation is orchestrated in filamentous fungi and how it could be

  1. The rules of gene expression in plants: Organ identity and gene body methylation are key factors for regulation of gene expression in Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Gutiérrez Rodrigo A

    2008-09-01

    Full Text Available Abstract Background Microarray technology is a widely used approach for monitoring genome-wide gene expression. For Arabidopsis, there are over 1,800 microarray hybridizations representing many different experimental conditions on Affymetrix™ ATH1 gene chips alone. This huge amount of data offers a unique opportunity to infer the principles that govern the regulation of gene expression in plants. Results We used bioinformatics methods to analyze publicly available data obtained using the ATH1 chip from Affymetrix. A total of 1887 ATH1 hybridizations were normalized and filtered to eliminate low-quality hybridizations. We classified and compared control and treatment hybridizations and determined differential gene expression. The largest differences in gene expression were observed when comparing samples obtained from different organs. On average, ten-fold more genes were differentially expressed between organs as compared to any other experimental variable. We defined "gene responsiveness" as the number of comparisons in which a gene changed its expression significantly. We defined genes with the highest and lowest responsiveness levels as hypervariable and housekeeping genes, respectively. Remarkably, housekeeping genes were best distinguished from hypervariable genes by differences in methylation status in their transcribed regions. Moreover, methylation in the transcribed region was inversely correlated (R2 = 0.8 with gene responsiveness on a genome-wide scale. We provide an example of this negative relationship using genes encoding TCA cycle enzymes, by contrasting their regulatory responsiveness to nitrate and methylation status in their transcribed regions. Conclusion Our results indicate that the Arabidopsis transcriptome is largely established during development and is comparatively stable when faced with external perturbations. We suggest a novel functional role for DNA methylation in the transcribed region as a key determinant

  2. A New Factorization Method to Factorize RSA Public Key Encryption

    Directory of Open Access Journals (Sweden)

    Bhagvant Ram Ambedkar

    2011-11-01

    Full Text Available The security of public key encryption such as RSA scheme relied on the integer factoring problem. The security of RSA algorithm is based on positive integer N, because each transmitting node generates pair of keys such as public and private. Encryption and decryption of any message depends on N. Where, N is the product of two prime numbers and pair of key generation is dependent on these prime numbers. The factorization of N is very intricate. In this paper a New Factorization method is proposed to obtain the factor of positive integer N. The proposed work focuses on factorization of all trivial and nontrivial integer numbers and requires fewer steps for factorization process of RSA modulus N. The New Factorization method is based on Pollard rho factorization method. Experimental results shown that factorization speed is fast as compare existing methods.

  3. CDC25B Involved in Proliferation of Sertoli Cells of New Born Calves Through FSH and Possibly Being Key Regulating Factor

    Institute of Scientific and Technical Information of China (English)

    Tian Ya-guang

    2016-01-01

    The effects of FSH on the proliferation of sertoli cells of new born calves were studied in order to provide some data for theoretical research and practical use of spermatogenesis in vitro. Different concentrations of FSH (0, 0.01, 0.02, 0.04, and 0.08 IU• mL-1) were taken to treat bovine sertoli cellsin vitro culture, the number of sertoli cells and the expression of seven genes were determined at 6, 12 and 24 h after FSH treatments. FSH could significantly promote the proliferation ofin vitrocultured sertoli cells. FSH had no significant effects on the expression of CDC25A and could significantly improve the expression of CDC25B. 0.04 IU• mL-1 and 0.08 IU• mL-1 FSH treatments decreased the expression of CDC25C at 12 h. 0.08 IU• mL-1 FSH treatment decreased the expression of CDC25C at 24 h. 0.04 IU• mL-1 FSH could significantly decrease the expression of GSK-3β and improve the expression ofβ-catenin at 6, 12 and 24 h. 0.02, 0.04 and 0.08 IU• mL-1 FSH treatments enhanced the expressions of CYCLIND1 and C-MYC. In conclusion, FSH promoted the proliferation of sertoli cells and 0.04 IU• mL-1 FSH concentration could significantly promote the proliferation ofin vitrocultured sertoli cells. FSH promoted the proliferation of sertoli cells by CDC25B and WNT/β-catenin and CDC25B might be the key regulator to the proliferating rate of sertoli cells of bovine calf.

  4. Conformational transitions of the catalytic domain of heme-regulated eukaryotic initiation factor 2α kinase, a key translational regulatory molecule.

    Science.gov (United States)

    Sreejith, R K; Suresh, C G; Bhosale, Siddharth H; Bhavnani, Varsha; Kumar, Avinash; Gaikwad, Sushama M; Pal, Jayanta K

    2012-01-01

    In mammalian cells, the heme-regulated inhibitor (HRI) plays a critical role in the regulation of protein synthesis at the initiation step through phosphorylation of α-subunit of the eukaryotic initiation factor 2 (eIF2). In this study we have cloned and performed biophysical characterization of the kinase catalytic domain (KD) of rabbit HRI. The KD described here comprises kinase 1, the kinase insertion domain (KI) and kinase 2. We report here the existence of an active and stable monomer of HRI (KD). The HRI (KD) containing three tryptophan residues was examined for its conformational transitions occurring under various denaturing conditions using steady-state and time-resolved tryptophan fluorescence, circular dichroism (CD) and hydrophobic dye binding. The parameter A and phase diagram analysis revealed multi-state unfolding and existence of three stable intermediates during guanidine hydrochloride (Gdn-HCl) induced unfolding of HRI (KD). The protein treated with 6 M Gdn-HCl showed collisional and static mechanism of acrylamide quenching and the constants (K(sv) = 3.08 M(-1) and K(s)= 5.62 M(-1)) were resolved using time resolved fluorescence titration. Based on pH, guanidine hydrochloride and temperature mediated transitions, HRI (KD) appears to exemplify a rigid molten globule-like intermediate with compact secondary structure, altered tertiary structure and exposed hydrophobic patches at pH 3.0. The results indicate the inherent structural stability of HRI (KD), a member of the class of stress response proteins.

  5. FACTORS REGULATING LIBERAL TRANSLATION

    Institute of Scientific and Technical Information of China (English)

    龚海红

    2012-01-01

    Literal translation and liberal translation are two important methods and both play key roles in translation.However,some textbooks say that most translations are literal translations while others maintain most are liberal ones,besides,some others suggest a combination of the two.This paper focuses on the facts that regulate liberal translation.Because of the differences in culture,society,history,geography,and so on,there exists a great difference between Chinese language and English language,which does naturally lead to the liberal translation.

  6. 76 FR 68314 - Special Local Regulations; Key West World Championship, Atlantic Ocean; Key West, FL

    Science.gov (United States)

    2011-11-04

    ... SECURITY Coast Guard 33 CFR Part 100 RIN 1625-AA08 Special Local Regulations; Key West World Championship, Atlantic Ocean; Key West, FL AGENCY: Coast Guard, DHS. ACTION: Temporary final rule. SUMMARY: The Coast... Key West, Florida during the Key West World Championship, a series of high-speed boat races. The...

  7. SARS: Key factors in crisis management.

    Science.gov (United States)

    Tseng, Hsin-Chao; Chen, Thai-Form; Chou, Shieu-Ming

    2005-03-01

    This study was conducted at a single hospital selected in Taipei during the SARS (Severe Acute Respiratory Syndrome) outbreak from March to July, 2003 in Taiwan. During this period of time, 104 SARS patients were admitted to the hospital. There were no negative reports related to the selected hospital despite its being located right in the center of an area struck by the epidemic. The purpose of this study was to identify the key factors enabling the hospital to survive SARS unscathed. Data were collected from in-depth interviews with the nursing directors and nursing managers of the SARS units, along with a review of relevant hospital documents. The five key elements identified as survival factors during this SARS crisis are as follows: 1. good control of timing for crisis management, 2. careful decision-making, 3. thorough implementation, 4. effective communication, and 5. trust between management and employees. The results of this study reconfirmed the selected hospital as a model for good crisis management during the SARS epidemic.

  8. KEY FACTORS IN MARKETING FOCUSED SERVICES BUSINESSES

    Directory of Open Access Journals (Sweden)

    Doris Yohanna Martínez Castrillón

    2016-07-01

    Full Text Available This article aims to identify the key success factors in the marketing area and describe them as managerial allies for companies that wish to position themselves in the market under a good sustainable performance , for it has been consulted theoretical references of Marketing as a management partner with collection and integration of data. Methodologically, it is located within the type of descriptive research field, with a design of transactional non-experimental, with an intentional non-probabilistic stratified sample of four reporting units. The findings established fifteen (15 points of influence called "key success factors (FCE in the area of marketing, and managerial allies of service companies in the security, surveillance and protection sector in industrial, commercial and residential sectors. Finally, it is intended that the actions of marketing service companies should focus to the welfare of both the organization, such as users, both in the environment, and economic, social and technological, characterized by ethics, sustainable development and transparency to respond appropriately.

  9. T-bet as a key regulator of mucosal immunity.

    Science.gov (United States)

    Mohamed, Rami; Lord, Graham M

    2016-04-01

    Initially understood to be a key regulator of interferon-γ-producing helper T cells, our knowledge of T-bet's functional roles has expanded to encompass a growing range of cellular lineages. In addition to regulating other interferon-γ-producing adaptive immune cells, it is now clear that T-bet plays a fundamental role in the regulation of innate immune responses across mucosal surfaces. This homeostatic role is demonstrated by the spontaneous colitis that occurs when T-bet is deleted from innate immune cells in RAG(-/-) mice. Using this model as a focal point, we review our understanding of T-bet's regulation of adaptive and innate immune systems, focusing particularly on mucosal populations including innate lymphoid cells, dendritic cells and intraepithelial lymphocytes. With the increasingly diverse effects of T-bet on different lineages, the classical binding-centric paradigm of T-bet's molecular functionality has increasingly struggled to account for the versatility of T-bet's biological effects. Recent recognition of the synergistic interactions between T-bet and other canonical transcription factors has led to a co-operative paradigm that has provided greater explanatory power. Synthesizing insights from ChIP-seq and comparative biology, we expand the co-operative paradigm further and suggest a network approach as a powerful way to understand and model T-bet's diverse functionality.

  10. The estrogen receptor α is the key regulator of the bifunctional role of FoxO3a transcription factor in breast cancer motility and invasiveness

    Science.gov (United States)

    Sisci, Diego; Maris, Pamela; Cesario, Maria Grazia; Anselmo, Wanda; Coroniti, Roberta; Trombino, Giovanna Elvi; Romeo, Francesco; Ferraro, Aurora; Lanzino, Marilena; Aquila, Saveria; Maggiolini, Marcello; Mauro, Loredana; Morelli, Catia; Andò, Sebastiano

    2013-01-01

    The role of the Forkhead box class O (FoxO)3a transcription factor in breast cancer migration and invasion is controversial. Here we show that FoxO3a overexpression decreases motility, invasiveness, and anchorage-independent growth in estrogen receptor α-positive (ERα+) cancer cells while eliciting opposite effects in ERα-silenced cells and in ERα-negative (ERα−) cell lines, demonstrating that the nuclear receptor represents a crucial switch in FoxO3a control of breast cancer cell aggressiveness. In ERα+ cells, FoxO3a-mediated events were paralleled by a significant induction of Caveolin-1 (Cav1), an essential constituent of caveolae negatively associated to tumor invasion and metastasis. Cav1 induction occurs at the transcriptional level through FoxO3a binding to a Forkhead responsive core sequence located at position −305/−299 of the Cav1 promoter. 17β-estradiol (E2) strongly emphasized FoxO3a effects on cell migration and invasion, while ERα and Cav1 silencing were able to reverse them, demonstrating that both proteins are pivotal mediators of these FoxO3a controlled processes. In vivo, an immunohistochemical analysis on tissue sections from patients with ERα+ or ERα− invasive breast cancers or in situ ductal carcinoma showed that nuclear FoxO3a inversely (ERα+) or directly (ERα−) correlated with the invasive phenotype of breast tumors. In conclusion, FoxO3a role in breast cancer motility and invasion depends on ERα status, disclosing a novel aspect of the well-established FoxO3a/ERα interplay. Therefore FoxO3a might become a pursuable target to be suitably exploited in combination therapies either in ERα+ or ERα− breast tumors. PMID:24047697

  11. KEY PERFORMING FACTORS OF LEADING ROMANIAN COMPANIES

    Directory of Open Access Journals (Sweden)

    BURJA CAMELIA

    2014-08-01

    Full Text Available The analysis of financial economic ratios provides managers and external partners feedback on the results obtained from operational activities and the associated performance and risks. This paper studies the functional dependence of the companies’ success (on performance over internal financial management elements. The research was carried out for the most traded non-financial securities Bucharest listed companies and covers the period 2011- 2013. To carry out its purpose it analyzed the interdependence between the key financial ratios, studying the impact of liquidity ratios, solvency and efficiency on profitability. The study provides empirical evidences to identify factors that have ensured the performance of companies and their ranking in the segment of the most traded companies in Romania. Results suggest the view that the source of company success on the capital market lies in the positive signals sent to investors regarding profitability and the low risk of solvency. This study gives additional information for managerial decision-making in order to create more value and a better positioning of the companies in the market

  12. Key factors of enterprise innovation activity

    Directory of Open Access Journals (Sweden)

    Pichugina Maryna Anatoliivna

    2015-02-01

    Full Text Available The article deals with the studies of factors and conditions that define enterprise innovative activity. It is distinguished factors that influence the orientation on innovation of a company and factors that influence the innovation ability. It is noted an interdependence between innovative ability, orientation and activity. The article is also dedicated to analyses of influence specific industry characteristics and inner view of enterprise. It is discussed the influence of such factors as knowledge base, the organizational learning mechanisms, an external openness and the structure of innovative connections on the company opportunities to innovate. It is tried to focus on the impact of the environment on enterprise capabilities.

  13. Key Succes Factors for Organic Farming Development

    Directory of Open Access Journals (Sweden)

    Muhammad Ali Ramdhani

    2012-07-01

    Full Text Available The aim of this research is to determine the weight from determinant factors in developing organic farming in Garut District, West Java, Indonesia. Determinant factor in the research are determined based on judgment from the respondent. Determinant factors in developing farming are classified by some aspects such as technology, social and politic, economic and environment. The weight of each factor is counted by using weight method based on Analytic Hierarchy Process (AHP Model. The result of synthesis shows that respondents prefer organic farming method than conventional method. However, to implement organic farming extensively needs program or policy support from stakeholders on sub-criteria who tend to make organic farming better. The programs including orientation on quantity improvement in organic farming yield, provision of equipments, and raw materials, farmer’s performance, financial support, provision of market, and decreasing organic farming business risk.

  14. Personality, a key factor in personalized medicine?

    NARCIS (Netherlands)

    Boersma, Gretha J.; Benthem, Lambertus; van Beek, Andre P.; van Dijk, Gertjan; Scheurink, Anton J. W.

    2011-01-01

    The incidence of health problems resulting from obesity is growing and obesity and its related diseases has become one of the main causes in death in industrialized societies. Environmental influences are crucial for the interactions between genetic, neurohormonal and metabolic factors that may be

  15. Personality, a key factor in personalized medicine?

    NARCIS (Netherlands)

    Boersma, Gretha J.; Benthem, Lambertus; van Beek, Andre P.; van Dijk, Gertjan; Scheurink, Anton J. W.

    2011-01-01

    The incidence of health problems resulting from obesity is growing and obesity and its related diseases has become one of the main causes in death in industrialized societies. Environmental influences are crucial for the interactions between genetic, neurohormonal and metabolic factors that may be i

  16. KEY FACTORS FOR A CONTINUOUS IMPROVEMENT PROCESS

    Directory of Open Access Journals (Sweden)

    Hector Ricardo Formento

    2013-11-01

    Full Text Available The goal of this work was to examine the content of continuous improvement strategies, taking into account the important role they play in building competitiveness. This paper argues that several specific issues must be taken into account in order to reach successful outcomes. This work starts with a literature review on the matter. On this basis, we designed a survey administered to a group of 30 large companies, each of which is renowned leader in Argentina. Finally, we compared the development of continuous improvement process in companies with very effective results and with scarce results. Differences that emerged from this comparison enabled us to identify critical factors for achieving a successful improvement process. As there are no recent researches on continuous improvement programs in Argentina, this paper contributes to recognizing and systematizing what has been done, comparing it with theoretical framework and uncovering research gaps for future studies. However, further research must confirm these findings and move forward on the analysis of intangible factors, like: internal communications, climate, culture, self reflexion, consensus, etc.

  17. Sirtuin 1 Deacetylase: A Key Regulator of Hepatic Lipid Metabolism

    OpenAIRE

    Kemper, Jongsook Kim; Choi, Sunge; Kim, Dong Hyun

    2013-01-01

    Obesity is a serious medical problem worldwide and disruption of metabolic/energy homeostasis plays a pivotal role in this global epidemic. In obese people, fatty liver (steatosis) develops, which increases the risk for diabetes, cardiovascular disease, and even, liver cancer. Sirtuin 1 (SIRT1) is a NAD+-dependent deacetylase that functions as a key metabolic/energy sensor and mediates homeostatic responses to nutrient availability. Accumulating evidence indicates that SIRT1 is a master regul...

  18. Copper as a key regulator of cell signalling pathways.

    Science.gov (United States)

    Grubman, Alexandra; White, Anthony R

    2014-05-22

    Copper is an essential element in many biological processes. The critical functions associated with copper have resulted from evolutionary harnessing of its potent redox activity. This same property also places copper in a unique role as a key modulator of cell signal transduction pathways. These pathways are the complex sequence of molecular interactions that drive all cellular mechanisms and are often associated with the interplay of key enzymes including kinases and phosphatases but also including intracellular changes in pools of smaller molecules. A growing body of evidence is beginning to delineate the how, when and where of copper-mediated control over cell signal transduction. This has been driven by research demonstrating critical changes to copper homeostasis in many disorders including cancer and neurodegeneration and therapeutic potential through control of disease-associated cell signalling changes by modulation of copper-protein interactions. This timely review brings together for the first time the diverse actions of copper as a key regulator of cell signalling pathways and discusses the potential strategies for controlling disease-associated signalling processes using copper modulators. It is hoped that this review will provide a valuable insight into copper as a key signal regulator and stimulate further research to promote our understanding of copper in disease and therapy.

  19. Key factors influencing the implementation success of home telecare application.

    NARCIS (Netherlands)

    Postema, T.R.F.; Peeters, J.M.; Friele, R.D.

    2012-01-01

    Rationale: The introduction of home telecare in healthcare organizations has shown mixed results in practice. The aim of this study is to arrive at a set of key factors that can be used in further implementation of video communication. We argue that key factors are mainly found in the organizational

  20. Model of key success factors for Business Intelligence implementation

    Directory of Open Access Journals (Sweden)

    Peter Mesaros

    2016-07-01

    Full Text Available New progressive technologies recorded growth in every area. Information-communication technologies facilitate the exchange of information and it facilitates management of everyday activities in enterprises. Specific modules (such as Business Intelligence facilitate decision-making. Several studies have demonstrated the positive impact of Business Intelligence to decision-making. The first step is to put in place the enterprise. The implementation process is influenced by many factors. This article discusses the issue of key success factors affecting to successful implementation of Business Intelligence. The article describes the key success factors for successful implementation and use of Business Intelligence based on multiple studies. The main objective of this study is to verify the effects and dependence of selected factors and proposes a model of key success factors for successful implementation of Business Intelligence. Key success factors and the proposed model are studied in Slovak enterprises.

  1. The concept of key success factors: Theory and method

    DEFF Research Database (Denmark)

    Grunert, Klaus G.; Ellegaard, Charlotte

    1992-01-01

    and resources required to be successful in a given market. We adopt the last view. 2. The actual key success factors on a market, and those key success factors perceived by decision-makers in companies operating in the market, will be different. A number of psychological mechanisms result in misperceptions...... or resource that a business can i in, which, on the market the business is operating on, explains a major part of the observable differences in perceived value and/or relative costs. 4. Key success factors differ from core skills and resources, which are prerequisites for being on a market, but do not explain...... of the causes of success on a market. Both the actual key success factors on a market, and the way they are perceived by decision-makers, are amenable to scientific analysis. Such an analysis can improve performance of decision-makers on that market. 3. The major immediate causes of success on any market...

  2. Acceptance of TEL: Key Success Factors and Reasons of Failure

    NARCIS (Netherlands)

    Johnscher, Patrick; Kelle, Sebastian; Sigurðarson, Steinn

    2009-01-01

    Johnscher, P., Kelle, S., & Sigurðarson, S. (2008). Acceptance of TEL: Key Success Factors and Reasons of Failure. Presentation at the Prolearn Summer School on Technology Enhanced Learning & Knowledge Management 2008. March, 28, 2008, Ohrid, Fyr of Macedonia.

  3. Sirtuin 1 deacetylase: a key regulator of hepatic lipid metabolism.

    Science.gov (United States)

    Kemper, Jongsook Kim; Choi, Sung-E; Kim, Dong Hyun

    2013-01-01

    Obesity is a serious medical problem worldwide and disruption of metabolic/energy homeostasis plays a pivotal role in this global epidemic. In obese people, fatty liver (steatosis) develops, which increases the risk for diabetes, cardiovascular disease, and even, liver cancer. Sirtuin 1 (SIRT1) is a NAD+-dependent deacetylase that functions as a key metabolic/energy sensor and mediates homeostatic responses to nutrient availability. Accumulating evidence indicates that SIRT1 is a master regulator of the transcriptional networks that control hepatic lipid metabolism. During energy-deprived conditions, SIRT1 deacetylates and alters the expression and activities of key transcriptional regulators involved in hepatic lipogenesis, fatty acid β-oxidation, and cholesterol/bile acid metabolism. This review will discuss the latest advances in this field, focusing on beneficial roles of SIRT1 in hepatic lipid metabolism including its potential as a therapeutic target for treatment of steatosis and other obesity-related metabolic diseases. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Key Planning Factors for Recovery from a Chemical Warfare Agent Incident

    Science.gov (United States)

    2012-07-01

    chemical scenario involving the release of a blister agent (mustard lewisite) would result in a waste that the State of Colorado would regulate as... Waste Management ................................................................. 24 4.3 Key Planning Factors: Recovery Planning...Planning Factors, this document presents a chemical warfare agent scenario featuring Agent Yellow, a blister agent. Agent Yellow is a mixture of

  5. Regulation of sucrose metabolism in higher plants: localization and regulation of activity of key enzymes

    Science.gov (United States)

    Winter, H.; Huber, S. C.; Brown, C. S. (Principal Investigator)

    2000-01-01

    Sucrose (Suc) plays a central role in plant growth and development. It is a major end product of photosynthesis and functions as a primary transport sugar and in some cases as a direct or indirect regulator of gene expression. Research during the last 2 decades has identified the pathways involved and which enzymes contribute to the control of flux. Availability of metabolites for Suc synthesis and 'demand' for products of sucrose degradation are important factors, but this review specifically focuses on the biosynthetic enzyme sucrose-phosphate synthase (SPS), and the degradative enzymes, sucrose synthase (SuSy), and the invertases. Recent progress has included the cloning of genes encoding these enzymes and the elucidation of posttranslational regulatory mechanisms. Protein phosphorylation is emerging as an important mechanism controlling SPS activity in response to various environmental and endogenous signals. In terms of Suc degradation, invertase-catalyzed hydrolysis generally has been associated with cell expansion, whereas SuSy-catalyzed metabolism has been linked with biosynthetic processes (e.g., cell wall or storage products). Recent results indicate that SuSy may be localized in multiple cellular compartments: (1) as a soluble enzyme in the cytosol (as traditionally assumed); (2) associated with the plasma membrane; and (3) associated with the actin cytoskeleton. Phosphorylation of SuSy has been shown to occur and may be one of the factors controlling localization of the enzyme. The purpose of this review is to summarize some of the recent developments relating to regulation of activity and localization of key enzymes involved in sucrose metabolism in plants.

  6. An Analysis of Key Factors Affecting Chinese ESL Students’ Listening

    Institute of Scientific and Technical Information of China (English)

    苏君; 郭润玉

    2012-01-01

      With the proposal of Internet-based CET, more emphasis need be attached to listening skill. In order to improve stu⁃dents’ listening skill, linguistic knowledge, psychological factors and cultural background knowledge, as three key factors affect⁃ing Chinese ESL students, have been analyzed and the improving solutions have been suggested.

  7. Snail as a key regulator of PRL-3 gene in colorectal cancer.

    Science.gov (United States)

    Zheng, Ping; Meng, Hui-Min; Gao, Wei-Zhe; Chen, Lin; Liu, Xun-Hua; Xiao, Zheng-Quan; Liu, Yong-Xia; Sui, Hong-Mei; Zhou, Jun; Liu, Yu-Hong; Li, Jian-Ming

    2011-10-15

    The regulators of a key metastasis gene PRL-3 in colorectal cancer (CRC) are still largely unknown. We found three potential binding sites of Snail, a key transcriptional factor involved in the epithelial-mesenchymal transition (EMT), in the region of PRL-3 promoter (located at -642 to -383). Moreover, our results showed that one of the Snail binding sites (located at -624 to -619) was the key element to maintain promoter activity of human PRL-3 gene. The transcriptional activity of PRL-3 promoter was abolished after the Snail binding site (located at -624 to -619) was mutated. Both promoter activity and protein expression of PRL-3 in CRC cell lines could be regulated by Snail. In clinical samples of CRC and metastatic lymph node of CRC, expression of PRL-3 protein was correlated with expression of Snail protein. Functional studies using gene over-expression and knockdown methods indicated that Snail promoted proliferation, cell adhesion and migration of human CRC cells. In SW480 cells with PRL-3 stable knockdown, cell proliferation increased after Snail was up-regulated. Our data first reveal transcriptional factor Snail as a key regulator of PRL-3 in CRC. The link between Snail and PRL-3 suggests a new potential mechanism of Snail contributing to progression and metastasis of CRC.

  8. Key Success Factors of an E-Learning Course

    Directory of Open Access Journals (Sweden)

    Sylwia Kossakowska-Pisarek

    2012-06-01

    Full Text Available The article focuses on key success factors of an e-learning course based on the experience from a pilot course Effective Business Communication. It advocates the need to concentrate on specific key areas when assessing an e-learning course. These areas are vital for an appropriate preparation and conducting of an e-learning course and comprise among others fostering collaboration between participants, supporting autonomy and reflection on the process of learning and developing learners’ community.

  9. Fibrinogen as a key regulator of inflammation in disease.

    Science.gov (United States)

    Davalos, Dimitrios; Akassoglou, Katerina

    2012-01-01

    The interaction of coagulation factors with the perivascular environment affects the development of disease in ways that extend beyond their traditional roles in the acute hemostatic cascade. Key molecular players of the coagulation cascade like tissue factor, thrombin, and fibrinogen are epidemiologically and mechanistically linked with diseases with an inflammatory component. Moreover, the identification of novel molecular mechanisms linking coagulation and inflammation has highlighted factors of the coagulation cascade as new targets for therapeutic intervention in a wide range of inflammatory human diseases. In particular, a proinflammatory role for fibrinogen has been reported in vascular wall disease, stroke, spinal cord injury, brain trauma, multiple sclerosis, Alzheimer's disease, rheumatoid arthritis, bacterial infection, colitis, lung and kidney fibrosis, Duchenne muscular dystrophy, and several types of cancer. Genetic and pharmacologic studies have unraveled pivotal roles for fibrinogen in determining the extent of local or systemic inflammation. As cellular and molecular mechanisms for fibrinogen functions in tissues are identified, the role of fibrinogen is evolving from a marker of vascular rapture to a multi-faceted signaling molecule with a wide spectrum of functions that can tip the balance between hemostasis and thrombosis, coagulation and fibrosis, protection from infection and extensive inflammation, and eventually life and death. This review will discuss some of the main molecular links between coagulation and inflammation and will focus on the role of fibrinogen in inflammatory disease highlighting its unique structural properties, cellular targets, and signal transduction pathways that make it a potent proinflammatory mediator and a potential therapeutic target.

  10. Hepatotoxicity of piperazine designer drugs: up-regulation of key enzymes of cholesterol and lipid biosynthesis.

    Science.gov (United States)

    Arbo, Marcelo Dutra; Melega, Simone; Stöber, Regina; Schug, Markus; Rempel, Eugen; Rahnenführer, Jörg; Godoy, Patricio; Reif, Raymond; Cadenas, Cristina; de Lourdes Bastos, Maria; Carmo, Helena; Hengstler, Jan G

    2016-12-01

    The piperazine derivatives most frequently consumed for recreational purposes are 1-benzylpiperazine, 1-(3,4-methylenedioxybenzyl) piperazine, 1-(3-trifluoromethylphenyl) piperazine and 1-(4-methoxyphenyl) piperazine. Generally, they are consumed as capsules, tablets or pills but also in powder or liquid forms. Currently, the precise mechanism by which piperazine designer drugs induce hepatotoxicity and whether they act by a common pathway is unclear. To answer this question, we performed a gene array study with rat hepatocytes incubated with the four designer drugs. Non-cytotoxic concentrations were chosen that neither induce a decrease in reduced glutathione or ATP depletion. Analysis of the gene array data showed a large overlap of gene expression alterations induced by the four drugs. This 'piperazine designer drug consensus signature' included 101 up-regulated and 309 down-regulated probe sets (p cholesterol biosynthesis represented a dominant overrepresented motif. Key enzymes of cholesterol biosynthesis up-regulated by all four piperazine drugs include sterol C4-methyloxidase, isopentyl-diphosphate-Δ-isomerase, Cyp51A1, squalene epoxidase and farnesyl diphosphate synthase. Additionally, glycoprotein transmembrane nmb, which participates in cell adhesion processes, and fatty acid desaturase 1, an enzyme that regulates unsaturation of fatty acids, were also up-regulated by the four piperazine designer drugs. Regarding the down-regulated probe sets, only one gene was common to all four piperazine derivatives, the betaine-homocysteine-S-methyltransferase 2. Analysis of transcription factor binding sites of the 'piperazine designer drug consensus signature' identified the sterol regulatory element binding protein (SREBP-1) as strongly overrepresented in the up-regulated genes. SREBP transcription factors are known to regulate multiple genes of cholesterol metabolism. In conclusion, the present study shows that piperazine designer drugs act by up-regulating key

  11. Positioning and deciding : key factors for talent development in soccer

    NARCIS (Netherlands)

    Kannekens, R.; Elferink-Gemser, M. T.; Visscher, C.

    2011-01-01

    Talent identification and development implicate recognizing youth players who will be successful in the future and guiding them to the top. A major determinant of this success is tactical skills. To identify possible key factors that help in predicting success over time, this study assesses the

  12. Key factors for successful export performance for small firms

    NARCIS (Netherlands)

    Brouthers, L.E.; Nakos, G.; Hadjimarcou, J.; Brouthers, K.D.

    2009-01-01

    What key factors result in superior export performance for small firms from small countries? Drawing on the internationalization process model and organizational learning theory, the authors hypothesize and find that (1) emphasizing international sales while (2) restricting exports to a few foreign

  13. Key factors relevant to In-service teacher training

    Institute of Scientific and Technical Information of China (English)

    汪晖

    2016-01-01

    Successful continuing professional development (CPD) is beneficial not only to teachers' professional growth, but also to the development of their school and children. This essay will explain some key factors, regarding needs analysis, approach, goals and objectives, training methodology, assessment, in my essay.

  14. Positioning and deciding : key factors for talent development in soccer

    NARCIS (Netherlands)

    Kannekens, R.; Elferink-Gemser, M. T.; Visscher, C.

    2011-01-01

    Talent identification and development implicate recognizing youth players who will be successful in the future and guiding them to the top. A major determinant of this success is tactical skills. To identify possible key factors that help in predicting success over time, this study assesses the tact

  15. Graduate Entrepreneurship Incubation Environments: A Framework of Key Success Factors

    Science.gov (United States)

    Al-Dajani, Haya; Dedoussis, Evangelos; Watson, Erika; Tzokas, Nikalaos

    2014-01-01

    The benchmarking framework developed in this study is specifically designed for higher education institutions to consider when developing environments to encourage entrepreneurship among their students, graduates and staff. The objective of the study was to identify key success factors of Graduate Entrepreneurship Incubator Environments (GEIEs)…

  16. Graduate Entrepreneurship Incubation Environments: A Framework of Key Success Factors

    Science.gov (United States)

    Al-Dajani, Haya; Dedoussis, Evangelos; Watson, Erika; Tzokas, Nikalaos

    2014-01-01

    The benchmarking framework developed in this study is specifically designed for higher education institutions to consider when developing environments to encourage entrepreneurship among their students, graduates and staff. The objective of the study was to identify key success factors of Graduate Entrepreneurship Incubator Environments (GEIEs)…

  17. Functional Imaging of Autonomic Regulation: Methods and Key Findings

    Directory of Open Access Journals (Sweden)

    Paul M Macey

    2016-01-01

    Full Text Available Central nervous system processing of autonomic function involves a network of regions throughout the brain which can be visualized and measured with neuroimaging techniques, notably functional magnetic resonance imaging (fMRI. The development of fMRI procedures has both confirmed and extended earlier findings from animal models, and human stroke and lesion studies. Assessments with fMRI can elucidate interactions between different central sites in regulating normal autonomic patterning, and demonstrate how disturbed systems can interact to produce aberrant regulation during autonomic challenges. Understanding autonomic dysfunction in various illnesses reveals mechanisms that potentially lead to interventions in the impairments. The objectives here are to: 1 describe the fMRI neuroimaging methodology for assessment of autonomic neural control, 2 outline the widespread, lateralized distribution of function in autonomic sites in the normal brain which includes structures from the neocortex through the medulla and cerebellum, 3 illustrate the importance of the time course of neural changes when coordinating responses, and how those patterns are impacted in conditions of sleep-disordered breathing, and 4 highlight opportunities for future research studies with emerging methodologies. Methodological considerations specific to autonomic testing include timing of challenges relative to the underlying fMRI signal, spatial resolution sufficient to identify autonomic brainstem nuclei, blood pressure and blood oxygenation influences on the fMRI signal, and the sustained timing, often measured in minutes of challenge periods and recovery. Key findings include the lateralized nature of autonomic organization, which is reminiscent of asymmetric motor, sensory and language pathways. Testing brain function during autonomic challenges demonstrate closely-integrated timing of responses in connected brain areas during autonomic challenges, and the involvement with

  18. Chameleon Hashes Without Key Exposure Based on Factoring

    Institute of Scientific and Technical Information of China (English)

    Wei Gao; Xue-Li Wang; Dong-Qing Xie

    2007-01-01

    Chameleon hash is the main primitive to construct a chameleon signature scheme which provides non-repudiation and non-transferability simultaneously.However, the initial chameleon hash schemes suffer from the key exposure problem: non-transferability is based on an unsound assumption that the designated receiver is willing to abuse his private key regardless of its exposure.Recently, several key-exposure-free chameleon hashes have been constructed based on RSA assumption and SDH (strong Diffie-Hellman) assumption.In this paper, we propose a factoring-based chameleon hash scheme which is proven to enjoy all advantages of the previous schemes.In order to support it, we propose a variant Rabin signature scheme which is proven secure against a new type of attack in the random oracle model.

  19. CREB: A Key Regulator of Normal and Neoplastic Hematopoiesis

    Directory of Open Access Journals (Sweden)

    Salemiz Sandoval

    2009-01-01

    Full Text Available The cAMP response element-binding protein (CREB is a nuclear transcription factor downstream of cell surface receptors and mitogens that is critical for normal and neoplastic hematopoiesis. Previous work from our laboratory demonstrated that a majority of patients with acute myeloid leukemia (AML and acute lymphoid leukemia (ALL overexpress CREB in the bone marrow. To understand the role of CREB in leukemogenesis, we examined the biological effect of CREB overexpression on primary leukemia cells, leukemia cell lines, and CREB overexpressing transgenic mice. Our results demonstrated that CREB overexpression leads to an increase in cellular proliferation and survival. Furthermore, CREB transgenic mice develop a myeloproliferative disorder with aberrant myelopoiesis in both the bone marrow and spleen. Additional research from other groups has shown that the expression of the cAMP early inducible repressor (ICER, a CREB repressor, is also deregulated in leukemias. And, miR-34b, a microRNA that negative regulates CREB expression, is expressed at lower levels in myeloid leukemia cell lines compared to that of healthy bone marrow. Taken together, these data suggest that CREB plays a role in cellular transformation. The data also suggest that CREB-specific signaling pathways could possibly serve as potential targets for therapeutic intervention.

  20. Rot is a key regulator of Staphylococcus aureus biofilm formation

    Science.gov (United States)

    Mootz, Joe M.; Benson, Meredith A.; Heim, Cortney E.; Crosby, Heidi A.; Kavanaugh, Jeffrey S.; Dunman, Paul M.; Kielian, Tammy; Torres, Victor J.; Horswill, Alexander R.

    2015-01-01

    AUTHOR SUMMARY Staphylococcus aureus is a significant cause of chronic biofilm infections on medical implants. We investigated the biofilm regulatory cascade and discovered that the repressor of toxins (Rot) is part of this pathway. A USA300 community-associated methicillin-resistant S. aureus (CA-MRSA) strain deficient in Rot was unable to form a biofilm using multiple different assays, and we found rot mutants in other strain lineages were also biofilm deficient. By performing a global analysis of transcripts and protein production controlled by Rot, we observed that all the secreted protease genes were upregulated in a rot mutant, and we hypothesized that this regulation could be responsible for the biofilm phenotype. To investigate this question, we determined that Rot bound to the protease promoters, and we observed that activity levels of these enzymes, in particular the cysteine proteases, were increased in a rot mutant. By inactivating these proteases, biofilm capacity was restored to the mutant, demonstrating they are responsible for the biofilm negative phenotype. Finally, we tested the rot mutant in a mouse catheter model of biofilm infection and observed a significant reduction in biofilm burden. Thus S. aureus uses the transcription factor Rot to repress secreted protease levels in order to build a biofilm. PMID:25612137

  1. Faculty perceptions of key factors in interprofessional education.

    Science.gov (United States)

    Loversidge, Jacqueline; Demb, Ada

    2015-01-01

    Embedding interprofessional education (IPE) into academic programs presents structural, curricular and human factor challenges. Nurses and physicians comprise the dominant dyad in healthcare, and therefore nursing and medical faculty are key in guiding future IPE approaches. However, faculty experiences with IPE are rarely reported. This paper presents perceptions of medical and nursing faculty about key factors related to IPE for pre-licensure medical and nursing students. Semi-structured interviews with 32 faculty from three Midwest universities were analyzed thematically in this phenomenological study based on collaboration and cooperation theories. Findings clustered into six categories. Specific subthemes little discussed in the literature are addressed in detail. Study participants felt the most powerful interprofessional student experiences were authentic and faculty-facilitated, that constructive clinical environments were crucial, that curriculum design challenges included disparities between undergraduate and graduate education, and that leadership commitment to full-time and adjunct faculty engagement and development was imperative.

  2. Key success factors when implementing strategic manufacturing initiatives

    OpenAIRE

    Minarro-Viseras, Enrique; Baines, Timothy; Sweeney, Mike

    2005-01-01

    Purpose – This paper reports the study of key success factors (KSFs) in the project management of the implementation of strategic manufacturing initiatives (SMIs). Design/methodology/approach – In order to gather the experience and knowledge of many industries, from different geographic locations, in a broad range of types and sizes of SMIs, a questionnaire-based survey of practitioners worldwide was selected as the most appropriate research method among those available. Findings – The identi...

  3. KEY FACTORS INFLUENCING PURCHASE INTENTIONS TOWARDS AUTOMOBILES IN PAKISTAN

    Directory of Open Access Journals (Sweden)

    SYED NAVEED ALTAF

    2016-04-01

    Full Text Available In this paper the authors identify and investigate the key factors which influence intentions to purchase passenger cars among consumers in Pakistan. A questionnaire was developed to check the significance of these key variables identified from previous studies, especially those conducted in the context of automobile purchasing in Asian countries. Faculty members from universities of two major cities in Pakistan were selected at random as respondents for this study. The findings of the study will be useful to both managers in the auto industry as well as policy makers. It will help managers in the auto industry to gain a better understanding of consumer intentions and identify the factors which influence them. Policy makers in Pakistan’s auto sector would benefit from the insights of this study when developing the long overdue Auto Policy. Analysis of the data collected has revealed that the three key factors identified from studies in other Asian countries are also relevant for Pakistani auto consumers.

  4. Key Factors Influencing Customer Satisfaction in Korea's Mobile Service Sector

    Directory of Open Access Journals (Sweden)

    JAE YOUNG KIM

    2013-12-01

    Full Text Available Advances in wireless technology have expanded the existing internet environment and accelerated the rapid development of mobile service. Many previous studies were conducted on users’ needs and satisfaction prior to the expansion of the mobile service. Thus, the impact of mobile service factors on user satisfaction has important implications for both academics and practitioners. This study investigates the factors affecting user satisfaction related to mobile service. First, this study extracts key factors (antecedents and consequences from reviewing the previous studies. Second, the study empirically examines the causal relationships among the factors. Data collected from 256 users in Korea were tested for the research model using the Visual PLS approach. The results reveal that the proposed model is significantly supported in the effect of perceived quality and self-efficacy on customer satisfaction via perceived ease of use and usefulness.

  5. Exploring key factors in online shopping with a hybrid model.

    Science.gov (United States)

    Chen, Hsiao-Ming; Wu, Chia-Huei; Tsai, Sang-Bing; Yu, Jian; Wang, Jiangtao; Zheng, Yuxiang

    2016-01-01

    Nowadays, the web increasingly influences retail sales. An in-depth analysis of consumer decision-making in the context of e-business has become an important issue for internet vendors. However, factors affecting e-business are complicated and intertwined. To stimulate online sales, understanding key influential factors and causal relationships among the factors is important. To gain more insights into this issue, this paper introduces a hybrid method, which combines the Decision Making Trial and Evaluation Laboratory (DEMATEL) with the analytic network process, called DANP method, to find out the driving factors that influence the online business mostly. By DEMATEL approach the causal graph showed that "online service" dimension has the highest degree of direct impact on other dimensions; thus, the internet vendor is suggested to made strong efforts on service quality throughout the online shopping process. In addition, the study adopted DANP to measure the importance of key factors, among which "transaction security" proves to be the most important criterion. Hence, transaction security should be treated with top priority to boost the online businesses. From our study with DANP approach, the comprehensive information can be visually detected so that the decision makers can spotlight on the root causes to develop effectual actions.

  6. Unity power factor switching regulator

    Science.gov (United States)

    Rippel, Wally E. (Inventor)

    1983-01-01

    A single or multiphase boost chopper regulator operating with unity power factor, for use such as to charge a battery is comprised of a power section for converting single or multiphase line energy into recharge energy including a rectifier (10), one inductor (L.sub.1) and one chopper (Q.sub.1) for each chopper phase for presenting a load (battery) with a current output, and duty cycle control means (16) for each chopper to control the average inductor current over each period of the chopper, and a sensing and control section including means (20) for sensing at least one load parameter, means (22) for producing a current command signal as a function of said parameter, means (26) for producing a feedback signal as a function of said current command signal and the average rectifier voltage output over each period of the chopper, means (28) for sensing current through said inductor, means (18) for comparing said feedback signal with said sensed current to produce, in response to a difference, a control signal applied to the duty cycle control means, whereby the average inductor current is proportionate to the average rectifier voltage output over each period of the chopper, and instantaneous line current is thereby maintained proportionate to the instantaneous line voltage, thus achieving a unity power factor. The boost chopper is comprised of a plurality of converters connected in parallel and operated in staggered phase. For optimal harmonic suppression, the duty cycles of the switching converters are evenly spaced, and by negative coupling between pairs 180.degree. out-of-phase, peak currents through the switches can be reduced while reducing the inductor size and mass.

  7. PII, the key regulator of nitrogen metabolism in the cyanobacteria

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ying; ZHAO JinDong

    2008-01-01

    PII proteins are a protein family important to signal transduction in bacteria and plants. PII plays a critical role in regulation of carbon and nitrogen metabolism in cyanobacteria. Through conformation change and covalent modification, which are regulated by 2-oxoglutarate, PII interacts with different target proteins in response to changes of cellular energy status and carbon and nitrogen sources in cyanobacteria and regulates cellular metabolism. This article reports recent progress in PII research in cyanobacteria and discusses the mechanism of PII regulation of cellular metabolism.

  8. Key Odorants Regulate Food Attraction in Drosophila melanogaster.

    Science.gov (United States)

    Giang, Thomas; He, Jianzheng; Belaidi, Safaa; Scholz, Henrike

    2017-01-01

    In insects, the search for food is highly dependent on olfactory sensory input. Here, we investigated whether a single key odorant within an odor blend or the complexity of the odor blend influences the attraction of Drosophila melanogaster to a food source. A key odorant is defined as an odorant that elicits a difference in the behavioral response when two similar complex odor blends are offered. To validate that the observed behavioral responses were elicited by olfactory stimuli, we used olfactory co-receptor Orco mutants. We show that within a food odor blend, ethanol functions as a key odorant. In addition to ethanol other odorants might serve as key odorants at specific concentrations. However, not all odorants are key odorants. The intensity of the odor background influences the attractiveness of the key odorants. Increased complexity is only more attractive in a concentration-dependent range for single compounds in a blend. Orco is necessary to discriminate between two similarly attractive odorants when offered as single odorants and in food odor blends, supporting the importance of single odorant recognition in odor blends. These data strongly indicate that flies use more than one strategy to navigate to a food odor source, depending on the availability of key odorants in the odor blend and the alternative odor offered.

  9. Key Odorants Regulate Food Attraction in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Thomas Giang

    2017-09-01

    Full Text Available In insects, the search for food is highly dependent on olfactory sensory input. Here, we investigated whether a single key odorant within an odor blend or the complexity of the odor blend influences the attraction of Drosophila melanogaster to a food source. A key odorant is defined as an odorant that elicits a difference in the behavioral response when two similar complex odor blends are offered. To validate that the observed behavioral responses were elicited by olfactory stimuli, we used olfactory co-receptor Orco mutants. We show that within a food odor blend, ethanol functions as a key odorant. In addition to ethanol other odorants might serve as key odorants at specific concentrations. However, not all odorants are key odorants. The intensity of the odor background influences the attractiveness of the key odorants. Increased complexity is only more attractive in a concentration-dependent range for single compounds in a blend. Orco is necessary to discriminate between two similarly attractive odorants when offered as single odorants and in food odor blends, supporting the importance of single odorant recognition in odor blends. These data strongly indicate that flies use more than one strategy to navigate to a food odor source, depending on the availability of key odorants in the odor blend and the alternative odor offered.

  10. Functional interaction of hepatic nuclear factor-4 and peroxisome proliferator-activated receptor-gamma coactivator 1alpha in CYP7A1 regulation is inhibited by a key lipogenic activator, sterol regulatory element-binding protein-1c.

    Science.gov (United States)

    Ponugoti, Bhaskar; Fang, Sungsoon; Kemper, Jongsook Kim

    2007-11-01

    Insulin inhibits transcription of cholesterol 7alpha-hydroxylase (Cyp7a1), a key gene in bile acid synthesis, and the hepatic nuclear factor-4 (HNF-4) site in the promoter was identified as a negative insulin response sequence. Using a fasting/feeding protocol in mice and insulin treatment in HepG2 cells, we explored the inhibition mechanisms. Expression of sterol regulatory element-binding protein-1c (SREBP-1c), an insulin-induced lipogenic factor, inversely correlated with Cyp7a1 expression in mouse liver. Interaction of HNF-4 with its coactivator, peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha), was observed in livers of fasted mice and was reduced after feeding. Conversely, HNF-4 interaction with SREBP-1c was increased after feeding. In vitro studies suggested that SREBP-1c competed with PGC-1alpha for direct interaction with the AF2 domain of HNF-4. Reporter assays showed that SREBP-1c, but not of a SREBP-1c mutant lacking the HNF-4 interacting domain, inhibited HNF-4/PGC-1alpha transactivation of Cyp7a1. SREBP-1c also inhibited PGC-1alpha-coactivation of estrogen receptor, constitutive androstane receptor, pregnane X receptor, and farnesoid X receptor, implying inhibition of HNF-4 by SREBP-1c could extend to other nuclear receptors. In chromatin immunoprecipitation studies, HNF-4 binding to the promoter was not altered, but PGC-1alpha was dissociated, SREBP-1c and histone deacetylase-2 (HDAC2) were recruited, and acetylation of histone H3 was decreased upon feeding. Adenovirus-mediated expression of a SREBP-1c dominant-negative mutant, which blocks the interaction of SREBP-1c and HNF-4, partially but significantly reversed the inhibition of Cyp7a1 after feeding. Our data show that SREBP-1c functions as a non-DNA-binding inhibitor and mediates, in part, suppression of Cyp7a1 by blocking functional interaction of HNF-4 and PGC-1alpha. This mechanism may be relevant to known repression of many other HNF-4 target genes upon

  11. Identifying key hospital service quality factors in online health communities.

    Science.gov (United States)

    Jung, Yuchul; Hur, Cinyoung; Jung, Dain; Kim, Minki

    2015-04-07

    The volume of health-related user-created content, especially hospital-related questions and answers in online health communities, has rapidly increased. Patients and caregivers participate in online community activities to share their experiences, exchange information, and ask about recommended or discredited hospitals. However, there is little research on how to identify hospital service quality automatically from the online communities. In the past, in-depth analysis of hospitals has used random sampling surveys. However, such surveys are becoming impractical owing to the rapidly increasing volume of online data and the diverse analysis requirements of related stakeholders. As a solution for utilizing large-scale health-related information, we propose a novel approach to identify hospital service quality factors and overtime trends automatically from online health communities, especially hospital-related questions and answers. We defined social media-based key quality factors for hospitals. In addition, we developed text mining techniques to detect such factors that frequently occur in online health communities. After detecting these factors that represent qualitative aspects of hospitals, we applied a sentiment analysis to recognize the types of recommendations in messages posted within online health communities. Korea's two biggest online portals were used to test the effectiveness of detection of social media-based key quality factors for hospitals. To evaluate the proposed text mining techniques, we performed manual evaluations on the extraction and classification results, such as hospital name, service quality factors, and recommendation types using a random sample of messages (ie, 5.44% (9450/173,748) of the total messages). Service quality factor detection and hospital name extraction achieved average F1 scores of 91% and 78%, respectively. In terms of recommendation classification, performance (ie, precision) is 78% on average. Extraction and

  12. Rab proteins: The key regulators of intracellular vesicle transport

    Energy Technology Data Exchange (ETDEWEB)

    Bhuin, Tanmay [Cell and Developmental Biology Unit, Department of Zoology, The University of Burdwan, Golapbag 713104 (India); Roy, Jagat Kumar, E-mail: jkroy@bhu.ac.in [Cytogenetics Laboratory, Department of Zoology, Banaras Hindu University, Varanasi 221005 (India)

    2014-10-15

    Vesicular/membrane trafficking essentially regulates the compartmentalization and abundance of proteins within the cells and contributes in many signalling pathways. This membrane transport in eukaryotic cells is a complex process regulated by a large and diverse array of proteins. A large group of monomeric small GTPases; the Rabs are essential components of this membrane trafficking route. Most of the Rabs are ubiquitously expressed proteins and have been implicated in vesicle formation, vesicle motility/delivery along cytoskeleton elements and docking/fusion at target membranes through the recruitment of effectors. Functional impairments of Rabs affecting transport pathways manifest different diseases. Rab functions are accompanied by cyclical activation and inactivation of GTP-bound and GDP-bound forms between the cytosol and membranes which is regulated by upstream regulators. Rab proteins are characterized by their distinct sub-cellular localization and regulate a wide variety of endocytic, transcytic and exocytic transport pathways. Mutations of Rabs affect cell growth, motility and other biological processes. - Highlights: • Rab proteins regulate different signalling pathways. • Deregulation of Rabs is the fundamental causes of a variety of human diseases. • This paper gives potential directions in developing therapeutic targets. • This paper also gives ample directions for modulating pathways central to normal physiology. • These are the huge challenges for drug discovery and delivery in near future.

  13. Key factors of successful JIT integration with IBS - An overview

    Science.gov (United States)

    Asri, Mohammad Azwanie Naim Mohammad; Nawi, Mohd Nasrun Mohd; Nadarajan, Santhirasegaran

    2016-08-01

    The Just-In-Time (JIT) philosophy has been used for many decades to increase productivity through waste elimination process. The purpose of this paper is to contribute to the knowledge by addressing the transportation and material delivery activities in Industrialized Building System (IBS) and integrating JIT to improve the performance of those activities. The literature review has been conducted through relevant database. It was found that there is a need for more holistic approach to be adopted to integrate JIT in IBS project. This paper discusses the key success factors for effective integration between JIT and IBS in the context of transportation and material delivery activities.

  14. KEY FACTORS IN WORKING CAPITAL MANAGEMENT IN THE BRAZILIAN MARKET

    Directory of Open Access Journals (Sweden)

    Wilson Toshiro Nakamura

    2012-01-01

    Full Text Available Many studies have been conducted in corporate finance regarding long-term investment and financing decisions. However, short-term asset investments play a significant role in the balance sheet of companies. Moreover, financial managers dedicate significantamounts of time and effort to the subject of working capital management, balancing current assets and liabilities. This paper provides insights regarding the key factors of working capital management by exploring the internal variables of a number of companies. This study used data from 2,976 Brazilian public companies from 2001 to 2008, and found that debt level, size and growth rate can affect the working capital management of companies.

  15. Rab proteins: the key regulators of intracellular vesicle transport.

    Science.gov (United States)

    Bhuin, Tanmay; Roy, Jagat Kumar

    2014-10-15

    Vesicular/membrane trafficking essentially regulates the compartmentalization and abundance of proteins within the cells and contributes in many signalling pathways. This membrane transport in eukaryotic cells is a complex process regulated by a large and diverse array of proteins. A large group of monomeric small GTPases; the Rabs are essential components of this membrane trafficking route. Most of the Rabs are ubiquitously expressed proteins and have been implicated in vesicle formation, vesicle motility/delivery along cytoskeleton elements and docking/fusion at target membranes through the recruitment of effectors. Functional impairments of Rabs affecting transport pathways manifest different diseases. Rab functions are accompanied by cyclical activation and inactivation of GTP-bound and GDP-bound forms between the cytosol and membranes which is regulated by upstream regulators. Rab proteins are characterized by their distinct sub-cellular localization and regulate a wide variety of endocytic, transcytic and exocytic transport pathways. Mutations of Rabs affect cell growth, motility and other biological processes.

  16. The Candida albicans-specific gene EED1 encodes a key regulator of hyphal extension.

    LENUS (Irish Health Repository)

    Martin, Ronny

    2011-04-01

    The extension of germ tubes into elongated hyphae by Candida albicans is essential for damage of host cells. The C. albicans-specific gene EED1 plays a crucial role in this extension and maintenance of filamentous growth. eed1Δ cells failed to extend germ tubes into long filaments and switched back to yeast growth after 3 h of incubation during growth on plastic surfaces. Expression of EED1 is regulated by the transcription factor Efg1 and ectopic overexpression of EED1 restored filamentation in efg1Δ. Transcriptional profiling of eed1Δ during infection of oral tissue revealed down-regulation of hyphal associated genes including UME6, encoding another key transcriptional factor. Ectopic overexpression of EED1 or UME6 rescued filamentation and damage potential in eed1Δ. Transcriptional profiling during overexpression of UME6 identified subsets of genes regulated by Eed1 or Ume6. These data suggest that Eed1 and Ume6 act in a pathway regulating maintenance of hyphal growth thereby repressing hyphal-to-yeast transition and permitting dissemination of C. albicans within epithelial tissues.

  17. Key Factors Influencing Sustainable Development of a Green Energy Industry in Taiwan

    Directory of Open Access Journals (Sweden)

    Wen-Chih Huang

    2013-01-01

    Full Text Available The main purpose of this paper was to apply the fuzzy analytic hierarchy process (FAHP approach to explore key factors influencing the sustainable development of a green energy industry in Taiwan. Based on the literature and experts' opinions, a hierarchical structure with five assessment aspects and fifteen development factors was first constructed, and a FAHP algorithm model was then proposed. Finally, based on the AHP experts' questionnaires, we used the FAHP approach to evaluate the key factors. The results showed the following. (1 “Technology” is the most important aspect influencing sustainable development of green energy industry in Taiwan. (2 In order of relative importance, the top six key factors influencing sustainable development of green energy industry in Taiwan are “establishment of key technological capabilities,” “degree of integration of relevant laws and regulations,” “establishment of an industry chain,” “key raw materials and production equipment,” “protection of intellectual property,” and “preferential purchase price rates and various subsidies,” respectively.

  18. The microbiome: A key regulator of stress and neuroinflammation

    Directory of Open Access Journals (Sweden)

    Kieran Rea

    2016-10-01

    In this review, the involvement of the gastrointestinal microbiota in stress-mediated and immune-mediated modulation of neuroendocrine, immune and neurotransmitter systems and the consequential behaviour is considered. We also focus on the mechanisms by which commensal gut microbiota can regulate neuroinflammation and further aim to exploit our understanding of their role in stress-related disorders as a consequence of neuroinflammatory processes.

  19. Factors that regulate embryonic gustatory development

    Directory of Open Access Journals (Sweden)

    Krimm Robin F

    2007-09-01

    Full Text Available Abstract Numerous molecular factors orchestrate the development of the peripheral taste system. The unique anatomy/function of the taste system makes this system ideal for understanding the mechanisms by which these factors function; yet the taste system is underutilized for this role. This review focuses on some of the many factors that are known to regulate gustatory development, and discusses a few topics where more work is needed. Some attention is given to factors that regulate epibranchial placode formation, since gustatory neurons are thought to be primarily derived from this region. Epibranchial placodes appear to arise from a pan-placodal region and a number of regulatory factors control the differentiation of individual placodes. Gustatory neuron differentiation is regulated by a series of transcription factors and perhaps bone morphongenic proteins (BMP. As neurons differentiate, they also proliferate such that their numbers exceed those in the adult, and this is followed by developmental death. Some of these cell-cycling events are regulated by neurotrophins. After gustatory neurons become post-mitotic, axon outgrowth occurs. Axons are guided by multiple chemoattractive and chemorepulsive factors, including semaphorins, to the tongue epithelium. Brain derived neurotrophic factor (BDNF, functions as a targeting factor in the final stages of axon guidance and is required for gustatory axons to find and innervate taste epithelium. Numerous factors are involved in the development of gustatory papillae including Sox-2, Sonic hedge hog and Wnt-β-catenin signaling. It is likely that just as many factors regulate taste bud differentiation; however, these factors have not yet been identified. Studies examining the molecular factors that regulate terminal field formation in the nucleus of the solitary tract are also lacking. However, it is possible that some of the factors that regulate geniculate ganglion development, outgrowth, guidance and

  20. Mineral Availability as a Key Regulator of Soil Carbon Storage.

    Science.gov (United States)

    Yu, Guanghui; Xiao, Jian; Hu, Shuijin; Polizzotto, Matthew L; Zhao, Fangjie; McGrath, Steve P; Li, Huan; Ran, Wei; Shen, Qirong

    2017-05-02

    Mineral binding is a major mechanism for soil carbon (C) stabilization, and mineral availability for C binding critically affects C storage. Yet, the mechanisms regulating mineral availability are poorly understood. Here, we showed that organic amendments in three long-term (23, 154, and 170 yrs, respectively) field experiments significantly increased mineral availability, particularly of short-range-ordered (SRO) phases. Two microcosm studies demonstrated that the presence of roots significantly increased mineral availability and promoted the formation of SRO phases. Mineral transformation experiments and isotopic labeling experiments provided direct evidence that citric acid, a major component of root exudates, promoted the formation of SRO minerals, and that SRO minerals acted as "nuclei" for C retention. Together, these findings indicate that soil organic amendments initialize a positive feedback loop by increasing mineral availability and promoting the formation of SRO minerals for further C binding, thereby possibly serving as a management tool for enhancing carbon storage in soils.

  1. Germline transcription: a key regulator of accessibility and recombination.

    Science.gov (United States)

    Abarrategui, Iratxe; Krangel, Michael S

    2009-01-01

    The developmental control of V(D)J recombination is imposed at the level of chromatin accessibility of recombination signal sequences (RSSs) to the recombinase machinery. Cis-acting transcriptional regulatory elements such as promoters and enhancers play a central role in the control of accessibility in vivo. However, the molecular mechanisms by which these elements influence accessibility are still under investigation. Although accessibility for V(D)J recombination is usually accompanied by germline transcription at antigen receptor loci, the functional significance of this transcription in directing RSS accessibility has been elusive. In this chapter, we review past studies outlining the complex relationship between V(D)J recombination and transcription as well as our current understanding on how chromatin structure is regulated during gene expression. We then summarize recent work that directly addresses the functional role of transcription in V(D)J recombination.

  2. Hypothalamic Lipids: Key Regulators of Whole Body Energy Balance.

    Science.gov (United States)

    González-García, Ismael; Fernø, Johan; Diéguez, Carlos; Nogueiras, Rubén; López, Miguel

    2017-01-01

    Hypothalamic lipid metabolism plays a major role in the physiological regulation of energy balance. Modulation of several enzymatic activities that control lipid biosynthesis, such as fatty acid synthase and AMP-activated protein kinase, impacts both feeding and energy expenditure. However, lipids can also cause pathological alterations in the hypothalamus. Lipotoxicity is promoted by excess lipids in tissues not suitable for their storage. A large amount of evidence has demonstrated that lipotoxicity is a pathophysiological mechanism leading to metabolic diseases such as insulin resistance, cardiomyopathy, atherosclerosis, and steatohepatitis. Current data have reported that, similar to what is observed in peripheral tissues, complex lipids such as ceramides and sphingolipids act as lipotoxic species at the hypothalamic level to impact metabolism. Here, we will review what is currently known about hypothalamic lipid metabolism and the modulation of energy homeostasis. © 2016 S. Karger AG, Basel.

  3. MicroRNAs Regulate Key Effector Pathways of Senescence

    Directory of Open Access Journals (Sweden)

    Andrea Feliciano

    2011-01-01

    Full Text Available MicroRNAs (miRNAs are small (approximately 22 nt noncoding endogenous RNA molecules that regulate gene expression and protein coding by base pairing with the 3′ untranslated region (UTR of target mRNAs. miRNA expression is associated with cancer pathogenesis because miRNAs are intimately linked to cancer development. Senescence blocks cell proliferation, representing an important barrier that cells must bypass to reach malignancy. Importantly, certain miRNAs have been shown to have an important role during cellular senescence, which is also involved in human tumorigenesis. Therefore, therapeutic induction of senescence by drugs or miRNA-based therapies is a potential method to treat cancer by inducing a persistent growth arrest in tumors.

  4. Key factors affecting mechanical behavior of metallic glass nanowires

    Science.gov (United States)

    Zhang, Qi; Li, Qi-Kai; Li, Mo

    2017-01-01

    Both strengthening and weakening trends with decreasing diameter have been observed for metallic glass nanowires, sometimes even in the samples with the same chemical composition. How to reconcile the results has reminded a puzzle. Since the detailed stress state and microstructure of metallic glass nanowires may differ from each other significantly depending on preparation, to discover the intrinsic size effect it is necessary to study metallic glass nanowires fabricated differently. Here we show the complex size effects from one such class of metallic glass nanowires prepared by casting using molecular dynamics simulations. As compared with the nanowires of the same composition prepared by other methods, the cast nanowires deform nearly homogeneously with much lower strength but better ductility; and also show strengthening in tension but weakening in compression with decreasing wire diameter. The subtle size dependence is shown to be related to the key factors including internal and surface stress state, atomic structure variation, and presence of various gradients. The complex interplay of these factors at decreasing size leads to the different deformation behaviors.

  5. Phosphodiesterase 1 regulation is a key mechanism in vascular aging

    DEFF Research Database (Denmark)

    Niño, Paula K Bautista; Durik, Matej; Danser, A H Jan

    2015-01-01

    Reduced nitric oxide (NO)/cGMP signalling is observed in age-related vascular disease. We hypothesize that this disturbed signalling involves effects of genomic instability, a primary causal factor in aging, on vascular smooth muscle cells (VSMCs) and that the underlying mechanism plays a role.......0061, P=2.89×10(-5)). In summary, these results show that genomic instability and cellular senescence in VSMCs increase PDE1 expression. This might play a role in aging-related loss of vasodilator function, VSMC senescence, increased blood pressure and vascular hypertrophy....

  6. Competing Endogenous RNA: The Key to Posttranscriptional Regulation

    Directory of Open Access Journals (Sweden)

    Rituparno Sen

    2014-01-01

    Full Text Available Competing endogenous RNA, ceRNA, vie with messenger RNAs (mRNAs for microRNAs (miRNAs with shared miRNAs responses elements (MREs and act as modulator of miRNA by influencing the available level of miRNA. It has recently been discovered that, apart from protein-coding ceRNAs, pseudogenes, long noncoding RNAs (lncRNAs, and circular RNAs act as miRNA “sponges” by sharing common MRE, inhibiting normal miRNA targeting activity on mRNA. These MRE sharing elements form the posttranscriptional ceRNA network to regulate mRNA expression. ceRNAs are widely implicated in many biological processes. Recent studies have identified ceRNAs associated with a number of diseases including cancer. This brief review focuses on the molecular mechanism of ceRNA as part of the complex post-transcriptional regulatory circuit in cell and the impact of ceRNAs in development and disease.

  7. Fibroblast growth factor 21 - a key player in cardiovascular disorders?

    Science.gov (United States)

    Lenart-Lipińska, Monika; Duma, Dariusz; Hałabiś, Magdalena; Dziedzic, Marcin; Solski, Janusz

    2016-06-15

    Fibroblast growth factor 21 (FGF21) is a newly discovered adipokine, synthesized by several organs, mostly by the liver, which was introduced as a potent metabolic regulator and insulin-sensitizing factor. Numerous animal studies have demonstrated that FGF21 improves glucose and lipids metabolism and exerts anti-inflammatory effects. However, data obtained from human studies have shown contradictory results, in which circulating FGF21 levels were often elevated in obesity, dyslipidemia, type 2 diabetes (DM2) and other conditions connected with insulin resistance. This increase in basal FGF21 concentrations observed in patients with obesity and other conditions related to insulin resistance was being explained as a compensatory response to the underlying metabolic disturbances or tissue resistance to FGF21 action. Furthermore, the results of clinical trials have shown that increased FGF21 concentrations were associated with increased cardiovascular (CV) risk and had a prognostic value in CV outcomes. In recent years, it has been reported that FGF21 may exert cardioprotective effects. This mini-review aims to summarize the current state of knowledge about the role of FGF21 in CV disorders, and discuss the molecular mechanism underlying the anti-atherogenic properties of this compound.

  8. Key Response Planning Factors for the Aftermath of Nuclear Terrorism

    Energy Technology Data Exchange (ETDEWEB)

    Buddemeier, B R; Dillon, M B

    2009-01-21

    Despite hundreds of above-ground nuclear tests and data gathered from Hiroshima and Nagasaki, the effects of a ground-level, low-yield nuclear detonation in a modern urban environment are still the subject of considerable scientific debate. Extensive review of nuclear weapon effects studies and discussions with nuclear weapon effects experts from various federal agencies, national laboratories, and technical organizations have identified key issues and bounded some of the unknowns required to support response planning for a low-yield, ground-level nuclear detonation in a modern U.S. city. This study, which is focused primarily upon the hazards posed by radioactive fallout, used detailed fallout predictions from the advanced suite of three-dimensional (3-D) meteorology and plume/fallout models developed at Lawrence Livermore National Laboratory (LLNL), including extensive global Key Response Planning Factors for the Aftermath of Nuclear Terrorism geographical and real-time meteorological databases to support model calculations. This 3-D modeling system provides detailed simulations that account for complex meteorology and terrain effects. The results of initial modeling and analysis were presented to federal, state, and local working groups to obtain critical, broad-based review and feedback on strategy and messaging. This effort involved a diverse set of communities, including New York City, National Capitol Regions, Charlotte, Houston, Portland, and Los Angeles. The largest potential for reducing casualties during the post-detonation response phase comes from reducing exposure to fallout radiation. This can be accomplished through early, adequate sheltering followed by informed, delayed evacuation.B The response challenges to a nuclear detonation must be solved through multiple approaches of public education, planning, and rapid response actions. Because the successful response will require extensive coordination of a large number of organizations, supplemented by

  9. Evolution of plant conducting cells: perspectives from key regulators of vascular cell differentiation.

    Science.gov (United States)

    Ohtani, Misato; Akiyoshi, Nobuhiro; Takenaka, Yuto; Sano, Ryosuke; Demura, Taku

    2017-01-01

    One crucial problem that plants faced during their evolution, particularly during the transition to growth on land, was how to transport water, nutrients, metabolites, and small signaling molecules within a large, multicellular body. As a solution to this problem, land plants developed specific tissues for conducting molecules, called water-conducting cells (WCCs) and food-conducting cells (FCCs). The well-developed WCCs and FCCs in extant plants are the tracheary elements and sieve elements, respectively, which are found in vascular plants. Recent molecular genetic studies revealed that transcriptional networks regulate the differentiation of tracheary and sieve elements, and that the networks governing WCC differentiation are largely conserved among land plant species. In this review, we discuss the molecular evolution of plant conducting cells. By focusing on the evolution of the key transcription factors that regulate vascular cell differentiation, the NAC transcription factor VASCULAR-RELATED NAC-DOMAIN for WCCs and the MYB-coiled-coil (CC)-type transcription factor ALTERED PHLOEM DEVELOPMENT for sieve elements, we describe how land plants evolved molecular systems to produce the specialized cells that function as WCCs and FCCs. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  10. Key success factors in enterprises practicing social marketing

    Directory of Open Access Journals (Sweden)

    Lin, Mong-Mei

    2014-11-01

    Full Text Available Enterprises could create multi-service values of customer satisfaction, enterprise profit, and social benefit through Social Marketing. Constructing a positive Social Service Value Chain to achieve mind management in marketing would reinforce the core competitive advantages of an enterprise, enhance high-quality services, and lead the enterprise to sustainable management. With the Delphi Method, a questionnaire is applied to assess the key success factors in enterprises practicing Social Marketing. The superiors and the employees in Formosa Plastics Group were selected as the research participants for 200 questionnaires. A total of 133 valid copies are retrieved, with a retrieval rate of 67%. According to the overall weights of the key success factors in enterprises practicing Social Marketing, the following summary is concluded. 1. The evaluation criteria in Organizational Characteristics are ordered in the following way: Intrinsic Structure, Internal Environment, Cost Effectiveness, Organizational Advantage, Organizational Weakness, and Inspiration. 2. The evaluation criteria in the External Environment are ordered this way: Information Resources, Environmental Opportunities, and Environmental Threats. 3. The order of the evaluation criteria in Marketing Strategy is Appropriate Media, Targeted Objects, Market Selection, Market Response, and Behavioral Change. 4. The evaluation criteria in Process Orientation are ordered in the following way: Tracking Adjustment, Feedback Systems, Operation Performance, and Operation Processes.A través del márquetin social, las empresas podrían crear valores de multiservicio para la satisfacción del cliente, para incrementar los beneficios de la empresa y para beneficiar a la sociedad. La construcción de una Cadena de Valor de Servicio Social positiva para conseguir una gestión mental en el márquetin reforzaría las principales ventajas competitivas de una empresa, realzaría servicios de alta calidad y

  11. Positioning and deciding: key factors for talent development in soccer.

    Science.gov (United States)

    Kannekens, R; Elferink-Gemser, M T; Visscher, C

    2011-12-01

    Talent identification and development implicate recognizing youth players who will be successful in the future and guiding them to the top. A major determinant of this success is tactical skills. To identify possible key factors that help in predicting success over time, this study assesses the tactical skills of 105 elite youth soccer players who participated in a talent development program at an earlier stage of their sport career (mean age 17.8±0.9). These skills were related to their adult performance level, specifically whether they became professionals (n=52) or amateurs (n=53). Defenders, midfielders and attackers completed the Tactical Skills Inventory for Sports with scales for declarative and procedural knowledge in either attacking or defensive situations. A logistic regression analysis was performed to identify the tactical skills that contribute to professional performance level in adulthood. Positioning and deciding appeared to be the tactical skill that best predicts adult performance level (P<0.05). This is especially true for midfielders, with the correct classification of elite youth players in the range of 80%. For players scoring high on this skill, the odds ratios indicated a 6.60 times greater chance that a player became a professional than players scoring low (P<0.05). © 2010 John Wiley & Sons A/S.

  12. A Sensitivity Analysis Approach to Identify Key Environmental Performance Factors

    Directory of Open Access Journals (Sweden)

    Xi Yu

    2014-01-01

    Full Text Available Life cycle assessment (LCA is widely used in design phase to reduce the product’s environmental impacts through the whole product life cycle (PLC during the last two decades. The traditional LCA is restricted to assessing the environmental impacts of a product and the results cannot reflect the effects of changes within the life cycle. In order to improve the quality of ecodesign, it is a growing need to develop an approach which can reflect the changes between the design parameters and product’s environmental impacts. A sensitivity analysis approach based on LCA and ecodesign is proposed in this paper. The key environmental performance factors which have significant influence on the products’ environmental impacts can be identified by analyzing the relationship between environmental impacts and the design parameters. Users without much environmental knowledge can use this approach to determine which design parameter should be first considered when (redesigning a product. A printed circuit board (PCB case study is conducted; eight design parameters are chosen to be analyzed by our approach. The result shows that the carbon dioxide emission during the PCB manufacture is highly sensitive to the area of PCB panel.

  13. The Assistant Manager - a Key Factor of the Managerial Team

    Directory of Open Access Journals (Sweden)

    Lecturer Ph. D. Niculina Vargolici

    2009-05-01

    Full Text Available The new economic context, marked by the crisis and by radical transformations of the labor market, generates the need for more and more sophisticated skills for the assistant manager. That is because the efficiency of the secretarial activity implies both strategic skills and complex abilities, starting from knowledge about the specific activity of the company/institution where the person works as assistant manager, to connected areas such as: management, marketing, human resources, brand communication, company’s culture etc. Whether the manager changes his job together with the “boss”, or the boss is changed and he is bond to adapt to new conditions, a strong team spirit between the manager and his assistant is one of the most important elements that contribute to the productivity and efficiency of the both. The loyalty to the boss and to the company where he works, his adaptation capacity, his competence and his professionalism make the today’s assistant manager a key factor of the managerial team. The essence of the assistant manager job consists in making more efficient the managerial activities, namely, to make it respond to the expectations expressed or not of the manager, or even to anticipate them.

  14. The histone acetyltransferase MOF is a key regulator of the embryonic stem cell core transcriptional network.

    Science.gov (United States)

    Li, Xiangzhi; Li, Li; Pandey, Ruchi; Byun, Jung S; Gardner, Kevin; Qin, Zhaohui; Dou, Yali

    2012-08-03

    Pluripotent embryonic stem cells (ESCs) maintain self-renewal and the potential for rapid response to differentiation cues. Both ESC features are subject to epigenetic regulation. Here we show that the histone acetyltransferase Mof plays an essential role in the maintenance of ESC self-renewal and pluripotency. ESCs with Mof deletion lose characteristic morphology, alkaline phosphatase (AP) staining, and differentiation potential. They also have aberrant expression of the core transcription factors Nanog, Oct4, and Sox2. Importantly, the phenotypes of Mof null ESCs can be partially suppressed by Nanog overexpression, supporting the idea that Mof functions as an upstream regulator of Nanog in ESCs. Genome-wide ChIP-sequencing and transcriptome analyses further demonstrate that Mof is an integral component of the ESC core transcriptional network and that Mof primes genes for diverse developmental programs. Mof is also required for Wdr5 recruitment and H3K4 methylation at key regulatory loci, highlighting the complexity and interconnectivity of various chromatin regulators in ESCs.

  15. Hexokinase is a key regulator of energy metabolism and ROS activity in insect lifespan extension

    Science.gov (United States)

    Lin, Xian-Wu; Xu, Wei-Hua

    2016-01-01

    Developmental arrest (diapause) is a ‘non-aging’ state that is similar to the Caenorhabditis elegans dauer stage and Drosophila lifespan extension. Diapause results in low metabolic activity and a profound extension of insect lifespan. Here, we cloned the Helicoverpa armigera Hexokinase (HK) gene, a gene that is critical for the developmental arrest of this species. HK expression and activity levels were significantly increased in nondiapause-destined pupae compared with those of diapause-destined pupae. Downregulation of HK activity reduced cell viability and delayed pupal development by reducing metabolic activity and increasing ROS activity, which suggests that HK is a key regulator of insect development. We then identified the transcription factors Har-CREB, -c-Myc, and -POU as specifically binding the Har-HK promoter and regulating its activity. Intriguingly, Har-POU and -c-Myc are specific transcription factors for HK expression, whereas Har-CREB is nonspecific. Furthermore, Har-POU and -c-Myc could respond to ecdysone, which is an upstream hormone. Therefore, low ecdysone levels in diapause-destined individuals lead to low Har-POU and -c-Myc expression levels, ultimately repressing Har-HK expression and inducing entry into diapause or lifespan extension. PMID:26852422

  16. The Neuroplastin adhesion molecules: key regulators of neuronal plasticity and synaptic function.

    Science.gov (United States)

    Beesley, Philip W; Herrera-Molina, Rodrigo; Smalla, Karl-Heinz; Seidenbecher, Constanze

    2014-11-01

    The Neuroplastins Np65 and Np55 are neuronal and synapse-enriched immunoglobulin superfamily molecules that play important roles in a number of key neuronal and synaptic functions including, for Np65, cell adhesion. In this review we focus on the physiological roles of the Neuroplastins in promoting neurite outgrowth, regulating the structure and function of both inhibitory and excitatory synapses in brain, and in neuronal and synaptic plasticity. We discuss the underlying molecular and cellular mechanisms by which the Neuroplastins exert their physiological effects and how these are dependent upon the structural features of Np65 and Np55, which enable them to bind to a diverse range of protein partners. In turn this enables the Neuroplastins to interact with a number of key neuronal signalling cascades. These include: binding to and activation of the fibroblast growth factor receptor; Np65 trans-homophilic binding leading to activation of p38 MAPK and internalization of glutamate (GluR1) receptor subunits; acting as accessory proteins for monocarboxylate transporters, thus affecting neuronal energy supply, and binding to GABAA α1, 2 and 5 subunits, thus regulating the composition and localization of GABAA receptors. An emerging theme is the role of the Neuroplastins in regulating the trafficking and subcellular localization of specific binding partners. We also discuss the involvement of Neuroplastins in a number of pathophysiological conditions, including ischaemia, schizophrenia and breast cancer and the role of a single nucleotide polymorphism in the human Neuroplastin (NPTN) gene locus in impairment of cortical development and cognitive functions. Neuroplastins are neuronal cell adhesion molecules, which induce neurite outgrowth and play important roles in synaptic maturation and plasticity. This review summarizes the functional implications of Neuroplastins for correct synaptic membrane protein localization, neuronal energy supply, expression of LTP and LTD

  17. Cooperation of patient as key factor to overcome oral habits

    Directory of Open Access Journals (Sweden)

    Magdalena Lesmana

    2009-06-01

    Full Text Available Introduction: Orthodontic treatments have developed rapidly on the last decade even though; the sophisticated treatment has been limited by patient’s behavior. Orthodontist should acknowledge that the success of treatment not only depends on the knowledge and skill of the operator, but on the patient’s behavior as well, which is very critical to overcome the oral habit, including anterior tongue thrust swallow (ATTS. Patient’s cooperation is the key factor to set prognosis of oral habit correction and have to be proven through analysis of questioners. Methods: Patient cooperation scale (PCS was made for this research involving 68 orthodontic patients for correction of ATTS from Faculty of Dentistry Indonesia University and Ladokgi as respondents. PCS assessment was based on data sets of: Patient awareness of ATTS (PAw, Patient Acceptance to receive treatment (PAc, and Patient Comfortable for using appliances (PC. The evaluation was obtained by calculation the total score of 10 items from each component, which gave 0–30 range of scale and would be 0–90 range of cooperation scale as the final result. Result: PCS assessment can be based on data sets of PAw, PAc, and PC. It is valid and reliable. The score for the cooperative patients range between 0–25. The higher the score from this questionnaire shows less cooperation from respondent. On the other hand, the lower the score showed better cooperation. Conclusion: PCS can be used for the prognosis of the successful oral habits correction and has a significant relation with the length of successful treatment.

  18. Identification of the key regulating genes of diminished ovarian reserve (DOR) by network and gene ontology analysis.

    Science.gov (United States)

    Pashaiasl, Maryam; Ebrahimi, Mansour; Ebrahimie, Esmaeil

    2016-09-01

    Diminished ovarian reserve (DOR) is one of the reasons for infertility that not only affects both older and young women. Ovarian reserve assessment can be used as a new prognostic tool for infertility treatment decision making. Here, up- and down-regulated gene expression profiles of granulosa cells were analysed to generate a putative interaction map of the involved genes. In addition, gene ontology (GO) analysis was used to get insight intol the biological processes and molecular functions of involved proteins in DOR. Eleven up-regulated genes and nine down-regulated genes were identified and assessed by constructing interaction networks based on their biological processes. PTGS2, CTGF, LHCGR, CITED, SOCS2, STAR and FSTL3 were the key nodes in the up-regulated networks, while the IGF2, AMH, GREM, and FOXC1 proteins were key in the down-regulated networks. MIRN101-1, MIRN153-1 and MIRN194-1 inhibited the expression of SOCS2, while CSH1 and BMP2 positively regulated IGF1 and IGF2. Ossification, ovarian follicle development, vasculogenesis, sequence-specific DNA binding transcription factor activity, and golgi apparatus are the major differential groups between up-regulated and down-regulated genes in DOR. Meta-analysis of publicly available transcriptomic data highlighted the high coexpression of CTGF, connective tissue growth factor, with the other key regulators of DOR. CTGF is involved in organ senescence and focal adhesion pathway according to GO analysis. These findings provide a comprehensive system biology based insight into the aetiology of DOR through network and gene ontology analyses.

  19. Chromatin regulator PRC2 is a key regulator of epigenetic plasticity in glioblastoma.

    Science.gov (United States)

    Natsume, Atsushi; Ito, Motokazu; Katsushima, Keisuke; Ohka, Fumiharu; Hatanaka, Akira; Shinjo, Keiko; Sato, Shinya; Takahashi, Satoru; Ishikawa, Yuta; Takeuchi, Ichiro; Shimogawa, Hiroki; Uesugi, Motonari; Okano, Hideyuki; Kim, Seung U; Wakabayashi, Toshihiko; Issa, Jean-Pierre J; Sekido, Yoshitaka; Kondo, Yutaka

    2013-07-15

    Tumor cell plasticity contributes to functional and morphologic heterogeneity. To uncover the underlying mechanisms of this plasticity, we examined glioma stem-like cells (GSC) where we found that the biologic interconversion between GSCs and differentiated non-GSCs is functionally plastic and accompanied by gain or loss of polycomb repressive complex 2 (PRC2), a complex that modifies chromatin structure. PRC2 mediates lysine 27 trimethylation on histone H3 and in GSC it affected pluripotency or development-associated genes (e.g., Nanog, Wnt1, and BMP5) together with alterations in the subcellular localization of EZH2, a catalytic component of PRC2. Intriguingly, exogenous expression of EZH2-dNLS, which lacks nuclear localization sequence, impaired the repression of Nanog expression under differentiation conditions. RNA interference (RNAi)-mediated attenuation or pharmacologic inhibition of EZH2 had little to no effect on apoptosis or bromodeoxyuridine incorporation in GSCs, but it disrupted morphologic interconversion and impaired GSC integration into the brain tissue, thereby improving survival of GSC-bearing mice. Pathologic analysis of human glioma specimens revealed that the number of tumor cells with nuclear EZH2 is larger around tumor vessels and the invasive front, suggesting that nuclear EZH2 may help reprogram tumor cells in close proximity to this microenvironment. Our results indicate that epigenetic regulation by PRC2 is a key mediator of tumor cell plasticity, which is required for the adaptation of glioblastoma cells to their microenvironment. Thus, PRC2-targeted therapy may reduce tumor cell plasticity and tumor heterogeneity, offering a new paradigm for glioma treatment.

  20. Partition of some key regulating services in terrestrial ecosystems: Meta-analysis and review

    Energy Technology Data Exchange (ETDEWEB)

    Viglizzo, E.F., E-mail: evigliz@cpenet.com.ar [INTA, EEA Anguil, Grupo de Investigaciones en Gestión Ambiental (GIGA), Av. Spinetto 785, 6300 Santa Rosa, La Pampa (Argentina); INCITAP-CONICET, Ruta 35, km 335, 6300 Santa Rosa, La Pampa (Argentina); UNLPam, Facultad de Ciencias Exactas y Naturales, Av. Uruguay 151, 6300 Santa Rosa, La Pampa (Argentina); Jobbágy, E.G. [CONICET, Andes 950, 5700 San Luis, San Luis (Argentina); Grupo de Estudios Ambientales IMASL, Ejército de los, Andes 950, 5700 San Luis, San Luis (Argentina); Ricard, M.F. [INCITAP-CONICET, Ruta 35, km 335, 6300 Santa Rosa, La Pampa (Argentina); UNLPam, Facultad de Ciencias Exactas y Naturales, Av. Uruguay 151, 6300 Santa Rosa, La Pampa (Argentina); Paruelo, J.M. [Laboratorio de Análisis Regional y Teledetección, Departamento de Métodos Cuantitativos Sistemas de información, Facultad de Agronomía and IFEVA, Universidad de Buenos Aires and CONICET, Av. San Martín 4453, 1417 Buenos Aires (Argentina)

    2016-08-15

    Our knowledge about the functional foundations of ecosystem service (ES) provision is still limited and more research is needed to elucidate key functional mechanisms. Using a simplified eco-hydrological scheme, in this work we analyzed how land-use decisions modify the partition of some essential regulatory ES by altering basic relationships between biomass stocks and water flows. A comprehensive meta-analysis and review was conducted based on global, regional and local data from peer-reviewed publications. We analyzed five datasets comprising 1348 studies and 3948 records on precipitation (PPT), aboveground biomass (AGB), AGB change, evapotranspiration (ET), water yield (WY), WY change, runoff (R) and infiltration (I). The conceptual framework was focused on ES that are associated with the ecological functions (e.g., intermediate ES) of ET, WY, R and I. ES included soil protection, carbon sequestration, local climate regulation, water-flow regulation and water recharge. To address the problem of data normality, the analysis included both parametric and non-parametric regression analysis. Results demonstrate that PPT is a first-order biophysical factor that controls ES release at the broader scales. At decreasing scales, ES are partitioned as result of PPT interactions with other biophysical and anthropogenic factors. At intermediate scales, land-use change interacts with PPT modifying ES partition as it the case of afforestation in dry regions, where ET and climate regulation may be enhanced at the expense of R and water-flow regulation. At smaller scales, site-specific conditions such as topography interact with PPT and AGB displaying different ES partition formats. The probable implications of future land-use and climate change on some key ES production and partition are discussed. - Highlights: • The partition of regulatory services in ecosystems poses a major policy challenge. • We examined how partitions occur at the hydrosphere

  1. The Development of Electronic Payment System for Universities in Indonesia: On Resolving Key Success Factors

    CERN Document Server

    Moertini, Veronica S; Kemit, Hery M; Saputro, Nico

    2011-01-01

    It is known that IT projects are high-risk. To achieve project success, the strategies to avoid and reduce risks must be designed meticulously and implemented accordingly. This paper presents methods for avoiding and reducing risks throughout the development of an information system, specifically electronic payment system to handle tuition in the universities in Indonesia. The university policies, regulations and system models are design in such a way to resolve the project key success factors. By implementing the proposed methods, the system has been successfully developed and currently operated. The research is conducted in Parahyangan Catholic University, Bandung, Indonesia.

  2. Health: A Key Factor in the Evaluation of Day Care.

    Science.gov (United States)

    Bollin, Gail G.

    Research has inadequately examined why health has become a problem in the day care setting. Health regulations for day care have not been researched in the day care setting per se but have been imposed on day care by the medical community working from a hospital model. Day care research has presumed that having antecedent health regulations in…

  3. Exploring the Functional Disorder and Corresponding Key Transcription Factors in Intraductal Papillary Mucinous Neoplasms Progression

    Directory of Open Access Journals (Sweden)

    Guiying Bai

    2015-01-01

    Full Text Available This study has analyzed the gene expression patterns of an IPMN microarray dataset including normal pancreatic ductal tissue (NT, intraductal papillary mucinous adenoma (IPMA, intraductal papillary mucinous carcinoma (IPMC, and invasive ductal carcinoma (IDC samples. And eight clusters of differentially expressed genes (DEGs with similar expression pattern were detected by k-means clustering. Then a survey map of functional disorder in IPMN progression was established by functional enrichment analysis of these clusters. In addition, transcription factors (TFs enrichment analysis was used to detect the key TFs in each cluster of DEGs, and three TFs (FLI1, ERG, and ESR1 were found to significantly regulate DEGs in cluster 1, and expression of these three TFs was validated by qRT-PCR. All these results indicated that these three TFs might play key roles in the early stages of IPMN progression.

  4. Energy efficiency and CO2: is electricity the key factor?

    Energy Technology Data Exchange (ETDEWEB)

    Bamberger, Y.

    2007-07-01

    Europe must face soon to the depletion of fossil energy resources. Efficiency in end energy uses is a key to prepare this challenge. First, the report shows that significant energy efficiency capacities remain in the main economy sectors in France and Europe: buildings, industry, transportation. The key technologies, mainly electricity-driven, are briefly presented, together with the related main tracks for R and D: heat pumps, thermal insulation, induction and mechanical vapour compression for industry, plugged hybrid vehicle, LED sources for lighting. Their ability to decrease CO2 emissions is shown. Control equipment and users behaviour are pointed out, mainly with the key role of price energy with recent French experience : load shifting, peak shaving. Finally, the report shows that a firm policy, based on high performance equipments, could lead to a significant decrease of energy needs in France around 2030.

  5. Nrf2 as a key player of redox regulation in cardiovascular diseases.

    Science.gov (United States)

    Barančík, M; Grešová, L; Barteková, M; Dovinová, I

    2016-09-19

    The oxidative stress plays an important role in the development of cardiovascular diseases (CVD). In CVD progression an aberrant redox regulation was observed. In this regulation levels of reactive oxygen species (ROS) play an important role in cellular signaling, where Nrf2 is the key regulator of redox homeostasis. Keap1-Nrf2-ARE system regulates a great set of detoxificant and antioxidant enzymes in cells after ROS and electrophiles exposure. In this review we focus on radical-generating systems in cardiovascular system as well as on Nrf2 as a target against oxidative stress and a key player of redox regulation in cardiovascular diseases. We also summarize the current knowledge about the role of Nrf2 in pathophysiology of several CVD (hypertension, cardiac hypertrophy, cardiomyopathies) as well as in cardioprotection against myocardial ischemia/ reperfusion injury.

  6. Identification of key contributory factors responsible for vascular dysfunction in idiopathic recurrent spontaneous miscarriage.

    Directory of Open Access Journals (Sweden)

    Priyanka Banerjee

    Full Text Available Poor endometrial perfusion during implantation window is reported to be one of the possible causes of idiopathic recurrent spontaneous miscarriage (IRSM. We have tested the hypothesis that certain angiogenic and vasoactive factors are associated with vascular dysfunction during implantation window in IRSM and, therefore, could play a contributory role in making the endometrium unreceptive in these women. This is a prospective case-controlled study carried out on 66 women with IRSM and age and BMI matched 50 fertile women serving as controls. Endometrial expression of pro-inflammatory (IL-1β, TNF-α, IFN-γ, TGF-β1, anti-inflammatory (IL-4, -10, angiogenesis-associated cytokines (IL-2, -6, -8, angiogenic and vasoactive factors including prostaglandin E2 (PGE2, vascular endothelial growth factor (VEGF, endothelial nitric oxide synthase (eNOS, nitric oxide (NO and adrenomedullin (ADM were measured during implantation window by ELISA. Subendometrial blood flow (SEBF was assessed by color Doppler ultrasonography. Multivariate analysis was used to identify the significant factor(s responsible for vascular dysfunction in IRSM women during window of implantation and further correlated with vascular dysfunction. Endometrial expression of pro-inflammatory cytokines and PGE2 were up-regulated and anti-inflammatory and angiogenesis-associated cytokines down-regulated in IRSM women as compared with controls. Further, the angiogenic and vasoactive factors including VEGF, eNOS, NO and ADM were found to be down-regulated and SEBF grossly affected in these women. Multivariate analysis identified IL-10, followed by VEGF and eNOS as the major factors contributing towards vascular dysfunction in IRSM women. Moreover, these factors strongly correlated with blood flow impairment. This study provides an understanding that IL-10, VEGF and eNOS are the principal key components having a contributory role in endometrial vascular dysfunction in women with IRSM. Down-regulation

  7. What are the key sucess factors of MOOC platforms?

    OpenAIRE

    Bento, Lourenço de Moura Souto

    2014-01-01

    This thesis analyzes key characteristics of Massive Open Online Courses (MOOCs) platforms in order to assess what makes such platforms successful. Three challenges of MOOC platforms were determined from the review of the literature: dropout rates, sustainability and plagiarism. Primary data was gathered from a sample of MOOC platforms, both on the characteristics of the platforms themselves and their internet traffic data. We performed a statistical correlation analysis using Traffic Rank as ...

  8. THE MANAGEMENT OF KNOWLEDGE WORKERS – KEY FACTOR OF SUCCES

    OpenAIRE

    Claudia-Elena ŢUCLEA; Gabriela ŢIGU

    2007-01-01

    The traditional companies are built on familiar bedrock of buildings, plants, and inventories. Competitive advantage is viewed in terms of scale and volume stemming from high-capacity use of machine-based factories. Such an approach fails to recognize how the leverage of knowledge is becoming a key to long-term success. Nowadays, organizations must recognize that power resides in the minds of their best people, who are diffused throughout the business and the organizations are becoming more d...

  9. Key Success Factors for Organizational Innovation in the Fashion Industry

    Directory of Open Access Journals (Sweden)

    Fabio De Felice

    2013-08-01

    on the Balanced Scorecard (BSC and the Analytic Network Process (ANP, called ‘MAB’ – Multi-criteria Assessment Balanced Scorecard. Firstly, key performance indicators (KPIs are evaluated in order to assess the performance level of a typical fashion industry. The development of an index system and methods is aimed to form a set of useful tools for policy-makers to facilitate the transformation of an industrial development mode and support the performance of the fashion industry.

  10. Key Success Factors for Organizational Innovation in the Fashion Industry

    OpenAIRE

    Fabio De Felice; Antonella Petrillo

    2013-01-01

    In the current phase of globalization, the fashion industry is an important sector where firm strategies are frequently oriented towards product personalization – more than product customization – with a reduced price. The fashion industry relates to the ability to provide customized products or services through flexible processes in high volume and at a reasonably low cost, which are currently key variables for the fashion supply chain. Performance concepts – which usually refer to three pil...

  11. Exploring the Key Factors of Knowledge Sharing via Employee Weblogs

    Directory of Open Access Journals (Sweden)

    Saeed Rahimi Moghadam

    2013-10-01

    Full Text Available In this study, two dependent variables of individual's intention and attitude have been defined for knowledge sharing via the employee weblog and independent variables have been determined in 3 groups of social influence factor, technology acceptance factor and social cognitive factor with subset variables including the subjective norm, social identity, group norm (first group, perceived usefulness, perceived ease of use, perceived enjoyment (second group, self-efficacy, personal outcome expectation, altruism and trust (third group. This research reviews the previous studies in the field of knowledge sharing via the employee weblog. The main difference of this research with other studies is to collect and complete a full set of factors affecting the knowledge sharing according to the factors raised in previous studies. Finally the suggestions have been provided for conducting the statistical studies in Iran.

  12. Succesful Lean Manufacturing Implementation: Internal Key Influencing Factors

    Science.gov (United States)

    Virginia, Iuga; Claudiu, Kifor

    2015-09-01

    Manufacturing sectors and companies all over the world are successfully implementing lean principles within their processes. Nowadays, lean has become an indispensable part of global players. Companies worldwide need to be aware of multiple factors which weigh heavily on the success or failure of lean implementation. This paper focuses on giving a brief and structured overview over the fundamental organizational factors which play a substantial role for the lean manufacturing (LM) implementation process. The study below focuses on internal factors which are indispensable for a successful LM implementation within organizations. It is imperative that these internal factors are known, recognized and taken into consideration during the whole LM implementation process. Ignoring their influence on the process's implementation may lead to endangering the expected results or to making the process more difficult which could result in much higher human resource consumption.

  13. Characterization of Key Helicobacter pylori Regulators Identifies a Role for ArsRS in Biofilm Formation.

    Science.gov (United States)

    Servetas, Stephanie L; Carpenter, Beth M; Haley, Kathryn P; Gilbreath, Jeremy J; Gaddy, Jennifer A; Merrell, D Scott

    2016-09-15

    Helicobacter pylori must be able to rapidly respond to fluctuating conditions within the stomach. Despite this need for constant adaptation, H. pylori encodes few regulatory proteins. Of the identified regulators, the ferric uptake regulator (Fur), the nickel response regulator (NikR), and the two-component acid response system (ArsRS) are each paramount to the success of this pathogen. While numerous studies have individually examined these regulatory proteins, little is known about their combined effect. Therefore, we constructed a series of isogenic mutant strains that contained all possible single, double, and triple regulatory mutations in Fur, NikR, and ArsS. A growth curve analysis revealed minor variation in growth kinetics across the strains; these were most pronounced in the triple mutant and in strains lacking ArsS. Visual analysis showed that strains lacking ArsS formed large aggregates and a biofilm-like matrix at the air-liquid interface. Biofilm quantification using crystal violet assays and visualization via scanning electron microscopy (SEM) showed that all strains lacking ArsS or containing a nonphosphorylatable form of ArsR (ArsR-D52N mutant) formed significantly more biofilm than the wild-type strain. Molecular characterization of biofilm formation showed that strains containing mutations in the ArsRS pathway displayed increased levels of cell aggregation and adherence, both of which are key to biofilm development. Furthermore, SEM analysis revealed prevalent coccoid cells and extracellular matrix formation in the ArsR-D52N, ΔnikR ΔarsS, and Δfur ΔnikR ΔarsS mutant strains, suggesting that these strains may have an exacerbated stress response that further contributes to biofilm formation. Thus, H. pylori ArsRS has a previously unrecognized role in biofilm formation. Despite a paucity of regulatory proteins, adaptation is key to the survival of H. pylori within the stomach. While prior studies have focused on individual regulatory proteins

  14. An Analysis of Key Factors in Developing a Smart City

    Directory of Open Access Journals (Sweden)

    Aidana Šiurytė

    2016-06-01

    Full Text Available The concept Smart City is used widely but it is perceived differently as well. Literature review reveals key elements of the Smart City – Information and Communication Technologies and Smart Citizens. Nevertheless, raising public awareness is not a priority of local municipalities which are trying to develop cities. Focus group discussion aims to analyse citizens’ insights in regards to the Smart City and their contribution to creation of it. Case study of Vilnius examines a position of mu-nicipality in developing city as smart. Study contains suggestions for the improvement of communication in the city. Methods employed: comparative literature analysis, focus group investigation, case study.

  15. A systems biological approach to identify key transcription factors and their genomic neighborhoods in human sarcomas

    Institute of Scientific and Technical Information of China (English)

    Antti Ylip(a)(a); Olli Yli-Harja; Wei Zhang; Matti Nykter

    2011-01-01

    Identification of genetic signatures is the main objective for many computational oncology studies. The signature usually consists of numerous genes that are differentially expressed between two clinically distinct groups of samples, such as tumor subtypes. Prospectively, many signatures have been found to generalize poorly to other datasets and, thus, have rarely been accepted into clinical use. Recognizing the limited success of traditionally generated signatures, we developed a systems biology-based framework for robust identification of key transcription factors and their genomic regulatory neighborhoods. Application of the framework to study the differences between gastrointestinal stromal tumor (GIST) and leiomyosarcoma (LMS) resulted in the identification of nine transcription factors (SRF, NKX2-5, CCDC6, LEF1, VDR, ZNF250, TRIM63, MAF, and MYC). Functional annotations of the obtained neighborhoods identified the biological processes which the key transcription factors regulate differently between the tumor types. Analyzing the differences in the expression patterns using our approach resulted in a more robust genetic signature and more biological insight into the diseases compared to a traditional genetic signature.

  16. Protein Synthesis Initiation Factors: Phosphorylation and Regulation

    Energy Technology Data Exchange (ETDEWEB)

    Karen S. Browning

    2009-06-15

    The initiation of the synthesis of proteins is a fundamental process shared by all living organisms. Each organism has both shared and unique mechanisms for regulation of this vital process. Higher plants provide for a major amount of fixation of carbon from the environment and turn this carbon into food and fuel sources for our use. However, we have very little understanding of how plants regulate the synthesis of the proteins necessary for these metabolic processes. The research carried out during the grant period sought to address some of these unknowns in the regulation of protein synthesis initiation. Our first goal was to determine if phosphorylation plays a significant role in plant initiation of protein synthesis. The role of phosphorylation, although well documented in mammalian protein synthesis regulation, is not well studied in plants. We showed that several of the factors necessary for the initiation of protein synthesis were targets of plant casein kinase and showed differential phosphorylation by the plant specific isoforms of this kinase. In addition, we identified and confirmed the phosphorylation sites in five of the plant initiation factors. Further, we showed that phosphorylation of one of these factors, eIF5, affected the ability of the factor to participate in the initiation process. Our second goal was to develop a method to make initiation factor 3 (eIF3) using recombinant methods. To date, we successfully cloned and expressed 13/13 subunits of wheat eIF3 in E. coli using de novo gene construction methods. The final step in this process is to place the subunits into three different plasmid operons for co-expression. Successful completion of expression of eIF3 will be an invaluable tool to the plant translation community.

  17. Key Factors for Development of China's Petrochemical Industry

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ 1 Worldwide Market Volume and Development Trends of the Petrochemical Industry (1) Periodicity and Fluctuation The petrochemical industry has a typical periodicity that is shaped primarily by supply and demand on one hand and on the other hand by newly added capacity being put into production, operating rate and other uncertainty factors.

  18. Key factors governing alkaline pretreatment of waste activated sludge

    Institute of Scientific and Technical Information of China (English)

    Xianli Shi; Li Deng; Fangfang Sun; Jieyu Liang; Xu Deng

    2015-01-01

    Alkaline pretreatment is an effective technology to disintegrate sewage sludge, where alkali dosage and sludge concentration are two important factors. pH value or alkali concentration is usually adjusted in order to deter-mine a proper dosage of alkali. Our work has found that this is not a good strategy. A new parameter, the ratio of alkali to sludge (Ra/s), is more sensitive in controlling the alkali dosage. The sludge concentration Cs and reten-tion time t are two other important factors to consider. The validity of these arguments is confirmed with model-ing and experiments. The individual effect of Ra/s, Cs and t was studied separately. Then the combined effect of these three factors was evaluated. The sludge disintegration degree of 44.7%was achieved with the optimized factors. Furthermore, an alkaline-microwave combined pretreatment process was carried out under these optimized conditions. A high disintegration degree of 62.3%was achieved while the energy consumption of microwave was much lower than previously reported.

  19. Migration towards fibre to the home: key cost factors

    Science.gov (United States)

    Zhou, L. W.; Mas Machuca, C.; Zhao, R.; Grunert, K.

    2010-12-01

    This paper presents a comprehensive cost model for migration towards FTTH, some case study results from different network area scenarios, as well as the identification of the most important cost factors to be considered by operators aiming at increasing the profitability of their networks.

  20. Key success factors behind electronic medical record adoption in Thailand.

    Science.gov (United States)

    Narattharaksa, Kanida; Speece, Mark; Newton, Charles; Bulyalert, Damrongsak

    2016-09-19

    Purpose The purpose of this paper is to investigate the elements that health care personnel in Thailand believe are necessary for successful adoption of electronic medical record (EMR) systems. Design/methodology/approach Initial qualitative in-depth interviews with physicians to adapt key elements from the literature to the Thai context. The 12 elements identified included things related to managing the implementation and to IT expertise. The nationwide survey was supported by the Ministry of Public Health and returned 1,069 usable questionnaires (response rate 42 percent) from a range of medical personnel. Findings The key elements clearly separated into a managerial dimension and an IT dimension. All were considered fairly important, but managerial expertise was more critical. In particular, there should be clear EMR project goals and scope, adequate budget allocation, clinical staff must be involved in implementation, and the IT should facilitate good electronic communication. Research limitations/implications Thailand is representative of middle-income developing countries, but there is no guarantee findings can be generalized. National policies differ, as do economic structures of health care industries. The focus is on management at the organizational level, but future research must also examine macro-level issues, as well as gain more depth into thinking of individual health care personnel. Practical implications Technical issues of EMR implementation are certainly important. However, it is clear actual adoption and use of the system also depends very heavily on managerial issues. Originality/value Most research on EMR implementation has been in developed countries, and has often focussed more on technical issues rather than examining managerial issues closely. Health IT is also critical in developing economies, and management of health IT implementation must be well understood.

  1. Behaviour, the key factor for sports injury prevention.

    Science.gov (United States)

    Verhagen, Evert A L M; van Stralen, Maartje M; van Mechelen, Willem

    2010-11-01

    Safety in sports and physical activity is an important prerequisite for continuing participation in sports, as well as for maintenance of a healthy physically active lifestyle. For this reason, prevention, reduction and control of sports injuries are important goals for society as a whole. Recent advances in sports medicine discuss the need for research on real-life injury prevention. Such views call for a more behavioural approach when it comes to actual sports injury prevention. Nevertheless, the role of behaviour in sports injury prevention remains under-researched. In order to push the field of sports injury prevention forward, this article provides an overview of the relationship between behaviour and sports injury risk. Different types of behaviour relate to injury risk factors and injury mechanisms. Behaviour that influences risk factors and injury mechanisms is not confined only to the athlete. Various types of behaviour by, for example, the coach, referee, physical therapist or sports associations, also influence risk factors and injury mechanisms. In addition, multiple behaviours often act together. Some types of behaviour may directly affect injury risk and are by definition a risk factor. Other behaviours may only affect risk factors and injury mechanisms, and influence injury risk indirectly. Recent ideas on injury prevention that call for studies on real-life injury prevention still rely heavily on preventive measures that are established through efficacy research. A serious limitation in such an approach is that one expects that proven preventive measures will be adopted if the determinants and influences of sports safety behaviours are understood. Therefore, if one truly wants to prevent sports injuries in a real-life situation, a broader research focus is needed. In trying to do so, we need to look at lessons learned from other fields of injury prevention research.

  2. Quantitative transcription dynamic analysis reveals candidate genes and key regulators for ethanol tolerance in Saccharomyces cerevisiae.

    Science.gov (United States)

    Ma, Menggen; Liu, Lewis Z

    2010-06-10

    associated with heat shock proteins, trehalose-glycolysis-pentose phosphate pathways and PDR gene family are accountable for the tolerant yeast to withstand the ethanol stress, maintain active metabolisms, and complete ethanol fermentation under the ethanol stress. Transcription factor Msn4p appeared to be a key regulator of gene interactions for ethanol-tolerance in the tolerant yeast Y-50316.

  3. Quantitative transcription dynamic analysis reveals candidate genes and key regulators for ethanol tolerance in Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Ma Menggen

    2010-06-01

    and enhanced expressions of ethanol-tolerance genes associated with heat shock proteins, trehalose-glycolysis-pentose phosphate pathways and PDR gene family are accountable for the tolerant yeast to withstand the ethanol stress, maintain active metabolisms, and complete ethanol fermentation under the ethanol stress. Transcription factor Msn4p appeared to be a key regulator of gene interactions for ethanol-tolerance in the tolerant yeast Y-50316.

  4. Glycation and Hypoxia: Two Key Factors for Adipose Tissue Dysfunction.

    Science.gov (United States)

    Matafome, Paulo; Rodrigues, Tiago; Seica, Raquel

    2015-01-01

    Many aspects of adipose tissue pathophysiology in metabolic diseases have been described in the last years. One of such aspects is certainly hypoxia, which was shown to develop in adipose tissue of obese individuals and animal models. Recent data suggest two main factors for adipose tissue hypoxia: adipocyte hypertrophy and vascular dysfunction. In addition, glycation was also shown to induce morphological and functional alterations in adipose tissue. In particular, methylglyoxal directly formed from glucose was shown to potently induce AGE formation in vivo and to contribute to metabolic and vascular alterations in adipose tissue. Glycation and hypoxia are both thought to be on the basis of low grade inflammatory activation, further increasing metabolic dysregulation in adipose tissue. This review summarizes the current knowledge about the factors that contribute for tissue hypoxia and the role of glycation, not only at the vascular level, but also at the metabolic, oxidative and inflammatory levels.

  5. Product quality as a key factor of the enterprise competitiveness

    Directory of Open Access Journals (Sweden)

    Oksana Bilan

    2014-11-01

    Full Text Available The main approaches to the definition of the category "product quality" are considered in the article. The definition of product quality as the set of characteristics that reflect the necessary consumer properties of products are formulated by the author. The factors of forming of the products quality are analysed, advantages that will be got by an enterprise from improving product quality and factors that stimulate or restrain this process are defined. Main reasons of objective necessity to increase the level of quality of products (services and realization of management and providing of necessary products quality based on a continuous cycle are distinguished. Directions of improvement of product quality due to the certification of the quality management system of an enterprise in accordance with ISO 9001, improvement of raw materials quality, improvement of material and technical support of production, improvement of labour quality, the orientation of the enterprise on consumer demand and quality control are suggested

  6. Nuclear transport factors: global regulation of mitosis.

    Science.gov (United States)

    Forbes, Douglass J; Travesa, Anna; Nord, Matthew S; Bernis, Cyril

    2015-08-01

    The unexpected repurposing of nuclear transport proteins from their function in interphase to an equally vital and very different set of functions in mitosis was very surprising. The multi-talented cast when first revealed included the import receptors, importin alpha and beta, the small regulatory GTPase RanGTP, and a subset of nuclear pore proteins. In this review, we report that recent years have revealed new discoveries in each area of this expanding story in vertebrates: (a) The cast of nuclear import receptors playing a role in mitotic spindle regulation has expanded: both transportin, a nuclear import receptor, and Crm1/Xpo1, an export receptor, are involved in different aspects of spindle assembly. Importin beta and transportin also regulate nuclear envelope and pore assembly. (b) The role of nucleoporins has grown to include recruiting the key microtubule nucleator - the γ-TuRC complex - and the exportin Crm1 to the mitotic kinetochores of humans. Together they nucleate microtubule formation from the kinetochores toward the centrosomes. (c) New research finds that the original importin beta/RanGTP team have been further co-opted by evolution to help regulate other cellular and organismal activities, ranging from the actual positioning of the spindle within the cell perimeter, to regulation of a newly discovered spindle microtubule branching activity, to regulation of the interaction of microtubule structures with specific actin structures. (d) Lastly, because of the multitudinous roles of karyopherins throughout the cell cycle, a recent large push toward testing their potential as chemotherapeutic targets has begun to yield burgeoning progress in the clinic.

  7. Etiology of obesity: two "key issues" and other emerging factors

    OpenAIRE

    Lluis Serra-Majem; Inmaculada Bautista-Castaño

    2013-01-01

    The current obesity epidemic is known to have coincided with profound societal changes involving both physical activity levels and food consumption patterns as well as demographic and cultural changes affecting the conduct of human beings in various ways. On the other hand, obesity is a complex and multifactorial chronic disease that usually becomes manifest in childhood and adolescence. Its origin is a genetic and environmental interchange, of which environmental or behavioral factors play t...

  8. Key Success Factors of Innovation in Multinational Agrifood Prospector Companies

    OpenAIRE

    Fortuin, F.T.J.M.; Batterink, M.H.; Omta, S.W.F. (Onno)

    2007-01-01

    The Wageningen Innovation Assessment Tool (WIAT) assesses a company’s drivers and barriers to innovation and benchmarks the critical success and failure factors of its innovation projects with data of agrifood prospector companies around the world. The present paper discusses its application in 12 multinational agrifood prospector companies in the Netherlands and France. It is concluded that WIAT by uncovering the tacit knowledge of the innovation project team creates opportunities for subs...

  9. Key factors regarding decolorization of synthetic anthraquinone and azo dyes.

    Science.gov (United States)

    Boonyakamol, A; Imai, T; Chairattanamanokorn, P; Higuchi, T; Sekine, M

    2009-07-01

    The factors affecting decolorization of anthraquinone dye represented by Reactive Blue 4 (RB4) and azo dye represented by Methyl Orange (MO) were studied in batch experiments under mesophilic (35 degrees C) and thermophilic (55 degrees C) anaerobic conditions. The results indicated differences in decolorization properties of the dyes with different chromophore structures. In abiotic conditions, MO could be decolorized by a physicochemical reaction when it was sterilized at 121 degrees C together with sludge cells or glucose. RB4 only showed absorption onto the cell mass. The presence of a redox mediator accelerated the decolorizing reaction when supplied together with glucose in the presence of sterilized sludge cells. In biotic conditions, the results indicated that the biological activity of microorganisms was an important factor in decolorization. The main factor involved in decolorization was the conversion of cosubstrate as electron donor, which reacted with dye as an electron acceptor in electron transfer. Redox mediators, anthraquinone-2-sulfonic acid, and anthraquinone could accelerate decolorization even if a small amount (0.2 mM) was applied. On the other hand, a high concentration of redox mediator (1.0 mM) had an inhibitory effect on decolorization especially under thermophilic conditions. In addition, the decolorization of dye was accelerated by increasing treatment temperature, as shown in biotic treatments. Based on these results, increasing the treatment temperature could be used to improve the decolorizing process of textile dye wastewater treatment, especially for recalcitrant dyes such as anthraquinone.

  10. C/EBPβ is a transcriptional key regulator of IL-36α in murine macrophages.

    Science.gov (United States)

    Nerlich, Andreas; Ruangkiattikul, Nanthapon; Laarmann, Kristin; Janze, Nina; Dittrich-Breiholz, Oliver; Kracht, Michael; Goethe, Ralph

    2015-08-01

    Interleukin (IL)-36α - one of the novel members of the IL-1 family of cytokines - is a potent regulator of dendritic and T cells and plays an important role in inflammatory processes like experimental skin inflammation in mice and in mouse models for human psoriasis. Here, we demonstrate that C/EBPβ, a transcription factor required for the selective expression of inflammatory genes, is a key activator of the Il36A gene in murine macrophages. RNAi-mediated suppression of C/EBPβ expression in macrophages (C/EBPβ(low) cells) significantly impaired Il36A gene induction following challenge with LPS. Despite the presence of five predicted C/EBP binding sites, luciferase reporter assays demonstrated that C/EBPβ confers responsiveness to LPS primarily through a half-CRE•C/EBP element in the proximal Il36A promoter. Electrophoretic mobility shift assays showed that C/EBPβ but not CREB proteins interact with this critical half-CRE•C/EBP element. In addition, overexpression of C/EBPβ in C/EBPβ(low) cells enhanced the expression of Il36A whereas CREB-1 had no effect. Finally, chromatin immunoprecipitation confirmed that C/EBPβ but neither CREB-1, ATF-2 nor ATF4 is directly recruited to the proximal promoter region of the Il36A gene. Together, these findings demonstrate an essential role of C/EBPβ in the regulation of the Il36A gene via the proximal half-CRE•C/EBP element in response to inflammatory stimuli.

  11. Self-regulated learning: A key learning effect of feedback in a ...

    African Journals Online (AJOL)

    Self-regulated learning: A key learning effect of feedback in a problem-based learning context. ... Small-group student tutorials are a major component of PBL. ... qualitative study in which individual interviews and focus group discussions were ...

  12. The CD10 enzyme is a key player to identify and regulate human mammary stem cells.

    Science.gov (United States)

    Bachelard-Cascales, Elodie; Chapellier, Marion; Delay, Emmanuel; Pochon, Gaetan; Voeltzel, Thibault; Puisieux, Alain; Caron de Fromentel, Claude; Maguer-Satta, Véronique

    2010-06-01

    The major components of the mammary ductal tree are an inner layer of luminal cells, an outer layer of myoepithelial cells, and a basement membrane that separates the ducts from the underlying stroma. Cells in the outer layer express CD10, a zinc-dependent metalloprotease that regulates the growth of the ductal tree during mammary gland development. To define the steps in the human mammary lineage at which CD10 acts, we have developed an in vitro assay for human mammary lineage progression. We show that sorting for CD10 and EpCAM cleanly separates progenitors from differentiated luminal cells and that the CD10-high EpCAM-low population is enriched for early common progenitor and mammosphere-forming cells. We also show that sorting for CD10 enriches sphere-forming cells from other tissue types, suggesting that it may provide a simple tool to identify stem or progenitor populations in tissues for which lineage studies are not currently possible. We demonstrate that the protease activity of CD10 and the adhesion function of beta1-integrin are required to prevent differentiation of mammary progenitors. Taken together, our data suggest that integrin-mediated contact with the basement membrane and cleavage of signaling factors by CD10 are key elements in the niche that maintains the progenitor and stem cell pools in the mammary lineage.

  13. Key Factors Influencing Rapid Development of Potentially Dune-Stabilizing Moss-Dominated Crusts.

    Science.gov (United States)

    Bu, Chongfeng; Zhang, Kankan; Zhang, Chunyun; Wu, Shufang

    2015-01-01

    Biological soil crusts (BSCs) are a widespread photosynthetic ground cover in arid and semiarid areas. They have many positive ecological functions, such as increasing soil stability, and reducing water and wind erosion. Using artificial technology to achieve the rapid development of BSCs is expected to become a low-cost and highly beneficial ecological restoration measure. In the present study, typical moss-dominated crusts in a region characterized by mobile dunes (Mu Us Sandland, China) were collected, and a 40-day cultivation experiment was performed to investigate key factors, including watering frequency, light intensity and a nutrient addition, which affect the rapid development of moss crusts and their optimal combination. The results demonstrated that watering frequency and illumination had a significant positive effect (P=0.049, three-factor ANOVA) and a highly significant, complicated effect (P=0.000, three-factor ANOVA), respectively, on the plant density of bryophytes, and a highly significant positive effect on the chlorophyll a and exopolysaccharide contents (P=0.000, P=0.000; P=0.000, P=0.000; one-way ANOVA). Knop nutrient solution did not have a significant positive but rather negative effect on the promotion of moss-dominated crust development (P=0.270, three-factor ANOVA). Moss-dominated crusts treated with the combination of moderate-intensity light (6,000 lx) + high watering frequency (1 watering/2 days) - Knop had the highest moss plant densities, while the treatment with high-intensity light (12,000 lx) + high watering frequency (1 watering/2 days) + Knop nutrient solution had higher chlorophyll a contents than that under other treatments. It is entirely feasible to achieve the rapid development of moss crusts under laboratory conditions by regulating key factors and creating the right environment. Future applications may seek to use cultured bryophytes to control erosion in vulnerable areas with urgent needs.

  14. Key Factors Influencing Rapid Development of Potentially Dune-Stabilizing Moss-Dominated Crusts.

    Directory of Open Access Journals (Sweden)

    Chongfeng Bu

    Full Text Available Biological soil crusts (BSCs are a widespread photosynthetic ground cover in arid and semiarid areas. They have many positive ecological functions, such as increasing soil stability, and reducing water and wind erosion. Using artificial technology to achieve the rapid development of BSCs is expected to become a low-cost and highly beneficial ecological restoration measure. In the present study, typical moss-dominated crusts in a region characterized by mobile dunes (Mu Us Sandland, China were collected, and a 40-day cultivation experiment was performed to investigate key factors, including watering frequency, light intensity and a nutrient addition, which affect the rapid development of moss crusts and their optimal combination. The results demonstrated that watering frequency and illumination had a significant positive effect (P=0.049, three-factor ANOVA and a highly significant, complicated effect (P=0.000, three-factor ANOVA, respectively, on the plant density of bryophytes, and a highly significant positive effect on the chlorophyll a and exopolysaccharide contents (P=0.000, P=0.000; P=0.000, P=0.000; one-way ANOVA. Knop nutrient solution did not have a significant positive but rather negative effect on the promotion of moss-dominated crust development (P=0.270, three-factor ANOVA. Moss-dominated crusts treated with the combination of moderate-intensity light (6,000 lx + high watering frequency (1 watering/2 days - Knop had the highest moss plant densities, while the treatment with high-intensity light (12,000 lx + high watering frequency (1 watering/2 days + Knop nutrient solution had higher chlorophyll a contents than that under other treatments. It is entirely feasible to achieve the rapid development of moss crusts under laboratory conditions by regulating key factors and creating the right environment. Future applications may seek to use cultured bryophytes to control erosion in vulnerable areas with urgent needs.

  15. SUSTAINABLE INSURANCE AS A KEY FACTOR OF SUSTAINABLE DEVELOPMENT SUPPORT

    Directory of Open Access Journals (Sweden)

    L. Volokhova

    2015-04-01

    Full Text Available The role of the insurance sector in the sustainability development support was determined and the possible measures of economic and social loss reduction, based on risk management, risk transfer, and sustainable investment, were proposed. A crucial necessity of the community resilience improvement and cooperation with other stakeholders was indicated. Sustainable insurance sector plays a determinant role in the process of sustainable development as it possess vital leverages to enable and facilitate community resilience, and, therefore, to reduce the possible loss from Economic, Social and Governance issues (ESG issues. First of all, this could be achieved by the means of proper risk management, namely risk assessment and risk reduction. Second, risk transfer will help communities to cope with actual damage made and cover the loss. Finally, sustainable investment activity may be used to make sure that business sector respects the key principles of sustainable development in its day-to-day activity. Cooperation with all the stakeholders of sustainable development, especially governments and communities, will help to develop a better expertize of risk management and create more effective tools for risk reduction. Implementing principles of sustainable investment into the core of their business values, insurance companies are likely to enjoy the improvement of their image and status, higher quality of their investment portfolio, and smaller refund sums payed on claims.

  16. THE MANAGEMENT OF KNOWLEDGE WORKERS – KEY FACTOR OF SUCCES

    Directory of Open Access Journals (Sweden)

    Claudia-Elena ŢUCLEA

    2007-01-01

    Full Text Available The traditional companies are built on familiar bedrock of buildings, plants, and inventories. Competitive advantage is viewed in terms of scale and volume stemming from high-capacity use of machine-based factories. Such an approach fails to recognize how the leverage of knowledge is becoming a key to long-term success. Nowadays, organizations must recognize that power resides in the minds of their best people, who are diffused throughout the business and the organizations are becoming more dependent on people than ever before. The recruitment and the employment of knowledge workers are becoming very important issues from Romanian managers. The competitiveness is the only chance to deal with a very challenging market, especially after European integration. In this paper we present the results of a survey of the opinions of Romanian managers about the most effective strategies for recruitment, motivation and retention the knowledge workers. The study investigated two groups of managers: the first group included the managers who never were involved in activities related to human resources, and the second, the managers who have been involved. The managers from the first group chose theoretical the strategies they considered most effective; the managers for the second group indicated the strategies they applied.

  17. Key biogeochemical factors affecting soil carbon storage in Posidonia meadows

    KAUST Repository

    Serrano, Oscar

    2016-08-15

    Biotic and abiotic factors influence the accumulation of organic carbon (C-org) in seagrass ecosystems. We surveyed Posidonia sinuosa meadows growing in different water depths to assess the variability in the sources, stocks and accumulation rates of Corg. We show that over the last 500 years, P. sinuosa meadows closer to the upper limit of distribution (at 2-4 m depth) accumulated 3- to 4-fold higher C-org stocks (averaging 6.3 kg C-org m(-2) at 3- to 4-fold higher rates (12.8 gC(org) m(-2) yr(-1) ) compared to meadows closer to the deep limits of distribution (at 6-8 m depth; 1.8 kg C-org m(-2) and 3.6 g C-org m(-2) yr(-1) . In shallower meadows, C-org stocks were mostly derived from seagrass detritus (88% in average) compared to meadows closer to the deep limit of distribution (45% on average). In addition, soil accumulation rates and fine-grained sediment content (< 0.125 mm) in shallower meadows (2.0 mm yr(-1) and 9 %, respectively) were approximately 2-fold higher than in deeper meadows (1.2 mm yr(-1) and 5 %, respectively). The C-org stocks and accumulation rates accumulated over the last 500 years in bare sediments (0.6 kg C-org m(-2) and 1.2 g C-org m(-2) yr(-1)were 3- to 11-fold lower than in P. sinuosa meadows, while fine-grained sediment content (1 %) and seagrass detritus contribution to the Corg pool (20 %) were 8- and 3-fold lower than in Posidonia meadows, respectively. The patterns found support the hypothesis that Corg storage in seagrass soils is influenced by interactions of biological (e.g., meadow productivity, cover and density), chemical (e.g., recalcitrance of Corg stocks) and physical (e.g., hydrodynamic energy and soil accumulation rates) factors within the meadow. We conclude that there is a need to improve global estimates of seagrass carbon storage accounting for biogeochemical factors driving variability within habitats.

  18. Enzymatic biodiesel synthesis. Key factors affecting efficiency of the process

    Energy Technology Data Exchange (ETDEWEB)

    Szczesna Antczak, Miroslawa; Kubiak, Aneta; Antczak, Tadeusz; Bielecki, Stanislaw [Institute of Technical Biochemistry, Faculty of Biotechnology and Food Sciences, Technical University of Lodz, Stefanowskiego 4/10, 90-924 Lodz (Poland)

    2009-05-15

    Chemical processes of biodiesel production are energy-consuming and generate undesirable by-products such as soaps and polymeric pigments that retard separation of pure methyl or ethyl esters of fatty acids from glycerol and di- and monoacylglycerols. Enzymatic, lipase-catalyzed biodiesel synthesis has no such drawbacks. Comprehension of the latter process and an appreciable progress in production of robust preparations of lipases may soon result in the replacement of chemical catalysts with enzymes in biodiesel synthesis. Engineering of enzymatic biodiesel synthesis processes requires optimization of such factors as: molar ratio of substrates (triacylglycerols: alcohol), temperature, type of organic solvent (if any) and water activity. All of them are correlated with properties of lipase preparation. This paper reports on the interplay between the crucial parameters of the lipase-catalyzed reactions carried out in non-aqueous systems and the yield of biodiesel synthesis. (author)

  19. Clinician acceptance is the key factor for sustainable telehealth services.

    Science.gov (United States)

    Wade, Victoria A; Eliott, Jaklin A; Hiller, Janet E

    2014-05-01

    Telehealth, the delivery of health care services at a distance using information and communications technology, has been slow to be adopted and difficult to sustain. Researchers developing theories concerning the introduction of complex change into health care usually take a multifactorial approach; we intentionally sought a single point of intervention that would have maximum impact on implementation. We conducted a qualitative interview study of 36 Australian telehealth services, sampled for maximum variation, and used grounded theory methods to develop a model from which we chose the most important factor affecting the success of telehealth. We propose that clinician acceptance explains much of the variation in the uptake, expansion, and sustainability of Australian telehealth services, and that clinician acceptance could, in most circumstances, overcome low demand, technology problems, workforce pressure, and lack of resourcing. We conclude that our model offers practical advice to those seeking to implement change with limited resources.

  20. Etiology of obesity: two "key issues" and other emerging factors

    Directory of Open Access Journals (Sweden)

    Lluis Serra-Majem

    2013-09-01

    Full Text Available The current obesity epidemic is known to have coincided with profound societal changes involving both physical activity levels and food consumption patterns as well as demographic and cultural changes affecting the conduct of human beings in various ways. On the other hand, obesity is a complex and multifactorial chronic disease that usually becomes manifest in childhood and adolescence. Its origin is a genetic and environmental interchange, of which environmental or behavioral factors play the most important role, stemming from an imbalance between energy intake and expenditure. Still and all, it is rather simplistic to assume that obesity is only due to excessive consumption and/or deficient physical activity levels. Currently, various lines of investigation have been initiated that evaluate the determinants of obesity, of which nutrigenomics and gut microbiota deserve special attention.

  1. UNIVERSITIES AND INCUBATORS: KEY FACTORS DRIVING ENTREPRENEURSHIP AND SOCIOECONOMIC DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    Liane Mahlmann Kipper

    2014-12-01

    Full Text Available Economic diversification is an utterly important factor for regions that are directly or indirectly related to any productive mechanisms and seek to strengthen their foundations for the generation of jobs and income. Within this context, to invest in business preparation and maturation, especially in the ones related to the technological area, turns out to be an interesting mean of diversifying a regional economy that is facing the risk of stagnation. This study considers the importance of the role taken on by universities and their incubators in driving entrepreneurship and supporting the creation of new companies and the innovative capacity of a country through knowledge transfer amongst universities and companies, generating benefits and socioeconomic progress in a country. It also conducts a case study on a company of the information technology area, recently incubated and whose major objective consists in becoming part of this economic diversification basis.

  2. 6-Gingerol Protects against Nutritional Steatohepatitis by Regulating Key Genes Related to Inflammation and Lipid Metabolism

    Directory of Open Access Journals (Sweden)

    Thing-Fong Tzeng

    2015-02-01

    Full Text Available Non-alcoholic fatty liver disease, including non-alcoholic steatohepatitis (NASH, appears to be increasingly common worldwide. The aim of the study was to investigate the effects of 6-gingerol ((S-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl-3-decanone, a bioactive ingredient of plants belonging to the Zingiberaceae family, on experimental models of NASH. In HepG2 cells, 6-gingerol (100 μmol/L treatment inhibited free fatty acids mixture (0.33 mmol/L palmitate and 0.66 mmol/L oleate-induced triglyceride and inflammatory marker accumulations. Male C57BL/6 mice were fed with a methionine and choline-deficient (MCD diet to induce steatohepatitis. After four weeks of MCD diet feeding, the mice were dosed orally with 6-gingerol (25, 50 or 100 mg/kg/day once daily for another four weeks. 6-Gingerol (100 mg/kg/day attenuated liver steatosis and necro-inflammation in MCD diet-fed mice. The expressions of inflammatory cytokine genes, including those for monocyte chemoattractant protein-1, tumor necrosis factor-α, and interleukin-6, and nuclear transcription factor (NF-κB, which were increased in the livers of MCD diet-fed mice, were attenuated by 6-gingerol. 6-Gingerol possesses a repressive property on hepatic steatosis, which is associated with induction of peroxisome proliferator-activated receptor α. Our study demonstrated the protective role of 6-gingerol in ameliorating nutritional steatohepatitis. The effect was mediated through regulating key genes related to lipid metabolism and inflammation.

  3. Fructose: A Key Factor in the Development of Metabolic Syndrome and Hypertension

    Directory of Open Access Journals (Sweden)

    Zeid Khitan

    2013-01-01

    Full Text Available Diabetes mellitus and the metabolic syndrome are becoming leading causes of death in the world. Identifying the etiology of diabetes is key to prevention. Despite the similarity in their structures, fructose and glucose are metabolized in different ways. Uric acid, a byproduct of uncontrolled fructose metabolism is known risk factor for hypertension. In the liver, fructose bypasses the two highly regulated steps in glycolysis, glucokinase and phosphofructokinase, both of which are inhibited by increasing concentrations of their byproducts. Fructose is metabolized by fructokinase (KHK. KHK has no negative feedback system, and ATP is used for phosphorylation. This results in intracellular phosphate depletion and the rapid generation of uric acid due to activation of AMP deaminase. Uric acid, a byproduct of this reaction, has been linked to endothelial dysfunction, insulin resistance, and hypertension. We present possible mechanisms by which fructose causes insulin resistance and suggest actions based on this association that have therapeutic implications.

  4. Risk factor control is key in diabetic nephropathy.

    Science.gov (United States)

    Lewis, Gareth; Maxwell, Alexander P

    2014-02-01

    Prolonged duration of diabetes, poor glycaemic control and hypertension are major risk factors for both diabetic nephropathy and cardiovascular disease. Optimising blood sugar control together with excellent control of blood pressure can reduce the risk of developing diabetic nephropathy. Diabetic nephropathy should be considered in any patient with diabetes when persistent albuminuria develops. Microalbuminuria is the earliest clinically detectable indicator of diabetic nephropathy risk. The majority of patients with diabetic nephropathy are appropriately diagnosed based on elevated urinary albumin excretion and/or reduced 0032-6518 renal function. Patients with type 2 diabetes should have annual urinary ACR measurements from the time of diabetes diagnosis while those with type 1 diabetes should commence five years after diagnosis. Blood pressure lowering to 130/80mmHg and reduction of proteinuria to diabetic nephropathy and reduces the number of cardiovascular events. Drugs that block the renin-angiotensin-aldosterone system (RAAS) are effective in reducing proteinuria, managing hypertension and reducing cardiovascular risk. Unless there are clear contraindications or intolerance all patients with diabetic nephropathy should be prescribed an ACEI or ARB. Stopping an ACEI or ARB during intercurrent illness or times of volume depletion is critically important. Patients with diabetic nephropathy should have at least yearly measurements of blood pressure, renal function and urinary ACR.

  5. Key factors influencing the implementation success of a home telecare application.

    NARCIS (Netherlands)

    Postema, T.R.F.; Peeters, J.M.; Freide, R.D.

    2012-01-01

    Rationale The introduction of home telecare in healthcare organizations has shown mixed results in practice. The aim of this study is to arrive at a set of key factors that can be used in further implementation of video communication. We argue that key factors are mainly found in the organizational

  6. Key Factors Contributing The Succes of Informal Sector Business Owners In Makssar

    OpenAIRE

    Rahman, Abdul

    2013-01-01

    - The purposess of this research are to investigate the key factors contributed to the informal sector businesses success how the key factors formed and how unique the key factaors contributed to daily profit The researh was undertaken in Makassar City South Sulawesi Indonesia by asking 450 respondent using listed indicators mentioned in questionmaires observasing the informal sector bussiness in several street in Makassar and asking the participants to list the importan indicators which a...

  7. The transcription factor NFATp plays a key role in susceptibility to TB in mice.

    Directory of Open Access Journals (Sweden)

    Laura E Via

    Full Text Available In T cells, the transcription factor nuclear factor of activated T cells p (NFATp is a key regulator of the cytokine genes tumor necrosis factor (TNF and interferon-γ (IFN-γ. Here, we show that NFATp-deficient (NFATp(-/- mice have a dramatic and highly significant increase in mortality after Mycobacterium tuberculosis (MTb infection as compared to mortality of control animals after MTb infection. Animals deficient in NFATp have significantly impaired levels of TNF and IFN-γ transcription and protein expression in naïve or total CD4(+ T cells, but display wild-type levels of TNF mRNA or protein from MTb-stimulated dendritic cells (DC. The rapid mortality and disease severity observed in MTb-infected NFATp(-/- mice is associated with dysregulated production of TNF and IFN-γ in the lungs, as well as with increased levels of TNF, in their serum. Furthermore, global blocking of TNF production by injection of a TNF neutralizaing agent at 6 weeks, but not 12 weeks, post-MTb-infection further decreased the survival rate of both wild-type and NFATp(-/- mice, indicating an early role for TNF derived from cells from the monocyte lineage in containment of infection. These results thus demonstrate that NFATp plays a critical role in immune containment of TB disease in vivo, through the NFATp-dependent expression of TNF and IFN-γ in T cells.

  8. Adaptive Content and Process Scaffolding: A key to facilitating students’ self-regulated learning with hypermedia

    Directory of Open Access Journals (Sweden)

    Roger Azevedo

    2011-03-01

    Full Text Available In this mixed-method study, we converged product and process data to examine the effectiveness of three human scaffolding conditions in facilitating students’ learning about the circulatory system and the deployment of key self-regulatory processes during a 40-minute hypermedia learning task. Undergraduate students (N = 123 were randomly assigned to one of three scaffolding conditions (adaptive content and process scaffolding [ACPS], adaptive process scaffolding [APS], and no scaffolding [NS] and were trained to use a hypermedia environment to learn about the circulatory system. The product data revealed that the students in the ACPS condition gained significantly more declarative knowledge than did those in the other two comparison conditions. In addition, ACPS was statistically significantly associated with qualitative shifts in the students’ mental models of the topic, whereas the other two conditions were not. The verbal protocol data revealed that students in the ACPS condition utilized only a few regulatory processes, engaged in help-seeking behavior, and relied on the tutor to regulate their learning. By contrast, the verbal protocol data indicated that learners in the APS condition regulated their learning by using several key monitoring activities and learning strategies, while those in the NS condition were less effective at regulating their learning and used fewer key self-regulatory processes during the activity. We propose several design principles for adaptive hypermedia learning environments based on these findings.

  9. 7α-Hydroxypregnenolone, a new key regulator of amphibian locomotion: discovery, progress and prospect.

    Science.gov (United States)

    Tsutsui, Kazuyoshi; Haraguchi, Shogo; Matsunaga, Masahiro; Koyama, Teppei; Do Rego, Jean-Luc; Vaudry, Hubert

    2012-05-01

    Seasonally-breeding amphibians have served as excellent animal models to investigate the biosynthesis and biological actions of neurosteroids. Previous studies have demonstrated that the brain of amphibians possesses key steroidogenic enzymes and produces pregnenolone, a precursor of steroid hormones, and other various neurosteroids. We recently found that the brain of seasonally-breeding newts actively produces 7α-hydroxypregnenolone, a previously undescribed amphibian neurosteroid. This novel amphibian neurosteroid acts as a neuronal modulator to stimulate locomotor activity in newts. Subsequently, the mode of action of 7α-hydroxypregnenolone has been demonstrated in the newt brain. 7α-Hydroxypregnenolone stimulates locomotor activity through activation of the dopaminergic system. To understand the functional significance of 7α-hydroxypregnenolone in the regulation of locomotor activity, diurnal and seasonal changes in synthesis of 7α-hydroxypregnenolone have also been demonstrated in the newt brain. Melatonin derived from the pineal gland and eyes regulates 7α-hydroxypregnenolone synthesis in the brain, thus inducing diurnal locomotor changes. Prolactin, an adenohypophyseal hormone, regulates 7α-hydroxypregnenolone synthesis in the brain, and also induces seasonal locomotor changes. In addition, 7α-hydroxypregnenolone mediates corticosterone action to increase locomotor activity under stress. This review summarizes the discovery, progress and prospect of 7α-hydroxypregnenolone, a new key regulator of amphibian locomotion.

  10. MicroRNAs: Key Regulators in the Central Nervous System and Their Implication in Neurological Diseases

    Directory of Open Access Journals (Sweden)

    Dan-Dan Cao

    2016-05-01

    Full Text Available MicroRNAs (miRNAs are a class of small, well-conserved noncoding RNAs that regulate gene expression post-transcriptionally. They have been demonstrated to regulate a lot of biological pathways and cellular functions. Many miRNAs are dynamically regulated during central nervous system (CNS development and are spatially expressed in adult brain indicating their essential roles in neural development and function. In addition, accumulating evidence strongly suggests that dysfunction of miRNAs contributes to neurological diseases. These observations, together with their gene regulation property, implicated miRNAs to be the key regulators in the complex genetic network of the CNS. In this review, we first focus on the ways through which miRNAs exert the regulatory function and how miRNAs are regulated in the CNS. We then summarize recent findings that highlight the versatile roles of miRNAs in normal CNS physiology and their association with several types of neurological diseases. Subsequently we discuss the limitations of miRNAs research based on current studies as well as the potential therapeutic applications and challenges of miRNAs in neurological disorders. We endeavor to provide an updated description of the regulatory roles of miRNAs in normal CNS functions and pathogenesis of neurological diseases.

  11. MicroRNAs: Key Regulators in the Central Nervous System and Their Implication in Neurological Diseases.

    Science.gov (United States)

    Cao, Dan-Dan; Li, Lu; Chan, Wai-Yee

    2016-05-28

    MicroRNAs (miRNAs) are a class of small, well-conserved noncoding RNAs that regulate gene expression post-transcriptionally. They have been demonstrated to regulate a lot of biological pathways and cellular functions. Many miRNAs are dynamically regulated during central nervous system (CNS) development and are spatially expressed in adult brain indicating their essential roles in neural development and function. In addition, accumulating evidence strongly suggests that dysfunction of miRNAs contributes to neurological diseases. These observations, together with their gene regulation property, implicated miRNAs to be the key regulators in the complex genetic network of the CNS. In this review, we first focus on the ways through which miRNAs exert the regulatory function and how miRNAs are regulated in the CNS. We then summarize recent findings that highlight the versatile roles of miRNAs in normal CNS physiology and their association with several types of neurological diseases. Subsequently we discuss the limitations of miRNAs research based on current studies as well as the potential therapeutic applications and challenges of miRNAs in neurological disorders. We endeavor to provide an updated description of the regulatory roles of miRNAs in normal CNS functions and pathogenesis of neurological diseases.

  12. Tumor necrosis factor receptor-associated factor 3 is a positive regulator of pathological cardiac hypertrophy.

    Science.gov (United States)

    Jiang, Xi; Deng, Ke-Qiong; Luo, Yuxuan; Jiang, Ding-Sheng; Gao, Lu; Zhang, Xiao-Fei; Zhang, Peng; Zhao, Guang-Nian; Zhu, Xueyong; Li, Hongliang

    2015-08-01

    Cardiac hypertrophy, a common early symptom of heart failure, is regulated by numerous signaling pathways. Here, we identified tumor necrosis factor receptor-associated factor 3 (TRAF3), an adaptor protein in tumor necrosis factor-related signaling cascades, as a key regulator of cardiac hypertrophy in response to pressure overload. TRAF3 expression was upregulated in hypertrophied mice hearts and failing human hearts. Four weeks after aortic banding, cardiac-specific conditional TRAF3-knockout mice exhibited significantly reduced cardiac hypertrophy, fibrosis, and dysfunction. Conversely, transgenic mice overexpressing TRAF3 in the heart developed exaggerated cardiac hypertrophy in response to pressure overload. TRAF3 also promoted an angiotensin II- or phenylephrine-induced hypertrophic response in isolated cardiomyocytes. Mechanistically, TRAF3 directly bound to TANK-binding kinase 1 (TBK1), causing increased TBK1 phosphorylation in response to hypertrophic stimuli. This interaction between TRAF3 and TBK1 further activated AKT signaling, which ultimately promoted the development of cardiac hypertrophy. Our findings not only reveal a key role of TRAF3 in regulating the hypertrophic response but also uncover TRAF3-TBK1-AKT as a novel signaling pathway in the development of cardiac hypertrophy and heart failure. This pathway may represent a potential therapeutic target for this pathological process.

  13. The STARS signaling pathway: a key regulator of skeletal muscle function.

    Science.gov (United States)

    Lamon, Séverine; Wallace, Marita A; Russell, Aaron P

    2014-09-01

    During the last decade, the striated muscle activator of Rho signaling (STARS), a muscle-specific protein, has been proposed to play an increasingly important role in skeletal muscle growth, metabolism, regeneration and stress adaptation. STARS influences actin dynamics and, as a consequence, regulates the myocardin-related transcription factor A/serum response factor (MRTF-A/SRF) transcriptional program, a well-known pathway controlling skeletal muscle development and function. Muscle-specific stress conditions, such as exercise, positively regulates, while disuse and degenerative muscle diseases are associated with a downregulation of STARS and its downstream partners, suggesting a pivotal role for STARS in skeletal muscle health. This review provides a comprehensive overview of the known role and regulation of STARS and the members of its signaling pathway, RhoA, MRTF-A and SRF, in skeletal muscle.

  14. Regulation of translesion DNA synthesis: Posttranslational modification of lysine residues in key proteins.

    Science.gov (United States)

    McIntyre, Justyna; Woodgate, Roger

    2015-05-01

    Posttranslational modification of proteins often controls various aspects of their cellular function. Indeed, over the past decade or so, it has been discovered that posttranslational modification of lysine residues plays a major role in regulating translesion DNA synthesis (TLS) and perhaps the most appreciated lysine modification is that of ubiquitination. Much of the recent interest in ubiquitination stems from the fact that proliferating cell nuclear antigen (PCNA) was previously shown to be specifically ubiquitinated at K164 and that such ubiquitination plays a key role in regulating TLS. In addition, TLS polymerases themselves are now known to be ubiquitinated. In the case of human polymerase η, ubiquitination at four lysine residues in its C-terminus appears to regulate its ability to interact with PCNA and modulate TLS. Within the past few years, advances in global proteomic research have revealed that many proteins involved in TLS are, in fact, subject to a previously underappreciated number of lysine modifications. In this review, we will summarize the known lysine modifications of several key proteins involved in TLS; PCNA and Y-family polymerases η, ι, κ and Rev1 and we will discuss the potential regulatory effects of such modification in controlling TLS in vivo.

  15. Regulation of antimicrobial resistance by extracytoplasmic function (ECF) sigma factors.

    Science.gov (United States)

    Woods, Emily C; McBride, Shonna M

    2017-01-30

    Extracytoplasmic function (ECF) sigma factors are a subfamily of σ(70) sigma factors that activate genes involved in stress-response functions. In many bacteria, ECF sigma factors regulate resistance to antimicrobial compounds. This review will summarize the ECF sigma factors that regulate antimicrobial resistance in model organisms and clinically relevant pathogens.

  16. Regulation of Memory Formation by the Transcription Factor XBP1.

    Science.gov (United States)

    Martínez, Gabriela; Vidal, René L; Mardones, Pablo; Serrano, Felipe G; Ardiles, Alvaro O; Wirth, Craig; Valdés, Pamela; Thielen, Peter; Schneider, Bernard L; Kerr, Bredford; Valdés, Jose L; Palacios, Adrian G; Inestrosa, Nibaldo C; Glimcher, Laurie H; Hetz, Claudio

    2016-02-16

    Contextual memory formation relies on the induction of new genes in the hippocampus. A polymorphism in the promoter of the transcription factor XBP1 was identified as a risk factor for Alzheimer's disease and bipolar disorders. XBP1 is a major regulator of the unfolded protein response (UPR), mediating adaptation to endoplasmic reticulum (ER) stress. Using a phenotypic screen, we uncovered an unexpected function of XBP1 in cognition and behavior. Mice lacking XBP1 in the nervous system showed specific impairment of contextual memory formation and long-term potentiation (LTP), whereas neuronal XBP1s overexpression improved performance in memory tasks. Gene expression analysis revealed that XBP1 regulates a group of memory-related genes, highlighting brain-derived neurotrophic factor (BDNF), a key component in memory consolidation. Overexpression of BDNF in the hippocampus reversed the XBP1-deficient phenotype. Our study revealed an unanticipated function of XBP1 in cognitive processes that is apparently unrelated to its role in ER stress. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  17. Regulation of Memory Formation by the Transcription Factor XBP1

    Directory of Open Access Journals (Sweden)

    Gabriela Martínez

    2016-02-01

    Full Text Available Contextual memory formation relies on the induction of new genes in the hippocampus. A polymorphism in the promoter of the transcription factor XBP1 was identified as a risk factor for Alzheimer’s disease and bipolar disorders. XBP1 is a major regulator of the unfolded protein response (UPR, mediating adaptation to endoplasmic reticulum (ER stress. Using a phenotypic screen, we uncovered an unexpected function of XBP1 in cognition and behavior. Mice lacking XBP1 in the nervous system showed specific impairment of contextual memory formation and long-term potentiation (LTP, whereas neuronal XBP1s overexpression improved performance in memory tasks. Gene expression analysis revealed that XBP1 regulates a group of memory-related genes, highlighting brain-derived neurotrophic factor (BDNF, a key component in memory consolidation. Overexpression of BDNF in the hippocampus reversed the XBP1-deficient phenotype. Our study revealed an unanticipated function of XBP1 in cognitive processes that is apparently unrelated to its role in ER stress.

  18. Fibroblast growth factor signaling in metabolic regulation

    Directory of Open Access Journals (Sweden)

    Vera eNies

    2016-01-01

    Full Text Available The prevalence of obesity is a growing health problem. Obesity is strongly associated with several comorbidities, such as non-alcoholic fatty liver disease, certain cancers, insulin resistance and type 2 diabetes, which all reduce life expectancy and life quality. Several drugs have been put forward in order to treat these diseases, but many of them have detrimental side effects. The unexpected role of the family of fibroblast growth factors in the regulation of energy metabolism provides new approaches to the treatment of metabolic diseases, and offers a valuable tool to gain more insight into metabolic regulation. The known beneficial effects of FGF19 and FGF21 on metabolism, together with recently discovered similar effects of FGF1 suggest that FGFs and their derivatives carry great potential as novel therapeutics to treat metabolic conditions. To facilitate the development of new therapies with improved targeting and minimal side effects, a better understanding of the molecular mechanism of action of FGFs is needed.In this review we will discuss what is currently known about the physiological roles of FGF signaling in tissues important for metabolic homeostasis. In addition, we will discuss current concepts regarding their pharmacological properties and effector tissues in the context of metabolic disease. Also the recent progress in the development of FGF variants will be reviewed. Our goal is to provide a comprehensive overview of the current concepts and consensuses regarding FGF signaling in metabolic health and disease, and to provide starting points for the development of FGF-based therapies against metabolic conditions.

  19. The histone variant macroH2A is an epigenetic regulator of key developmental genes

    DEFF Research Database (Denmark)

    Buschbeck, Marcus; Uribesalgo, Iris; Wibowo, Indra;

    2009-01-01

    variants at many genes encoding key regulators of development and cell fate decisions. On these genes, the presence of macroH2A1+2 is a repressive mark that overlaps locally and functionally with Polycomb repressive complex 2. We demonstrate that macroH2A1+2 contribute to the fine-tuning of temporal...... activation of HOXA cluster genes during neuronal differentiation. Furthermore, elimination of macroH2A2 function in zebrafish embryos produced severe but specific phenotypes. Taken together, our data demonstrate that macroH2A variants constitute an important epigenetic mark involved in the concerted...... regulation of gene expression programs during cellular differentiation and vertebrate development....

  20. A novel "complement-metabolism-inflammasome axis" as a key regulator of immune cell effector function.

    Science.gov (United States)

    Arbore, Giuseppina; Kemper, Claudia

    2016-07-01

    The inflammasomes are intracellular multiprotein complexes that induce and regulate the generation of the key pro-inflammatory cytokines IL-1β and IL-18 in response to infectious microbes and cellular stress. The activation of inflammasomes involves several upstream signals including classic pattern or danger recognition systems such as the TLRs. Recently, however, the activation of complement receptors, such as the anaphylatoxin C3a and C5a receptors and the complement regulator CD46, in conjunction with the sensing of cell metabolic changes, for instance increased amino acid influx and glycolysis (via mTORC1), have emerged as additional critical activators of the inflammasome. This review summarizes recent advances in our knowledge about complement-mediated inflammasome activation, with a specific focus on a novel "complement - metabolism - NLRP3 inflammasome axis."

  1. 78 FR 33221 - Special Local Regulation; Annual Swim Around Key West, Atlantic Ocean and Gulf of Mexico; Key...

    Science.gov (United States)

    2013-06-04

    ... on Cow Key Channel and West back to origin. Safety vessels will precede the first participating... environmental risk to health or risk to safety that might disproportionately affect children. 11. Indian Tribal... Coordination with Indian Tribal Governments, because it would not have a substantial direct effect on one or...

  2. Enhanced Two-Factor Authentication and Key Agreement Using Dynamic Identities in Wireless Sensor Networks

    Directory of Open Access Journals (Sweden)

    I-Pin Chang

    2015-11-01

    Full Text Available Key agreements that use only password authentication are convenient in communication networks, but these key agreement schemes often fail to resist possible attacks, and therefore provide poor security compared with some other authentication schemes. To increase security, many authentication and key agreement schemes use smartcard authentication in addition to passwords. Thus, two-factor authentication and key agreement schemes using smartcards and passwords are widely adopted in many applications. Vaidya et al. recently presented a two-factor authentication and key agreement scheme for wireless sensor networks (WSNs. Kim et al. observed that the Vaidya et al. scheme fails to resist gateway node bypassing and user impersonation attacks, and then proposed an improved scheme for WSNs. This study analyzes the weaknesses of the two-factor authentication and key agreement scheme of Kim et al., which include vulnerability to impersonation attacks, lost smartcard attacks and man-in-the-middle attacks, violation of session key security, and failure to protect user privacy. An efficient and secure authentication and key agreement scheme for WSNs based on the scheme of Kim et al. is then proposed. The proposed scheme not only solves the weaknesses of previous approaches, but also increases security requirements while maintaining low computational cost.

  3. Impact of Duty Hour Regulations on Medical Students’ Education: Views of Key Clinical Faculty

    Science.gov (United States)

    Levine, Rachel B.; Miller, Redonda G.; Ashar, Bimal H.; Bass, Eric B.; Rice, Tasha; Cofrancesco, Joseph

    2008-01-01

    BACKGROUND Teaching faculty have valuable perspectives on the impact of residency duty hour regulations on medical students. OBJECTIVE The objective of this study was to elicit faculty views on the impact of residency duty hour regulations on medical students’ educational experience on inpatient medicine rotations. DESIGN AND PARTICIPANTS We conducted a National Survey of Key Clinical Faculty (KCF) at 40 internal medicine residency programs affiliated with U.S. medical schools using a random sample stratified by National Institutes of Health funding and program size. MEASUREMENTS This study measures KCF opinions on the effect of duty hour regulations on students’ education. RESULTS Of 154 KCF targeted, 111 responded (72%). Fifty-two percent of KCF reported worsening in the overall quality of students’ education compared to just 2.7% reporting improvement (p < 0.001). In multivariate analysis adjusted for gender, academic rank, specialty, and years of teaching experience, faculty who spent ≥15 hours per week teaching were more likely to report worsening in medical students’ level of responsibility on inpatient teams [odds ratio (OR) 3.1; 95% confidence interval (CI) 1.3–7.6], ability to follow patients throughout hospitalization (OR 3.2; 95% CI 1.3–7.9), ability to develop working relationships with residents (OR 2.3; 95% CI 1.0–5.2), and the overall quality of students’ education (OR 3.3; 95% CI 1.4–8.1) compared to faculty who spent less time teaching. CONCLUSION Key clincal faculty report concerns about the impact of duty hour regulations on aspects of medical students’ education in internal medicine. Medical schools and residency programs should identify ways to ensure optimal educational experiences for students within duty hour requirements. PMID:18612749

  4. Dopamine is a key regulator in the signalling pathway underlying predator-induced defences in Daphnia.

    Science.gov (United States)

    Weiss, Linda C; Leese, Florian; Laforsch, Christian; Tollrian, Ralph

    2015-10-07

    The waterflea Daphnia is a model to investigate the genetic basis of phenotypic plasticity resulting from one differentially expressed genome. Daphnia develops adaptive phenotypes (e.g. morphological defences) thwarting predators, based on chemical predator cue perception. To understand the genomic basis of phenotypic plasticity, the description of the precedent cellular and neuronal mechanisms is fundamental. However, key regulators remain unknown. All neuronal and endocrine stimulants were able to modulate but not induce defences, indicating a pathway of interlinked steps. A candidate able to link neuronal with endocrine responses is the multi-functional amine dopamine. We here tested its involvement in trait formation in Daphnia pulex and Daphnia longicephala using an induction assay composed of predator cues combined with dopaminergic and cholinergic stimulants. The mere application of both stimulants was sufficient to induce morphological defences. We determined dopamine localization in cells found in close association with the defensive trait. These cells serve as centres controlling divergent morphologies. As a mitogen and sclerotization agent, we anticipate that dopamine is involved in proliferation and structural formation of morphological defences. Furthermore, dopamine pathways appear to be interconnected with endocrine pathways, and control juvenile hormone and ecdysone levels. In conclusion, dopamine is suggested as a key regulator of phenotypic plasticity. © 2015 The Author(s).

  5. Dynamics of the Transcriptome during Human Spermatogenesis: Predicting the Potential Key Genes Regulating Male Gametes Generation.

    Science.gov (United States)

    Zhu, Zijue; Li, Chong; Yang, Shi; Tian, Ruhui; Wang, Junlong; Yuan, Qingqing; Dong, Hui; He, Zuping; Wang, Shengyue; Li, Zheng

    2016-01-12

    Many infertile men are the victims of spermatogenesis disorder. However, conventional clinical test could not provide efficient information on the causes of spermatogenesis disorder and guide the doctor how to treat it. More effective diagnosis and treating methods could be developed if the key genes that regulate spermatogenesis were determined. Many works have been done on animal models, while there are few works on human beings due to the limited sample resources. In current work, testis tissues were obtained from 27 patients with obstructive azoospermia via surgery. The combination of Fluorescence Activated Cell Sorting and Magnetic Activated Cell Sorting was chosen as the efficient method to sort typical germ cells during spermatogenesis. RNA Sequencing was carried out to screen the change of transcriptomic profile of the germ cells during spermatogenesis. Differential expressed genes were clustered according to their expression patterns. Gene Ontology annotation, pathway analysis, and Gene Set Enrichment Analysis were carried out on genes with specific expression patterns and the potential key genes such as HOXs, JUN, SP1, and TCF3 which were involved in the regulation of spermatogenesis, with the potential value serve as molecular tools for clinical purpose, were predicted.

  6. Fibroblast Growth Factor 21 Mediates Glycemic Regulation by Hepatic JNK

    Directory of Open Access Journals (Sweden)

    Santiago Vernia

    2016-03-01

    Full Text Available The cJun NH2-terminal kinase (JNK-signaling pathway is implicated in metabolic syndrome, including dysregulated blood glucose concentration and insulin resistance. Fibroblast growth factor 21 (FGF21 is a target of the hepatic JNK-signaling pathway and may contribute to the regulation of glycemia. To test the role of FGF21, we established mice with selective ablation of the Fgf21 gene in hepatocytes. FGF21 deficiency in the liver caused marked loss of FGF21 protein circulating in the blood. Moreover, the protective effects of hepatic JNK deficiency to suppress metabolic syndrome in high-fat diet-fed mice were not observed in mice with hepatocyte-specific FGF21 deficiency, including reduced blood glucose concentration and reduced intolerance to glucose and insulin. Furthermore, we show that JNK contributes to the regulation of hepatic FGF21 expression during fasting/feeding cycles. These data demonstrate that the hepatokine FGF21 is a key mediator of JNK-regulated metabolic syndrome.

  7. Regulation of the fetal hemoglobin silencing factor BCL11A

    Science.gov (United States)

    Basak, Anindita; Sankaran, Vijay G.

    2016-01-01

    The clinical severity of sickle cell disease and β-thalassemia, the major disorders of β-globin, can be ameliorated by increased production of fetal hemoglobin (HbF). Here, we provide a brief overview of the fetal-to-adult hemoglobin switch that occurs in humans shortly after birth and review our current understanding of one of the most potent known regulators of this switching process, the multiple zinc finger–containing transcription factor BCL11A. Originally identified in genome-wide association studies, multiple orthogonal lines of evidence have validated BCL11A as a key regulator of hemoglobin switching and as a promising therapeutic target for HbF induction. We discuss recent studies that have highlighted its importance in silencing the HbF-encoding genes and discuss opportunities that exist to further understand the regulation of BCL11A and its mechanism of action, which could provide new insight into opportunities to induce HbF for therapeutic purposes. PMID:26963603

  8. STAT3 is a key transcriptional regulator of cancer stem cell marker CD133 in HCC

    Science.gov (United States)

    Ghoshal, Sarani; Fuchs, Bryan C.

    2016-01-01

    Cancer stem cell (CSC) marker CD133 was found to be upregulated in many cancers including hepatocellular carcinoma (HCC). However, the molecular mechanism of CD133 regulation in the liver tumor microenvironment has remained elusive. In this study Won and colleagues report that interleukin-6 (IL-6) mediated signal transducer and activator of transcription factor 3 (STAT3) signaling and hypoxia enhance the expression of CD133 and promote the progression of HCC. PMID:27275460

  9. Screening the key microRNAs and transcription factors in prostate cancer based on microRNA functional synergistic relationships.

    Science.gov (United States)

    Feng, Fan; Wu, Jitao; Gao, Zhenli; Yu, Shengqiang; Cui, Yuanshan

    2017-01-01

    Prostate cancer (PC) is a common neoplasm, and metastatic PC remains incurable. The study aims to screen key microRNAs (miRNAs) and transcription factors (TFs) involved in PC.The miRNA expression profile dataset (GSE45604) was downloaded from Gene Expression Omnibus database, including 50 PC and 10 normal specimens. Differentially expressed miRNAs (DEmiRNAs) were identified through limma package in R, and DEmiRNA-DEmiRNA co-regulation network was constructed based on the number of co-regulated target genes. Functional enrichment analysis of co-regulated target genes was performed using clusterProfiler package in R, and miRNA interactions sharing at least 1 functional term were used to construct a DEmiRNA-DEmiRNA functional synergistic network (MFSN). Based on Transcriptional Regulatory Element Database, cancer-related TFs which were co-regulated by DEmiRNAs were utilized to construct a DEmiRNA-TF regulation network.A total of 66 DEmiRNAs were identified, including 7 up-regulated miRNAs with 18,642 target genes and 59 down-regulated miRNAs with 130,694 target genes. Then, the DEmiRNA-DEmiRNA co-regulation network was constructed, including 66 DEmiRNAs and 2024 co-regulation relationships. In MFSN, hsa-miR-1184, hsa-miR-1207-5p, and hsa-miR-24 had significant functional synergistic relationships. The DEmiRNA-TF network contained 6 up-regulated DEmiRNAs and 4 of them were highlighted, as hsa-miR-1184, hsa-miR-1207-5p, hsa-miR-182, and hsa-miR-183. In subnetwork of the 4 miRNAs, peroxisome proliferative activated receptor, alpha (PPARA) and cyclic AMP-responsive element modulator (CREM) were the critical regulated TFs.Four up-regulated miRNAs (hsa-miR-1207-5p, hsa-miR-1184, hsa-miR-182, and hsa-miR-183) and 2 TFs (PPARA and CREM) were identified as key regulators in PC progression. The above 4 miRNAs might participate in PC progression by targeting PPARA and CREM.

  10. Screening the key microRNAs and transcription factors in prostate cancer based on microRNA functional synergistic relationships

    Science.gov (United States)

    Feng, Fan; Wu, Jitao; Gao, Zhenli; Yu, Shengqiang; Cui, Yuanshan

    2017-01-01

    Abstract Prostate cancer (PC) is a common neoplasm, and metastatic PC remains incurable. The study aims to screen key microRNAs (miRNAs) and transcription factors (TFs) involved in PC. The miRNA expression profile dataset (GSE45604) was downloaded from Gene Expression Omnibus database, including 50 PC and 10 normal specimens. Differentially expressed miRNAs (DEmiRNAs) were identified through limma package in R, and DEmiRNA–DEmiRNA co-regulation network was constructed based on the number of co-regulated target genes. Functional enrichment analysis of co-regulated target genes was performed using clusterProfiler package in R, and miRNA interactions sharing at least 1 functional term were used to construct a DEmiRNA–DEmiRNA functional synergistic network (MFSN). Based on Transcriptional Regulatory Element Database, cancer-related TFs which were co-regulated by DEmiRNAs were utilized to construct a DEmiRNA–TF regulation network. A total of 66 DEmiRNAs were identified, including 7 up-regulated miRNAs with 18,642 target genes and 59 down-regulated miRNAs with 130,694 target genes. Then, the DEmiRNA–DEmiRNA co-regulation network was constructed, including 66 DEmiRNAs and 2024 co-regulation relationships. In MFSN, hsa-miR-1184, hsa-miR-1207-5p, and hsa-miR-24 had significant functional synergistic relationships. The DEmiRNA–TF network contained 6 up-regulated DEmiRNAs and 4 of them were highlighted, as hsa-miR-1184, hsa-miR-1207-5p, hsa-miR-182, and hsa-miR-183. In subnetwork of the 4 miRNAs, peroxisome proliferative activated receptor, alpha (PPARA) and cyclic AMP-responsive element modulator (CREM) were the critical regulated TFs. Four up-regulated miRNAs (hsa-miR-1207-5p, hsa-miR-1184, hsa-miR-182, and hsa-miR-183) and 2 TFs (PPARA and CREM) were identified as key regulators in PC progression. The above 4 miRNAs might participate in PC progression by targeting PPARA and CREM. PMID:28072703

  11. The autoregulatory loop: A common mechanism of regulation of key sex determining genes in insects

    Indian Academy of Sciences (India)

    Suresh Kumar Kumar; Gajula Gopinath; Nagraj Sambrani; Kallare P Arunkumar

    2016-06-01

    Sex determination in most insects is structured as a gene cascade, wherein a primary signal is passed through a series of sex-determining genes, culminating in a downstream double-switch known as doublesex that decides the sexual fate of the embryo. From the literature available on sex determination cascades, it becomes apparent that sex determination mechanisms have evolved rapidly. The primary signal that provides the cue to determine the sex of the embryo varies remarkably, not only among taxa, but also within taxa. Furthermore, the upstream key gene in the cascade also varies between species and even among closely related species. The order Insecta alone provides examples of astoundingly complex diversity of upstream key genes in sex determination mechanisms. Besides, unlike key upstream genes, the downstream double-switch gene is alternatively spliced to form functional sex-specific isoforms. This sex-specific splicing is conserved across insect taxa. The genes involved in the sex determination cascade such as Sex-lethal (Sxl) in Drosophila melanogaster, transformer (tra) in many other dipterans, coleopterans and hymenopterans, Feminizer (fem) in Apis mellifera, and IGF-II mRNA-binding protein (Bmimp) in Bombyx mori are reported to be regulated by an autoregulatory positive feedback loop. In this review, by taking examples from various insects, we propose the hypothesis that autoregulatory loop mechanisms of sex determination might be a general strategy. We also discuss the possible reasons for the evolution of autoregulatory loops in sex determination cascades and their impact on binary developmental choices.

  12. The autoregulatory loop: A common mechanism of regulation of key sex determining genes in insects.

    Science.gov (United States)

    Sawanth, Suresh Kumar; Gopinath, Gajula; Sambrani, Nagraj; Arunkumar, Kallare P

    2016-06-01

    Sex determination in most insects is structured as a gene cascade, wherein a primary signal is passed through a series of sex-determining genes, culminating in a downstream double-switch known as doublesex that decides the sexual fate of the embryo. From the literature available on sex determination cascades, it becomes apparent that sex determination mechanisms have evolved rapidly. The primary signal that provides the cue to determine the sex of the embryo varies remarkably, not only among taxa, but also within taxa. Furthermore, the upstream key gene in the cascade also varies between species and even among closely related species. The order Insecta alone provides examples of astoundingly complex diversity of upstream key genes in sex determination mechanisms. Besides, unlike key upstream genes, the downstream double-switch gene is alternatively spliced to form functional sex-specific isoforms. This sex-specific splicing is conserved across insect taxa. The genes involved in the sex determination cascade such as Sex-lethal (Sxl) in Drosophila melanogaster, transformer (tra) in many other dipterans, coleopterans and hymenopterans, Feminizer (fem) in Apis mellifera, and IGF-II mRNA-binding protein (Bmimp) in Bombyx mori are reported to be regulated by an autoregulatory positive feedback loop. In this review, by taking examples from various insects, we propose the hypothesis that autoregulatory loop mechanisms of sex determination might be a general strategy. We also discuss the possible reasons for the evolution of autoregulatory loops in sex determination cascades and their impact on binary developmental choices.

  13. STATc is a key regulator of the transcriptional response to hyperosmotic shock

    Directory of Open Access Journals (Sweden)

    Eichinger Ludwig

    2007-05-01

    Full Text Available Abstract Background Dictyostelium discoideum is frequently subjected to environmental changes in its natural habitat, the forest soil. In order to survive, the organism had to develop effective mechanisms to sense and respond to such changes. When cells are faced with a hypertonic environment a complex response is triggered. It starts with signal sensing and transduction and leads to changes in cell shape, the cytoskeleton, transport processes, metabolism and gene expression. Certain aspects of the Dictyostelium osmotic stress response have been elucidated, however, no comprehensive picture was available up to now. Results To better understand the D. discoideum response to hyperosmotic conditions, we performed gene expression profiling using DNA microarrays. The transcriptional profile of cells treated with 200 mM sorbitol during a 2-hour time course revealed a time-dependent induction or repression of 809 genes, more than 15% of the genes on the array, which peaked 45 to 60 minutes after the hyperosmotic shock. The differentially regulated genes were applied to cluster analysis and functional annotation using gene GO terms. Two main responses appear to be the down-regulation of the metabolic machinery and the up-regulation of the stress response system, including STATc. Further analysis of STATc revealed that it is a key regulator of the transcriptional response to hyperosmotic shock. Approximately 20% of the differentially regulated genes were dependent on the presence of STATc. Conclusion At least two signalling pathways are activated in Dictyostelium cells subjected to hypertonicity. STATc is responsible for the transcriptional changes of one of them.

  14. Peroxisome proliferator-activated receptor-gamma gene: a key regulator of adipocyte differentiation in chickens.

    Science.gov (United States)

    Wang, Y; Mu, Y; Li, H; Ding, N; Wang, Q; Wang, Y; Wang, S; Wang, N

    2008-02-01

    The peroxisome proliferator-activated receptors (PPAR) are members of the nuclear hormone receptor superfamily. Peroxisome proliferator-activated receptor-gamma is regarded as a "master regulator" of adipocyte differentiation in mammals. The current study was designed to investigate the function and regulatory mechanism of PPARgamma in chicken adipogenesis by RNA interference. Preadipocytes were isolated from the abdominal fat tissue of 12-d-old chickens and cultured. Small-interference PPARgamma RNA (siPPARgamma) was synthesized by in vitro transcription and transfected into chicken preadipocytes by using liposomes. The suppressive effect of siPPARgamma was detected by real-time reverse-transcription PCR and reverse-transcription PCR. The results showed that transient transfection with siPPARgamma significantly inhibited differentiation and enhanced proliferation of chicken preadipocytes (P adipogenesis-associated adipocyte fatty acid-binding protein gene was down-regulated when PPARgamma was silenced. The current work indicates that PPARgamma is a key regulator of chicken preadipocyte differentiation.

  15. GC/MS-based metabolomic studies reveal key roles of glycine in regulating silk synthesis in silkworm, Bombyx mori.

    Science.gov (United States)

    Chen, Quanmei; Liu, Xinyu; Zhao, Ping; Sun, Yanhui; Zhao, Xinjie; Xiong, Ying; Xu, Guowang; Xia, Qingyou

    2015-02-01

    Metabolic profiling of silkworm, especially the factors that affect silk synthesis at the metabolic level, is little known. Herein, metabolomic method based on gas chromatography-mass spectrometry was applied to identify key metabolic changes in silk synthesis deficient silkworms. Forty-six differential metabolites were identified in Nd group with the defect of silk synthesis. Significant changes in the levels of glycine and uric acid (up-regulation), carbohydrates and free fatty acids (down-regulation) were observed. The further metabolomics of silk synthesis deficient silkworms by decreasing silk proteins synthesis using knocking out fibroin heavy chain gene or extirpating silk glands operation showed that the changes of the metabolites were almost consistent with those of the Nd group. Furthermore, the increased silk yields by supplying more glycine or its related metabolite confirmed that glycine is a key metabolite to regulate silk synthesis. These findings provide important insights into the regulation between metabolic profiling and silk synthesis.

  16. Key Factors for the Successful Operation of Clusters: The Case for Slovenia

    Directory of Open Access Journals (Sweden)

    Gajšek Brigita

    2016-05-01

    Full Text Available Background and Purpose: Companies are increasingly specializing and developing those key areas with which they can compete on the global market and are linking in clusters that are ingredient of territorial competitiveness. Clusters can play a competitive role in global value chains but once being successful, they may decline. For this reason, researching key factors for the successful operation of clusters in Slovenia is beneficial.

  17. Key Factors for the Successful Operation of Clusters: The Case for Slovenia

    OpenAIRE

    Gajšek Brigita; Kovač Jure

    2016-01-01

    Background and Purpose: Companies are increasingly specializing and developing those key areas with which they can compete on the global market and are linking in clusters that are ingredient of territorial competitiveness. Clusters can play a competitive role in global value chains but once being successful, they may decline. For this reason, researching key factors for the successful operation of clusters in Slovenia is beneficial.

  18. Identification of key transcription factors in caerulein-induced pancreatitis through expression profiling data.

    Science.gov (United States)

    Qi, Dachuan; Wu, Bo; Tong, Danian; Pan, Ye; Chen, Wei

    2015-08-01

    The current study aimed to isolate key transcription factors (TFs) in caerulein-induced pancreatitis, and to identify the difference between wild type and Mist1 knockout (KO) mice, in order to elucidate the contribution of Mist1 to pancreatitis. The gene profile of GSE3644 was downloaded from the Gene Expression Omnibus database then analyzed using the t-test. The isolated differentially expressed genes (DEGs) were mapped into a transcriptional regulatory network derived from the Integrated Transcription Factor Platform database and in the network, the interaction pairs involving at least one DEG were screened. Fisher's exact test was used to analyze the functional enrichment of the target genes. A total of 1,555 and 3,057 DEGs were identified in the wild type and Mist1KO mice treated with caerulein, respectively. DEGs screened in Mist1KO mice were predominantly enriched in apoptosis, mitogen-activated protein kinase signaling and other cancer-associated pathways. A total of 188 and 51 TFs associated with pathopoiesis were isolated in Mist1KO and wild type mice, respectively. Out of the top 10 TFs (ranked by P-value), 7 TFs, including S-phase kinase-associated protein 2 (Skp2); minichromosome maintenance complex component 3 (Mcm3); cell division cycle 6 (Cdc6); cyclin B1 (Ccnb1); mutS homolog 6 (Msh6); cyclin A2 (Ccna2); and cyclin B2 (Ccnb2), were expressed in the two types of mouse. These TFs were predominantly involved in phosphorylation, DNA replication, cell division and DNA mismatch repair. In addition, specific TFs, including minichromosome maintenance complex component 7 (Mcm7); lymphoid-specific helicase (Hells); and minichromosome maintenance complex component 6 (Mcm6), that function in the unwinding of DNA were identified to participate in Mist1KO pancreatitis. The DEGs, including Cdc6, Mcm6, Msh6 and Wdr1 are closely associated with the regulation of caerulein-induced pancreatitis. Furthermore, other identified TFs were also involved in this type of

  19. KDEL receptor 1 regulates T-cell homeostasis via PP1 that is a key phosphatase for ISR.

    Science.gov (United States)

    Kamimura, Daisuke; Katsunuma, Kokichi; Arima, Yasunobu; Atsumi, Toru; Jiang, Jing-jing; Bando, Hidenori; Meng, Jie; Sabharwal, Lavannya; Stofkova, Andrea; Nishikawa, Naoki; Suzuki, Hironao; Ogura, Hideki; Ueda, Naoko; Tsuruoka, Mineko; Harada, Masaya; Kobayashi, Junya; Hasegawa, Takanori; Yoshida, Hisahiro; Koseki, Haruhiko; Miura, Ikuo; Wakana, Shigeharu; Nishida, Keigo; Kitamura, Hidemitsu; Fukada, Toshiyuki; Hirano, Toshio; Murakami, Masaaki

    2015-06-17

    KDEL receptors are responsible for retrotransporting endoplasmic reticulum (ER) chaperones from the Golgi complex to the ER. Here we describe a role for KDEL receptor 1 (KDELR1) that involves the regulation of integrated stress responses (ISR) in T cells. Designing and using an N-ethyl-N-nitrosourea (ENU)-mutant mouse line, T-Red (naïve T-cell reduced), we show that a point mutation in KDELR1 is responsible for the reduction in the number of naïve T cells in this model owing to an increase in ISR. Mechanistic analysis shows that KDELR1 directly regulates protein phosphatase 1 (PP1), a key phosphatase for ISR in naïve T cells. T-Red KDELR1 does not associate with PP1, resulting in reduced phosphatase activity against eIF2α and subsequent expression of stress responsive genes including the proapoptotic factor Bim. These results demonstrate that KDELR1 regulates naïve T-cell homeostasis by controlling ISR.

  20. Identifying Key Factors for Introducing GPS-Based Fleet Management Systems to the Logistics Industry

    Directory of Open Access Journals (Sweden)

    Yi-Chung Hu

    2015-01-01

    Full Text Available The rise of e-commerce and globalization has changed consumption patterns. Different industries have different logistical needs. In meeting needs with different schedules logistics play a key role. Delivering a seamless service becomes a source of competitive advantage for the logistics industry. Global positioning system-based fleet management system technology provides synergy to transport companies and achieves many management goals such as monitoring and tracking commodity distribution, energy saving, safety, and quality. A case company, which is a subsidiary of a very famous food and retail conglomerate and operates the largest shipping line in Taiwan, has suffered from the nonsmooth introduction of GPS-based fleet management systems in recent years. Therefore, this study aims to identify key factors for introducing related systems to the case company. By using DEMATEL and ANP, we can find not only key factors but also causes and effects among key factors. The results showed that support from executives was the most important criterion but it has the worst performance among key factors. It is found that adequate annual budget planning, enhancement of user intention, and collaboration with consultants with high specialty could be helpful to enhance the faith of top executives for successfully introducing the systems to the case company.

  1. ATF2, a paradigm of the multifaceted regulation of transcription factors in biology and disease.

    Science.gov (United States)

    Watson, Gregory; Ronai, Ze'ev; Lau, Eric

    2017-02-15

    Stringent transcriptional regulation is crucial for normal cellular biology and organismal development. Perturbations in the proper regulation of transcription factors can result in numerous pathologies, including cancer. Thus, understanding how transcription factors are regulated and how they are dysregulated in disease states is key to the therapeutic targeting of these factors and/or the pathways that they regulate. Activating transcription factor 2 (ATF2) has been studied in a number of developmental and pathological conditions. Recent findings have shed light on the transcriptional, post-transcriptional, and post-translational regulatory mechanisms that influence ATF2 function, and thus, the transcriptional programs coordinated by ATF2. Given our current knowledge of its multiple levels of regulation and function, ATF2 represents a paradigm for the mechanistic complexity that can regulate transcription factor function. Thus, increasing our understanding of the regulation and function of ATF2 will provide insights into fundamental regulatory mechanisms that influence how cells integrate extracellular and intracellular signals into a genomic response through transcription factors. Characterization of ATF2 dysfunction in the context of pathological conditions, particularly in cancer biology and response to therapy, will be important in understanding how pathways controlled by ATF2 or other transcription factors might be therapeutically exploited. In this review, we provide an overview of the currently known upstream regulators and downstream targets of ATF2.

  2. Epidermal development in mammals: key regulators, signals from beneath, and stem cells.

    Science.gov (United States)

    Liu, Shuang; Zhang, Huishan; Duan, Enkui

    2013-05-24

    Epidermis is one of the best-studied tissues in mammals that contain types of stem cells. Outstanding works in recent years have shed great light on behaviors of different epidermal stem cell populations in the homeostasis and regeneration of the epidermis as well as hair follicles. Also, the molecular mechanisms governing these stem cells are being elucidated, from genetic to epigenetic levels. Compared with the explicit knowledge about adult skin, embryonic development of the epidermis, especially the early period, still needs exploration. Furthermore, stem cells in the embryonic epidermis are largely unstudied or ambiguously depicted. In this review, we will summarize and discuss the process of embryonic epidermal development, with focuses on some key molecular regulators and the role of the sub-epidermal mesenchyme. We will also try to trace adult epidermal stem cell populations back to embryonic development. In addition, we will comment on in vitro derivation of epidermal lineages from ES cells and iPS cells.

  3. Using the key success factor concept in competitor intelligence and benchmarking

    DEFF Research Database (Denmark)

    Bisp, Søren; Sørensen, Elin; Grunert, Klaus G.

    1997-01-01

    A key success factor is regarded as a skill or a resource that a business can invest in, which explains a major part of the observable differences in perceived value of the offer and/or relative costs of bringing that offer to the marketplace. Key success factors are potentially useful...... in structuring the generation of market intelligence in competitor analysis and benchmarking. To this end, a method was developed, based on a reverse laddering procedure, which elicits decision-makers' subjec causal maps. When aggregated, these maps can be used to derive competitor analysis systems. The paper...

  4. The EU Clinical Trials Regulation: key priorities, purposes and aims and the implications for public health.

    Science.gov (United States)

    Flear, Mark L

    2016-03-01

    The replacement of the European Union (EU) Clinical Trials Directive by the new Clinical Trials Regulation (CTR), which entered into force on 16 June 2014 but will not apply before 28 May 2016, provides an opportunity to review the legal and political context within which this important aspect of research law and policy sits and to reflect on the implications for public health. My aim in this article is to relate the context to the key purposes and aims of EU law and policy on clinical trials in order to explain and clarify its orientation. On that basis, I argue that the CTR and the changes it introduces to the law on clinical trials are part of the EU's continued focus on market optimisation. It is this focus that orients and directs the wider pharmaceutical development pipeline, but that undermines the achievement of key public health objectives. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  5. Schwann cells and their transcriptional network: Evolution of key regulators of peripheral myelination.

    Science.gov (United States)

    Stolt, C Claus; Wegner, Michael

    2016-06-15

    As derivatives of the neural crest, Schwann cells represent a vertebrate invention. Their development and differentiation is under control of a newly constructed, vertebrate-specific regulatory network that contains Sox10, Oct6 and Krox20 as cornerstones and central regulators of peripheral myelination. In this review, we discuss the function and relationship of these transcription factors among each other and in the context of their regulatory network, and present ideas of how neofunctionalization may have helped to recruit them to their novel task in Schwann cells. This article is part of a Special Issue entitled SI: Myelin Evolution.

  6. Identification and Characterization of Multiple Intermediate Alleles of the Key Genes Regulating Brassinosteroid Biosynthesis Pathways

    Science.gov (United States)

    Du, Junbo; Zhao, Baolin; Sun, Xin; Sun, Mengyuan; Zhang, Dongzhi; Zhang, Shasha; Yang, Wenyu

    2017-01-01

    Most of the early identified brassinosteroid signaling and biosynthetic mutants are null mutants, exhibiting extremely dwarfed phenotypes and male sterility. These null mutants are usually unable to be directly transformed via a routinely used Agrobacterium-mediated gene transformation system and therefore are less useful for genetic characterization of the brassinosteroid (BR)-related pathways. Identification of intermediate signaling mutants such as bri1–5 and bri1–9 has contributed drastically to the elucidation of BR signaling pathway using both genetic and biochemical approaches. However, intermediate mutants of key genes regulating BR biosynthesis have seldom been reported. Here we report identification of several intermediate BR biosynthesis mutants mainly resulted from leaky transcriptions due to the insertions of T-DNAs in the introns. These mutants are semi-dwarfed and fertile and capable to be transformed. These intermediate mutants could be useful tools for future discovery and analyses of novel components regulating BR biosynthesis and catabolism via genetic modifier screen. PMID:28138331

  7. Regulations of the key mediators in inflammation and atherosclerosis by Aspirin in human macrophages

    Directory of Open Access Journals (Sweden)

    Zhang Li

    2010-02-01

    Full Text Available Abstract Although its role to prevent secondary cardiovascular complications has been well established, how acetyl salicylic acid (ASA, aspirin regulates certain key molecules in the atherogenesis is still not known. Considering the role of matrix metalloproteinase-9 (MMP-9 to destabilize the atherosclerotic plaques, the roles of the scavenger receptor class BI (SR-BI and ATP-binding cassette transporter A1 (ABCA1 to promote cholesterol efflux in the foam cells at the plaques, and the role of NF-κB in the overall inflammation related to the atherosclerosis, we addressed whether these molecules are all related to a common mechanism that may be regulated by acetyl salicylic acid. We investigated the effect of ASA to regulate the expressions and activities of these molecules in THP-1 macrophages. Our results showed that ASA inhibited MMP-9 mRNA expression, and caused the decrease in the MMP-9 activities from the cell culture supernatants. In addition, it inhibited the nuclear translocation of NF-κB p65 subunit, thus the activity of this inflammatory molecule. On the contrary, acetyl salicylic acid induced the expressions of ABCA1 and SR-BI, two molecules known to reduce the progression of atherosclerosis, at both mRNA and protein levels. It also stimulated the cholesterol efflux out of macrophages. These data suggest that acetyl salicylic acid may alleviate symptoms of atherosclerosis by two potential mechanisms: maintaining the plaque stability via inhibiting activities of inflammatory molecules MMP-9 and NF-κB, and increasing the cholesterol efflux through inducing expressions of ABCA1 and SR-BI.

  8. The Key Regulator for Language and Speech Development, FOXP2, is a Novel Substrate for SUMOylation.

    Science.gov (United States)

    Meredith, Leslie J; Wang, Chiung-Min; Nascimento, Leticia; Liu, Runhua; Wang, Lizhong; Yang, Wei-Hsiung

    2016-02-01

    Transcription factor forkhead box protein P2 (FOXP2) plays an essential role in the development of language and speech. However, the transcriptional activity of FOXP2 regulated by the post-translational modifications remains unknown. Here, we demonstrated that FOXP2 is clearly defined as a SUMO target protein at the cellular levels as FOXP2 is covalently modified by both SUMO1 and SUMO3. Furthermore, SUMOylation of FOXP2 was significantly decreased by SENP2 (a specific SUMOylation protease). We further showed that FOXP2 is selectively SUMOylated in vivo on a phylogenetically conserved lysine 674 but the SUMOylation does not alter subcellular localization and stability of FOXP2. Interestingly, we observed that human etiological FOXP2 R553H mutation robustly reduces its SUMOylation potential as compared to wild-type FOXP2. In addition, the acidic residues downstream the core SUMO motif on FOXP2 are required for its full SUMOylation capacity. Finally, our functional analysis using reporter gene assays showed that SUMOylation may modulate transcriptional activity of FOXP2 in regulating downstream target genes (DISC1, SRPX2, and MiR200c). Altogether, we provide the first evidence that FOXP2 is a substrate for SUMOylation and SUMOylation of FOXP2 plays a functional role in regulating its transcriptional activity.

  9. Regulative change targeting energy performance of buildings in Sweden. Key drivers and main implications

    Energy Technology Data Exchange (ETDEWEB)

    Fuglseth, Bente Beckstroem

    2009-02-15

    This report has explored changes in two regulations targeting energy performance of buildings in Sweden, energy requirements and certification of buildings. The objective has been to investigate the effect of the implementation of the EU directive on energy performance of buildings (EPBD) on these two regulations and to what degree the directive can explain the regulative changes. The analytical framework has also included domestic factors; the influence of the national government and the organizational field. The analysis revealed that whereas the EPBD has acted only as facilitator in connection with the changes in energy requirements, it has been the sole driver of some of the changes in Sweden's new certification system. Several of the changes during the period studied can however be traced to the national government and the organizational field. But the EPBD has also worked as a facilitator of the changes promoted by domestic actors. The directive has been used to legitimize radical changes that would have been difficult to implement in other ways. (Author). 40 refs., 2 tabs

  10. INTELLECTUAL POTENTIAL OF RUSSIA AS ONE OF THE KEY FACTORS IN THE MODERNIZATION

    Directory of Open Access Journals (Sweden)

    A. A. Agafonov

    2013-01-01

    Full Text Available The article describes an influence of the government support of science, education and the scientific manpower preparation system on innovation development ofRussia. It has been hypothesized that the key factor of Russian economy modernization should be the increase of financial support of research efforts and the education system.

  11. Distributed Speech Recognition Systems and Some Key Factors Affecting It's Performance

    Institute of Scientific and Technical Information of China (English)

    YE Lei; YANG Zhen

    2003-01-01

    In this paper we first analyze the Distributed Speech Recognition (DSR) system and the key factors that affect it's performance and then focus on the research on the relationship between the length of testing speech and the recognition accuracy of the system. Some experimental results are given at last.

  12. Decisive key-factors influencing farm households' soil and water conservation investments

    NARCIS (Netherlands)

    Kessler, A.

    2006-01-01

    In the inter-Andean valleys of Bolivia decisive key-factors influencing farm households' soil and water conservation investments were determined. The household's progressiveness most influences the decision how much to invest; dynamic and responsible families are among the first. Economic stratum is

  13. Key Success Factors of Innovation Projects of Vegetable Breeding Companies in China

    NARCIS (Netherlands)

    Liu Zhen, Zhen; Kemp, R.G.M.; Jongsma, M.A.; Huang, Caicheng; Dons, J.J.M.; Omta, S.W.F.

    2014-01-01

    The vegetable breeding industry is generally recognized as an innovation-driven industry. However, innovation is costly, time-consuming and uncertain. This study aims to identify the key success factors of innovation project performance of vegetable breeding companies (VBCs) in China. Based on empir

  14. Myopic Loss Aversion: Demystifying the Key Factors Influencing Decision Problem Framing

    Science.gov (United States)

    Hardin, Andrew M.; Looney, Clayton Arlen

    2012-01-01

    Advancement of myopic loss aversion theory has been hamstrung by conflicting results, methodological inconsistencies, and a piecemeal approach toward understanding the key factors influencing decision problem framing. A series of controlled experiments provides a more holistic view of the variables promoting myopia. Extending the information…

  15. A qualitative study of the key factors in implementing telemedical monitoring of diabetic foot ulcer patients

    DEFF Research Database (Denmark)

    Rasmussen, B.S.B.; Jensen, L.K.; Frøkjær, J.

    2015-01-01

    of a telemedical intervention. We posed the following research question: What are the key organizational factors in the implementation of telemedicine in wound care? METHODS: In connection with a randomized controlled trial of telemedical intervention for patients with diabetic foot ulcers in the region...

  16. Srebf1a is a key regulator of transcriptional control for adipogenesis.

    Science.gov (United States)

    Ayala-Sumuano, Jorge-Tonatiuh; Velez-Delvalle, Cristina; Beltrán-Langarica, Alicia; Marsch-Moreno, Meytha; Cerbón-Solorzano, Jorge; Kuri-Harcuch, Walid

    2011-01-01

    Adipogenesis is regulated by a complex cascade of transcriptional factors, but little is known about the early events that regulate the adipogenic program. Here, we report the role of the srebf1a gene in the differentiation of fibroblastic 3T3-F442A cells. We found that expression of srebf1a depended on GSK3β activity and that GSK3β activity was necessary for C/EBPβ phosphorylation at Thr188. Knockdown of srebf1a inhibited the adipogenic program because it blocked the expression of genes encoding PPARγ2, C/EBPα, SREBP1c and even FABP4, demonstrating that SREBP1a activation is upstream of these three essential adipogenic transcription factors. Kinetic analysis during differentiation illustrated that the order of expression of adipogenic genes was the following: cebpb, srebf1a, pparg2, cebpa, srebp1c and fabp4. Our data suggest that srebf1a acts as an essential link between the GSK3β-C/EBPβ signaling axis and the beginning of the adipogenic transcriptional cascade.

  17. An EJC factor RBM8a regulates anxiety behaviors.

    Science.gov (United States)

    Alachkar, A; Jiang, D; Harrison, M; Zhou, Y; Chen, G; Mao, Y

    2013-07-01

    Neuroplasticity depends on the precise timing of gene expression, which requires accurate control of mRNA stability and rapid elimination of abnormal mRNA. Nonsense-mediated mRNA decay (NMD) is an RNA surveillance mechanism that ensures the speedy degradation of mRNAs carrying premature termination codons (PTCs). This mechanism relies on several key Exon Junction Complex (EJC) factors to distinguish PTCs from normal stop codons. NMD degrades not only aberrant transcripts carrying PTCs, but also normal transcripts harboring a normal stop codon [1]. Intriguingly, mutations in an NMD factor, Upf3b, have been found in patients with autism [2, 3]. A binding partner of Upf3b, RBM8a, is located in the 1q21.1 copy-number variation (CNV) associated with mental retardation, autism [4], schizophrenia [5], and microcephaly [6]. However, the functions of EJC factors and their roles in behavioral regulation are still elusive. RBM8a protein is a core component of the EJC that plays an important role in NMD. Recent genetic study indicated that RBM8a gain-of-function significantly associated with intellectual disability [7]. In this study we investigated the effect of RBM8a overexpression on affective behaviors in mice. Lentivirus expressing RBM8a was infused into the hippocampus of adult mice to conduct behavioral studies including social interaction, open field, elevated plus maze, and forced swimming tests. Our results showed that overexpression of RBM8a in the mouse dentate gyrus (DG) leads to increased anxiety-like behavior, abnormal social interaction and decreased immobile time in forced swimming test (FST). To examine the underlying mechanism, we found that overexpressing RBM8a in cultured primary neurons lead to significant higher frequency of miniature excitatory postsynaptic currents (mEPSCs). To explore the underlying mechanism of RBM8a mediated behavioral changes, RNA-immunoprecipitation (RNA-IP) detected that RBM8a binds to CaMK2, GluR1 and Egr1 mRNA, suggesting that

  18. Regulation of the Ets transcription factor Tel

    NARCIS (Netherlands)

    Roukens, Mark Guido

    2010-01-01

    In this thesis we report novel studies on the molecular regulation of the transcriptional repressor Tel (Translocation Ets Leukemia). The work in this thesis is presented as follows: Chapter 1 is an introduction which summarizes the literature about Tel and its Drosophila orthologue Yan as it was k

  19. Retinoic acid regulates the expression of photoreceptor transcription factor NRL.

    Science.gov (United States)

    Khanna, Hemant; Akimoto, Masayuki; Siffroi-Fernandez, Sandrine; Friedman, James S; Hicks, David; Swaroop, Anand

    2006-09-15

    NRL (neural retina leucine zipper) is a key basic motif-leucine zipper (bZIP) transcription factor, which orchestrates rod photoreceptor differentiation by activating the expression of rod-specific genes. The deletion of Nrl in mice results in functional cones that are derived from rod precursors. However, signaling pathways modulating the expression or activity of NRL have not been elucidated. Here, we show that retinoic acid (RA), a diffusible factor implicated in rod development, activates the expression of NRL in serum-deprived Y79 human retinoblastoma cells and in primary cultures of rat and porcine photoreceptors. The effect of RA is mimicked by TTNPB, a RA receptor agonist, and requires new protein synthesis. DNaseI footprinting and electrophoretic mobility shift assays (EMSA) using bovine retinal nuclear extract demonstrate that RA response elements (RAREs) identified within the Nrl promoter bind to RA receptors. Furthermore, in transiently transfected Y79 and HEK293 cells the activity of Nrl-promoter driving a luciferase reporter gene is induced by RA, and this activation is mediated by RAREs. Our data suggest that signaling by RA via RA receptors regulates the expression of NRL, providing a framework for delineating early steps in photoreceptor cell fate determination.

  20. Regulation of alternative sigma factor use.

    Science.gov (United States)

    Österberg, Sofia; del Peso-Santos, Teresa; Shingler, Victoria

    2011-01-01

    Alternative bacterial sigma factors bind the catalytic core RNA polymerase to confer promoter selectivity on the holoenzyme. The different holoenzymes are thus programmed to recognize the distinct promoter classes in the genome to allow coordinated activation of discrete sets of genes needed for adaptive responses. To form the holoenzymes, the different sigma factors must be available to compete for their common substrate (core RNA polymerase). This review highlights (a) the roles of antisigma factors in controlling the availability of alternative sigma factors and (b) the involvement of diverse regulatory molecules that promote the use of alternative sigma factors through subversion of the domineering housekeeping σ(70). The latter include the nucleotide alarmone ppGpp and small proteins (DksA, Rsd, and Crl), which directly target the transcriptional machinery to mediate their effects.

  1. Key Factors of Quality in the Sector of Tourism Services Providers: Case Study: Czech Republic

    Directory of Open Access Journals (Sweden)

    Ida Vajčnerová

    2014-01-01

    Full Text Available The paper summarizes main results of partial research aimed at detection of the key factors affecting quality in the sector of tourism services providers, namely tour operators and travel agencies. A primary questionnaire survey was conducted; the researched factors were distributed in the context of service quality dimensions (Grönroos model; the dimensions were tested in relation to sex, age and education of the respondents (ANOVA; Brown-Forsythe test. Assurance was identified as the most important dimension. The output of the study is determining the significance of individual quality factors from the perspective of a potential customer when selecting a service provider.

  2. Studies of key success factors of product development success: A reinterpretation of results

    DEFF Research Database (Denmark)

    Plichta, Kirsten; Harmsen, Hanne

    . The theoretical tradition of the resource-based perspective provides ­ at least to some extent ­ an account of this causality. An important point in the paper is that the key factors of success in the empi studies are not factors causally related to success, but at the most a number of valuable resources and thus......In this paper the general validity of the research area of key factors of success in product development is discussed. To be more specific we argue that validity hinges on the causal relation between success and success factrors ­ a relation that unaccounted for in the empirical studies...... the necessary but not sufficient conditions for success. A second issue in the paper is the discussion of how the empirical results may be implemented in firms. The results of the empirical studies show managers where to concentrate their efforts in order to raise the rate of successful products...

  3. Human-specific hypomethylation of CENPJ, a key brain size regulator.

    Science.gov (United States)

    Shi, Lei; Lin, Qiang; Su, Bing

    2014-03-01

    Both the enlarged brain and concurrent highly developed cognitive skills are often seen as distinctive characteristics that set humans apart from other primates. Despite this obvious differentiation, the genetic mechanisms that underlie such human-specific traits are not clearly understood. In particular, whether epigenetic regulations may play a key role in human brain evolution remain elusive. In this study, we used bisulfite sequencing to compare the methylation patterns of four known genes that regulate brain size (ASPM, CDK5RAP2, CENPJ, and MCPH1) in the prefrontal cortex among several primate species spanning the major lineages of primates (i.e., humans, great apes, lesser apes, and Old World monkeys). The results showed a human-specific hypomethylation in the 5' UTR of CENPJ in the brain, where methylation levels among humans are only about one-third of those found among nonhuman primates. Similar methylation patterns were also detected in liver, kidney, and heart tissues, although the between-species differences were much less pronounced than those in the brain. Further in vitro methylation assays indicated that the methylation status of the CENPJ promoter could influence its expression. We also detected a large difference in CENPJ expression in the human and nonhuman primate brains of both adult individuals and throughout the major stages of fetal brain development. The hypomethylation and comparatively high expression of CENPJ in the central nervous system of humans suggest that a human-specific--and likely heritable--epigenetic modification likely occurred during human evolution, potentially leading to a much larger neural progenitor pool during human brain development, which may have eventually contributed to the dramatically enlarged brain and highly developed cognitive abilities associated with humans.

  4. Specificity determinants for autoproteolysis of LexA, a key regulator of bacterial SOS mutagenesis.

    Science.gov (United States)

    Mo, Charlie Y; Birdwell, L Dillon; Kohli, Rahul M

    2014-05-20

    Bacteria utilize the tightly regulated stress response (SOS) pathway to respond to a variety of genotoxic agents, including antimicrobials. Activation of the SOS response is regulated by a key repressor-protease, LexA, which undergoes autoproteolysis in the setting of stress, resulting in derepression of SOS genes. Remarkably, genetic inactivation of LexA's self-cleavage activity significantly decreases acquired antibiotic resistance in infection models and renders bacteria hypersensitive to traditional antibiotics, suggesting that a mechanistic study of LexA could help inform its viability as a novel target for combating acquired drug resistance. Despite structural insights into LexA, a detailed knowledge of the enzyme's protease specificity is lacking. Here, we employ saturation and positional scanning mutagenesis on LexA's internal cleavage region to analyze >140 mutants and generate a comprehensive specificity profile of LexA from the human pathogen Pseudomonas aeruginosa (LexAPa). We find that the LexAPa active site possesses a unique mode of substrate recognition. Positions P1-P3 prefer small hydrophobic residues that suggest specific contacts with the active site, while positions P5 and P1' show a preference for flexible glycine residues that may facilitate the conformational change that permits autoproteolysis. We further show that stabilizing the β-turn within the cleavage region enhances LexA autoproteolytic activity. Finally, we identify permissive positions flanking the scissile bond (P4 and P2') that are tolerant to extensive mutagenesis. Our studies shed light on the active site architecture of the LexA autoprotease and provide insights that may inform the design of probes of the SOS pathway.

  5. Regulated assembly of transcription factors and control of transcription initiation.

    Science.gov (United States)

    Beckett, D

    2001-11-30

    Proteins that function in regulation of transcription initiation are typically homo or hetero-oligomeric. Results of recent biophysical studies of transcription regulators indicate that the assembly of these proteins is often subject to regulation. This regulation of assembly dictates the frequency of transcription initiation via its influence on the affinity of a transcription regulator for DNA and its affect on target site selection. Factors that modulate transcription factor assembly include binding of small molecules, post-translational modification, DNA binding and interactions with other proteins. Here, the results of recent structural and/or thermodynamic studies of a number of transcription regulators that are subject to regulated assembly are reviewed. The accumulated data indicate that this phenomenon is ubiquitous and that mechanisms utilized in eukaryotes and prokaryotes share common features. Copyright 2001 Academic Press.

  6. Ets-1 regulates intracellular glutathione levels: key target for resistant ovarian cancer.

    Science.gov (United States)

    Verschoor, Meghan L; Singh, Gurmit

    2013-11-15

    Ovarian cancer is characterized by high rates of metastasis and therapeutic resistance. Many chemotherapeutic agents rely on the induction of oxidative stress to cause cancer cell death, thus targeting redox regulation is a promising strategy to overcome drug resistance. We have used a tetracycline-inducible Ets-1 overexpression model derived from 2008 ovarian cancer cells in the present study. To examine the role of Ets-1 in glutathione regulation we have measured intracellular reactive oxygen species and glutathione levels, as well as glutathione peroxidase enzyme activity. Glutathione synthesis was limited using transsulfuration or Sx(c)- pathway blocking agents, and glutamate release was measured to confirm Sx(c)- blockade. Cell viability following drug treatment was assessed via crystal violet assay. Oxidative stress was induced through glucose oxidase treatment, which produces hydrogen peroxide by glucose oxidation. The protein expressions of redox-related factors were measured through western blotting. Overexpression of Ets-1 was associated with decreased intracellular ROS, concomitantly with increased intracellular GSH, GPX antioxidant activity, and Sx(c)- transporter activity. Under basal conditions, inhibition of the transsulfuration pathway resulted in decreased GSH levels and GPX activity in all cell lines, whereas inhibition of Sx(c)- by sulfasalazine decreased GPX activity in Ets-1-expressing cells only. However, under oxidative stress the intracellular GSH levels decreased significantly in correlation with increased Ets-1 expression following sulfasalazine treatment. In this study we have identified a role for proto-oncogene Ets-1 in the regulation of intracellular glutathione levels, and examined the effects of the anti-inflammatory drug sulfasalazine on glutathione depletion using an ovarian cancer cell model. The findings from this study show that Ets-1 mediates enhanced Sx(c)- activity to increase glutathione levels under oxidative stress

  7. Regulation of the transforming growth factor β pathway by reversible ubiquitylation.

    Science.gov (United States)

    Al-Salihi, Mazin A; Herhaus, Lina; Sapkota, Gopal P

    2012-05-01

    The transforming growth factor β (TGFβ) signalling pathway plays a central role during embryonic development and in adult tissue homeostasis. It regulates gene transcription through a signalling cascade from cell surface receptors to intracellular SMAD transcription factors and their nuclear cofactors. The extent, duration and potency of signalling in response to TGFβ cytokines are intricately regulated by complex biochemical processes. The corruption of these regulatory processes results in aberrant TGFβ signalling and leads to numerous human diseases, including cancer. Reversible ubiquitylation of pathway components is a key regulatory process that plays a critical role in ensuring a balanced response to TGFβ signals. Many studies have investigated the mechanisms by which various E3 ubiquitin ligases regulate the turnover and activity of TGFβ pathway components by ubiquitylation. Moreover, recent studies have shed new light into their regulation by deubiquitylating enzymes. In this report, we provide an overview of current understanding of the regulation of TGFβ signalling by E3 ubiquitin ligases and deubiquitylases.

  8. PS integrins and laminins: key regulators of cell migration during Drosophila embryogenesis.

    Science.gov (United States)

    Urbano, Jose M; Domínguez-Giménez, Paloma; Estrada, Beatriz; Martín-Bermudo, María D

    2011-01-01

    During embryonic development, there are numerous cases where organ or tissue formation depends upon the migration of primordial cells. In the Drosophila embryo, the visceral mesoderm (vm) acts as a substrate for the migration of several cell populations of epithelial origin, including the endoderm, the trachea and the salivary glands. These migratory processes require both integrins and laminins. The current model is that αPS1βPS (PS1) and/or αPS3βPS (PS3) integrins are required in migrating cells, whereas αPS2βPS (PS2) integrin is required in the vm, where it performs an as yet unidentified function. Here, we show that PS1 integrins are also required for the migration over the vm of cells of mesodermal origin, the caudal visceral mesoderm (CVM). These results support a model in which PS1 might have evolved to acquire the migratory function of integrins, irrespective of the origin of the tissue. This integrin function is highly specific and its specificity resides mainly in the extracellular domain. In addition, we have identified the Laminin α1,2 trimer, as the key extracellular matrix (ECM) component regulating CVM migration. Furthermore, we show that, as it is the case in vertebrates, integrins, and specifically PS2, contributes to CVM movement by participating in the correct assembly of the ECM that serves as tracks for migration.

  9. Gut instincts: microbiota as a key regulator of brain development, ageing and neurodegeneration.

    Science.gov (United States)

    Dinan, Timothy G; Cryan, John F

    2017-01-15

    There is a growing realisation that the gut-brain axis and its regulation by the microbiota may play a key role in the biological and physiological basis of neurodevelopmental, age-related and neurodegenerative disorders. The routes of communication between the microbiota and brain are being unravelled and include the vagus nerve, gut hormone signalling, the immune system, tryptophan metabolism or by way of microbial metabolites such as short chain fatty acids. The importance of early life gut microbiota in shaping future health outcomes is also emerging. Disturbances of this composition by way of antibiotic exposure, lack of breastfeeding, infection, stress and the environmental influences coupled with the influence of host genetics can result in long-term effects on physiology and behaviour, at least in animal models. It is also worth noting that mode of delivery at birth influences microbiota composition with those born by Caesarean section having a distinctly different microbiota in early life to those born per vaginum. At the other extreme of life, ageing is associated with a narrowing in microbial diversity and healthy ageing correlates with a diverse microbiome. Recently, the gut microbiota has been implicated in a variety of conditions including depression, autism, schizophrenia and Parkinson's disease. There is still considerable debate as to whether or not the gut microbiota changes are core to the pathophysiology of such conditions or are merely epiphenomenal. It is plausible that such neuropsychiatric disorders might be treated in the future by targeting the microbiota either by microbiota transplantation, antibiotics or psychobiotics.

  10. PS integrins and laminins: key regulators of cell migration during Drosophila embryogenesis.

    Directory of Open Access Journals (Sweden)

    Jose M Urbano

    Full Text Available During embryonic development, there are numerous cases where organ or tissue formation depends upon the migration of primordial cells. In the Drosophila embryo, the visceral mesoderm (vm acts as a substrate for the migration of several cell populations of epithelial origin, including the endoderm, the trachea and the salivary glands. These migratory processes require both integrins and laminins. The current model is that αPS1βPS (PS1 and/or αPS3βPS (PS3 integrins are required in migrating cells, whereas αPS2βPS (PS2 integrin is required in the vm, where it performs an as yet unidentified function. Here, we show that PS1 integrins are also required for the migration over the vm of cells of mesodermal origin, the caudal visceral mesoderm (CVM. These results support a model in which PS1 might have evolved to acquire the migratory function of integrins, irrespective of the origin of the tissue. This integrin function is highly specific and its specificity resides mainly in the extracellular domain. In addition, we have identified the Laminin α1,2 trimer, as the key extracellular matrix (ECM component regulating CVM migration. Furthermore, we show that, as it is the case in vertebrates, integrins, and specifically PS2, contributes to CVM movement by participating in the correct assembly of the ECM that serves as tracks for migration.

  11. Key Economic Parameters for an Optimal Pharmacy Network in a Regulated Environment

    Directory of Open Access Journals (Sweden)

    Franjo MLINARIC

    2016-10-01

    Full Text Available Pharmacies are an integral part of the modern healthcare system which strives for a holistic and effi cient care. General practitioners and pharmacists are held in high esteem among local communities as they are the fi rst point of contact when people have health issues. However, a strong demand for health services in developed countries and its present fi nancing schemes undermined the sustainability of the whole health system (8.9% of GDP in 2013 and growing. According to WHO and EU recommendations, the whole healthcare system shall accept a holistic approach and focus on education, prevention and proper medicine consume. Part of this strategy is a seamless care concept, where medical doctors and pharmacists build a team around the well-being of a patient. Financing scheme incentives and KPI’s (key performance indicators will be focused on keeping people healthy, instead of paying for procedures. The future healthcare ecosystem obliges pharmacists to optimize network coverage and to extend health services. Nevertheless, their growth strategy needs to be gradual, considering the present level of network coverage, the low pace of private and public expenditures for medicine and services, and the fact that a new fi nancing model for pharmacies is still unknown. Thus, we expect the development of pharmacy network in regulated environment to be fi nanced predominantly from retained earnings in publicly owned pharmacies and by awarding pharmacy concessions.

  12. Transcription factor regulation by mechanical stress.

    Science.gov (United States)

    Mendez, Melissa G; Janmey, Paul A

    2012-05-01

    New technologies and interest in cell mechanics are generating exciting new discoveries about how material properties and forces affect biological structure and function. Mechanical forces are transduced via a variety of mechanisms, recently beginning to be revealed, into signals capable of altering cell function and structure. Responses to physical stimuli occur at multiple levels, from changes in the structures of single proteins to global cascades capable of altering cell proliferation and differentiation. This review describes recent findings in which physical stimuli were shown to modulate transcription factor activity, including that of armadillo/β-catenin, serum response factor (SRF), yes-associated protein (YAP) and nuclear factor κB (NF-κB). Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Plastid sigma factors: Their individual functions and regulation in transcription.

    Science.gov (United States)

    Chi, Wei; He, Baoye; Mao, Juan; Jiang, Jingjing; Zhang, Lixin

    2015-09-01

    Sigma factors are the predominant factors involved in transcription regulation in bacteria. These factors can recruit the core RNA polymerase to promoters with specific DNA sequences and initiate gene transcription. The plastids of higher plants originating from an ancestral cyanobacterial endosymbiont also contain sigma factors that are encoded by a small family of nuclear genes. Although all plastid sigma factors contain sequences conserved in bacterial sigma factors, a considerable number of distinct traits have been acquired during evolution. The present review summarises recent advances concerning the regulation of the structure, function and activity of plastid sigma factors since their discovery nearly 40 years ago. We highlight the specialised roles and overlapping redundant functions of plastid sigma factors according to their promoter selectivity. We also focus on the mechanisms that modulate the activity of sigma factors to optimise plastid function in response to developmental cues and environmental signals. This article is part of a Special Issue entitled: Chloroplast Biogenesis.

  14. Factors Influencing Oral Bioavailability of Thai Mango Seed Kernel Extract and Its Key Phenolic Principles.

    Science.gov (United States)

    Jiamboonsri, Pimsumon; Pithayanukul, Pimolpan; Bavovada, Rapepol; Leanpolchareanchai, Jiraporn; Yin, Taijun; Gao, Song; Hu, Ming

    2015-11-30

    Mango seed kernel extract (MSKE) and its key components (gallic acid, GA; methyl gallate, MG; and pentagalloyl glucopyranose, PGG) have generated interest because of their pharmacological activities. To develop the potential use of the key components in MSKE as natural therapeutic agents, their pharmacokinetic data are necessary. Therefore, this study was performed to evaluate the factors affecting their oral bioavailability as pure compounds and as components in MSKE. The in vitro chemical stability, biological stability, and absorption were evaluated in Hanks' Balanced Salt Solution, Caco-2 cell and rat fecal lysates, and the Caco-2 cell model, respectively. The in vivo oral pharmacokinetic behavior was elucidated in Sprague-Dawley rats. The key components were unstable under alkaline conditions and in Caco-2 cell lysates or rat fecal lysates. The absorptive permeability coefficient followed the order MG > GA > PGG. The in vivo results exhibited similar pharmacokinetic trends to the in vitro studies. Additionally, the co-components in MSKE may affect the pharmacokinetic behaviors of the key components in MSKE. In conclusion, chemical degradation under alkaline conditions, biological degradation by intestinal cell and colonic microflora enzymes, and low absorptive permeability could be important factors underlying the oral bioavailability of these polyphenols.

  15. Factors Influencing Oral Bioavailability of Thai Mango Seed Kernel Extract and Its Key Phenolic Principles

    Directory of Open Access Journals (Sweden)

    Pimsumon Jiamboonsri

    2015-11-01

    Full Text Available Mango seed kernel extract (MSKE and its key components (gallic acid, GA; methyl gallate, MG; and pentagalloyl glucopyranose, PGG have generated interest because of their pharmacological activities. To develop the potential use of the key components in MSKE as natural therapeutic agents, their pharmacokinetic data are necessary. Therefore, this study was performed to evaluate the factors affecting their oral bioavailability as pure compounds and as components in MSKE. The in vitro chemical stability, biological stability, and absorption were evaluated in Hanks’ Balanced Salt Solution, Caco-2 cell and rat fecal lysates, and the Caco-2 cell model, respectively. The in vivo oral pharmacokinetic behavior was elucidated in Sprague-Dawley rats. The key components were unstable under alkaline conditions and in Caco-2 cell lysates or rat fecal lysates. The absorptive permeability coefficient followed the order MG > GA > PGG. The in vivo results exhibited similar pharmacokinetic trends to the in vitro studies. Additionally, the co-components in MSKE may affect the pharmacokinetic behaviors of the key components in MSKE. In conclusion, chemical degradation under alkaline conditions, biological degradation by intestinal cell and colonic microflora enzymes, and low absorptive permeability could be important factors underlying the oral bioavailability of these polyphenols.

  16. The Lnk adaptor protein: a key regulator of normal and pathological hematopoiesis.

    Science.gov (United States)

    Velazquez, Laura

    2012-12-01

    The development and function of blood cells are regulated by specific growth factors/cytokines and their receptors' signaling pathways. In this way, these factors influence cell survival, proliferation and differentiation of hematopoietic cells. Central to this positive and/or negative control are the adaptor proteins. Since their identification 10 years ago, members of the Lnk adaptor protein family have proved to be important activators and/or inhibitors in the hematopoietic, immune and vascular system. In particular, the generation of animal and cellular models for the Lnk and APS proteins has helped establish the physiological role of these molecules through the identification of their specific signaling pathways and the characterization of their binding partners. Moreover, the recent identification of mutations in the LNK gene in myeloproliferative disorders, as well as the correlation of a single nucleotide polymorphism on LNK with hematological, immune and vascular diseases have suggested its involvement in the pathophysiology of these malignancies. The latter findings have thus raised the possibility of addressing Lnk signaling for the treatment of certain human diseases. This review therefore describes the pathophysiological role of this adaptor protein in hematological malignancies and the potential benefits of Lnk therapeutic targeting.

  17. Bcl-2 is a novel interacting partner for the 2-oxoglutarate carrier and a key regulator of mitochondrial glutathione

    Science.gov (United States)

    Wilkins, Heather M.; Marquardt, Kristin; Lash, Lawrence H.; Linseman, Daniel A.

    2011-01-01

    Despite making up only a minor fraction of the total cellular glutathione, recent studies indicate that the mitochondrial glutathione pool is essential for cell survival. Selective depletion of mitochondrial glutathione is sufficient to sensitize cells to mitochondrial oxidative stress (MOS)1 and intrinsic apoptosis. Glutathione is synthesized exclusively in the cytoplasm and must be actively transported into mitochondria. Therefore, regulation of mitochondrial glutathione transport is a key factor in maintaining the antioxidant status of mitochondria. Bcl-2 is resident in the outer mitochondrial membrane where it acts as a central regulator of the intrinsic apoptotic cascade. In addition, Bcl-2 displays an antioxidant-like function that has been linked experimentally to the regulation of cellular glutathione content. We have previously demonstrated a novel interaction between recombinant Bcl-2 and reduced glutathione (GSH) which was antagonized by either Bcl-2 homology-3 domain (BH3) mimetics or a BH3-only protein, recombinant Bim. These previous findings prompted us to investigate if this novel Bcl-2/GSH interaction might play a role in regulating mitochondrial glutathione transport. Incubation of primary cultures of cerebellar granule neurons (CGNs) with the BH3 mimetic, HA14-1, induced MOS and caused specific depletion of the mitochondrial glutathione pool. Bcl-2 was co-immunoprecipitated with GSH following chemical cross-linking in CGNs and this Bcl-2/GSH interaction was antagonized by pre-incubation with HA14-1. Moreover, both HA14-1 and recombinant Bim inhibited GSH transport into isolated rat brain mitochondria. To further investigate a possible link between Bcl-2 function and mitochondrial glutathione transport, we next examined if Bcl-2 associated with the 2-oxoglutarate carrier (OGC), an inner mitochondrial membrane protein known to transport glutathione in liver and kidney. Following co-transfection of CHO cells, Bcl-2 was co-immunoprecipitated with OGC

  18. KEY FACTORS OF THE RUSSIAN ECONOMIC SOVEREIGNTY ENSURING IN CONDIDIONS OF THE MODERN GLOBAL ECONOMY

    Directory of Open Access Journals (Sweden)

    Melnikov A. B.

    2015-09-01

    Full Text Available The purpose of this article is the analysis of the key factors of the Russian economic sovereignty ensuring now. As a result, we have identified the weaknesses in the economy and proposed the ways of solving some problems. The analysis of the mechanism of budget allocation under the anti-crisis plan of the government was performed as well. The prospects for the global oil market, the capital market and the exchange rate of the Russian currency were presented

  19. A Key Factor Affecting L2 (English) Vocabulary Acquisition:L2 (English) Proficiency

    Institute of Scientific and Technical Information of China (English)

    周祁林

    2014-01-01

    There are some certain factors affecting L2 ( English) vocabulary acquisition such as L2 ( English) proficiency, readers’ purpose and the habit of reading, and the difficulty of target words and context, among which the first plays a key role. The paper, through a review of the relevant experimental researches, reaches a conclusion that L2 ( English) proficiency does influence much upon L2 vocabulary acquisition.

  20. Environmental factors regulating soil organic matter chlorination

    Science.gov (United States)

    Svensson, Teresia; Montelius, Malin; Reyier, Henrik; Rietz, Karolina; Karlsson, Susanne; Lindberg, Cecilia; Andersson, Malin; Danielsson, Åsa; Bastviken, David

    2016-04-01

    Natural chlorination of organic matter is common in soils. Despite the widespread abundance of soil chlorinated soil organic matter (SOM), frequently exceeding soil chloride abundance in surface soils, and a common ability of microorganisms to produce chlorinated SOM, we lack fundamental knowledge about dominating processes and organisms responsible for the chlorination. To take one step towards resolving the terrestrial chlorine (Cl) puzzle, this study aims to analyse how environmental factors influence chlorination of SOM. Four factors were chosen for this study: soil moisture (W), nitrogen (N), chloride (Cl) and organic matter quality (C). These factors are all known to be important for soil processes. Laboratory incubations with 36Cl as a Cl tracer were performed in a two soil incubation experiments. It was found that addition of chloride and nitrogen seem to hamper the chlorination. For the C treatment, on the other hand, the results show that chlorination is enhanced by increased availability of labile organic matter (glucose and maltose). Even higher chlorination was observed when nitrogen and water were added in combination with labile organic matter. The effect that more labile organic matter strongly stimulated the chlorination rates was confirmed by the second separate experiment. These results indicate that chlorination was not primarily a way to cut refractory organic matter into digestible molecules, representing one previous hypothesis, but is related with microbial metabolism in other ways that will be further discussed in our presentation.

  1. Recognition and Empirical Research on Key Influencing Factors of Low Carbon Development for Logistics Company

    Directory of Open Access Journals (Sweden)

    Xiang-Yun Duan

    2015-01-01

    Full Text Available The questionnaire paper used was work out by modifying the existing mature research scale and interviewing the experts and enterprises. The purpose of this study is to explore the key influencing factors of low carbon development for logistics companies by using the data from the questionnaire, which might contribute to further investigation of low carbon development pathway. Through correlation and stepwise regression analysis, differences between influencing factors and impact-degree were found since specific environmental behaviors of low carbon logistics might vary significantly. The driving factor of low carbon input comes from external points such as government and public external pressure, so the low carbon input is driven by an outside force. Yet, low carbon operation is significantly affected by internal factors such as low carbon behavior capacity, which is driven by an inside force.

  2. Exploring the Key Risk Factors for Application of Cloud Computing in Auditing

    Directory of Open Access Journals (Sweden)

    Kuang-Hua Hu

    2016-08-01

    Full Text Available In the cloud computing information technology environment, cloud computing has some advantages such as lower cost, immediate access to hardware resources, lower IT barriers to innovation, higher scalability, etc., but for the financial audit information flow and processing in the cloud system, CPA (Certified Public Accountant firms need special considerations, for example: system problems, information security and other related issues. Auditing cloud computing applications is the future trend in the CPA firms, given this issue is an important factor for them and very few studies have been conducted to investigate this issue; hence this study seeks to explore the key risk factors for the cloud computing and audit considerations. The dimensions/perspectives of the application of cloud computing audit considerations are huge and cover many criteria/factors. These risk factors are becoming increasingly complex, and interdependent. If the dimensions could be established, the mutually influential relations of the dimensions and criteria determined, and the current execution performance established; a prioritized improvement strategy designed could be constructed to use as a reference for CPA firm management decision making; as well as provide CPA firms with a reference for build auditing cloud computing systems. Empirical results show that key risk factors to consider when using cloud computing in auditing are, in order of priority for improvement: Operations (D, Automating user provisioning (C, Technology Risk (B and Protection system (A.

  3. From tyrosine to melanin: Signaling pathways and factors regulating melanogenesis

    Directory of Open Access Journals (Sweden)

    Zuzanna Rzepka

    2016-06-01

    Full Text Available Melanins are natural pigments of skin, hair and eyes and can be classified into two main types: brown to black eumelanin and yellow to reddish-brown pheomelanin. Biosynthesis of melanins takes place in melanosomes, which are specialized cytoplasmic organelles of melanocytes - dendritic cells located in the basal layer of the epidermis, uveal tract of the eye, hair follicles, as well as in the inner ear, central nervous system and heart. Melanogenesis is a multistep process and begins with the conversion of amino acid L-tyrosine to DOPAquinone. The addition of cysteine or glutathione to DOPAquinone leads to the intermediates formation, followed by subsequent transformations and polymerization to the final product, pheomelanin. In the absence of thiol compounds DOPAquinone undergoes an intramolecular cyclization and oxidation to form DOPAchrome, which is then converted to 5,6-dihydroksyindole (DHI or 5,6-dihydroxyindole-2-carboxylic acid (DHICA. Eumelanin is formed by polymerization of DHI and DHICA and their quinones. Regulation of melanogenesis is achieved by physical and biochemical factors. The article presents the intracellular signaling pathways: cAMP/PKA/CREB/MITF cascade, MAP kinases cascade, PLC/DAG/PKCβ cascade and NO/cGMP/PKG cascade, which are involved in the regulation of expression and activity of the melanogenesis-related proteins by ultraviolet radiation and endogenous agents (cytokines, hormones. Activity of the key melanogenic enzyme, tyrosinase, is also affected by pH and temperature. Many pharmacologically active substances are able to inhibit or stimulate melanin biosynthesis, as evidenced by in vitro studies on cultured pigment cells.

  4. Key success factors for clinical knowledge management systems: Comparing physician and hospital manager viewpoints.

    Science.gov (United States)

    Chang, Sho-Fang; Hsieh, Ping-Jung; Chen, Hui-Fang

    2015-01-01

    The study explores the perceptions of physicians and hospital managers regarding the key success factors (KSFs) of a clinical knowledge management system (CKMS). It aims to eliminate the perception gap and gain more insights for a successful CKMS.A survey was conducted in four medical centers in Taiwan. A total of 340 questionnaires, including 15 for hospital managers and 70 for physicians in each hospital, were administered. The effective response rates are 78.3% and 56.1% respectively. Partial least square (PLS) were used to analyze the data.The results identified six KSFs of CKMS including system software and hardware, knowledge quality, system quality, organizational factors, user satisfaction, and policy factors. User satisfaction and policy factors have direct effects on perceived CKMS performance. Knowledge quality is regarded as an antecedent to user satisfaction, while system quality is the antecedent to both user satisfaction and policy factors. System software and hardware was supported only by managers, and organizational factors were supported only by physicians.Among the factors, this study highlighted the policy factor. Besides, the study provides hospital managers additional insights into physician requirements for organizational support. Third, more physician participation and involvement are recommended when introducing and developing a CKMS.

  5. Substance P and Calcitonin Gene-Related Peptide: Key Regulators of Cutaneous Microbiota Homeostasis

    Science.gov (United States)

    N’Diaye, Awa; Gannesen, Andrei; Borrel, Valérie; Maillot, Olivier; Enault, Jeremy; Racine, Pierre-Jean; Plakunov, Vladimir; Chevalier, Sylvie; Lesouhaitier, Olivier; Feuilloley, Marc G. J.

    2017-01-01

    Neurohormones diffuse in sweat and epidermis leading skin bacterial microflora to be largely exposed to these host factors. Bacteria can sense a multitude of neurohormones, but their role in skin homeostasis was only investigated recently. The first study focused on substance P (SP), a neuropeptide produced in abundance by skin nerve terminals. SP is without effect on the growth of Gram-positive (Bacillus cereus, Staphylococcus aureus, and Staphylococcus epidermidis) and Gram-negative (Pseudomonas fluorescens) bacteria. However, SP is stimulating the virulence of Bacillus and Staphylococci. The action of SP is highly specific with a threshold below the nanomolar level. Mechanisms involved in the response to SP are different between bacteria although they are all leading to increased adhesion and/or virulence. The moonlighting protein EfTu was identified as the SP-binding site in B. cereus and Staphylococci. In skin nerve terminals, SP is co-secreted with the calcitonin gene-related peptide (CGRP), which was shown to modulate the virulence of S. epidermidis. This effect is antagonized by SP. Identification of the CGRP sensor, DnaK, allowed understanding this phenomenon as EfTu and DnaK are apparently exported from the bacterium through a common system before acting as SP and CGRP sensors. Many other neuropeptides are expressed in skin, and their potential effects on skin bacteria remain to be investigated. Integration of these host signals by the cutaneous microbiota now appears as a key parameter in skin homeostasis. PMID:28194136

  6. Key success factors of health research centers: A mixed method study

    Science.gov (United States)

    Tofighi, Shahram; Teymourzadeh, Ehsan; Heydari, Majid

    2017-01-01

    Background In order to achieve success in future goals and activities, health research centers are required to identify their key success factors. Objective This study aimed to extract and rank the factors affecting the success of research centers at one of the medical universities in Iran. Methods This study is a mixed method (qualitative-quantitative) study, which was conducted between May to October in 2016. The study setting was 22 health research centers. In qualitative phase, we extracted the factors affecting the success in research centers through purposeful interviews with 10 experts of centers, and classified them into themes and sub-themes. In the quantitative phase, we prepared a questionnaire and scored and ranked the factors recognized by 54 of the study samples by Friedman test. Results Nine themes and 42 sub-themes were identified. Themes included: strategic orientation, management, human capital, support, projects, infrastructure, communications and collaboration, paradigm and innovation and they were rated respectively as components of success in research centers. Among the 42 identified factors, 10 factors were ranked respectively as the key factors of success, and included: science and technology road map, strategic plan, evaluation indexes, committed human resources, scientific evaluation of members and centers, innovation in research and implementation, financial support, capable researchers, equipment infrastructure and teamwork. Conclusion According to the results, the strategic orientation was the most important component in the success of research centers. Therefore, managers and authorities of research centers should pay more attention to strategic areas in future planning, including the science and technology road map and strategic plan.

  7. An Analysis of the Key Factors Affecting Learners' Listening Comprehension%An Analysis of the Key Factors Affecting Learners' Listening Comprehension

    Institute of Scientific and Technical Information of China (English)

    王丽君

    2011-01-01

    With the purpose of improving the teaching of listening, this paper attempts to explore the key factors that hinder the improvement of students' listening comprehension. The research results indicate that problems mainly lie in the lack of a solid language foundation, cultural background knowledge, appropriate acquisition strategy and skills as well as enough practice and in the end the writer offers some suggestions on how to improve students' listening comprehension.%为了提高听力课堂的教学效果,本文探讨分析了影响提高学习者英语听力理解力的主要因素,它们是坚实的语言基础、相关文化背景知识、学习策略和技巧以及大量的语言实践,最后作者就如何提高听力提出了相关的建议。

  8. Effect of key factors on cold orbital forging of a spur bevel gear

    Institute of Scientific and Technical Information of China (English)

    庄武豪; 董丽颖

    2016-01-01

    Cold orbital forging is an advanced spur bevel gear forming technology. Generally, the spur bevel gear in the cold orbital forging process is formed by two steps: the preforming step and the final step. Due to the great importance of the final step to gear forming and its complication with interactive factors, this work aims at examining the influence of key factors on the final step in cold orbital forging of a spur bevel gear. Using the finite element (FE) method and control variate method, the influence rules of four key factors, rotation velocity of the upper tool,n, feeding velocity of the lower tool,v, tilted angle of the upper tool,γ, friction factor between the tools and the billet,m, on the geometry and the deformation inhomogeneity of the cold orbital forged gear are thoroughly clarified. The research results show that the flash becomes more homogeneous with increasingv, increasingm, decreasing n or decreasingγ. And the deformation of the gear becomes more homogeneous with increasingv, decreasingn or decreasingγ. Finally, a corresponding experiment is conducted, which verifies the accuracy of FE simulation conclusions.

  9. Key Factors for Selecting an Agile Method: A Systematic Literature Review

    Directory of Open Access Journals (Sweden)

    Mashal Kasem Alqudah

    2017-04-01

    Full Text Available Agile methods have become popular in recent years because the success rate of project development using Agile methods is better than structured design methods. Nevertheless, less than 50 percent of projects implemented using Agile methods are considered successful, and selecting the wrong Agile method is one of the reasons for project failure. Selecting the most appropriate Agile method is a challenging task because there are so many to choose from. In addition, potential adopters believe that migrating to an Agile method involves taking a drastic risk. Therefore, to assist project managers and other decision makers, this study aims to identify the key factors that should be considered when selecting an appropriate Agile method. A systematic literature review was performed to elicit these factors in an unbiased manner and then content analysis was used to analyze the resultant data. It was found that the nature of project, development team skills, project constraints, customer involvement and organizational culture are the key factors that should guide decision makers in the selection of an appropriate Agile method based on the value these factors have for different organizations and/or different projects.

  10. Effect of 3 Key Factors on Average End to End Delay and Jitter in MANET

    Directory of Open Access Journals (Sweden)

    Saqib Hakak

    2015-01-01

    Full Text Available A mobile ad-hoc network (MANET is a self-configuring infrastructure-less network of mobile devices connected by wireless links where each node or mobile device is independent to move in any desired direction and thus the links keep moving from one node to another. In such a network, the mobile nodes are equipped with CSMA/CA (carrier sense multiple access with collision avoidance transceivers and communicate with each other via radio. In MANETs, routing is considered one of the most difficult and challenging tasks. Because of this, most studies on MANETs have focused on comparing protocols under varying network conditions. But to the best of our knowledge no one has studied the effect of other factors on network performance indicators like throughput, jitter and so on, revealing how much influence a particular factor or group of factors has on each network performance indicator. Thus, in this study the effects of three key factors, i.e. routing protocol, packet size and DSSS rate, were evaluated on key network performance metrics, i.e. average delay and average jitter, as these parameters are crucial for network performance and directly affect the buffering requirements for all video devices and downstream networks.

  11. Key factors in the successful implementation of enterprise resource planning system

    Directory of Open Access Journals (Sweden)

    Farajollah Rahnavard

    2014-04-01

    Full Text Available Enterprise Resource Planning Systems (ERP are considered as the newest and most effective tools of enterprise resource planning and include an interconnected information, management and engineering system that meets all the needs of an organization. ERP implementation is costly and time-consuming and makes fundamental change in the process, if not implemented correctly it will cause challenges in most parts of the organization and will certainly fail. Therefore, the identification of key success factors in implementing ERP helps organizations avoid the loss of the project. This research aims to identify key success factors for ERP by examining 185 managers, professionals, experts of the Information and Communication Technology Institute associated with the Ministry of Communications and Information Technology of Iran. A questionnaire was used to collect data. Findings from exploratory factor analysis indicate that five factors: 1 user friendliness, flexible and consistency 2 establishment of project management; 3 alignment with user needs; 4 Management of organizational changes, and 5 observing the principles of successful implementation of ERP affect the institute and the corresponding suggestions are proposed consistent with these findings.

  12. Examining the Key Factors Affecting e-Service Quality of Small Online Apparel Businesses in Malaysia

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    Che Nawi Noorshella

    2015-04-01

    Full Text Available e-Service quality (eSQ is increasingly recognized as an important aspect, as well as the key to determining the competitive advantage and factor in the long-term retention of firms operating online. This study, therefore, is aimed at identifying the key determinants of eSQ among the small online apparel businesses in Malaysia. This study used a cross-sectional design, and data were collected from 765 customers who purchased apparel online at the point-of-purchase. Findings of this study indicate that “product information quality,” “website design,” “security and privacy,” and “expected consumer service” are the key determinants of eSQ among small online apparel businesses in Malaysia. The implication for the owner-managers of the apparel businesses in Malaysia is that they must be aware of the significance of the key eSQ indicators while designing their businesses, to attract and retain customers.

  13. Two-Factor User Authentication with Key Agreement Scheme Based on Elliptic Curve Cryptosystem

    Directory of Open Access Journals (Sweden)

    Juan Qu

    2014-01-01

    Full Text Available A password authentication scheme using smart card is called two-factor authentication scheme. Two-factor authentication scheme is the most accepted and commonly used mechanism that provides the authorized users a secure and efficient method for accessing resources over insecure communication channel. Up to now, various two-factor user authentication schemes have been proposed. However, most of them are vulnerable to smart card loss attack, offline password guessing attack, impersonation attack, and so on. In this paper, we design a password remote user authentication with key agreement scheme using elliptic curve cryptosystem. Security analysis shows that the proposed scheme has high level of security. Moreover, the proposed scheme is more practical and secure in contrast to some related schemes.

  14. A consideration of select pre-trauma factors as key vulnerabilities in PTSD

    Science.gov (United States)

    Bomyea, Jessica; Risbrough, Victoria; Lang, Ariel J.

    2012-01-01

    Posttraumatic stress disorder (PTSD) is a pathological response to a traumatic event. A number of risk and vulnerability factors predicting PTSD development have been identified in the literature. Many of these variables are specific factors occurring during and after exposure to a traumatic event or are not measured prospectively to assess temporal sequence. Recent research, however, has begun to focus on pre-trauma individual differences that could contribute to risk for developing PTSD. The present review proposes that a number of biological and cognitive vulnerability factors place individuals at risk for PTSD development prior to the actual experience of trauma. Accordingly, this review provides a summary of evidence for a select number of these factors as pre-trauma vulnerabilities to PTSD. Included is a discussion of biological factors, including molecular genetic studies of systems regulating serotonin, catecholamines, and glucocorticoids as well as aspects of the neuroendocrine system. Specific cognitive factors are also considered, including intelligence, neuropsychological functioning and cognitive biases such as negative attributional style and appraisals. For each factor, the present review summarizes evidence to date regarding PTSD vulnerability and highlights directions for future research in this area. PMID:22917742

  15. Key Success Factors of 3rd Generation Mobile Network Services for M-Commerce in Malaysia

    Directory of Open Access Journals (Sweden)

    Saravanan Muthaiyah

    2004-01-01

    Full Text Available While there has been a great deal of excitement in view of M-commerce, very little is actually known about conditions and critical success factors for successful introduction of the 3rd generation mobile network services here in Malaysia. This study investigates the factors for successful diffusion of 3G network services and their role in advancing an interactive marketplace. 3G which simply means 3rd generation mobile communications technology has been widely discussed by many telecommunications service providers. It was launched by the International Telecommunication Union (ITU some 13 years ago. 3G is viewed as an enabler of M-Commerce here in Malaysia. However, true success of this technology depends on various factors. The objective of this study is to investigate significant key enablers of 3G deployment and adoption in Malaysia. An insight into the critical factors to be considered for the deployment of 3G technology in Malaysia and experiences of other countries will be used as a benchmark to understand the mitigating factors of 3G deployment. Critical factors such as cost to of service, interoperability of standards, insufficiency of mobile services or content and deficiency of the laws will be discussed in this study. The study also discusses diffusion barriers and drivers for the rapid service diffusion of 3G mobile networks.

  16. Analysis of the Investment in Wood Processing and Furniture Manufacturing Entities by Key Factors of Competitiveness

    Directory of Open Access Journals (Sweden)

    Renata Ojurović

    2013-06-01

    Full Text Available Processing of wood and manufacture of wood and cork products, excluding furniture, manufacture of straw and plaiting goods (C16 and manufacture of furniture (C31 were the most competitive activities of the Republic of Croatia in the European market in the late 1980s and early 1990s. Those activities began losing their market share at the end of 1994, and no significant positive change in market competitiveness has been recorded since then. The question is how to achieve and maintain competitiveness, which is the condition of survival in an increasingly demanding environment. Preliminary and previous research on investments points to the assumption that the problem of competitiveness in the observed economic branch essentially boils down to a problem in the quality and efficiency of the investments of associated business entities. This paper tries to give answers to the following questions: What is the investment policy, is there an internal factor for lagging behind in competitiveness, what the other reasons are and how competitiveness can be achieved. By analyzing the investment in key factors of competitiveness in the period 2007 to 2010, consistently established by this paper, the existing data on investment of wood processing and furniture manufacturing entities will be identified, and an AHP investment model will be proposed that takes into account the simultaneous influence of all of the key factors of competitiveness and is the best indicator of the direction to be taken, with the final aim of achieving competitiveness.

  17. Detection of key factors in the extraction and quantification of lycopene from tomato and tomato products.

    Science.gov (United States)

    Periago, María Jesús; Rincón, Francisco; Jacob, Karin; García-Alonso, Javier; Ros, Gaspar

    2007-10-31

    The analytical process of lycopene extraction and photometrical determination was critically examined for raw tomato and processed tomato products by means of a 2 IV (15-10) Plackett-Burman experimental design in order to identify the key factors (KFs) involved. Fifteen apparent key factors (AKFs) reported in the literature were selected: sample weight (X1); volume of extraction solution (X2); antioxidant concentration (BHT, X3); neutralizing agent concentration (MgCO 3, X4); light presence during lycopene extraction (X5), homogenization velocity (X6) and time (X7), agitation time (X8), and temperature (X9) during the extraction process; water volume for separation of polar/nonpolar phases (X11); presence of inert atmosphere throughout the process (X12); time (X13), temperature (X14), and light presence (X10) during separation of phases and time delay for reading (X15). In general, higher lycopene concentrations in samples led to a higher number of key factors (KF). Thus, for raw tomato (lycopene range 1.22-2.29 mg/100 g) no KF were found, whereas for tomato sauce (lycopene range from 5.80 to 8.60 mg/100 g) one KF (X4) and for tomato paste (lycopene range from 35.80 to 51.27 mg/100 g) five KFs (X1, X2, X4, X11, and X12) were detected. For lycopene paste, X1 and X2 were identified as the KFs with the greatest impact on results, although in fact the X1/X2 ratio was the real cause. The results suggest that, with increased processing, the physical and chemical structure of lycopene becomes less important since the identified KFs explain almost 90% of variability in tomato paste but only 32% in raw tomato.

  18. Export experience and key success factors in cross-border trade: Evidence from Southern Africa

    Directory of Open Access Journals (Sweden)

    Shepherd Dhliwayo

    2017-01-01

    Full Text Available Orientation: Cross-border trade (CBT is an important economic activity that contributes to the development of many economies of the developing world.Research purpose:  The two primary aims of the study were to find out the major factors needed to succeed in cross-border trading and whether the importance of these factors significantly decreased with export experience.Motivation for the study: The economic contribution of cross-border trade (CBT is often understated. As a result, it does not get the attention it deserves.Research design, approach and method: Data were collected in Gauteng from 146 cross-border traders from 10 Southern African Development Community (SADC countries. A cross-sectional research design was used.Main findings: The major key success factors were found to be skills/knowledge in; markets and supplies; financial management; and border issues. The importance of these factors was found to not significantly change with levels of export experience.Practical/managerial implications:  Stakeholders should know that small firms of differing export experience require the same interventions to succeed. Interventions should empower traders to better access markets and supplies, improve their financial management skills and ease border constraints.Contribution/value-add: Few studies on cross border trading have been carried out in the Southern African Development Community region. The key success factors and the constraints in this type of trade had not been adequately explored. The economic contribution of CBT, which usually goes unnoticed, was highlighted. Interventions to appropriately address the challenges faced, such as trading legitimacy and border harassment, were suggested.

  19. Key Human Factors of Vehicle Interior Occupant Packaging in SAE Standard

    Institute of Scientific and Technical Information of China (English)

    DING Yi; HU Ping; JIN Chun-ning; WU Xiao-jun

    2007-01-01

    Fourteen SAE standards related to accommodation and occupant packaging for vehicle interior are studied.The influencing factors,key reference accommodation points and major design dimensions and their relationships of occupant packaging and ergonomics during the vehicle interior layout design and development are analyzed.Prototypes are presented to verify the results and how to achieve the packaging is shown.Automobile designers can achieve significant practical guidance for human safety,efficiency accommodation and occupant packaging of all passengers during the vehicle design process.

  20. PII,the key regulator of nitrogen metabolism in the cyanobacteria

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    PII proteins are a protein family important to signal transduction in bacteria and plants. PII plays a critical role in regulation of carbon and nitrogen metabolism in cyanobacteria. Through conformation change and covalent modification, which are regulated by 2-oxoglutarate, PII interacts with different target proteins in response to changes of cellular energy status and carbon and nitrogen sources in cyanobacteria and regulates cellular metabolism. This article reports recent progress in PII research in cyanobacteria and discusses the mechanism of PII regulation of cellular metabolism .

  1. Occupancy by key transcription factors is a more accurate predictor of enhancer activity than histone modifications or chromatin accessibility.

    Science.gov (United States)

    Dogan, Nergiz; Wu, Weisheng; Morrissey, Christapher S; Chen, Kuan-Bei; Stonestrom, Aaron; Long, Maria; Keller, Cheryl A; Cheng, Yong; Jain, Deepti; Visel, Axel; Pennacchio, Len A; Weiss, Mitchell J; Blobel, Gerd A; Hardison, Ross C

    2015-01-01

    Regulated gene expression controls organismal development, and variation in regulatory patterns has been implicated in complex traits. Thus accurate prediction of enhancers is important for further understanding of these processes. Genome-wide measurement of epigenetic features, such as histone modifications and occupancy by transcription factors, is improving enhancer predictions, but the contribution of these features to prediction accuracy is not known. Given the importance of the hematopoietic transcription factor TAL1 for erythroid gene activation, we predicted candidate enhancers based on genomic occupancy by TAL1 and measured their activity. Contributions of multiple features to enhancer prediction were evaluated based on the results of these and other studies. TAL1-bound DNA segments were active enhancers at a high rate both in transient transfections of cultured cells (39 of 79, or 56%) and transgenic mice (43 of 66, or 65%). The level of binding signal for TAL1 or GATA1 did not help distinguish TAL1-bound DNA segments as active versus inactive enhancers, nor did the density of regulation-related histone modifications. A meta-analysis of results from this and other studies (273 tested predicted enhancers) showed that the presence of TAL1, GATA1, EP300, SMAD1, H3K4 methylation, H3K27ac, and CAGE tags at DNase hypersensitive sites gave the most accurate predictors of enhancer activity, with a success rate over 80% and a median threefold increase in activity. Chromatin accessibility assays and the histone modifications H3K4me1 and H3K27ac were sensitive for finding enhancers, but they have high false positive rates unless transcription factor occupancy is also included. Occupancy by key transcription factors such as TAL1, GATA1, SMAD1, and EP300, along with evidence of transcription, improves the accuracy of enhancer predictions based on epigenetic features.

  2. A simple repeat polymorphism in the MITF-M promoter is a key regulator of white spotting in dogs.

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    Izabella Baranowska Körberg

    Full Text Available The white spotting locus (S in dogs is colocalized with the MITF (microphtalmia-associated transcription factor gene. The phenotypic effects of the four S alleles range from solid colour (S to extreme white spotting (s(w. We have investigated four candidate mutations associated with the s(w allele, a SINE insertion, a SNP at a conserved site and a simple repeat polymorphism all associated with the MITF-M promoter as well as a 12 base pair deletion in exon 1B. The variants associated with white spotting at all four loci were also found among wolves and we conclude that none of these could be a sole causal mutation, at least not for extreme white spotting. We propose that the three canine white spotting alleles are not caused by three independent mutations but represent haplotype effects due to different combinations of causal polymorphisms. The simple repeat polymorphism showed extensive diversity both in dogs and wolves, and allele-sharing was common between wolves and white spotted dogs but was non-existent between solid and spotted dogs as well as between wolves and solid dogs. This finding was unexpected as Solid is assumed to be the wild-type allele. The data indicate that the simple repeat polymorphism has been a target for selection during dog domestication and breed formation. We also evaluated the significance of the three MITF-M associated polymorphisms with a Luciferase assay, and found conclusive evidence that the simple repeat polymorphism affects promoter activity. Three alleles associated with white spotting gave consistently lower promoter activity compared with the allele associated with solid colour. We propose that the simple repeat polymorphism affects cooperativity between transcription factors binding on either flanking sides of the repeat. Thus, both genetic and functional evidence show that the simple repeat polymorphism is a key regulator of white spotting in dogs.

  3. Peroxiredoxin 3 is a key molecule regulating adipocyte oxidative stress, mitochondrial biogenesis, and adipokine expression.

    Science.gov (United States)

    Huh, Joo Young; Kim, Yunghee; Jeong, Jaeho; Park, Jehyun; Kim, Inok; Huh, Kyu Ha; Kim, Yu Seun; Woo, Hyun Ae; Rhee, Sue Goo; Lee, Kong-Joo; Ha, Hunjoo

    2012-02-01

    Increased oxidative stress and mitochondrial dysfunction in obese adipocytes contribute to adipokine dysregulation, inflammation, and insulin resistance. Through an advanced proteomic analysis, we found that peroxiredoxin 3 (Prx3), a thioredoxin-dependent mitochondrial peroxidase, is highly expressed in 3T3-L1 adipocytes compared to preadipocytes. Interestingly, in obese db/db mice and human subjects, adipose Prx3 levels were significantly decreased, indicating its association with obesity. We therefore employed Prx3 knockout (KO) mice and transfected 3T3-L1 cells to examine the role of endogenous Prx3 in adipocyte metabolism. Prx3 KO mice had increased fat mass compared to wild-type due to adipocyte hypertrophy. Increased adipogenic transcription factors and lipogenic gene expression during differentiation of adipose tissue-derived stem cells from Prx3-deficient mice confirmed that these adipocytes are likely to accumulate fat. Mitochondrial protein carbonylation in Prx3 KO adipose tissue and mitochondrial superoxide level in Prx3 knockdown 3T3-L1 cells were increased showing aberrant regulation of oxidative stress. Proteomic analysis and gene expression analysis of Prx3 KO mice adipocytes also showed defect in mitochondria biogenesis along with enzymes involved in glucose/lipid metabolism and oxidative phosphorylation. In addition, expression level of adiponectin was downregulated and plasminogen activator inhibitor-1 was upregulated in Prx3 KO adipocytes. Impaired glucose tolerance and insulin resistance further implied metabolic dysregulation in Prx3 KO mice. These data suggest that endogenous Prx3 may play an essential role in maintaining normal characteristics of adipocytes and that defect in Prx3 alters mitochondrial redox state and function, and adipokine expression in adipocytes leading to metabolic alteration.

  4. Three-Factor User Authentication and Key Agreement Using Elliptic Curve Cryptosystem in Wireless Sensor Networks.

    Science.gov (United States)

    Park, YoHan; Park, YoungHo

    2016-12-14

    Secure communication is a significant issue in wireless sensor networks. User authentication and key agreement are essential for providing a secure system, especially in user-oriented mobile services. It is also necessary to protect the identity of each individual in wireless environments to avoid personal privacy concerns. Many authentication and key agreement schemes utilize a smart card in addition to a password to support security functionalities. However, these schemes often fail to provide security along with privacy. In 2015, Chang et al. analyzed the security vulnerabilities of previous schemes and presented the two-factor authentication scheme that provided user privacy by using dynamic identities. However, when we cryptanalyzed Chang et al.'s scheme, we found that it does not provide sufficient security for wireless sensor networks and fails to provide accurate password updates. This paper proposes a security-enhanced authentication and key agreement scheme to overcome these security weaknesses using biometric information and an elliptic curve cryptosystem. We analyze the security of the proposed scheme against various attacks and check its viability in the mobile environment.

  5. CHILD-PARENT VIOLENCE: MAIN CHARACTERISTICS, RISK FACTORS AND KEYS TO INTERVENTION

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    M. Luisa Martínez

    2015-09-01

    Full Text Available Child-parent Violence (hereinafter CPV is an increasingly evident problem in the social, health, and judicial protection systems which, however, continue to show a number of major deficiencies with respect to the main characteristics of CPV, the people involved, the underlying factors, and efficacious interventions. Nevertheless, there is a consensus regarding its devastating consequences. The present bibliographical review is focused on analysing the problem of CPV with the aim of offering useful data for future research and intervention proposals. Specifically, this paper provides a definition of CPV and its types, some data on prevalence, the main characteristics of aggressive children and abused parents, and the most important individual, family, school and community risk factors highlighted in the current scientific literature. The keys areas of intervention with this group are also presented.

  6. Key success factors for implementing Taiwan TrainQuali System (TTQS in Taiwanese enterprises

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    Tzong-Ru (Jiun-Shen Lee

    2015-01-01

    Full Text Available Facing the change of economic environment and the need of enhancing competitive advantages, small and medium-sized enterprises in Taiwan utilize ‘Taiwan TrainQuali System (TTQS’ on training talents. In order to maximize the benefits of TTQS implementation and increase the training efficiency, this paper aims to use ‘grey relational analysis (GRA’ to extract key success factors (KSFs from 46 factors, which influence the implementation of TTQS. Moreover, this study also verifies the KSFs with nine case companies which have won gold medals in TTQS evaluation and sum up 12 concrete practices as references for other enterprises in order to show how to implement the TTQS training quality system better in the future, and in turn enhance the quality and performance of human resource training.

  7. 77 FR 23425 - Revisions of Boundaries, Regulations and Zoning Scheme for Florida Keys National Marine Sanctuary...

    Science.gov (United States)

    2012-04-19

    ... Morkill, Refuge Manager, U.S. Fish and Wildlife Service, 28950 Watson Blvd., Big Pine Key, FL 33043... conservation strategies, expressed during and subsequent to management plan reviews; Periodic evaluation of..., zoning scheme, backcountry management agreement, environmental evaluation, and, if...

  8. Transcription factors involved in the regulation of natural killer cell development and function: an update

    Directory of Open Access Journals (Sweden)

    Martha Elia Luevano

    2012-10-01

    Full Text Available Natural Killer (NK cells belong to the innate immune system and are key effectors in the immune response against cancer and infection. Recent studies have contributed to the knowledge of events controlling NK cell fate. The use of knockout mice has enabled the discovery of key transcription factors (TFs essential for NK cell development and function. Yet, unwrapping the downstream targets of these TFs and their influence on NK cells remains a challenge. In this review we discuss the latest TFs described to be involved in the regulation of NK cell development and maturation.

  9. Nrf2 transcription factor gene regulates basal transcription of ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-10-19

    Oct 19, 2009 ... In contrast, there was no obvious effect on SOD2 in the Nrf2(+/+) mouse brain by any of the chemicals used . Key words: Nuclear ..... necrosis factor, selected anticancer drugs, and ionizing radiation. FASEB J. 7: 361-368.

  10. Key factors for the implementation of successful, stand-alone village electrification schemes in Peru

    Science.gov (United States)

    Sanchez-Campos, Teodoro

    The hypothesis of this work is that there are social, financial, technical, managerial institutional and political key factors that may either support or prevent the success of small stand alone energy systems in rural areas. This research work aims at contributing to the identification of such factors and study their relevance to the performance and sustainability of stand alone energy systems in rural areas; to meet its purpose, a wide range of literature was reviewed including rural electrification programmes and projects, research and development projects on access to electricity in rural areas, impact studies and others, and a field research survey was done the Andes and Upper Jungle regions in Peru. Nineteen possible critical factors were identified, thirteen with relevance at the local context (the community or village), and six with relevance at the national (or wider) context. From literature review it was found that the possible local critical factors were relevant only to four categories of factors instead of the six considered initially (i.e. social, financial, technological and managerial): the other two categories, political and institutional were found to be more relevant to the national context, therefore those were included in the group of possible critical factors of wider context. A series of questionnaires were designed to collect field data information, which was later used to analyse and establish the relation of each identified factor with the success of the systems studied. The survey research was implemented in 14 villages, 7 with small diesel sets and 7 with small hydropower schemes, all spread in the Andes and Upper Jungle of Peru, which were carefully selected to be representative of regions with isolated stand alone systems and with different socioeconomic background. Out of the 13 possible critical factors of local context, it was found that only 3 are really critical, the others are important but not critical; one of them (technical

  11. cAMP and EPAC are key players in the regulation of the signal transduction pathway involved in the α-hemolysin autophagic response.

    Directory of Open Access Journals (Sweden)

    María Belén Mestre

    Full Text Available Staphylococcus aureus is a microorganism that causes serious diseases in the human being. This microorganism is able to escape the phagolysosomal pathway, increasing intracellular bacterial survival and killing the eukaryotic host cell to spread the infection. One of the key features of S. aureus infection is the production of a series of virulence factors, including secreted enzymes and toxins. We have shown that the pore-forming toxin α-hemolysin (Hla is the S. aureus-secreted factor responsible for the activation of the autophagic pathway and that this response occurs through a PI3K/Beclin1-independent form. In the present report we demonstrate that cAMP has a key role in the regulation of this autophagic response. Our results indicate that cAMP is able to inhibit the autophagy induced by Hla and that PKA, the classical cAMP effector, does not participate in this regulation. We present evidence that EPAC and Rap2b, through calpain activation, are the proteins involved in the regulation of Hla-induced autophagy. Similar results were obtained in cells infected with different S. aureus strains. Interestingly, in this report we show, for the first time to our knowledge, that both EPAC and Rap2b are recruited to the S. aureus-containing phagosome. We believe that our findings have important implications in understanding innate immune processes involved in intracellular pathogen invasion of the host cell.

  12. Analyzing the key factors affecting the green supply chain management: A case study of steel industry

    Directory of Open Access Journals (Sweden)

    Hamideh Shekari

    2011-10-01

    Full Text Available Green supply chain management (GSCM has emerged as a proactive approach for improving environmental performance of processes and products in accordance with the requirements of environmental regulations. The aim of this paper is to determine and model the drivers of GSCM to put environmental activities into practice. Thirty-four measurement items are developed on the basis of opinions from industrial experts and the literature and the necessary data are collected. To validate the measurement scales for GSCM, we perform a factor analysis. The results show that a six-factor measurement model (including internal environmental management, green purchasing, cleaner production, recovery, eco-design and pollution fits the data acceptably. All of the measurement items significantly loaded on the constructs on which they were hypothesized to load. These results gave us confidence that the measures are indeed valid and reliable.

  13. BATF: Bringing (in) Another Th17-regulating Factor

    Institute of Scientific and Technical Information of China (English)

    Gustavo J. Martinez; Chen Dong

    2009-01-01

    T helper (Th) 17 cells are a recently identified subset of T cells that regulate tissue inflammation, and RORγt and RORα have been shown to be Th17-specific transcription factors that mediate Th17 cell generation. A new study of Batf-deficient mice shows that this AP-1 family transcription factor also regulates Th17 cell differentiation by binding to Th17-associated gene promoters and by maintaining RORa and RORgt expression, shedding new lights on current clinical modulation of Th17 cell function in inflammatory diseases.

  14. Beclin 1 regulates growth factor receptor signaling in breast cancer.

    Science.gov (United States)

    Rohatgi, R A; Janusis, J; Leonard, D; Bellvé, K D; Fogarty, K E; Baehrecke, E H; Corvera, S; Shaw, L M

    2015-10-16

    Beclin 1 is a haploinsufficient tumor suppressor that is decreased in many human tumors. The function of beclin 1 in cancer has been attributed primarily to its role in the degradative process of macroautophagy. However, beclin 1 is a core component of the vacuolar protein sorting 34 (Vps34)/class III phosphatidylinositoI-3 kinase (PI3KC3) and Vps15/p150 complex that regulates multiple membrane-trafficking events. In the current study, we describe an alternative mechanism of action for beclin 1 in breast cancer involving its control of growth factor receptor signaling. We identify a specific stage of early endosome maturation that is regulated by beclin 1, the transition of APPL1-containing phosphatidyIinositol 3-phosphate-negative (PI3P(-)) endosomes to PI3P(+) endosomes. Beclin 1 regulates PI3P production in response to growth factor stimulation to control the residency time of growth factor receptors in the PI3P(-)/APPL(+)-signaling-competent compartment. As a result, suppression of BECN1 sustains growth factor-stimulated AKT and ERK activation resulting in increased breast carcinoma cell invasion. In human breast tumors, beclin 1 expression is inversely correlated with AKT and ERK phosphorylation. Our data identify a novel role for beclin 1 in regulating growth factor signaling and reveal a mechanism by which loss of beclin 1 expression would enhance breast cancer progression.

  15. Geminin deletion increases the number of fetal hematopoietic stem cells by affecting the expression of key transcription factors.

    Science.gov (United States)

    Karamitros, Dimitris; Patmanidi, Alexandra L; Kotantaki, Panoraia; Potocnik, Alexandre J; Bähr-Ivacevic, Tomi; Benes, Vladimir; Lygerou, Zoi; Kioussis, Dimitris; Taraviras, Stavros

    2015-01-01

    Balancing stem cell self-renewal and initiation of lineage specification programs is essential for the development and homeostasis of the hematopoietic system. We have specifically ablated geminin in the developing murine hematopoietic system and observed profound defects in the generation of mature blood cells, leading to embryonic lethality. Hematopoietic stem cells (HSCs) accumulated in the fetal liver following geminin ablation, while committed progenitors were reduced. Genome-wide transcriptome analysis identified key HSC transcription factors as being upregulated upon geminin deletion, revealing a gene network linked with geminin that controls fetal hematopoiesis. In order to obtain mechanistic insight into the ability of geminin to regulate transcription, we examined Hoxa9 as an example of a key gene in definitive hematopoiesis. We demonstrate that in human K562 cells geminin is associated with HOXA9 regulatory elements and its absence increases HOXA9 transcription similarly to that observed in vivo. Moreover, silencing geminin reduced recruitment of the PRC2 component SUZ12 to the HOXA9 locus and resulted in an increase in RNA polymerase II recruitment and H3K4 trimethylation (H3K4me3), whereas the repressive marks H3K9me3 and H3K27me3 were reduced. The chromatin landscape was also modified at the regulatory regions of HOXA10 and GATA1. K562 cells showed a reduced ability to differentiate to erythrocytes and megakaryocytes upon geminin silencing. Our data suggest that geminin is indispensable for fetal hematopoiesis and regulates the generation of a physiological pool of stem and progenitor cells in the fetal hematopoietic system.

  16. Study of Key Factors Determinant Choice of Rail-Based Mass Transit

    Directory of Open Access Journals (Sweden)

    Ircham

    2016-07-01

    Full Text Available Pursuant to regulations of the Ministry of Transportation in 2002 about the type of transport based on the city size, the metropolis with a population of more than 1 million inhabitants are required to have the urban mass transit. Nevertheless, until now not all city-scale population of more than 1 million have mass public transport, either bus or rail-based. Especially for rail-based mass transit, indicated the existing regulations have not been able to challenge the development of rail-based urban mass transit. Learning from the literature study and the experience of countries that already have rail-based urban mass transit it has acquired nine main factors to be taken into account in developing a rail-based urban public transportation. This study was conducted by using Analytical Hierarchy Process method which was further validated through the implementation of the On Focus Group Discussion in the Jakarta City Transportation Council (DTKJ as well as in the City Development Planning Board (Bappeko Surabaya. Finally, the initial result shown five sequences determining factor for the determinant choice of rail-based mass transit, namely: fiscal or economic capacity of the region and society, transport policy, integrated public transport, land use, fare and travel time. Furthermore, the acquisition results of this study can be applied to the selected cities to address the challenges to urban mass transit development.

  17. 75 FR 72655 - Marine Sanitation Device Discharge Regulations for the Florida Keys National Marine Sanctuary

    Science.gov (United States)

    2010-11-26

    ... sanitation devices (MSDs) approved under the Clean Water Act (CWA), and by requiring that MSDs be secured to... approved MSDs incidental to vessel use. In certain protected zones, including Ecological Reserves... MSDs and vessel discharges within the Florida Keys region. In addition, several private, state, local...

  18. Neuropeptide W: a key player in the homeostatic regulation of feeding and energy metabolism?

    Science.gov (United States)

    Takenoya, Fumiko; Kageyama, Haruaki; Shiba, Kanako; Date, Yukari; Nakazato, Masamitsu; Shioda, Seiji

    2010-07-01

    Neuropeptide W (NPW), recently isolated from porcine hypothalamus, has been identified as the endogenous ligand for both NPBWR1 (GPR7) and NPBWR2 (GPR8), which belong to the orphan G protein-coupled receptor family. NPW is thought to play an important role in the regulation of feeding and drinking behavior, and to be related to the stress response. NPW-containing neurons are localized in several regions of the brain, including the hypothalamus, hippocampus, limbic system, midbrain, and brain stem. Accumulated evidence suggests that hypothalamic neuropeptides, such as neuropeptide Y (NPY), orexin, melanin-concentrating hormone (MCH), and proopiomelanocortin (POMC), are involved in the regulation of feeding behavior and energy homeostasis via neuronal circuits in the hypothalamus. NPW also forms part of the feeding-regulating neuronal circuitry in conjunction with other feeding-regulating peptide-containing neurons within the hypothalamus. We summarize our current understanding of the distribution of NPW and of the neuronal interactions between NPW and the different feeding-regulating peptide-containing neurons. This review also discusses evidence for the dichotomous actions of NPW on energy balance and the potential mechanisms involved.

  19. Key Factors Controlling the Applicability and Efficiency of Bioremediation of Chlorinated Ethenes In Situ

    Science.gov (United States)

    Zhang, M.; Yoshikawa, M.; Takeuchi, M.; Komai, T.

    2012-12-01

    Bioremediation has been considered as one of environmentally friendly and cost effective approaches for cleaning up the sites polluted by organic contaminants, such as chlorinated ethenes. Although bioremediation, in its widest sense, is not new, and many researches have been performed on bioremediation of different kinds of pollutants, an effective design and implication of in situ bioremediation still remains a challenging problem because of the complexity. Many factors may affect the applicability and efficiency of bioremediation of chlorinated ethenes in situ, which include the type and concentration of contaminants, biological, geological and hydro-geological conditions of the site, physical and chemical characteristics of groundwater and soils to be treated, as well as the constraints in engineering. In this presentation, an overview together with a detailed discussion on each factor will be provided. The influences of individual factors are discussed using the data obtained or cited from different sites and experiments, and thus under different environmental conditions. The results of this study illustrated that 1) the establishment of microbial consortium is of crucial importance for a complete degradation of chlorinated ethenes, 2) in situ control of favorable conditions for increasing microbial activities for bio-degradation through a designed pathway is the key to success, 3) the focus of a successful remediation system is to design an effective delivery process that is capable of producing adequate amendment mixing of contaminant-degrading bacteria, appropriate concentrations of electron acceptors, electron donors, and microbial nutrients in the subsurface treatment area.

  20. Key factors of eddy current separation for recovering aluminum from crushed e-waste.

    Science.gov (United States)

    Ruan, Jujun; Dong, Lipeng; Zheng, Jie; Zhang, Tao; Huang, Mingzhi; Xu, Zhenming

    2017-02-01

    Recovery of e-waste in China had caused serious pollutions. Eddy current separation is an environment-friendly technology of separating nonferrous metallic particles from crushed e-waste. However, due to complex particle characters, separation efficiency of traditional eddy current separator was low. In production, controllable operation factors of eddy current separation are feeding speed, (ωR-v), and Sp. There is little special information about influencing mechanism and critical parameters of these factors in eddy current separation. This paper provided the special information of these key factors in eddy current separation of recovering aluminum particles from crushed waste refrigerator cabinets. Detachment angles increased as the increase of (ωR-v). Separation efficiency increased with the growing of detachment angles. Aluminum particles were completely separated from plastic particles in critical parameters of feeding speed 0.5m/s and detachment angles greater than 6.61deg. Sp/Sm of aluminum particles in crushed waste refrigerators ranged from 0.08 to 0.51. Separation efficiency increased as the increase of Sp/Sm. This enlightened us to develop new separator to separate smaller nonferrous metallic particles in e-waste recovery. High feeding speed destroyed separation efficiency. However, greater Sp of aluminum particles brought positive impact on separation efficiency. Greater Sp could increase critical feeding speed to offer greater throughput of eddy current separation. This paper will guide eddy current separation in production of recovering nonferrous metals from crushed e-waste.

  1. Psychological factors mediate key symptoms of fibromyalgia through their influence on stress.

    Science.gov (United States)

    Malin, Katrina; Littlejohn, Geoffrey Owen

    2016-09-01

    The clinical features of fibromyalgia are associated with various psychological factors, including stress. We examined the hypothesis that the path that psychological factors follow in influencing fibromyalgia symptoms is through their direct effect on stress. Ninety-eight females with ACR 1990 classified fibromyalgia completed the following questionnaires: The Big 5 Personality Inventory, Fibromyalgia Impact Questionnaire, Perceived Stress Scale, Profile of Mood States, Mastery Scale, and Perceived Control of Internal States Scale. SPSS (PASW version 22) was used to perform basic t tests, means, and standard deviations to show difference between symptom characteristics. Pathway analysis using structural equation modelling (Laavan) examined the effect of stress on the relationships between psychological factors and the elements that define the fibromyalgia phenotype. The preferred model showed that the identified path clearly linked the psychological variables of anxiety, neuroticism and mastery, but not internal control, to the three key elements of fibromyalgia, namely pain, fatigue and sleep (p fibromyalgia symptoms. This has implications for the understanding of contributing mechanisms and the clinical care of patients with fibromyalgia.

  2. Regulation of spermatogenesis by paracrine/autocrine testicular factors

    Institute of Scientific and Technical Information of China (English)

    MahmoudHuleihel; EitanLunenfeld

    2004-01-01

    Spermatogenesis is a complex process regulated by endocrine and testicular paracrine/autocrine factors.Gonadotropins are involved in the regulation of several testicular paracrine factors, mainly of the IL-1 family and testicular hormones. Testicular cytokines and growth factors (such as IL-1, IL-6, TNF, IFN-T, LIF and SCF) were shown to affect both the germ cell proliferation and the Leydig and Sertoli cells functions and secretion. Cytokines and growth factors are produced by immune cells and in the interstitial and seminiferous tubular compartments by various testicular cells, including Sertoli, Leydig, peritubular cells, spermatogonia, differentiated spermatogonia and even spermatozoa. Corresponding cytokine and growth factor receptors were demonstrated on some of the testicular cells. These cytokines also control the secretion of the gonadotropins and testosterone in the testis. Under pathological conditions the levels of pro-inflammatory cytokines are increased and negatively affected spermatogenesis. Thus,the expression levels and the mechanisms involved in the regulation of testicular paracrine/autocrine factors should be considered in future therapeutic strategies for male infertility. (Asian J Androl 2004 Sep; 6: 259-268)

  3. LYRATE is a key regulator of leaflet initiation and lamina outgrowth in tomato.

    Science.gov (United States)

    David-Schwartz, Rakefet; Koenig, Daniel; Sinha, Neelima R

    2009-10-01

    Development of the flattened laminar structure in plant leaves requires highly regulated cell division and expansion patterns. Although tight regulation of these processes is essential during leaf development, leaf shape is highly diverse across the plant kingdom, implying that patterning of growth must be amenable to evolutionary change. Here, we describe the molecular identification of the classical tomato (Solanum lycopersicum) mutant lyrate, which is impaired in outgrowth of leaflet primodia and laminar tissues during compound leaf development. We found that the lyrate phenotype results from a loss-of-function mutation of the tomato JAGGED homolog, a well-described positive regulator of cell division in lateral organs. We demonstrate that LYRATE coordinates lateral outgrowth in the compound leaves of tomato by interacting with both the KNOX and auxin transcriptional networks and suggest that evolutionary changes in LYRATE expression may contribute to the fundamental difference between compound and simple leaves.

  4. [Health care networks in Germany: status quo and key success factors].

    Science.gov (United States)

    Wambach, Veit; Lindenthal, J

    2015-04-01

    One third of all practicing physicians are currently working in one of the 400 German health care networks. These physicians' networks bring together GPs and specialists and cooperate with different partners, for example, nursing homes, hospitals, and self-help groups. To increase the quality and the efficiency of care and patient satisfaction by improving the collaboration and communication between physicians and other health care providers.The example of the accountable care organization "Gesundheitsnetz Qualität und Effizienz" (QuE; Health Quality and Efficiency Network) in Nuremberg is used to show that it is possible to achieve an increase in efficiency while providing above-average quality of care and achieving high patient satisfaction. Additionally, the article deals with the status quo, the core objectives, and the key activities of previous generations of health care networks. Quality indicators, satisfaction surveys, and economic parameters are the basis for measuring and representing the above-average performance of physicians' networks. Regional health care networks offer an entire range of patient care, from outpatients and inpatients to the complementary sector, and thereby have excellent prospects for playing an even more important role in the German health care system. The key success factors are: the consideration of specific regional characteristics, their proximity to the patient, and consistent patient orientation.

  5. Adjuvants are Key Factors for the Development of Future Vaccines: Lessons from the Finlay Adjuvant Platform

    Science.gov (United States)

    Pérez, Oliver; Romeu, Belkis; Cabrera, Osmir; González, Elizabeth; Batista-Duharte, Alexander; Labrada, Alexis; Pérez, Rocmira; Reyes, Laura M.; Ramírez, Wendy; Sifontes, Sergio; Fernández, Nelson; Lastre, Miriam

    2013-01-01

    The development of effective vaccines against neglected diseases, especially those associated with poverty and social deprivation, is urgently needed. Modern vaccine technologies and a better understanding of the immune response have provided scientists with the tools for rational and safer design of subunit vaccines. Often, however, subunit vaccines do not elicit strong immune responses, highlighting the need to incorporate better adjuvants; this step therefore becomes a key factor for vaccine development. In this review we outline some key features of modern vaccinology that are linked with the development of better adjuvants. In line with the increased desire to obtain novel adjuvants for future vaccines, the Finlay Adjuvant Platform offers a novel approach for the development of new and effective adjuvants. The Finlay Adjuvants (AFs), AFPL (proteoliposome), and AFCo (cochleate), were initially designed for parenteral and mucosal applications, and constitute potent adjuvants for the induction of Th1 responses against several antigens. This review summarizes the status of the Finlay technology in producing promising adjuvants for unsolved-vaccine diseases including mucosal approaches and therapeutic vaccines. Ideas related to adjuvant classification, adjuvant selection, and their possible influence on innate recognition via multiple toll-like receptors are also discussed. PMID:24348475

  6. Myocardin-related transcription factor regulates Nox4 protein expression

    DEFF Research Database (Denmark)

    Rozycki, Matthew; Bialik, Janne Folke; Speight, Pam

    2016-01-01

    TGFβ-induced expression of the NADPH oxidase Nox4 is essential for fibroblast-myofibroblast transition. Rho has been implicated in Nox4 regulation, but the underlying mechanisms are largely unknown. Myocardin-related transcription factor (MRTF), a Rho/actin polymerization-controlled coactivator...... translocation of MRTF. Because the Nox4 promoter harbors a serum response factor/MRTF cis-element (CC(A/T)6GG box), we asked if MRTF (and thus cytoskeleton organization) could regulate Nox4 expression. We show that Nox4 protein is robustly induced in kidney tubular cells exclusively by combined application...... of contact uncoupling and TGFβ. Nox4 knockdown abrogates epithelial-myofibroblast transition-associated reactive oxygen species production. Laser capture microdissection reveals increased Nox4 expression in the tubular epithelium also during obstructive nephropathy. MRTF down-regulation/inhibition suppresses...

  7. Traumatic Brain Injury as a Risk Factor for Alzheimer's Disease: Is Inflammatory Signaling a Key Player?

    Science.gov (United States)

    Djordjevic, Jelena; Sabbir, Mohammad Golam; Albensi, Benedict C

    2016-01-01

    Traumatic brain injury (TBI) has become a significant medical and social concern within the last 30 years. TBI has acute devastating effects, and in many cases, seems to initiate long-term neurodegeneration. With advances in medical technology, many people are now surviving severe brain injuries and their long term consequences. Post trauma effects include communication problems, sensory deficits, emotional and behavioral problems, physical complications and pain, increased suicide risk, dementia, and an increased risk for chronic CNS diseases, such as Alzheimer's disease (AD). In this review, we provide an introduction to TBI and hypothesize how it may lead to neurodegenerative disease in general and AD in particular. In addition, we discuss the evidence that supports the hypothesis that TBI may lead to AD. In particular, we focus on inflammatory responses as key processes in TBI-induced secondary injury, with emphasis on nuclear factor kappa B (NF-κB) signaling.

  8. Redox-dependent regulation of epidermal growth factor receptor signaling

    Directory of Open Access Journals (Sweden)

    David E. Heppner

    2016-08-01

    Full Text Available Tyrosine phosphorylation-dependent cell signaling represents a unique feature of multicellular organisms, and is important in regulation of cell differentiation and specialized cell functions. Multicellular organisms also contain a diverse family of NADPH oxidases (NOXs that have been closely linked with tyrosine kinase-based cell signaling and regulate tyrosine phosphorylation via reversible oxidation of cysteine residues that are highly conserved within many proteins involved in this signaling pathway. An example of redox-regulated tyrosine kinase signaling involves the epidermal growth factor receptor (EGFR, a widely studied receptor system with diverse functions in normal cell biology as well as pathologies associated with oxidative stress such as cancer. The purpose of this Graphical Redox Review is to highlight recently emerged concepts with respect to NOX-dependent regulation of this important signaling pathway.

  9. Competences and knowledge: Key-factors in the smart city of the future

    Directory of Open Access Journals (Sweden)

    Saverio Salerno

    2014-12-01

    Full Text Available The effective and modern management of competence development, which represents a distinguishing key-factor in future Smart Cities, cannot be limited to the Learning Management exclusively, but rather be inclusive of aspects pertaining to Human Capital and Performance Management in a holistic vision that encompasses not only the sphere of operations but also the tactical and strategic levels. In particular, organizations need solutions that especially integrate Learning Management, Performance Management, and Human Resource Management (HRM. We propose an approach considering the competences as key-factors in the management and valorization of Human Capital and making use of a socio-constructivist learning model, based on the explicit (ontological modeling of domain competences as well as a learner and didactic oriented approach. Unlike most of the current solutions, far from the proposed vision and concentrated on specific functionalities and not on the processes as a whole, the solution offered by MOMA, spin-off of the Research Group of the University of Salerno led by Prof. Salerno, is here presented as a demonstrative case of the proposed methodology and approach. A distinctive feature of our proposal, supported by the MOMA solution is the adoption of semantic technologies that for instance allows for the discovery of unpredictable paths linking them in the Knowledge Graph. Finally, we discuss how this framework can be applied in the context of the Smart Cities of the future, taking advantage of the features, enabled especially by semantics, of researching, creating, combining, delivering and using in a creative manner the resources of superior quality offered by Smart Cities.

  10. Heme metabolism in stress regulation and protein production: from Cinderella to a key player

    DEFF Research Database (Denmark)

    Martinez Ruiz, José Luis; Petranovic, D.; Nielsen, Jens

    2016-01-01

    Heme biosynthesis is a highly conserved pathway which is present in all kingdoms, from Archaea to higher organisms such as plants and mammals. The heme molecule acts as a prosthetic group for different proteins and enzymes involved in energy metabolism and reactions involved in electron transfer...... regulation could impact our ability to develop more efficient yeast cell factories for heterologous protein production....

  11. Cytokinins as key regulators in plant–microbe–insect interactions: connecting plant growth and defence

    NARCIS (Netherlands)

    Giron, D.; Frago, E.; Glevarec, G.; Pieterse, C.M.J.; Dicke, M.

    2013-01-01

    1. Plant hormones play important roles in regulating plant growth and defence by mediating developmental processes and signalling networks involved in plant responses to a wide range of parasitic and mutualistic biotic interactions. 2. Plants are known to rapidly respond to pathogen and herbivore at

  12. Cytokinins as key regulators in plant-microbe-insect interactions: connecting plant growth and defence

    NARCIS (Netherlands)

    Giron, D.; Frago, E.; Glevarec, G.; Pieterse, C.M.J.; Dicke, M.

    2013-01-01

    Plant hormones play important roles in regulating plant growth and defence by mediating developmental processes and signalling networks involved in plant responses to a wide range of parasitic and mutualistic biotic interactions. Plants are known to rapidly respond to pathogen and herbivore attack b

  13. Rho proteins − the key regulators of cytoskeleton in the progression of mitosis and cytokinesis

    Directory of Open Access Journals (Sweden)

    Anna Klimaszewska

    2011-11-01

    Full Text Available The Rho proteins are members of the Ras superfamily of small GTPases. They are thought to be crucial regulators of multiple signal transduction pathways that influence a wide range of cellular functions, including migration, membrane trafficking, adhesion, polarity and cell shape changes. Thanks to their ability to control the assembly and organization of the actin and microtubule cytoskeletons, Rho GTPases are known to regulate mitosis and cytokinesis progression. These proteins are required for formation and rigidity of the cortex during mitotic cell rounding, mitotic spindle formation and attachment of the spindle microtubules to the kinetochore. In addition, during cytokinesis, they are involved in promoting division plane determination, contractile ring and cleavage furrow formation and abscission. They are also known as regulators of cell cycle progression at the G1/S and G2/M transition. Thus, the signal transduction pathways in which Rho proteins participate, appear to connect dynamics of actin and microtubule cytoskeletons to cell cycle progression. We review the current state of knowledge concerning the molecular mechanisms by which Rho GTPase signaling regulates remodeling of actin and microtubule cytoskeletons in order to control cell division progression.

  14. Cytokinins as key regulators in plant–microbe–insect interactions: connecting plant growth and defence

    NARCIS (Netherlands)

    Giron, D.; Frago, E.; Glevarec, G.; Pieterse, C.M.J.; Dicke, M.

    2013-01-01

    1. Plant hormones play important roles in regulating plant growth and defence by mediating developmental processes and signalling networks involved in plant responses to a wide range of parasitic and mutualistic biotic interactions. 2. Plants are known to rapidly respond to pathogen and herbivore

  15. PfsR is a key regulator of iron homeostasis in Synechocystis PCC 6803.

    Directory of Open Access Journals (Sweden)

    Dan Cheng

    Full Text Available Iron is an essential cofactor in numerous cellular processes. The iron deficiency in the oceans affects the primary productivity of phytoplankton including cyanobacteria. In this study, we examined the function of PfsR, a TetR family transcriptional regulator, in iron homeostasis of the cyanobacterium Synechocystis PCC 6803. Compared with the wild type, the pfsR deletion mutant displayed stronger tolerance to iron limitation and accumulated significantly more chlorophyll a, carotenoid, and phycocyanin under iron-limiting conditions. The mutant also maintained more photosystem I and photosystem II complexes than the wild type after iron deprivation. In addition, the activities of photosystem I and photosystem II were much higher in pfsR deletion mutant than in wild-type cells under iron-limiting conditions. The transcripts of pfsR were enhanced by iron limitation and inactivation of the gene affected pronouncedly expression of fut genes (encoding a ferric iron transporter, feoB (encoding a ferrous iron transporter, bfr genes (encoding bacterioferritins, ho genes (encoding heme oxygenases, isiA (encoding a chlorophyll-binding protein, and furA (encoding a ferric uptake regulator. The iron quota in pfsR deletion mutant cells was higher than in wild-type cells both before and after exposure to iron limitation. Electrophoretic mobility shift assays showed that PfsR bound to its own promoter and thereby auto-regulated its own expression. These data suggest that PfsR is a critical regulator of iron homeostasis.

  16. Cytokinins as key regulators in plant–microbe–insect interactions: connecting plant growth and defence

    NARCIS (Netherlands)

    Giron, D.; Frago, E.; Glevarec, G.; Pieterse, C.M.J.; Dicke, M.

    2013-01-01

    1. Plant hormones play important roles in regulating plant growth and defence by mediating developmental processes and signalling networks involved in plant responses to a wide range of parasitic and mutualistic biotic interactions. 2. Plants are known to rapidly respond to pathogen and herbivore at

  17. Cytokinins as key regulators in plant-microbe-insect interactions: connecting plant growth and defence

    NARCIS (Netherlands)

    Giron, D.; Frago, E.; Glevarec, G.; Pieterse, C.M.J.; Dicke, M.

    2013-01-01

    Plant hormones play important roles in regulating plant growth and defence by mediating developmental processes and signalling networks involved in plant responses to a wide range of parasitic and mutualistic biotic interactions. Plants are known to rapidly respond to pathogen and herbivore attack b

  18. PCP-B class pollen coat proteins are key regulators of the hydration checkpoint in Arabidopsis thaliana pollen-stigma interactions.

    Science.gov (United States)

    Wang, Ludi; Clarke, Lisa A; Eason, Russell J; Parker, Christopher C; Qi, Baoxiu; Scott, Rod J; Doughty, James

    2017-01-01

    The establishment of pollen-pistil compatibility is strictly regulated by factors derived from both male and female reproductive structures. Highly diverse small cysteine-rich proteins (CRPs) have been found to play multiple roles in plant reproduction, including the earliest stages of the pollen-stigma interaction. Secreted CRPs found in the pollen coat of members of the Brassicaceae, the pollen coat proteins (PCPs), are emerging as important signalling molecules that regulate the pollen-stigma interaction. Using a combination of protein characterization, expression and phylogenetic analyses we identified a novel class of Arabidopsis thaliana pollen-borne CRPs, the PCP-Bs (for pollen coat protein B-class) that are related to embryo surrounding factor (ESF1) developmental regulators. Single and multiple PCP-B mutant lines were utilized in bioassays to assess effects on pollen hydration, adhesion and pollen tube growth. Our results revealed that pollen hydration is severely impaired when multiple PCP-Bs are lost from the pollen coat. The hydration defect also resulted in reduced pollen adhesion and delayed pollen tube growth in all mutants studied. These results demonstrate that AtPCP-Bs are key regulators of the hydration 'checkpoint' in establishment of pollen-stigma compatibility. In addition, we propose that interspecies diversity of PCP-Bs may contribute to reproductive barriers in the Brassicaceae. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

  19. Oncogenic BRAF regulates melanoma proliferation through the lineage specific factor MITF.

    Directory of Open Access Journals (Sweden)

    Claudia Wellbrock

    Full Text Available The Microphthalmia-associated transcription factor (MITF is an important regulator of cell-type specific functions in melanocytic cells. MITF is essential for the survival of pigmented cells, but whereas high levels of MITF drive melanocyte differentiation, lower levels are required to permit proliferation and survival of melanoma cells. MITF is phosphorylated by ERK, and this stimulates its activation, but also targets it for degradation through the ubiquitin-proteosome pathway, coupling MITF degradation to its activation. We have previously shown that because ERK is hyper-activated in melanoma cells in which BRAF is mutated, the MITF protein is constitutively down-regulated. Here we describe another intriguing aspect of MITF regulation by oncogenic BRAF in melanoma cells. We show oncogenic BRAF up-regulates MITF transcription through ERK and the transcription factor BRN2 (N-Oct3. In contrast, we show that in melanocytes this pathway does not exist because BRN2 is not expressed, demonstrating that MITF regulation is a newly acquired function of oncogenic BRAF that is not performed by the wild-type protein. Critically, in melanoma cells MITF is required downstream of oncogenic BRAF because it regulates expression of key cell cycle regulatory proteins such as CDK2 and CDK4. Wild-type BRAF does not regulate this pathway in melanocytes. Thus, we show that oncogenic BRAF exerts exquisite control over MITF on two levels. It downregulates the protein by stimulating its degradation, but then counteracts this by increasing transcription through BRN2. Our data suggest that oncogenic BRAF plays a critical role in regulating MITF expression to ensure that its protein levels are compatible with proliferation and survival of melanoma cells. We propose that its ability to appropriate the regulation of this critical factor explains in part why BRAF is such a potent oncogene in melanoma.

  20. EXO70C2 is a key regulatory factor for optimal tip growth of pollen

    KAUST Repository

    Synek, Lukas

    2017-03-30

    The exocyst, an eukaryotic tethering complex, co-regulates targeted exocytosis as an effector of small GTPases in polarized cell growth. In land plants, several exocyst subunits are encoded by double or triple paralogs, culminating in tens of EXO70 paralogs. Out of 23 Arabidopsis EXO70 isoforms, we analyzed seven isoforms expressed in pollen. Genetic and microscopic analyses of single mutants in EXO70A2, C1, C2, F1, H3, H5, and H6 genes revealed that only a loss-of-function EXO70C2 allele resulted in a significant male-specific transmission defect (segregation 40%:51%:9%) due to aberrant pollen tube growth. Mutant pollen tubes grown in vitro exhibited enhanced growth rate and a decreased thickness of the tip cell wall, causing tip bursts. However, exo70C2 pollen tubes could frequently recover and restart their speedy elongation, resulting in a repetitive stop-and-go growth dynamics. A pollen-specific depletion of the closest paralog, EXO70C1, using ami-RNA in the exo70C2 mutant background resulted in a complete pollen-specific transmission defect, suggesting redundant functions of EXO70C1 and EXO70C2. Both EXO70C1 and EXO70C2, GFP-tagged and expressed under their native promoters, localized in the cytoplasm of pollen grains, pollen tubes, and also root trichoblast cells. Expression of EXO70C2-GFP complemented aberrant growth of exo70C2 pollen tubes. The absent EXO70C2 interactions with core exocyst subunits in the yeast two-hybrid assay, cytoplasmic localization, and genetic effect suggest an unconventional EXO70 function possibly as a regulator of exocytosis outside the exocyst complex. In conclusion, EXO70C2 is a novel factor contributing to the regulation of optimal tip growth of Arabidopsis pollen tubes.

  1. Structural imbalances as a key factor of unemployment in the Russian labor market

    Directory of Open Access Journals (Sweden)

    I V Trotsuk

    2015-12-01

    Full Text Available In recent years, the problems of the Russian labor market, especially the scale and characteristics of youth unemployment, get very emotional and negative coverage in the scientific and journalistic discourses. The authors seek to show without any emotional evaluations what are the objective macroeconomic causes of the current situation with unemployment, especially youth unemployment. First, the authors identify the main challenges the labor market faces today in terms of the interaction of its key actors (workers, owners of the means of production, educational institutions and various intermediaries, including the state regulating the features of labor recruitment. Second, the article shows the main trends of the last decade that change the structure of employment of the economically active population. Third, the authors name the basic structural imbalances in the Russian labor market, primarily structural and professional imbalance between the demand for labor, the demand for vocational training and offer of educational services, which is quite evident, albeit in different ways, in all spheres of the economy. Fourth, the article describes the specific features of the youth labor market as both affected and contributing to the structural imbalances. Finally, the authors propose a methodology of macroeconomic forecasting that may reduce the problems the Russian society faces in the field of employment.

  2. The Macrophage Is a Key Factor in Renal Injuries Caused by Glomerular Hyperfiltration

    Directory of Open Access Journals (Sweden)

    Sasaki,Motofumi

    2011-04-01

    Full Text Available Glomerular hyperfiltration is a common pathway leading to glomerulosclerosis in various kinds of kidney diseases. The 5/6 renal ablation is an established experimental animal model for glomerular hyperfiltration. On the other hand, low-grade inflammation is also a common mechanism for the progression of kidney diseases including diabetic nephropathy and atherosclerosis. Here we analyzed the gene expression profile in the remnant kidney tissues of 5/6 nephrectomized mice using a DNA microarray system and compared it with that of sham-operated control mice. The 5/6 nephrectomized mice showed glomerular hypertrophy and an increase in the extracellular matrix in the glomeruli. DNA microarray analysis indicated the up-regulated expression of various kinds of genes related to the inflammatory process in remnant kidneys. We confirmed the up-regulated expression of platelet factor-4, and monocyte chemoattractant protein-1, 2, and 5 in remnant kidneys by RT-PCR. The current results suggest that the inflammatory process is involved in the progression of glomerulosclerosis and is a common pathway of the pathogenesis of kidney disease.

  3. Arabidopsis Clade I TGA Factors Regulate Apoplastic Defences against the Bacterial Pathogen Pseudomonas syringae through Endoplasmic Reticulum-Based Processes

    OpenAIRE

    Lipu Wang; Pierre R Fobert

    2013-01-01

    During the plant immune response, large-scale transcriptional reprogramming is modulated by numerous transcription (co) factors. The Arabidopsis basic leucine zipper transcription factors TGA1 and TGA4, which comprise the clade I TGA factors, have been shown to positively contribute to disease resistance against virulent strains of the bacterial pathogen Pseudomonas syringae . Despite physically interacting with the key immune regulator, NON-EXPRESSOR OF PATHOGENESIS-RELATED GENES 1 (NPR1), f...

  4. ROP18 is a key factor responsible for virulence difference between Toxoplasma gondii and Neospora caninum.

    Science.gov (United States)

    Lei, Tao; Wang, Hui; Liu, Jing; Nan, Huizhu; Liu, Qun

    2014-01-01

    Toxoplasma gondii (T. gondii) and Neospora caninum (N. caninum) are both obligate intracellular protozoan parasites and share many common morphological and biological features. Despite these similarities the two parasites differ dramatically in virulence in mice, but the factors involved in virulence differences between the two parasites remain unknown. A secreted serine-threonine kinase called rhoptry protein 18 (ROP18) was identified to play a crucial role on virulence differences among different T. gondii clonal lineages. Intriguingly, we found that ROP18 in Nc1 strain of N. caninum (NcROP18) is a pseudogene due to several interrupting stop codons in the sequence in our previous studies. We assume that the difference of ROP18 leads to virulence difference between T. gondii and N. caninum. We constructed a transgenic N. caninum Nc1 stain by transfecting the TgROP18 from the T. gondii RH strain. Phenotype and virulence assays showed that the expression of TgROP18 in N. caninum did not affect the motility and cell invasion, but resulted in a significant increase in intracellular parasite proliferation and virulence in mice. Immunity-Related GTPase (IRG) phosphorylation assay showed that the transgenic parasite Nc1-TgROP18 was able to phosphorylate IRGs as T. gondii did. The present study indicated that the ROP18 plays a crucial role in virulence of the closely related parasites T. gondii and N. caninum and it is indeed a key factor responsible for the virulence difference between T. gondii and N. caninum.

  5. Organization of anti-phase synchronization pattern in neural networks: what are the key factors?

    Directory of Open Access Journals (Sweden)

    Dong eLi

    2011-12-01

    Full Text Available Anti-phase oscillation has been widely observed in cortical neuralnetwork. Elucidating the mechanism underlying the organization ofanti-phase pattern is of significance for better understanding morecomplicated pattern formations in brain networks. In dynamicalsystems theory, the organization of anti-phase oscillation patternhas usually been considered to relate to time-delay in coupling.This is consistent to conduction delays in real neural networks inthe brain due to finite propagation velocity of action potentials.However, other structural factors in cortical neural network, suchas modular organization (connection density and the coupling types(excitatory or inhibitory, could also play an important role. Inthis work, we investigate the anti-phase oscillation patternorganized on a two-module network of either neuronal cell model orneural mass model, and analyze the impact of the conduction delaytimes, the connection densities, and coupling types. Our resultsshow that delay times and coupling types can play key roles in thisorganization. The connection densities may have an influence on thestability if an anti-phase pattern exists due to the other factors.Furthermore, we show that anti-phase synchronization of slowoscillations can be achieved with small delay times if there isinteraction between slow and fast oscillations. These results aresignificant for further understanding more realistic spatiotemporaldynamics of cortico-cortical communications.

  6. A key inactivation factor of HeLa cell viability by a plasma flow

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Takehiko; Yokoyama, Mayo [Institute of Fluid Science, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577 (Japan); Johkura, Kohei, E-mail: sato@ifs.tohoku.ac.jp [Department of Histology and Embryology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621 (Japan)

    2011-09-21

    Recently, a plasma flow has been applied to medical treatment using effects of various kinds of stimuli such as chemical species, charged particles, heat, light, shock wave and electric fields. Among them, the chemical species are known to cause an inactivation of cell viability. However, the mechanisms and key factors of this event are not yet clear. In this study, we focused on the effect of H{sub 2}O{sub 2} in plasma-treated culture medium because it is generated in the culture medium and it is also chemically stable compared with free radicals generated by the plasma flow. To elucidate the significance of H{sub 2}O{sub 2}, we assessed the differences in the effects of plasma-treated medium and H{sub 2}O{sub 2}-added medium against inactivation of HeLa cell viability. These two media showed comparable effects on HeLa cells in terms of the survival ratios, morphological features of damage processes, permeations of H{sub 2}O{sub 2} into the cells, response to H{sub 2}O{sub 2} decomposition by catalase and comprehensive gene expression. The results supported that among chemical species generated in a plasma-treated culture medium, H{sub 2}O{sub 2} is one of the main factors responsible for inactivation of HeLa cell viability. (fast track communication)

  7. TOR (target of rapamycin) is a key regulator of triacylglycerol accumulation in microalgae.

    Science.gov (United States)

    Imamura, Sousuke; Kawase, Yasuko; Kobayashi, Ikki; Shimojima, Mie; Ohta, Hiroyuki; Tanaka, Kan

    2016-01-01

    Most microalgae abundantly accumulate lipid droplets (LDs) containing triacylglycerols (TAGs) under several stress conditions, but the underlying molecular mechanism of this accumulation remains unclear. In a recent study, we found that inhibition of TOR (target of rapamycin), a highly conserved protein kinase of eukaryotes, by rapamycin resulted in TAG accumulation in microalgae, indicating that TOR negatively regulates TAG accumulation. Here, we show that formation of intracellular LDs and TAG accumulation were also induced in the unicellular green alga Chlamydomonas reinhardtii after exposure to Torin1 or AZD8055, which are novel TOR inhibitors that inhibit TOR activity in a manner different from rapamycin. These results supported quite well our previous conclusion that TOR is a central regulator of TAG accumulation in microalgae.

  8. Regulation of lovastatin on a key inflammation-related microRNA in myocardial cells

    Institute of Scientific and Technical Information of China (English)

    Guo Weizao; Liu Huichen; Li Lin; Yang Man; Du Aihua

    2014-01-01

    Background Advances in the understanding of cardiovascular pathogenesis have highlighted that inflammation plays a central role in athemsclemtic coronary heart disease.Therefore,exploring pharmacologically based anti-inflammatory treatments to be used in cardiovascular therapeutics is worthwhile to promote the discovery of novel ways of treating cardiovascular disorders.Methods The myocardial cell line H9c2(2-1) was exposed to lipopolysacchadde (LPS) in culture and resulted in a cellular pro-inflammation status,miR-21 microRNA levels were detected using quantitative real-time polymerase chain reaction (Q-RT-PCR).The influence of Iovastatin on miR-21 under normal and pro-inflammatory conditions was tested after being added to the cell culture mixture for 24 hours.Conditional gene function of two predicted cardiovascular system relevant downstream targets of miR-21,protein phosphatase 1 regulatory subunit 3A (PPP1R3A) and signal transducer and activator of transcription 3 (STAT3),were analyzed with immunoblotting.Results Forty-eight hours of LPS treatment significantly increased the miR-21 to 170.71%±34.32% of control levels (P=0.002).Co-treatment with Iovastatin for 24 hours before harvesting attenuated the up-regulation of miR-21 (P=0.013).Twenty-four hours of Iovastatin exposure up-regulated PPP1R3A to 143.85%±21.89% of control levels in cardiomyocytes (P=0.023).Lovastatin up-regulated the phosphorylation level of STAT3 compared to the background LPS pretreatment (P=0.0077),this effect was significantly (P=0.018) blunted when miR-21 was functionally inhibited.Conclusions miR-21 plays a major role in the regulation of the cellular anti-inflammation effects of Iovastatin.

  9. Gasotransmitter regulation of ion channels: a key step in O2 sensing by the carotid body.

    Science.gov (United States)

    Prabhakar, Nanduri R; Peers, Chris

    2014-01-01

    Carotid bodies detect hypoxia in arterial blood, translating this stimulus into physiological responses via the CNS. It is long established that ion channels are critical to this process. More recent evidence indicates that gasotransmitters exert powerful influences on O2 sensing by the carotid body. Here, we review current understanding of hypoxia-dependent production of gasotransmitters, how they regulate ion channels in the carotid body, and how this impacts carotid body function.

  10. Group A PP2Cs evolved in land plants as key regulators of intrinsic desiccation tolerance.

    Science.gov (United States)

    Komatsu, Kenji; Suzuki, Norihiro; Kuwamura, Mayuri; Nishikawa, Yuri; Nakatani, Mao; Ohtawa, Hitomi; Takezawa, Daisuke; Seki, Motoaki; Tanaka, Maho; Taji, Teruaki; Hayashi, Takahisa; Sakata, Yoichi

    2013-01-01

    Vegetative desiccation tolerance is common in bryophytes, although this character has been lost in most vascular plants. The moss Physcomitrella patens survives complete desiccation if treated with abscisic acid (ABA). Group A protein phosphatases type 2C (PP2C) are negative regulators of abscisic acid signalling. Here we show that the elimination of Group A PP2C is sufficient to ensure P. patens survival to full desiccation, without ABA treatment, although its growth is severely hindered. Microarray analysis shows that the Group A PP2C-regulated genes exclusively overlap with genes exhibiting a high level of ABA induction. Group A PP2C disruption weakly affects ABA-activated kinase activity, indicating Group A PP2C action downstream of these kinases in the moss. We propose that Group A PP2C emerged in land plants to repress desiccation tolerance mechanisms, possibly facilitating plants propagation on land, whereas ABA releases the intrinsic desiccation tolerance from Group A PP2C regulation.

  11. Brain-derived neurotrophic factor, food intake regulation, and obesity.

    Science.gov (United States)

    Rosas-Vargas, Haydeé; Martínez-Ezquerro, José Darío; Bienvenu, Thierry

    2011-08-01

    Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a fundamental role in development and plasticity of the central nervous system (CNS). It is currently recognized as a major participant in the regulation of food intake. Multiple studies have shown that different regulators of appetite such as leptin, insulin and pancreatic polypeptide (PP) potentially exert anorexigenic effects through BDNF. Low circulating levels of BDNF are associated with a higher risk of eating disorders such as anorexia nervosa (AN) and bulimia nervosa (BN). Strict food restriction reduces BDNF and may trigger binge-eating episodes and weight gain. The existence of mutations that cause haploinsufficiency of BDNF as well as some genetic variants, notably the BDNF p.Val66Met polymorphism, are also associated with the development of obese phenotypes and hyperphagia. However, association of the Met allele with AN and BN, which have different phenotypic characteristics, shows clearly the existence of other relevant factors that regulate eating behavior. This may, in part, be explained by the epigenetic regulation of BDNF through mechanisms like DNA methylation and histone acetylation. Environmental factors, primarily during early development, are crucial to the establishment of these stable but reversible changes that alter the transcriptional expression and are transgenerationally heritable, with potential concomitant effects on the development of eating disorders and body weight control.

  12. Crystal Structure of the Pseudomonas aeruginosa Virulence Factor Regulator

    Energy Technology Data Exchange (ETDEWEB)

    Cordes, Timothy J.; Worzalla, Gregory A.; Ginster, Aaron M.; Forest, Katrina T. (UW)

    2012-09-07

    Virulence factor regulator (Vfr) enhances Pseudomonas aeruginosa pathogenicity through its role as a global transcriptional regulator. The crystal structure of Vfr shows that it is a winged-helix DNA-binding protein like its homologue cyclic AMP receptor protein (CRP). In addition to an expected primary cyclic AMP-binding site, a second ligand-binding site is nestled between the N-terminal domain and the C-terminal helix-turn-helix domain. Unlike CRP, Vfr is a symmetric dimer in the absence of DNA. Removal of seven disordered N-terminal residues of Vfr prvents the growth of P. aeruginosa.

  13. Key factors affecting the deployment of electricity generation technologies in energy technology scenarios

    Energy Technology Data Exchange (ETDEWEB)

    Ruoss, F.; Turton, H.; Hirschberg, S.

    2009-12-15

    This report presents the findings of a survey of key factors affecting the deployment of electricity generation technologies in selected energy scenarios. The assumptions and results of scenarios, and the different models used in their construction, are compared. Particular attention is given to technology assumptions, such as investment cost or capacity factors, and their impact on technology deployment. We conclude that the deployment of available technologies, i.e. their market shares, can only be explained from a holistic perspective, and that there are strong interactions between driving forces and competing technology options within a certain scenario. Already the design of a scenario analysis has important impacts on the deployment of technologies: the choice of the set of available technologies, the modeling approach and the definition of the storylines determine the outcome. Furthermore, the quantification of these storylines into input parameters and cost assumptions drives technology deployment, even though differences across the scenarios in cost assumptions are not observed to account for many of the observed differences in electricity technology deployment. The deployment can only be understood after a consideration of the interplay of technology options and the scale of technology deployment, which is determined by economic growth, end-use efficiency, and electrification. Some input parameters are of particular importance for certain technologies: CO{sub 2} prices, fuel prices and the availability of carbon capture and storage appear to be crucial for the deployment of fossil-fueled power plants; maximum construction rates and safety concerns determine the market share of nuclear power; the availability of suitable sites represents the most important factor for electricity generation from hydro and wind power plants; and technology breakthroughs are needed for solar photovoltaics to become cost-competitive. Finally, this analysis concludes with a

  14. Distributions of key exposure factors controlling the uptake of xenobiotic chemicals in an estuarine food web

    Energy Technology Data Exchange (ETDEWEB)

    Iannuzzi, T.J.; Harrington, N.W.; Shear, N.M.; Curry, C.L.; Carlson-Lynch, H.; Henning, M.H. [ChemRisk, Portland, ME (United States); Su, S.H. [Bailey Research Associates, Inc., New York, NY (United States); Rabbe, D.E. [Chemical Land Holdings, Inc., Kearny, NJ (United States)

    1996-11-01

    A critical evaluation of literature on the behavior, physiology, and ecology of common estuarine organisms was conducted in an attempt to develop probabilistic distributions for those variables that influence the uptake of xenobiotic chemicals from sediments, water, and food sources. The ranges, central tendencies, and distributions of several key parameter values were identified for dominant organisms from various trophic levels, including the polychaete Nereis virens, mummichog (Fundulus heteroclitus), blue crab (Callinectes sapidus), and striped bass (Morone saxatilis). The exposure factors of interest included ingestion rate for various food sources, growth rate, respiration rate, excretion rate, body weight, wet/dry weight ratio, lipid content, chemical assimilation efficiency, and food assimilation efficiency. These exposure factors are critical to the execution of mechanistic food web models, which, when properly calibrated, can be used to estimate tissue concentrations of nonionic chemicals in aquatic organisms based on knowledge of the bioenergetics and feeding interactions within a food web and the sediment and water concentrations of chemicals. In this article the authors describe the use of distributions for various exposure factors in the context of a mechanistic bioaccumulation model that is amenable to probabilistic analyses for multiple organisms within a food web. A case study is provided which compares the estimated versus measured concentrations of five polychlorinated biphenyl (PCB) congeners in a representative food web from the tidal portion of the Passaic River, New Jersey, USA. The results suggest that the model is accurate within an order of magnitude or less in estimating the bioaccumulation of PCBs in this food web without calibration. The results of a model sensitivity analysis suggest that the input parameters which most influence the output of the model are both chemical and organism specific.

  15. Some cultural factors affecting costs of fertility regulation.

    Science.gov (United States)

    Nag, M

    1984-01-01

    This paper presents a framework of the costs or constraints in the use of fertility regulation, reviews the existing knowledge on the subject in a cross-cultural context, and indicates the need for further studies. It is suggested that the apparent contradiction noted in fertility surveys between a couple's desire to have no more children or to postpone the next birth and actual behavior can be explained by the costs involved in the use of fertility regulation methods. The costs of fertility regulation can be broadly classified into 4 categories: 1) physical/health (disruption of menstrual cycle, side effects and health hazards of contraceptive methods, perceived health hazards based on ethno-physical concepts, and sacrifice of sexual pleasure); 2) psychic (violation of sexual modesty and human dignity, conflict with religious beliefs; 3) social opinion (challenges to spouse and sex role expectations, challenges to social influence group); and 4) economic (money, time). The economic costs of fertility regulation to individuals vary greatly according to the presence or absence of public sector family planning programs. A substantial part of these costs could be eliminated by national and international programs. So far, no study has focused on the costs of fertility regulation and factors affecting them. A methodology that combines elements of both a questionnaire survey and anthropological investigation and collects data on both the individual and community levels may be most amenable to assessing the impact of costs on the use or nonuse of fertility regulation.

  16. Probing molecular mechanisms of the Hsp90 chaperone: biophysical modeling identifies key regulators of functional dynamics.

    Directory of Open Access Journals (Sweden)

    Anshuman Dixit

    Full Text Available Deciphering functional mechanisms of the Hsp90 chaperone machinery is an important objective in cancer biology aiming to facilitate discovery of targeted anti-cancer therapies. Despite significant advances in understanding structure and function of molecular chaperones, organizing molecular principles that control the relationship between conformational diversity and functional mechanisms of the Hsp90 activity lack a sufficient quantitative characterization. We combined molecular dynamics simulations, principal component analysis, the energy landscape model and structure-functional analysis of Hsp90 regulatory interactions to systematically investigate functional dynamics of the molecular chaperone. This approach has identified a network of conserved regions common to the Hsp90 chaperones that could play a universal role in coordinating functional dynamics, principal collective motions and allosteric signaling of Hsp90. We have found that these functional motifs may be utilized by the molecular chaperone machinery to act collectively as central regulators of Hsp90 dynamics and activity, including the inter-domain communications, control of ATP hydrolysis, and protein client binding. These findings have provided support to a long-standing assertion that allosteric regulation and catalysis may have emerged via common evolutionary routes. The interaction networks regulating functional motions of Hsp90 may be determined by the inherent structural architecture of the molecular chaperone. At the same time, the thermodynamics-based "conformational selection" of functional states is likely to be activated based on the nature of the binding partner. This mechanistic model of Hsp90 dynamics and function is consistent with the notion that allosteric networks orchestrating cooperative protein motions can be formed by evolutionary conserved and sparsely connected residue clusters. Hence, allosteric signaling through a small network of distantly connected

  17. The vision of immigrant students about key factors and skills for access to college

    Directory of Open Access Journals (Sweden)

    Elena Cano García

    2015-05-01

    Full Text Available One of the most important challenges in education is working against absenteeism and school dropout. Especially relevant is the case of immigrant students who are a vulnerable group, fact that causes a high difference in results between immigrants and native students, so that only a very small percentage reaches college.For this reason, the study “Competencies and keys for an educational success from the perspective of college students’ children of immigrants” (2009 ARAF1 00010 has sought to identify the key factors and skills that college students from immigrant families in Catalonia (Spain feel have been useful for their educational success, educational success seen as the enrolment in programs beyond compulsory education.The study methodology has been predominantly qualitative using three different sources of data collection: life stories, audiovisual narratives and questionnaires. Specifically for this article we refer to the results analyzed through the life stories of 13 college students from immigrant backgrounds who had done all or part of their primary school in the Spanish education system, considering for their selecting the age of arrival, their nationality and the variety of universities and degrees where they were enrolled.The results of the study support the findings of previous researches (Aja et al.; Huguet & Navarro, 2006; Ferrer, 2009; OECD, 2010; Instituto de Evaluación, 2010. Student participants have referred to the importance of family expectations and support, especially when it has been given in conjunction with the school. They especially emphasized the role of mothers as a basic figure to encourage perseverance and dedication to studies. Moreover, in the educational environment it has been particularly appreciated the role the high school teachers who in many cases were the key on having great expectations for them and communicating these explicitly. Finally, regarding the competences, which have been the focus

  18. Nitrogen Dynamics are a Key Factor in Explaining Global Land Carbon Sink

    Science.gov (United States)

    Huntzinger, D. N.; Michalak, A. M.; Schwalm, C.; Ciais, P.; Schaefer, K. M.; King, A. W.; Wei, Y.; Cook, R. B.; Fisher, J. B.; Hayes, D. J.; Huang, M.; Ito, A.; Jain, A. K.; Lei, H.; Lu, C.; Maignan, F.; Mao, J.; Parazoo, N.; Peng, S.; Poulter, B.; Ricciuto, D. M.; Shi, X.; Tian, H.; Wang, W.; Zeng, N.; Zhao, F.

    2015-12-01

    The terrestrial carbon cycle plays a critical role in regulating the amount of anthropogenic emissions that remain in the atmosphere. Yet, land-atmosphere carbon dynamics are one of the largest sources of uncertainty in projections of future climate. Reducing this uncertainty requires understanding the relative role of various drivers to land carbon uptake. We use an ensemble of land surface models to quantify the influence of climate, land use history, atmospheric CO2, and nitrogen deposition on the strength of the net land sink over the past 110 years. Each model can be thought of as one realization of terrestrial carbon cycling and the factors most important in controlling land sink strength. Using a series of sensitivity simulations, we identify the dominant drivers to the net land sink that emerge consistently across models, both globally and regionally. We find that the relative importance of external forcing factors on the strength of net land carbon uptake varies considerably across models and depends strongly on whether nitrogen cycling is explicitly simulated. Models without a nitrogen cycle estimate cumulative land carbon uptake (since 1959) that is 3 times greater (93.3 ± 84.1 PgC) than global mass balance constraints (34.6 ± 41.6 PgC). Surprisingly, the greatest impacts are seen in the tropics, where coupled carbon-nitrogen cycle models estimate CO2 fertilization and climate affects that are ~60% weaker than models without a nitrogen cycle. The results highlight the importance of model structure on the inferred sensitivity of land carbon uptake to external forcing factors. The range in sensitivity across models is important for future climate projections since the differences in the processes that explain trends in net land sink strength between models with and without nitrogen dynamics can lead to very different future trajectories of atmospheric CO2 and thus climate.

  19. Bombyx mori P-element Somatic Inhibitor (BmPSI) Is a Key Auxiliary Factor for Silkworm Male Sex Determination

    Science.gov (United States)

    Chen, Shuqing; Zeng, Baosheng; James, Anthony A.; Tan, Anjiang; Huang, Yongping

    2017-01-01

    Manipulation of sex determination pathways in insects provides the basis for a wide spectrum of strategies to benefit agriculture and public health. Furthermore, insects display a remarkable diversity in the genetic pathways that lead to sex differentiation. The silkworm, Bombyx mori, has been cultivated by humans as a beneficial insect for over two millennia, and more recently as a model system for studying lepidopteran genetics and development. Previous studies have identified the B. mori Fem piRNA as the primary female determining factor and BmMasc as its downstream target, while the genetic scenario for male sex determination was still unclear. In the current study, we exploite the transgenic CRISPR/Cas9 system to generate a comprehensive set of knockout mutations in genes BmSxl, Bmtra2, BmImp, BmImpM, BmPSI and BmMasc, to investigate their roles in silkworm sex determination. Absence of Bmtra2 results in the complete depletion of Bmdsx transcripts, which is the conserved downstream factor in the sex determination pathway, and induces embryonic lethality. Loss of BmImp or BmImpM function does not affect the sexual differentiation. Mutations in BmPSI and BmMasc genes affect the splicing of Bmdsx and the female reproductive apparatus appeared in the male external genital. Intriguingly, we identify that BmPSI regulates expression of BmMasc, BmImpM and Bmdsx, supporting the conclusion that it acts as a key auxiliary factor in silkworm male sex determination. PMID:28103247

  20. Biological stress regulation in female adolescents: a key role for confiding.

    Science.gov (United States)

    Oskis, Andrea; Clow, Angela; Loveday, Catherine; Hucklebridge, Frank; Sbarra, David A

    2015-05-01

    Attachment behaviors play a critical role in regulating emotion within the context of close relationships, and attachment theory is currently used to inform evidence-based practice in the areas of adolescent health and social care. This study investigated the association between female adolescents' interview-based attachment behaviors and two markers of hypothalamic-pituitary-adrenal axis activity: cortisol and dehydroepiandrosterone (DHEA). Unlike the classic stress hormone cortisol, there is very limited investigation of DHEA-a quintessential developmental hormone-in relation to attachment, especially in adolescents. Fifty-five healthy females mean age 14.36 (±2.41) years participated in the attachment style interview. A smaller cortisol awakening response was related to anxious attachment attitudes, including more fear of rejection, whereas greater morning basal DHEA secretion was only predicted by lower levels of reported confiding in one's mother. These attachment-hormone relationships may be developmental markers in females, as they were independent of menarche status. These findings highlight that the normative shifts occurring in attachment to caregivers around adolescence are reflected in adolescents' biological stress regulation. We discuss how studying these shifts can be informed by evolutionary-developmental theory.

  1. The schistosome excretory system: a key to regulation of metabolism, drug excretion and host interaction.

    Science.gov (United States)

    Kusel, John R; McVeigh, Paul; Thornhill, Joyce A

    2009-08-01

    There is a gulf between the enormous information content of the various genome projects and the understanding of the life of the parasite in the host. In vitro studies with adult Schistosoma mansoni using several substrates suggest that the excretory system contains both P-glycoproteins and multiresistance proteins. If both these families of protein were active in vivo, they could regulate parasite metabolism and be responsible for the excretion of drugs. During skin penetration, membrane-impermeant molecules of a wide range of molecular weights can be taken into the cercaria and schistosomulum through the nephridiopore, through the surface membrane or through both. We speculate that this uptake process might stimulate novel signalling pathways involved in growth and development.

  2. The Role of miRNAs as Key Regulators in the Neoplastic Microenvironment

    Directory of Open Access Journals (Sweden)

    K. K. Wentz-Hunter

    2011-01-01

    Full Text Available The neoplastic microenvironment has been recognized to play a critical role in the development of cancer. Although a large body of evidence has established the importance of the cancer microenvironment, the manners of crosstalk between it and the cancer cells still remains unclear. Emerging mechanisms of communication include microRNAs (miRNAs. miRNAs are small noncoding RNA molecules that are involved in the posttranscriptional regulation of mRNA. Both intracellular and circulating miRNAs are differentially expressed in cancer and some of these alterations have been correlated with clinical patient outcomes. The role of miRNAs in the tumor microenvironment has only recently become a focus of research, however. In this paper, we discuss the influence of miRNAs on the tumor microenvironment as it relates to cancer progression. We conclude that miRNAs are a critical component in understanding invasion and metastasis of cancer cells.

  3. The Key to Mn Homeostasis in Plants: Regulation of Mn Transporters.

    Science.gov (United States)

    Shao, Ji Feng; Yamaji, Naoki; Shen, Ren Fang; Ma, Jian Feng

    2017-03-01

    Plants only require small amounts of manganese (Mn) for healthy growth, but Mn concentrations in soil solution vary from sub-micromolar to hundreds of micromolar across the growth period. Therefore, plants must deal with large Mn concentration fluctuations, but the molecular mechanisms underlying how plants cope with low and high Mn concentrations are poorly understood. In this Opinion we discuss the role of Mn transporters in the uptake, distribution, and detoxification of Mn in response to changes in Mn concentrations through their regulation at the transcriptional and protein levels, mainly focusing on rice, an Mn-tolerant and -accumulating species. We also propose mechanisms involved in the hyperaccumulation of Mn and future prospects for studying this specific trait. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. MicroRNAs: not ‘fine-tuners’ but key regulators of neuronal development and function

    Directory of Open Access Journals (Sweden)

    Gregory eDavis

    2015-11-01

    Full Text Available microRNAs (miRNAs are a class of short non-coding RNAs that operate as prominent post-transcriptional regulators of eukaryotic gene expression. miRNAs are abundantly expressed in the brain of most animals and exert diverse roles. The anatomical and functional complexity of brain requires the precise coordination of multi-layered gene regulatory networks. The flexibility, speed and reversibility of miRNA function provide precise temporal and spatial gene regulatory capabilities that are crucial for the correct functioning of the brain. Studies have shown that the underlying molecular mechanisms controlled by miRNAs in the nervous systems of invertebrate and vertebrate models are remarkably conserved in humans. We endeavour to provide insight into the roles of miRNAs in the nervous systems of these model organisms and discuss how such information may be used to inform regarding diseases of the human brain.

  5. Modeling and analysis of PM2.5 generation for key factors identification in China

    Science.gov (United States)

    Xia, Dehong; Jiang, Binfan; Xie, Yulei

    2016-06-01

    Recently, the PM2.5 pollution in China has occurred frequently and caused widely concern. In order to identify the key factors for PM2.5 generation, the formation characteristics of PM2.5 would be revealed. A property of electric neutrality of PM2.5 was proposed under the least-energy principle and verified through electricity-charge calculation in this paper. It indicated that PM2.5 is formed by the effect of electromagnetic force, including the effect of ionic bond, hydrogen bond and polarization. According to the analysis of interactive forces among different chemical components, a simulation model is developed for describing the random process of PM2.5 generation. In addition, an orthogonal test with two levels and four factors has been designed and carried out through the proposed model. From the text analysis, PM2.5 would be looser and suspend longer in atmosphere due to Organic Compound (OC) existing (OC can reduce about 67% of PM2.5 density). Considering that NH4+ is the only cation in the main chemical components of PM2.5, it would be vital for anions (such as SO42- and NO3-) to aggregate together for facilitating PM2.5 growing. Therefore, in order to relieve PM2.5 pollution, control strategies for OC and NH4+ would be enhanced by government through improving the quality of oils and solvent products, decreasing the amount of nitrogenous fertilizer utilization, or changing the fertilizing environment from dry condition to wet condition.

  6. ROP18 is a key factor responsible for virulence difference between Toxoplasma gondii and Neospora caninum.

    Directory of Open Access Journals (Sweden)

    Tao Lei

    Full Text Available Toxoplasma gondii (T. gondii and Neospora caninum (N. caninum are both obligate intracellular protozoan parasites and share many common morphological and biological features. Despite these similarities the two parasites differ dramatically in virulence in mice, but the factors involved in virulence differences between the two parasites remain unknown. A secreted serine-threonine kinase called rhoptry protein 18 (ROP18 was identified to play a crucial role on virulence differences among different T. gondii clonal lineages. Intriguingly, we found that ROP18 in Nc1 strain of N. caninum (NcROP18 is a pseudogene due to several interrupting stop codons in the sequence in our previous studies. We assume that the difference of ROP18 leads to virulence difference between T. gondii and N. caninum. We constructed a transgenic N. caninum Nc1 stain by transfecting the TgROP18 from the T. gondii RH strain. Phenotype and virulence assays showed that the expression of TgROP18 in N. caninum did not affect the motility and cell invasion, but resulted in a significant increase in intracellular parasite proliferation and virulence in mice. Immunity-Related GTPase (IRG phosphorylation assay showed that the transgenic parasite Nc1-TgROP18 was able to phosphorylate IRGs as T. gondii did. The present study indicated that the ROP18 plays a crucial role in virulence of the closely related parasites T. gondii and N. caninum and it is indeed a key factor responsible for the virulence difference between T. gondii and N. caninum.

  7. Sphingoid base 1-phosphate phosphatase: A key regulator of sphingolipid metabolism and stress response

    Science.gov (United States)

    Mandala, Suzanne M.; Thornton, Rosemary; Tu, Zhenxing; Kurtz, Myra B.; Nickels, Joseph; Broach, James; Menzeleev, Ramil; Spiegel, Sarah

    1998-01-01

    The sphingolipid metabolites ceramide and sphingosine-1-phosphate are second messengers with opposing roles in mammalian cell growth arrest and survival; their relative cellular level has been proposed to be a rheostat that determines the fate of cells. This report demonstrates that this rheostat is an evolutionarily conserved stress-regulatory mechanism that influences growth and survival of yeast. Although the role of sphingosine-1-phosphate in yeast was not previously examined, accumulation of ceramide has been shown to induce G1 arrest and cell death. We now have identified a gene in Saccharomyces cerevisiae, LBP1, that regulates the levels of phosphorylated sphingoid bases and ceramide. LBP1 was cloned from a yeast mutant that accumulated phosphorylated long-chain sphingoid bases and diverted sphingoid base intermediates from sphingolipid pathways to glycerophospholipid biosynthesis. LBP1 and its homolog, LBP2, encode very hydrophobic proteins that contain a novel-conserved sequence motif for lipid phosphatases, and both have long-chain sphingoid base phosphate phosphatase activity. In vitro characterization of Lbp1p shows that this phosphatase is Mg2+-independent with high specificity for phosphorylated long-chain bases, phytosphingosine and sphingosine. The deletion of LBP1 results in the accumulation of phosphorylated long-chain sphingoid bases and reduced ceramide levels. Moreover, deletion of LBP1 and LBP2 results in dramatically enhanced survival upon severe heat shock. Thus, these phosphatases play a previously unappreciated role in regulating ceramide and phosphorylated sphingoid base levels in yeast, and they modulate stress responses through sphingolipid metabolites in a manner that is reminiscent of their effects on mammalian cells. PMID:9419344

  8. Co-crystal structures of inhibitors with MRCKβ, a key regulator of tumor cell invasion.

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    Timo Heikkila

    Full Text Available MRCKα and MRCKβ (myotonic dystrophy kinase-related Cdc42-binding kinases belong to a subfamily of Rho GTPase activated serine/threonine kinases within the AGC-family that regulate the actomyosin cytoskeleton. Reflecting their roles in myosin light chain (MLC phosphorylation, MRCKα and MRCKβ influence cell shape and motility. We report further evidence for MRCKα and MRCKβ contributions to the invasion of cancer cells in 3-dimensional matrix invasion assays. In particular, our results indicate that the combined inhibition of MRCKα and MRCKβ together with inhibition of ROCK kinases results in significantly greater effects on reducing cancer cell invasion than blocking either MRCK or ROCK kinases alone. To probe the kinase ligand pocket, we screened 159 kinase inhibitors in an in vitro MRCKβ kinase assay and found 11 compounds that inhibited enzyme activity >80% at 3 µM. Further analysis of three hits, Y-27632, Fasudil and TPCA-1, revealed low micromolar IC(50 values for MRCKα and MRCKβ. We also describe the crystal structure of MRCKβ in complex with inhibitors Fasudil and TPCA-1 bound to the active site of the kinase. These high-resolution structures reveal a highly conserved AGC kinase fold in a typical dimeric arrangement. The kinase domain is in an active conformation with a fully-ordered and correctly positioned αC helix and catalytic residues in a conformation competent for catalysis. Together, these results provide further validation for MRCK involvement in regulation of cancer cell invasion and present a valuable starting point for future structure-based drug discovery efforts.

  9. Murine cytomegalovirus protein pM79 is a key regulator for viral late transcription.

    Science.gov (United States)

    Chapa, Travis J; Johnson, L Steven; Affolter, Christopher; Valentine, Mark C; Fehr, Anthony R; Yokoyama, Wayne M; Yu, Dong

    2013-08-01

    Herpesvirus genes are temporally expressed during permissive infections, but how their expression is regulated at late times is poorly understood. Previous studies indicate that the human cytomegalovirus (CMV) gene, UL79, is required for late gene expression. However, the mechanism remains to be fully elucidated, and UL79 homologues in other CMVs have not been studied. Here, we characterized the role of the conserved murine CMV (MCMV) gene M79. We showed that M79 encoded a protein (pM79) which was expressed with early-late kinetics and localized to nuclear viral replication compartments. M79 transcription was significantly decreased in the absence of viral DNA synthesis but markedly stimulated by pM79. To investigate its role, we created the recombinant virus SMin79, in which pM79 expression was disrupted. While marker-rescued virus grew efficiently in fibroblasts, SMin79 failed to produce infectious progeny but was rescued by pM79 expression in trans. During SMin79 infection, representative viral immediate-early and early gene products as well as viral DNA accumulated sufficiently. Formation of viral replication compartments also appeared normal. Pulsed-field gel electrophoresis analysis indicated that the overall structure of replicating viral DNA was indistinguishable between wild-type and SMin79 infection. Viral tiled array and quantitative PCR analysis revealed that many late transcripts sensitive to a viral DNA synthesis inhibitor (phosphonoacetic acid) were markedly reduced by pM79 mutation. This study indicates that cytomegaloviruses use a conserved mechanism to promote transcription at late stages of infection and that pM79 is a critical regulator for at least a subset of viral DNA synthesis-dependent transcripts.

  10. TCPs, WUSs, and WINDs: families of transcription factors that regulate shoot meristem formation, stem cell maintenance, and somatic cell differentiation.

    Science.gov (United States)

    Ikeda, Miho; Ohme-Takagi, Masaru

    2014-01-01

    In contrast to somatic mammalian cells, which cannot alter their fate, plant cells can dedifferentiate to form totipotent callus cells and regenerate a whole plant, following treatment with specific phytohormones. However, the regulatory mechanisms and key factors that control differentiation-dedifferentiation and cell totipotency have not been completely clarified in plants. Recently, several plant transcription factors that regulate meristem formation and dedifferentiation have been identified and include members of the TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR (TCP), WUSCHEL (WUS), and WOUND INDUCED DEDIFFERENTIATION (WIND1) families. WUS and WIND positively control plant cell totipotency, while TCP negatively controls it. Interestingly, TCP is a transcriptional activator that acts as a negative regulator of shoot meristem formation, and WUS is a transcriptional repressor that positively maintains totipotency of the stem cells of the shoot meristem. We describe here the functions of TCP, WUS, and WIND transcription factors in the regulation of differentiation-dedifferentiation by positive and negative transcriptional regulators.

  11. Differential gene expression regulated by oscillatory transcription factors.

    Directory of Open Access Journals (Sweden)

    Luca Cerone

    Full Text Available Cells respond to changes in the internal and external environment by a complex regulatory system whose end-point is the activation of transcription factors controlling the expression of a pool of ad-hoc genes. Recent experiments have shown that certain stimuli may trigger oscillations in the concentration of transcription factors such as NF-κB and p53 influencing the final outcome of the genetic response. In this study we investigate the role of oscillations in the case of three different well known gene regulatory mechanisms using mathematical models based on ordinary differential equations and numerical simulations. We considered the cases of direct regulation, two-step regulation and feed-forward loops, and characterized their response to oscillatory input signals both analytically and numerically. We show that in the case of indirect two-step regulation the expression of genes can be turned on or off in a frequency dependent manner, and that feed-forward loops are also able to selectively respond to the temporal profile of oscillating transcription factors.

  12. The Populus ARBORKNOX1 homeodomain transcription factor regulates woody growth through binding to evolutionarily conserved target genes of diverse function

    Science.gov (United States)

    Lijun Liu; Matthew S. Zinkgraf; H. Earl Petzold; Eric P. Beers; Vladimir Filkov; Andrew Groover

    2014-01-01

    The class I KNOX homeodomain transcription factor ARBORKNOX1 (ARK1) is a key regulator of vascular cambium maintenance and cell differentiation in Populus. Currently, basic information is lacking concerning the distribution, functional characteristics, and evolution of ARK1 binding in the Populus genome.

  13. An R2R3 MYB transcription factor associated with regulation of the anthocyanin biosynthetic pathway in Rosaceae (on linr)

    NARCIS (Netherlands)

    Wang, Kui-Lin; Bolitho, Karen; Grafton, Karryn; Kortstee, A.J.; Karunairetnam, Sakuntala; McGhie, T.K.; Espley, R.V.; Hellens, R.P.; Allan, A.C.

    2010-01-01

    Background - The control of plant anthocyanin accumulation is via transcriptional regulation of the genes encoding the biosynthetic enzymes. A key activator appears to be an R2R3 MYB transcription factor. In apple fruit, skin anthocyanin levels are controlled by a gene called MYBA or MYB1, while the

  14. The quality of engineering education is a key factor in development

    Directory of Open Access Journals (Sweden)

    Julio César Cañón Rodríguez

    2011-10-01

    Full Text Available The whole world is concerned about the quality of engineers’ education. The ideas regarding engineers’ social responsibility, scientific and technological updating and their professional commitment, along with the expectations of the society to which they belong, are conceived from the classroom and, consequently, should become the essence of curriculum design and therefore the raison d'être of teaching commitment. The magnitude of teaching commitment in engineering causes particular concern for higher education institutions and accompaniment regarding their teachers’ tasks. The quality of engineering curricula significantly depends on the quality of the teaching offered in them and, consequently, teachers’ qualifications and recognition of their importance have become key factors in curriculum management and compliance with commitments as stated in mission statements. Research involving around a thousand engineering professors in Colombia led to identifying the main features of the three fundamental moments regarding their teaching role; this, in turn, led to characterising teachers’ role in ensuring that improvement plans are carried out, resulting from engineering programme accreditation (i.e. making them accountable to society. The future of engineering training requires a major transformation regarding the task of teaching. The conventional image of teachers must provide for the concept of teacher programmes and simple compliance with curriculum guidelines must give way to initiatives and proposals promoting a teacher’s role as a vital/dynamic element in the classroom.

  15. Experimental infections with Mycoplasma agalactiae identify key factors involved in host-colonization.

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    Eric Baranowski

    Full Text Available Mechanisms underlying pathogenic processes in mycoplasma infections are poorly understood, mainly because of limited sequence similarities with classical, bacterial virulence factors. Recently, large-scale transposon mutagenesis in the ruminant pathogen Mycoplasma agalactiae identified the NIF locus, including nifS and nifU, as essential for mycoplasma growth in cell culture, while dispensable in axenic media. To evaluate the importance of this locus in vivo, the infectivity of two knock-out mutants was tested upon experimental infection in the natural host. In this model, the parental PG2 strain was able to establish a systemic infection in lactating ewes, colonizing various body sites such as lymph nodes and the mammary gland, even when inoculated at low doses. In these PG2-infected ewes, we observed over the course of infection (i the development of a specific antibody response and (ii dynamic changes in expression of M. agalactiae surface variable proteins (Vpma, with multiple Vpma profiles co-existing in the same animal. In contrast and despite a sensitive model, none of the knock-out mutants were able to survive and colonize the host. The extreme avirulent phenotype of the two mutants was further supported by the absence of an IgG response in inoculated animals. The exact role of the NIF locus remains to be elucidated but these data demonstrate that it plays a key role in the infectious process of M. agalactiae and most likely of other pathogenic mycoplasma species as many carry closely related homologs.

  16. Post-Mergers and Acquisitions: The Motives, Success Factors and Key Success Indicators

    Directory of Open Access Journals (Sweden)

    Hatem El Zuhairy

    2015-07-01

    Full Text Available There is a wide body of evidence showing a significant increase in the adoption of mergers and acquisitions (M&A worldwide. Moreover, research confirms that the integration and implementation stage (post-M&A has a major impact on the success or failure of a merger or acquisition. Therefore it has become increasingly important to explore the post-M&A phase further in order to support the management teams of organizations pursuing a merger or acquisition in meeting all their desired objectives. This paper proposes a framework to help in the successful execution of M&A. The framework contains three main elements: the motives, success factors and key success indicators (KSI. A qualitative research approach using the multiple case study methodology was conducted to test the framework. Ten case studies were selected from the industrial sector in Egypt and used to validate the research. The final version of the M&A framework was provided after applying the research results. Considering the practical implications of the M&A framework, a tool was proposed for its application in light of the balanced scorecard (BSC methodology. The proposed M&A scorecard tool should be used in the strategic planning and execution of M&A. Both the proposed M&A framework and the M&A scorecard tool should be used to guide the implementation of M&A in order to increase the success rate enjoyed by organizations.

  17. Key factors of the bussiness with purpose of maximazation of stock value

    Directory of Open Access Journals (Sweden)

    Maryam Adibzadeh

    2016-12-01

    Full Text Available The firms must attempt to realize procedures that are used by analyzers and stockholders for evaluating firm stocks and pay special attention to competitive advantages in compare to their competitors and be aware that what expectations of investors in what conditions and times and create some values for firm and finally transfer created value to stockholders. The main aim of the present research is achieving to high levels to maximization assets regarding to eightfold key factors of business and the current research in terms of purpose is applied research and in terms of type is descriptive research and it helps firms to consider this maximization in an operational way in mechanism of applying aims. Research population of the present research is including all superior and financial managers in Corporations of Accepted in Tehran Stock Exchange that the method of sampling was selected by simple random sampling. Data were collected by questionnaire and testing hypothesis was done by entering data to Matlab software and by using derivative system. The findings of the present research indicated that no existence of many indexes and sub-indexes of operation measurement are based on maximization of value in Corporations of Accepted in Tehran Stock Exchange.

  18. Key factors for causing poplar Ice Nucleation Active bacterial canker and its control techniques

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The isolation, culture and the active determination of poplar ice nucleation active (INA) bacteria and the inoculation tests in laboratory and field were conducted, and the varieties, distribution and number of poplar INA bacteria and its pathogenicity and freezing injury property were determined. The study results showed that the INA bacteria widely spread on poplar in Northeast China and caused the frozen injury for poplar under the frost condition in Spring or Autumn, which was the key factor to induce INA bacterial canker. Through evaluation and investigation of different poplar varieties and inoculation tests, fine disease-resistant varieties and strains of poplar suitable for Northeast China were selected. Further tests for strong seedling showed that burying cuttings in sand and covering with plastic film could effectively avoid the frostbite, frozen and drought damage, reduce INA bacteria infection, and promote poplar growth. INA bacterial canker was detected early by highly specialized antiserums of INA bacteria and the agglutinated test of ring-shaped boundary surface. The inducers such as streptomycin, phenylmercuric acetae, salicylic acid and heat-killed bacteria to immerse cuttings, have obvious induced disease-resistant effect. Before poplar sprouted in early spring, through spraying the solution of frostbite agent, the control effect also was obvious.

  19. Insights into key factors controlling GO stability in natural surface waters.

    Science.gov (United States)

    Gao, Yang; Ren, Xuemei; Tan, Xiaoli; Hayat, Tasawar; Alsaedi, Ahmed; Chen, Changlun

    2017-08-05

    The effects of pH, cations (Na(+), K(+), Mg(2+), Ca(2+) and Al(3+)), and anions (Cl(-), HCO3(-), HPO4(2-) and SO4(2-)) on graphene oxide (GO) stability were investigated to address the current limitations in the knowledge regarding the stability of GO in natural surface water and its underlying mechanism. The threshold values of cations that destabilize GO were obtained and affected by both pH and anions. By employing elemental mapping and studying the effects of polyacrylic acid (PAA) on GO sedimentation and the re-dispersion of GO aggregates, we find that the GO aggregates induced by Na(+) and K(+) via electric double layer suppression and by Ca(2+) and Al(3+) via strong complxing are difficult to re-disperse completely. Specifically, more PAA is needed to re-disperse GO aggregates than to stabilize GO, which suggests that after GO binds with heavy metal ions. It is less likely to be transported over a long distance even in natural water that are rich in natural organic matter. Finally, we find that the key factor controlling GO sedimentation in natural surface waters is its binding with Mg(2+) and Ca(2+). This study is expected to provide critical knowledge to more accurately predict the fate of GO in natural surface aquatic environments. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Corticotropin-releasing factor: a possible key to gut dysfunction in the critically ill.

    Science.gov (United States)

    Hill, Lauren T; Kidson, Susan H; Michell, William L

    2013-01-01

    Critically ill patients frequently display unexplained or incompletely explained features of gastrointestinal (GI) dysfunction, including gastric stasis, ileus, and diarrhea. This makes nutrition delivery challenging, and may contribute to poor outcomes. The typical bowel dysfunction seen in severely ill patients includes retarded gastric emptying, unsynchronized intestinal motility, and intestinal hyperpermeability. These functional changes appear similar to the corticotropin-releasing factor (CRF)-mediated bowel dysfunctions associated with stress of various types and some GI disorders and diseases. CRF has been shown to be present within the GI tract and its action on CRF receptors within the gut have been shown to reduce gastric emptying, alter intestinal motility, and increase intestinal permeability. However, the precise role of CRF in the GI dysfunction in critical illness remains unclear. In this short review, we provide an update on GI dysfunction during stress and review the possible role of CRF in the aetiology of gut dysfunction. We suggest that activation of CRF signaling pathways in critical illness might be key to understanding the mechanisms underlying the gut dysfunction that impairs enteral feeding in the intensive care unit.

  1. A genetic screen identifies BRCA2 and PALB2 as key regulators of G2 checkpoint maintenance

    DEFF Research Database (Denmark)

    Menzel, Tobias; Nähse-Kumpf, Viola; Kousholt, Arne Nedergaard;

    2011-01-01

    To identify key connections between DNA-damage repair and checkpoint pathways, we performed RNA interference screens for regulators of the ionizing radiation-induced G2 checkpoint, and we identified the breast cancer gene BRCA2. The checkpoint was also abrogated following depletion of PALB2......, an interaction partner of BRCA2. BRCA2 and PALB2 depletion led to premature checkpoint abrogation and earlier activation of the AURORA A-PLK1 checkpoint-recovery pathway. These results indicate that the breast cancer tumour suppressors and homologous recombination repair proteins BRCA2 and PALB2 are main...

  2. Nitrogen as a key regulator of flowering in Fagus crenata: understanding the physiological mechanism of masting by gene expression analysis.

    Science.gov (United States)

    Miyazaki, Yuko; Maruyama, Yosuke; Chiba, Yukako; Kobayashi, Masaki J; Joseph, Benesh; Shimizu, Kentaro K; Mochida, Keiichi; Hiura, Tsutom; Kon, Hirokazu; Satake, Akiko

    2014-10-01

    The role of resource availability in determining the incidence of masting has been widely studied, but how floral transition and initiation are regulated by the resource level is unclear. We tested the hypothesis that floral transition is stimulated by high resource availabiltiy in Fagus crenata based on a new technique, the expression analyses of flowering genes. We isolated F. crenata orthologues of FLOWERING LOCUS T, LEAFY and APETALA1, and confirmed their functions using transgenic Arabidopsis thaliana. We monitored the gene expression levels for 5 years and detected a cycle of on and off years, which was correlated with fluctuations of the shoot-nitrogen concentration. Nitrogen fertilisation resulted in the significantly higher expression of flowering genes than the control, where all of the fertilised trees flowered, whereas the control did not. Our findings identified nitrogen as a key regulator of mast flowering, thereby providing new empirical evidence to support the resource budget model.

  3. Cytosolic chloride ion is a key factor in lysosomal acidification and function of autophagy in human gastric cancer cell.

    Science.gov (United States)

    Hosogi, Shigekuni; Kusuzaki, Katsuyuki; Inui, Toshio; Wang, Xiangdong; Marunaka, Yoshinori

    2014-06-01

    The purpose of the present study was to clarify roles of cytosolic chloride ion (Cl(-) ) in regulation of lysosomal acidification [intra-lysosomal pH (pHlys )] and autophagy function in human gastric cancer cell line (MKN28). The MKN28 cells cultured under a low Cl(-) condition elevated pHlys and reduced the intra-lysosomal Cl(-) concentration ([Cl(-) ]lys ) via reduction of cytosolic Cl(-) concentration ([Cl(-) ]c ), showing abnormal accumulation of LC3II and p62 participating in autophagy function (dysfunction of autophagy) accompanied by inhibition of cell proliferation via G0 /G1 arrest without induction of apoptosis. We also studied effects of direct modification of H(+) transport on lysosomal acidification and autophagy. Application of bafilomycin A1 (an inhibitor of V-type H(+) -ATPase) or ethyl isopropyl amiloride [EIPA; an inhibitor of Na(+) /H(+) exchanger (NHE)] elevated pHlys and decreased [Cl(-) ]lys associated with inhibition of cell proliferation via induction of G0 /G1 arrest similar to the culture under a low Cl(-) condition. However, unlike low Cl(-) condition, application of the compound, bafilomycin A1 or EIPA, induced apoptosis associated with increases in caspase 3 and 9 without large reduction in [Cl(-) ]c compared with low Cl(-) condition. These observations suggest that the lowered [Cl(-) ]c primarily causes dysfunction of autophagy without apoptosis via dysfunction of lysosome induced by disturbance of intra-lysosomal acidification. This is the first study showing that cytosolic Cl(-) is a key factor of lysosome acidification and autophagy.

  4. Key Factors in the Success of an Organization's Information Security Culture: A Quantitative Study and Analysis

    Science.gov (United States)

    Pierce, Robert E.

    2012-01-01

    This research study reviewed relative literature on information security and information security culture within organizations to determine what factors potentially assist an organization in implementing, integrating, and maintaining a successful organizational information security culture. Based on this review of literature, five key factors were…

  5. Key Factors in the Success of an Organization's Information Security Culture: A Quantitative Study and Analysis

    Science.gov (United States)

    Pierce, Robert E.

    2012-01-01

    This research study reviewed relative literature on information security and information security culture within organizations to determine what factors potentially assist an organization in implementing, integrating, and maintaining a successful organizational information security culture. Based on this review of literature, five key factors were…

  6. DHN melanin biosynthesis in the plant pathogenic fungus Botrytis cinerea is based on two developmentally regulated key enzyme (PKS)-encoding genes.

    Science.gov (United States)

    Schumacher, Julia

    2016-02-01

    Botrytis cinerea is the causal agent of gray mold disease in various plant species and produces grayish macroconidia and/or black sclerotia at the end of the infection cycle. It has been suggested that the pigmentation is due to the accumulation of 1,8-dihydroxynaphthalene (DHN) melanin. To unravel its basis and regulation, the putative melanogenic and regulatory genes were identified and functionally characterized. Unlike other DHN melanin-producing fungi, B. cinerea and other Leotiomycetes contain two key enzyme (PKS)-encoding enzymes. Bcpks12 and bcpks13 are developmentally regulated and are required for melanogenesis in sclerotia and conidia respectively. BcYGH1 converts the BcPKS13 product and contributes thereby to conidial melanogenesis. In contrast, enzymes acting downstream in conversion of the PKS products (BcBRN2, BcSCD1 and BcBRN1) are required for both, sclerotial and conidial melanogenesis, suggesting that DHN melanogenesis in B. cinerea follows a non-linear pathway that is rather unusual for secondary metabolic pathways. Regulation of the melanogenic genes involves three pathway-specific transcription factors (TFs) that are clustered with bcpks12 or bcpks13 and other developmental regulators such as light-responsive TFs. Melanogenic genes are dispensable in vegetative mycelia for proper growth and virulence. However, DHN melanin is considered to contribute to the longevity of the reproduction structures.

  7. 25-Hydroxyvitamin D₃ 24-Hydroxylase: A Key Regulator of 1,25(OH)₂D₃ Catabolism and Calcium Homeostasis.

    Science.gov (United States)

    Veldurthy, Vaishali; Wei, Ran; Campbell, Megan; Lupicki, Kamil; Dhawan, Puneet; Christakos, Sylvia

    2016-01-01

    One of the most pronounced effects of the hormonally active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), is increased synthesis of 25-hydroxyvitamin D3 24-hydroxylase (CYP24A1), the enzyme responsible for the catabolism of 1,25(OH)2D3. Thus, 1,25(OH)2D3 regulates its own metabolism, protecting against hypercalcemia and limiting the levels of 1,25(OH)2D3 in cells. This chapter summarizes the catalytic properties of CYP24A1, the recent data related to the crystal structure of CYP24A1, the findings obtained from the generation of mice deficient for the Cyp24a1 gene as well as recent data identifying a causal role of a genetic defect in CYP24A1 in certain patients with idiopathic infantile hypercalcemia. This chapter also reviews the regulation of renal and placental CYP24A1 as well as the genomic mechanisms, including coactivators, repressors, and epigenetic modification, involved in modulating 1,25(OH)2D3 regulation of CYP24A1. We conclude with future research directions related to this key regulator of 1,25(OH)2D3 catabolism and calcium homeostasis.

  8. Long Non-Coding RNAs: Key Regulators of Epithelial-Mesenchymal Transition, Tumour Drug Resistance and Cancer Stem Cells

    Science.gov (United States)

    Heery, Richard; Finn, Stephen P.; Cuffe, Sinead; Gray, Steven G.

    2017-01-01

    Epithelial mesenchymal transition (EMT), the adoption by epithelial cells of a mesenchymal-like phenotype, is a process co-opted by carcinoma cells in order to initiate invasion and metastasis. In addition, it is becoming clear that is instrumental to both the development of drug resistance by tumour cells and in the generation and maintenance of cancer stem cells. EMT is thus a pivotal process during tumour progression and poses a major barrier to the successful treatment of cancer. Non-coding RNAs (ncRNA) often utilize epigenetic programs to regulate both gene expression and chromatin structure. One type of ncRNA, called long non-coding RNAs (lncRNAs), has become increasingly recognized as being both highly dysregulated in cancer and to play a variety of different roles in tumourigenesis. Indeed, over the last few years, lncRNAs have rapidly emerged as key regulators of EMT in cancer. In this review, we discuss the lncRNAs that have been associated with the EMT process in cancer and the variety of molecular mechanisms and signalling pathways through which they regulate EMT, and finally discuss how these EMT-regulating lncRNAs impact on both anti-cancer drug resistance and the cancer stem cell phenotype. PMID:28430163

  9. Environmental impact and risk assessments and key factors contributing to the overall uncertainties.

    Science.gov (United States)

    Salbu, Brit

    2016-01-01

    , ignoring sensitive history life stages of organisms and transgenerational effects. To link sources, ecosystem transfer and biological effects to future impact and risks, a series of models are usually interfaced, while uncertainty estimates are seldom given. The model predictions are, however, only valid within the boundaries of the overall uncertainties. Furthermore, the model predictions are only useful and relevant when uncertainties are estimated, communicated and understood. Among key factors contributing most to uncertainties, the present paper focuses especially on structure uncertainties (model bias or discrepancies) as aspects such as particle releases, ecosystem dynamics, mixed exposure, sensitive life history stages and transgenerational effects, are usually ignored in assessment models. Research focus on these aspects should significantly reduce the overall uncertainties in the impact and risk assessment of radioactive contaminated ecosystems.

  10. Key Success Factors in the Brazilian Coffee Agrichain: Present and Future Challenges

    Directory of Open Access Journals (Sweden)

    Luciana Florêncio de Almeida

    2017-01-01

    Full Text Available Coffee production has grown 100% in volume over the past 30 years, accounting for 144 million coffee bags produced in 2015. Brazil responded to 42% of this production, along with Vietnam (19%, Colombia (9%, Indonesia (8%, and Ethiopia (4% (OIC, 2016. Following this pace, the consumption expanded not only in such traditional markets as the United States (4.2 kg/year, Germany (6.9 kg/year, and France (5.7 kg/year but also in tea-driven markets, such as Japan, Korea, Russia, and China (CECAFE, 2013. In 2015, Brazil harvested 43.2 million 60-kg bags of green coffee, 32 million of which were of Arabica coffee and 11.2 million of a Conilon species (CONAB, 2016. The planted area in Brazil is 2.3 million hectares, and there are about 287,000 producers, predominantly mini- and small farmers. Having continental dimensions, the country presents a variety of climates, reliefs, altitudes, and latitudes that allow the production of a wide range of types and qualities of coffee (MAPA, 2016. This research aimed to clarify present and future challenges for the Brazilian coffee agrichain, considering the growing demand and also competitiveness between the coffee countries’ producers. To capture the vivid perception of the actors in the coffee chain, a qualitative approach was employed. The research was conducted in three phases. In the first phase, 10 coffee specialists were interviewed to identify the coffee sector’s main milestones for Brazil over the next 30 years. The findings culminated in eight key success factors for coffee-farming management. Finally, in the second phase, the results of phase two were submitted for analysis by 39 coffee farmers through three discussion panels held in the major producing regions: Sul de Minas (corresponding to 25% of the national production, Cerrado Mineiro (with 10%, and Matas de Minas (with 16% (MAPA, 2016. The third phase comprised the data analysis, aggregating the patterns by regions and by critical factors. The

  11. Schwann cell mitochondria as key regulators in the development and maintenance of peripheral nerve axons.

    Science.gov (United States)

    Ino, Daisuke; Iino, Masamitsu

    2017-03-01

    Formation of myelin sheaths by Schwann cells (SCs) enables rapid and efficient transmission of action potentials in peripheral axons, and disruption of myelination results in disorders that involve decreased sensory and motor functions. Given that construction of SC myelin requires high levels of lipid and protein synthesis, mitochondria, which are pivotal in cellular metabolism, may be potential regulators of the formation and maintenance of SC myelin. Supporting this notion, abnormal mitochondria are found in SCs of neuropathic peripheral nerves in both human patients and the relevant animal models. However, evidence for the importance of SC mitochondria in myelination has been limited, until recently. Several studies have recently used genetic approaches that allow SC-specific ablation of mitochondrial metabolic activity in living animals to show the critical roles of SC mitochondria in the development and maintenance of peripheral nerve axons. Here, we review current knowledge about the involvement of SC mitochondria in the formation and dysfunction of myelinated axons in the peripheral nervous system.

  12. Erk5 Is a Key Regulator of Naive-Primed Transition and Embryonic Stem Cell Identity

    Directory of Open Access Journals (Sweden)

    Charles A.C. Williams

    2016-08-01

    Full Text Available Embryonic stem cells (ESCs can self-renew or differentiate into any cell type, a phenomenon known as pluripotency. Distinct pluripotent states, termed naive and primed pluripotency, have been described. However, the mechanisms that control naive-primed pluripotent transition are poorly understood. Here, we perform a targeted screen for kinase inhibitors, which modulate the naive-primed pluripotent transition. We find that XMD compounds, which selectively inhibit Erk5 kinase and BET bromodomain family proteins, drive ESCs toward primed pluripotency. Using compound selectivity engineering and CRISPR/Cas9 genome editing, we reveal distinct functions for Erk5 and Brd4 in pluripotency regulation. We show that Erk5 signaling maintains ESCs in the naive state and suppresses progression toward primed pluripotency and neuroectoderm differentiation. Additionally, we identify a specialized role for Erk5 in defining ESC lineage selection, whereby Erk5 inhibits a cardiomyocyte-specific differentiation program. Our data therefore reveal multiple critical functions for Erk5 in controlling ESC identity.

  13. Transcription factor ICBP90 regulates the MIF promoter and immune susceptibility locus.

    Science.gov (United States)

    Yao, Jie; Leng, Lin; Sauler, Maor; Fu, Weiling; Zheng, Junsong; Zhang, Yi; Du, Xin; Yu, Xiaoqing; Lee, Patty; Bucala, Richard

    2016-02-01

    The immunoregulatory cytokine macrophage migration inhibitory factor (MIF) is encoded in a functionally polymorphic locus that is linked to the susceptibility of autoimmune and infectious diseases. The MIF promoter contains a 4-nucleotide microsatellite polymorphism (-794 CATT) that repeats 5 to 8 times in the locus, with greater numbers of repeats associated with higher mRNA levels. Because there is no information about the transcriptional regulation of these common alleles, we used oligonucleotide affinity chromatography and liquid chromatography-mass spectrometry to identify nuclear proteins that interact with the -794 CATT5-8 site. An analysis of monocyte nuclear lysates revealed that the transcription factor ICBP90 (also known as UHRF1) is the major protein interacting with the MIF microsatellite. We found that ICBP90 is essential for MIF transcription from monocytes/macrophages, B and T lymphocytes, and synovial fibroblasts, and TLR-induced MIF transcription is regulated in an ICBP90- and -794 CATT5-8 length-dependent manner. Whole-genome transcription analysis of ICBP90 shRNA-treated rheumatoid synoviocytes uncovered a subset of proinflammatory and immune response genes that overlapped with those regulated by MIF shRNA. In addition, the expression levels of ICBP90 and MIF were correlated in joint synovia from patients with rheumatoid arthritis. These findings identify ICBP90 as a key regulator of MIF transcription and provide functional insight into the regulation of the polymorphic MIF locus.

  14. Poplar MYB115 and MYB134 Transcription Factors Regulate Proanthocyanidin Synthesis and Structure.

    Science.gov (United States)

    James, Amy Midori; Ma, Dawei; Mellway, Robin; Gesell, Andreas; Yoshida, Kazuko; Walker, Vincent; Tran, Lan; Stewart, Don; Reichelt, Michael; Suvanto, Jussi; Salminen, Juha-Pekka; Gershenzon, Jonathan; Séguin, Armand; Constabel, C Peter

    2017-05-01

    The accumulation of proanthocyanidins is regulated by a complex of transcription factors composed of R2R3 MYB, basic helix-loop-helix, and WD40 proteins that activate the promoters of biosynthetic genes. In poplar (genus Populus), MYB134 is known to regulate proanthocyanidin biosynthesis by activating key flavonoid genes. Here, we characterize a second MYB regulator of proanthocyanidins, MYB115. Transgenic poplar overexpressing MYB115 showed a high-proanthocyanidin phenotype and reduced salicinoid accumulation, similar to the effects of MYB134 overexpression. Transcriptomic analysis of MYB115- and MYB134-overexpressing poplar plants identified a set of common up-regulated genes encoding proanthocyanidin biosynthetic enzymes and several novel uncharacterized MYB transcriptional repressors. Transient expression experiments demonstrated the capacity of both MYB134 and MYB115 to activate flavonoid promoters, but only in the presence of a basic helix-loop-helix cofactor. Yeast two-hybrid experiments confirmed the direct interaction of these transcription factors. The unexpected identification of dihydromyricetin in leaf extracts of both MYB115- and MYB134-overexpressing poplar led to the discovery of enhanced flavonoid B-ring hydroxylation and an increased proportion of prodelphinidins in proanthocyanidin of the transgenics. The dramatic hydroxylation phenotype of MYB115 overexpressors is likely due to the up-regulation of both flavonoid 3',5'-hydroxylases and cytochrome b5 Overall, this work provides new insight into the complexity of the gene regulatory network for proanthocyanidin synthesis in poplar. © 2017 American Society of Plant Biologists. All Rights Reserved.

  15. The Fuzzy Logic of MicroRNA Regulation: A Key to Control Cell Complexity.

    Science.gov (United States)

    Ripoli, Andrea; Rainaldi, Giuseppe; Rizzo, Milena; Mercatanti, Alberto; Pitto, Letizia

    2010-08-01

    Genomic and clinical evidence suggest a major role of microRNAs (miRNAs) in the regulatory mechanisms of gene expression, with a clear impact on development and physiology; miRNAs are a class of endogenous 22-25 nt single-stranded RNA molecules, that negatively regulate gene expression post-transcriptionally, by imperfect base pairing with the 3' UTR of the corresponding mRNA target. Because of this imperfection, each miRNA can bind multiple targets, and multiple miRNAs can bind the same mRNA target; although digital, the miRNAs control mechanism is characterized by an imprecise action, naturally understandable in the theoretical framework of fuzzy logic.A major practical application of fuzzy logic is represented by the design and the realization of efficient and robust control systems, even when the processes to be controlled show chaotic, deterministic as well unpredictable, behaviours. The vagueness of miRNA action, when considered together with the controlled and chaotic gene expression, is a hint of a cellular fuzzy control system. As a demonstration of the possibility and the effectiveness of miRNA based fuzzy mechanism, a fuzzy cognitive map -a mathematical formalism combining neural network and fuzzy logic- has been developed to study the apoptosis/proliferation control performed by the miRNA-17-92 cluster/E2F1/cMYC circuitry.When experimentally demonstrated, the concept of fuzzy control could modify the way we analyse and model gene expression, with a possible impact on the way we imagine and design therapeutic intervention based on miRNA silencing.

  16. Epithelial Barrier Regulation by Hypoxia-Inducible Factor.

    Science.gov (United States)

    Glover, Louise E; Colgan, Sean P

    2017-09-01

    Mucosal tissues represent surfaces that are exposed to the outside world and provide a conduit for internal and external communication. Tissues such as the intestine and the lung are lined by layer(s) of epithelial cells that, when organized in three dimensions, provide a critical barrier to the flux of luminal contents. This selective barrier is provided through the regulated expression of junctional proteins and mucins. Tissue oxygen metabolism is central to the maintenance of homeostasis in the mucosa. In some organs (e.g., the colon), low baseline Po2 determines tissue metabolism and results in basal expression of the transcription factor, hypoxia-inducible factor (HIF), which is enhanced after ischemia/inflammation. Recent studies have indicated that HIF contributes fundamentally to the expression of barrier-related genes and in the regulation of barrier-adaptive responses within the mucosa. Here, we briefly review recent literature on the topic of hypoxia and HIF regulation of barrier in mucosal health and during disease.

  17. FOXO Transcription Factors: Their Clinical Significance and Regulation

    Directory of Open Access Journals (Sweden)

    Yu Wang

    2014-01-01

    Full Text Available Members of the class O of forkhead box transcription factors (FOXO have important roles in metabolism, cellular proliferation, stress resistance, and apoptosis. The activity of FOXOs is tightly regulated by posttranslational modification, including phosphorylation, acetylation, and ubiquitylation. Activation of cell survival pathways such as phosphoinositide-3-kinase/AKT/IKK or RAS/mitogen-activated protein kinase phosphorylates FOXOs at different sites which regulate FOXOs nuclear localization or degradation. FOXO transcription factors are upregulated in a number of cell types including hepatocytes, fibroblasts, osteoblasts, keratinocytes, endothelial cells, pericytes, and cardiac myocytes. They are involved in a number of pathologic and physiologic processes that include proliferation, apoptosis, autophagy, metabolism, inflammation, cytokine expression, immunity, differentiation, and resistance to oxidative stress. These processes impact a number of clinical conditions such as carcinogenesis, diabetes, diabetic complications, cardiovascular disease, host response, and wound healing. In this paper, we focus on the potential role of FOXOs in different disease models and the regulation of FOXOs by various stimuli.

  18. Rhoptry protein 5 (ROP5) Is a Key Virulence Factor in Neospora caninum

    Science.gov (United States)

    Ma, Lei; Liu, Jing; Li, Muzi; Fu, Yong; Zhang, Xiao; Liu, Qun

    2017-01-01

    Neospora caninum, of the Apicomplexa phylum, is a common cause of abortions in cattle and nervous system dysfunction in dogs. Rhoptry proteins of Apicomplexa play an important role in virulence. The objectives of this study were to study functions of NcROP5 in N. caninum by deleting the NcROP5 gene from the wild Nc-1 strain. We selected NcROP5 in ToxoDB and successfully constructed an NcROP5 gene-deleted vector, pTCR-NcROP5-CD KO. Then we screened the NcROP5 knockout strains (ΔNcROP5) at the gene, protein and transcription levels. Plaque assay, host cell invasion assay and intracellular proliferation test showed that the ΔNcROP5 strain had less plaque space, weakened invasion capacity and slower intracellular growth. Animal testing showed significantly lower cerebral load of ΔNcROP5 than the load of the Nc-1 strain, as well as a loss of virulence for the ΔNcROP5 strains. Phenotypic analyses using the label-free LC-MS/MS assay-based proteomic method and KEGG pathway enrichment analysis showed a reduction of NcGRA7 transcription and altered expression of multiple proteins including the apicomplexan family of binding proteins. The present study indicated that ROP5 is a key virulence factor in N. caninum in mice. The proteomic profiling of Nc-1 and ΔNcROP5 provided some data on differential proteins. These data provide a foundation for future research of protein functions in N. caninum. PMID:28326073

  19. Measurement of immunotargeted plasmonic nanoparticles' cellular binding: a key factor in optimizing diagnostic efficacy

    Science.gov (United States)

    Fu, Kun; Sun, Jiantang; Bickford, Lissett R.; Lin, Alex W. H.; Halas, Naomi J.; Yu, Tse-Kuan; Drezek, Rebekah A.

    2008-01-01

    In this study, we use polarized light scattering to study immunotargeted plasmonic nanoparticles which bind to live SK-BR-3 human breast carcinoma cells. Gold nanoparticles can be conjugated to various biomolecules in order to target specific molecular signatures of disease. This specific targeting provides enhanced contrast in scattering-based optical imaging techniques. While there are papers which report the number of antibodies that bind per nanoparticle, there are almost no reports of the key factor which influences diagnostic or therapeutic efficacy using nanoparticles: the number of targeted nanoparticles that bind per cell. To achieve this goal, we have developed a 'negative' method of determining the binding concentration of those antibody/nanoparticle bioconjugates which are targeted specifically to breast cancer cells. Unlike previously reported methods, we collected unbound nanoparticle bioconjugates and measured the light scattering from dilute solutions of these particles so that quantitative binding information can be obtained. By following this process, the interaction effects of adjacent bound nanoparticles on the cell membrane can be avoided simply by measuring the light scattering from the unbound nanoparticles. Specifically, using nanoshells of two different sizes, we compared the binding concentrations of anti-HER2/nanoshell and anti-IgG/nanoshell bioconjugates targeted to HER2-positive SK-BR-3 breast cancer cells. The results indicate that, for anti-HER2/nanoshell bioconjugates, there are approximately 800-1600 nanoshells bound per cell; for anti-IgG/nanoshell bioconjugates, the binding concentration is significantly lower at nearly 100 nanoshells bound per cell. These results are also supported by dark-field microscopy images of the cells labeled with anti-HER2/nanoshell and anti-IgG/nanoshell bioconjugates.

  20. Measurement of immunotargeted plasmonic nanoparticles' cellular binding: a key factor in optimizing diagnostic efficacy

    Energy Technology Data Exchange (ETDEWEB)

    Fu Kun [Department of Bioengineering, Rice University, 6100 Main Street, MS-142, Houston, TX 77005 (United States); Sun Jiantang [Department of Bioengineering, Rice University, 6100 Main Street, MS-142, Houston, TX 77005 (United States); Bickford, Lissett R [Department of Bioengineering, Rice University, 6100 Main Street, MS-142, Houston, TX 77005 (United States); Lin, Alex W H [Department of Bioengineering, Rice University, 6100 Main Street, MS-142, Houston, TX 77005 (United States); Halas, Naomi J [Department of Electrical and Computer Engineering, Rice University, 6100 Main Street, MS-142, Houston, TX 77005 (United States); Yu, T-K [Department of Radiation Oncology, University of Texas, M D Anderson Cancer Center, Box 1202, 1515 Holcombe Boulevard, Houston, TX 77030 (United States); Drezek, Rebekah A [Department of Bioengineering, Rice University, 6100 Main Street, MS-142, Houston, TX 77005 (United States)

    2008-01-30

    In this study, we use polarized light scattering to study immunotargeted plasmonic nanoparticles which bind to live SK-BR-3 human breast carcinoma cells. Gold nanoparticles can be conjugated to various biomolecules in order to target specific molecular signatures of disease. This specific targeting provides enhanced contrast in scattering-based optical imaging techniques. While there are papers which report the number of antibodies that bind per nanoparticle, there are almost no reports of the key factor which influences diagnostic or therapeutic efficacy using nanoparticles: the number of targeted nanoparticles that bind per cell. To achieve this goal, we have developed a 'negative' method of determining the binding concentration of those antibody/nanoparticle bioconjugates which are targeted specifically to breast cancer cells. Unlike previously reported methods, we collected unbound nanoparticle bioconjugates and measured the light scattering from dilute solutions of these particles so that quantitative binding information can be obtained. By following this process, the interaction effects of adjacent bound nanoparticles on the cell membrane can be avoided simply by measuring the light scattering from the unbound nanoparticles. Specifically, using nanoshells of two different sizes, we compared the binding concentrations of anti-HER2/nanoshell and anti-IgG/nanoshell bioconjugates targeted to HER2-positive SK-BR-3 breast cancer cells. The results indicate that, for anti-HER2/nanoshell bioconjugates, there are approximately 800-1600 nanoshells bound per cell; for anti-IgG/nanoshell bioconjugates, the binding concentration is significantly lower at nearly 100 nanoshells bound per cell. These results are also supported by dark-field microscopy images of the cells labeled with anti-HER2/nanoshell and anti-IgG/nanoshell bioconjugates.

  1. Key factors in achieving firm adhesion in post–core restorations

    Directory of Open Access Journals (Sweden)

    Mikako Hayashi

    2008-07-01

    Full Text Available Adhesive post–core restorations using a combination of fiber reinforced posts (FRPs and resin composites have become the preferred choice worldwide in restoring pulpless teeth. The success of this method, especially because of the low incidence of root fracture, has been shown in many clinical studies in several countries. However, the method has also shown a tendency for the FRP to come detached from its post-space, and this potential flaw raises questions about the long-term durable prognoses of such restorations. The adhesive characteristics of post–core materials to root canal dentin have been widely investigated as part of the attempt to find a solution to the problem. Comprehensive understanding of the way that root canal dentin behaves in the post-space may be the key to achieving their better adhesion. Clinicians have to contend with the high stresses produced in the post-space because of its extremely high C-factor. When using light-cured and even dual-cured materials, ensuring deep and complete light penetration is essential to obtain even bonding strength throughout the post-space. Chemically cured adhesive materials, where the progress of curing is relatively slow and there is less stress caused by polymerization shrinkage, should be positively considered for the root canal bonding. In every case, careful attention needs to be paid to the negative effects that endodontic irrigation solutions, such as sodium hypochlorite and EDTA, have on root canal adhesion. Even after better adhesion of the FRP to root canal dentin has been achieved—and proved by high-quality long-term clinical studies, the concept of cusp-coverage in pulpless molars may need to be reconsidered based on a good conservative policy of minimal intervention.

  2. Role of PDI in regulating tissue factor: FVIIa activity.

    Science.gov (United States)

    Popescu, Narcis I; Lupu, Cristina; Lupu, Florea

    2010-04-01

    Cell exposed tissue factor (TF) is generally in a low procoagulant ("cryptic") state, and requires an activation step (decryption) to exhibit its full procoagulant potential. Recent data suggest that TF decryption may be regulated by the redox environment through the oxidoreductase activity of protein disulfide isomerase (PDI). In this article we review PDI contribution to different models of TF decryption, namely the disulfide switch model and the phosphatidylserine dynamics, and hypothesize on PDI contribution to TF self-association and association with lipid domains. Experimental evidence debate the disulfide switch model of TF decryption and its regulation by PDI. More recently we showed that PDI oxidoreductase activity regulates the phosphatidylserine equilibrium at the plasma membrane. Interestingly, PDI reductase activity could maintain TF in the reduced monomeric form, while also maintaining low exposure of PS, both states correlated with low procoagulant function. In contrast, PDI inhibition or oxidants may promote the adverse effects with a net increase in coagulation. The relative contribution of disulfide isomerization and PS exposure needs to be further analyzed to understand the redox control of TF procoagulant function. For the moment however TF regulation remains cryptic.

  3. Proteolysis of proBDNF is a key regulator in the formation of memory.

    Directory of Open Access Journals (Sweden)

    Philip Barnes

    Full Text Available It is essential to understand the molecular processes underlying long-term memory to provide therapeutic targets of aberrant memory that produce pathological behaviour in humans. Under conditions of recall, fully-consolidated memories can undergo reconsolidation or extinction. These retrieval-mediated memory processes may rely on distinct molecular processes. The cellular mechanisms initiating the signature molecular events are not known. Using infusions of protein synthesis inhibitors, antisense oligonucleotide targeting brain-derived neurotrophic factor (BDNF mRNA or tPA-STOP (an inhibitor of the proteolysis of BDNF protein into the hippocampus of the awake rat, we show that acquisition and extinction of contextual fear memory depended on the increased and decreased proteolysis of proBDNF (precursor BDNF in the hippocampus, respectively. Conditions of retrieval that are known to initiate the reconsolidation of contextual fear memory, a BDNF-independent memory process, were not correlated with altered proBDNF cleavage. Thus, the processing of BDNF was associated with the acquisition of new information and the updating of information about a salient stimulus. Furthermore, the differential requirement for the processing of proBDNF by tPA in distinct memory processes suggest that the molecular events actively engaged to support the storage and/or the successful retrieval of memory depends on the integration of ongoing experience with past learning.

  4. Proteoglycans: key regulators of pulmonary inflammation and the innate immune response to lung infection.

    Science.gov (United States)

    Gill, Sean; Wight, Thomas N; Frevert, Charles W

    2010-06-01

    Exposure to viruses and bacteria results in lung infections and places a significant burden on public health. The innate immune system is an early warning system that recognizes viruses and bacteria, which results in the rapid production of inflammatory mediators such as cytokines and chemokines and the pulmonary recruitment of leukocytes. When leukocytes emigrate from the systemic circulation through the extracellular matrix (ECM) in response to lung infection they encounter proteoglycans, which consist of a core protein and their associated glycosaminoglycans. In this review, we discuss how proteoglycans serve to modify the pulmonary inflammatory response and leukocyte migration through a number of different mechanisms including: (1) The ability of soluble proteoglycans or fragments of glycosaminoglycans to activate Toll-like receptor (TLRs) signaling pathways; (2) The binding and sequestration of cytokines, chemokines, and growth factors by proteoglycans; (3) the ability of proteoglycans and hyaluronan to facilitate leukocyte adhesion and sequestration; and (4) The interactions between proteoglycans and matrix metalloproteinases (MMP) that alter the function of these proteases. In conclusion, proteoglycans fine-tune tissue inflammation through a number of different mechanisms. Clarification of the mechanisms whereby proteoglycans modulate the pulmonary inflammatory response will most likely lead to new therapeutic approaches to inflammatory lung disease and lung infection.

  5. Cytokines and growth factors which regulate bone cell function

    Science.gov (United States)

    Seino, Yoshiki

    Everybody knows that growth factors are most important in making bone. Hormones enhance bone formation from a long distance. Growth factors promote bone formation as an autocrine or paracrine factor in nearby bone. BMP-2 through BMP-8 are in the TGF-β family. BMP makes bone by enchondral ossification. In bone, IGF-II is most abundant, second, TGF-β, and third IGF-I. TGF-β enhances bone formation mainly by intramembranous ossification in vivo. TGF-β affects both cell proliferation and differentiation, however, TGF-β mainly enhances bone formation by intramembranous ossification. Interestingly, TGF-β is increased by estrogen(E 2), androgen, vitamin D, TGF-β and FGF. IGF-I and IGF-II also enhance bone formation. At present it remains unclear why IGF-I is more active in bone formation than IGF-II, although IGF-II is more abundant in bone compared to IGF-I. However, if only type I receptor signal transduction promotes bone formation, the strong activity of IGF-I in bone formation is understandable. GH, PTH and E 2 promotes IGF-I production. Recent data suggest that hormones containing vitamin D or E 2 enhance bone formation through growth factors. Therefore, growth factors are the key to clarifying the mechanism of bone formation.

  6. Dynamic regulation of transcription factors by nucleosome remodeling.

    Science.gov (United States)

    Li, Ming; Hada, Arjan; Sen, Payel; Olufemi, Lola; Hall, Michael A; Smith, Benjamin Y; Forth, Scott; McKnight, Jeffrey N; Patel, Ashok; Bowman, Gregory D; Bartholomew, Blaine; Wang, Michelle D

    2015-06-05

    The chromatin landscape and promoter architecture are dominated by the interplay of nucleosome and transcription factor (TF) binding to crucial DNA sequence elements. However, it remains unclear whether nucleosomes mobilized by chromatin remodelers can influence TFs that are already present on the DNA template. In this study, we investigated the interplay between nucleosome remodeling, by either yeast ISW1a or SWI/SNF, and a bound TF. We found that a TF serves as a major barrier to ISW1a remodeling, and acts as a boundary for nucleosome repositioning. In contrast, SWI/SNF was able to slide a nucleosome past a TF, with concurrent eviction of the TF from the DNA, and the TF did not significantly impact the nucleosome positioning. Our results provide direct evidence for a novel mechanism for both nucleosome positioning regulation by bound TFs and TF regulation via dynamic repositioning of nucleosomes.

  7. MGMT expression: insights into its regulation. 1. Epigenetic factors

    Directory of Open Access Journals (Sweden)

    Iatsyshyna A. P.

    2013-03-01

    Full Text Available O6-methylguanine-DNA methyltransferase (MGMT is the DNA repair enzyme responsible for removing of alkylation adducts from the O6-guanine in DNA. Despite MGMT prevents mutations and cell death, this enzyme can provide resistance of cancer cells to alkylating agents of chemotherapy. The high intra- and inter-individual variations in the human MGMT expression level have been observed indicating to a complicated regulation of this gene. This review is focused on the study of epigenetic factors which could be potentially involved in regulation of the human MGMT gene expression. These include chromatin remodeling via histone modifications and DNA methylation of promoter region and gene body, as well as RNA-based mechanisms, alternative splicing, protein post- translational modifications, and other.

  8. Regulation of the Hippo Pathway Transcription Factor TEAD.

    Science.gov (United States)

    Lin, Kimberly C; Park, Hyun Woo; Guan, Kun-Liang

    2017-09-27

    The TEAD transcription factor family is best known for transcriptional output of the Hippo signaling pathway and has been implicated in processes such as development, cell growth and proliferation, tissue homeostasis, and regeneration. Our understanding of the functional importance of TEADs has increased dramatically since its initial discovery three decades ago. The majority of our knowledge of TEADs is in the context of Hippo signaling as nuclear DNA-binding proteins passively activated by Yes-associated protein (YAP) and transcriptional activator with PDZ-binding domain (TAZ), transcription coactivators downstream of the Hippo pathway. However, recent studies suggest that TEAD itself is actively regulated. Here, we highlight evidence demonstrating Hippo-independent regulation of TEADs and the potential impacts these studies may have on new cancer therapeutics. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Identification of the Key Risk Factors of the Internationalization Process of SMEs Operating in the Textile Industry

    Directory of Open Access Journals (Sweden)

    Lea Kubíčková

    2015-01-01

    Full Text Available The aim of this paper is to identify the key risk factors of the internationalization process of Czech SMEs operating in the textile industry. To reveal the key risk there was conducted the survey (2011–2012 among 803 Czech SMEs operating in the textile industry, 161 responses were processed. The obtained data were analyzed by statistical methods. Potential risks of entry into foreign market were rated according to their impact on businesses. The greatest influences on the process of successful internationalization have, according to obtained responces, following factors: shortage of capital, lack of the information on foreign markets and high transportation costs. Other factors that may impede the successful internationalization are language barriers, inexperience of management with the internationalization and high prices of products. Knowing the key risk it is easier for SMEs to manage it.

  10. Perceived and actual key success factors: A study of the yoghurt market in Denmark, Germany and the United Kingdom

    DEFF Research Database (Denmark)

    Grunert, Klaus G.; Sørensen, Elin

    /high degree of innovativeness, extensive marketing activities, (abundant) financial resources, s production, good logistics management, good product portfolio management, non-complex organisation, low retail prices, good relations with trade, extensive market knowledge. 4. According to managers' perceptions......Executive summary 1. We define a key success factor as a skill or resource that a business can invest in, which, on the market the business is operating on, explains a major part of the observable differences in perceived value and/or relative costs. The key success factors as perceived by managers...... need not be identical with the actual key success factors in a market. 2. Depth interviews with managers in yoghurt-producing companies in Denmark, Germany and the United Kingdom showed considerable variation in both substance and degree of detail in their perceptions of the determinants of success...

  11. Cdc42 is a key regulator of B cell differentiation and is required for antiviral humoral immunity

    DEFF Research Database (Denmark)

    Burbage, Marianne; Keppler, Selina J; Gasparrini, Francesca

    2015-01-01

    The small Rho GTPase Cdc42, known to interact with Wiskott-Aldrich syndrome (WAS) protein, is an important regulator of actin remodeling. Here, we show that genetic ablation of Cdc42 exclusively in the B cell lineage is sufficient to render mice unable to mount antibody responses. Indeed Cdc42-de...... and actin remodeling; defective antigen presentation and in vivo interaction with T cells; and a severe B cell-intrinsic block in plasma cell differentiation. Thus, our study presents a new perspective on Cdc42 as key regulator of B cell physiology.......The small Rho GTPase Cdc42, known to interact with Wiskott-Aldrich syndrome (WAS) protein, is an important regulator of actin remodeling. Here, we show that genetic ablation of Cdc42 exclusively in the B cell lineage is sufficient to render mice unable to mount antibody responses. Indeed Cdc42......-deficient mice are incapable of forming germinal centers or generating plasma B cells upon either viral infection or immunization. Such severe immune deficiency is caused by multiple and profound B cell abnormalities, including early blocks during B cell development; impaired antigen-driven BCR signaling...

  12. Hydrogen peroxide sensing, signaling and regulation of transcription factors

    Directory of Open Access Journals (Sweden)

    H. Susana Marinho

    2014-01-01

    Full Text Available The regulatory mechanisms by which hydrogen peroxide (H2O2 modulates the activity of transcription factors in bacteria (OxyR and PerR, lower eukaryotes (Yap1, Maf1, Hsf1 and Msn2/4 and mammalian cells (AP-1, NRF2, CREB, HSF1, HIF-1, TP53, NF-κB, NOTCH, SP1 and SCREB-1 are reviewed. The complexity of regulatory networks increases throughout the phylogenetic tree, reaching a high level of complexity in mammalians. Multiple H2O2 sensors and pathways are triggered converging in the regulation of transcription factors at several levels: (1 synthesis of the transcription factor by upregulating transcription or increasing both mRNA stability and translation; (ii stability of the transcription factor by decreasing its association with the ubiquitin E3 ligase complex or by inhibiting this complex; (iii cytoplasm–nuclear traffic by exposing/masking nuclear localization signals, or by releasing the transcription factor from partners or from membrane anchors; and (iv DNA binding and nuclear transactivation by modulating transcription factor affinity towards DNA, co-activators or repressors, and by targeting specific regions of chromatin to activate individual genes. We also discuss how H2O2 biological specificity results from diverse thiol protein sensors, with different reactivity of their sulfhydryl groups towards H2O2, being activated by different concentrations and times of exposure to H2O2. The specific regulation of local H2O2 concentrations is also crucial and results from H2O2 localized production and removal controlled by signals. Finally, we formulate equations to extract from typical experiments quantitative data concerning H2O2 reactivity with sensor molecules. Rate constants of 140 M−1 s−1 and ≥1.3 × 103 M−1 s−1 were estimated, respectively, for the reaction of H2O2 with KEAP1 and with an unknown target that mediates NRF2 protein synthesis. In conclusion, the multitude of H2O2 targets and mechanisms provides an opportunity for

  13. Nuclear Factor-κB: Activation and Regulation during Toll-like Receptor Signaling

    Institute of Scientific and Technical Information of China (English)

    Ruaidhrí J. Carmody; Youhai H. Chen

    2007-01-01

    Toll-like receptors (TLRs) recognize distinct microbial components to initiate the innate and adaptive immune responses. TLR activation culminates in the expression of appropriate pro-inflammatory and immunomodulatory factors to meet pathogenic challenges. The transcription factor NF-κB is the master regulator of all TLR-induced responses and its activation is the pivotal event in TLR-mediated activation of the innate immune response. Many of the key molecular events required for TLR-induced NF-κB activation have been elucidated. However, much remain to be learned about the ability of TLRs to generate pathogen-specific responses using a limited number of transcription factors. This review will focus on our current understanding of NF-κB activation by TLRs and potential mechanisms for achieving a signal-specific response through NF-κB.

  14. Regulation of cardiac microRNAs by serum response factor

    Directory of Open Access Journals (Sweden)

    Wei Jeanne Y

    2011-02-01

    Full Text Available Abstract Serum response factor (SRF regulates certain microRNAs that play a role in cardiac and skeletal muscle development. However, the role of SRF in the regulation of microRNA expression and microRNA biogenesis in cardiac hypertrophy has not been well established. In this report, we employed two distinct transgenic mouse models to study the impact of SRF on cardiac microRNA expression and microRNA biogenesis. Cardiac-specific overexpression of SRF (SRF-Tg led to altered expression of a number of microRNAs. Interestingly, downregulation of miR-1, miR-133a and upregulation of miR-21 occurred by 7 days of age in these mice, long before the onset of cardiac hypertrophy, suggesting that SRF overexpression impacted the expression of microRNAs which contribute to cardiac hypertrophy. Reducing cardiac SRF level using the antisense-SRF transgenic approach (Anti-SRF-Tg resulted in the expression of miR-1, miR-133a and miR-21 in the opposite direction. Furthermore, we observed that SRF regulates microRNA biogenesis, specifically the transcription of pri-microRNA, thereby affecting the mature microRNA level. The mir-21 promoter sequence is conserved among mouse, rat and human; one SRF binding site was found to be in the mir-21 proximal promoter region of all three species. The mir-21 gene is regulated by SRF and its cofactors, including myocardin and p49/Strap. Our study demonstrates that the downregulation of miR-1, miR-133a, and upregulation of miR-21 can be reversed by one single upstream regulator, SRF. These results may help to develop novel therapeutic interventions targeting microRNA biogenesis.

  15. The molecular clock regulates circadian transcription of tissue factor gene.

    Science.gov (United States)

    Oishi, Katsutaka; Koyanagi, Satoru; Ohkura, Naoki

    2013-02-01

    Tissue factor (TF) is involved in endotoxin-induced inflammation and mortality. We found that the circadian expression of TF mRNA, which peaked at the day to night transition (activity onset), was damped in the liver of Clock mutant mice. Luciferase reporter and chromatin immunoprecipitation analyses using embryonic fibroblasts derived from wild-type or Clock mutant mice showed that CLOCK is involved in transcription of the TF gene. Furthermore, the results of real-time luciferase reporter experiments revealed that the circadian expression of TF mRNA is regulated by clock molecules through a cell-autonomous mechanism via an E-box element located in the promoter region.

  16. Distributed Factorization Computation on Multiple Volunteered Mobile Resource to Break RSA Key

    Science.gov (United States)

    Jaya, I.; Hardi, S. M.; Tarigan, J. T.; Zamzami, E. M.; Sihombing, P.

    2017-01-01

    Similar to common asymmeric encryption, RSA can be cracked by usmg a series mathematical calculation. The private key used to decrypt the massage can be computed using the public key. However, finding the private key may require a massive amount of calculation. In this paper, we propose a method to perform a distributed computing to calculate RSA’s private key. The proposed method uses multiple volunteered mobile devices to contribute during the calculation process. Our objective is to demonstrate how the use of volunteered computing on mobile devices may be a feasible option to reduce the time required to break a weak RSA encryption and observe the behavior and running time of the application on mobile devices.

  17. Key Factors for the Successful Operation of Clusters: The Case for Slovenia

    National Research Council Canada - National Science Library

    Brigita Gajšek; Jure Kovač

    2016-01-01

    Background and Purpose: Companies are increasingly specializing and developing those key areas with which they can compete on the global market and are linking in clusters that are ingredient of territorial competitiveness...

  18. Regulation of root hair cell differentiation by R3 MYB transcription factors in tomato and Arabidopsis.

    Science.gov (United States)

    Tominaga-Wada, Rumi; Wada, Takuji

    2014-01-01

    CAPRICE (CPC) encodes a small protein with an R3 MYB motif and regulates root hair and trichome cell differentiation in Arabidopsis thaliana. Six additional CPC-like MYB proteins including TRIPTYCHON (TRY), ENHANCER OF TRY AND CPC1 (ETC1), ENHANCER OF TRY AND CPC2 (ETC2), ENHANCER OF TRY AND CPC3/CPC-LIKE MYB3 (ETC3/CPL3), TRICHOMELESS1 (TCL1), and TRICHOMELESS2/CPC-LIKE MYB4 (TCL2/CPL4) also have the ability to regulate root hair and/or trichome cell differentiation in Arabidopsis. In this review, we describe our latest findings on how CPC-like MYB transcription factors regulate root hair cell differentiation. Recently, we identified the tomato SlTRY gene as an ortholog of the Arabidopsis TRY gene. Transgenic Arabidopsis plants harboring SlTRY produced more root hairs, a phenotype similar to that of 35S::CPC transgenic plants. CPC is also known to be involved in anthocyanin biosynthesis. Anthocyanin accumulation was repressed in the SlTRY transgenic plants, suggesting that SlTRY can also influence anthocyanin biosynthesis. We concluded that tomato and Arabidopsis partially use similar transcription factors for root hair cell differentiation, and that a CPC-like R3 MYB may be a key common regulator of plant root-hair development.

  19. Transcription factors regulating B cell fate in the germinal centre.

    Science.gov (United States)

    Recaldin, T; Fear, D J

    2016-01-01

    Diversification of the antibody repertoire is essential for the normal operation of the vertebrate adaptive immune system. Following antigen encounter, B cells are activated, proliferate rapidly and undergo two diversification events; somatic hypermutation (followed by selection), which enhances the affinity of the antibody for its cognate antigen, and class-switch recombination, which alters the effector functions of the antibody to adapt the response to the challenge faced. B cells must then differentiate into antibody-secreting plasma cells or long-lived memory B cells. These activities take place in specialized immunological environments called germinal centres, usually located in the secondary lymphoid organs. To complete the germinal centre activities successfully, a B cell adopts a transcriptional programme that allows it to migrate to specific sites within the germinal centre, proliferate, modify its DNA recombination and repair pathways, alter its apoptotic potential and finally undergo terminal differentiation. To co-ordinate these processes, B cells employ a number of 'master regulator' transcription factors which mediate wholesale transcriptomic changes. These master transcription factors are mutually antagonistic and form a complex regulatory network to maintain distinct gene expression programs. Within this network, multiple points of positive and negative feedback ensure the expression of the 'master regulators', augmented by a number of 'secondary' factors that reinforce these networks and sense the progress of the immune response. In this review we will discuss the different activities B cells must undertake to mount a successful T cell-dependent immune response and describe how a regulatory network of transcription factors controls these processes.

  20. Key factors in marketing management which affect the competitiveness of the graphic communication sector in Barranquilla city, Colombia

    Directory of Open Access Journals (Sweden)

    Ernesto Cantillo Guerrero

    2013-03-01

    Full Text Available Rev.esc.adm.neg This article describes the key factors of marketing management that impact the competitiveness of the graphic companies located in Barranquilla, based on managers´ opinions. Following a method of exploration and description analysis, an instrument was applied to a group of managers belonging to this economic sector, showing that there are six factors which affect competitiveness. Finally, a correlational analysis was performed to establish the relationships among all these factors and also to describe the influence of the managerial theory on marketing and the relationships among all these factors when designing marketing strategies.

  1. Regulation of gonadotropins by corticotropin-releasing factor and urocortin

    Directory of Open Access Journals (Sweden)

    Kazunori eKageyama

    2013-02-01

    Full Text Available While stress activates the hypothalamic-pituitary-adrenal (HPA axis, it suppresses the hypothalamic-pituitary-gonadal (HPG axis. Corticotropin-releasing factor (CRF is a major regulatory peptide in the HPA axis during stress. Urocortin1 (Ucn1, a member of the CRF family of peptides, has a variety of physiological functions and both CRF and Ucn1 contribute to the stress response via G protein-coupled seven transmembrane receptors. Ucn2 and Ucn3, which belong to a separate paralogous lineage from CRF, are highly selective for the CRF type 2 receptor (CRF2 receptor. The HPA and HPG axes interact with each other, and gonadal function and reproduction are suppressed in response to various stressors. In this review, we focus on the regulation of gonadotropins by CRF and Ucn2 in pituitary gonadotrophs and of gonadotropin-releasing hormone (GnRH via CRF receptors in the hypothalamus. In corticotrophs, stress-induced increases in CRF stimulate Ucn2 production, which leads to the inhibition of gonadotropin secretion via the CRF2 receptor in the pituitary. GnRH in the hypothalamus is regulated by a variety of stress conditions. CRF is also involved in the suppression of the HPG axis, especially the GnRH pulse generator, via CRF receptors in the hypothalamus. Thus, complicated regulation of GnRH in the hypothalamus and gonadotropins in the pituitary via CRF receptors contributes to stress responses and adaptation of gonadal functions.

  2. An NAC transcription factor controls ethylene-regulated cell expansion in flower petals.

    Science.gov (United States)

    Pei, Haixia; Ma, Nan; Tian, Ji; Luo, Jing; Chen, Jiwei; Li, Jing; Zheng, Yi; Chen, Xiang; Fei, Zhangjun; Gao, Junping

    2013-10-01

    Cell expansion is crucial for plant growth. It is well known that the phytohormone ethylene functions in plant development as a key modulator of cell expansion. However, the role of ethylene in the regulation of this process remains unclear. In this study, 2,189 ethylene-responsive transcripts were identified in rose (Rosa hybrida) petals using transcriptome sequencing and microarray analysis. Among these transcripts, an NAC (for no apical meristem [NAM], Arabidopsis transcription activation factor [ATAF], and cup-shaped cotyledon [CUC])-domain transcription factor gene, RhNAC100, was rapidly and dramatically induced by ethylene in the petals. Interestingly, accumulation of the RhNAC100 transcript was modulated by ethylene via microRNA164-dependent posttranscriptional regulation. Overexpression of RhNAC100 in Arabidopsis (Arabidopsis thaliana) substantially reduced the petal size by repressing petal cell expansion. By contrast, silencing of RhNAC100 in rose petals using virus-induced gene silencing significantly increased petal size and promoted cell expansion in the petal abaxial subepidermis (P cellulose synthase and two aquaporin genes (Rosa hybrida Cellulose Synthase2 and R. hybrida Plasma Membrane Intrinsic Protein1;1/2;1) were identified as targets of RhNAC100. Our results suggest that ethylene regulates cell expansion by fine-tuning the microRNA164/RhNAC100 module and also provide new insights into the function of NAC transcription factors.

  3. Regulation of Nox enzymes expression in vascular pathophysiology: Focusing on transcription factors and epigenetic mechanisms.

    Science.gov (United States)

    Manea, Simona-Adriana; Constantin, Alina; Manda, Gina; Sasson, Shlomo; Manea, Adrian

    2015-08-01

    NADPH oxidases (Nox) represent a family of hetero-oligomeric enzymes whose exclusive biological function is the generation of reactive oxygen species (ROS). Nox-derived ROS are essential modulators of signal transduction pathways that control key physiological activities such as cell growth, proliferation, migration, differentiation, and apoptosis, immune responses, and biochemical pathways. Enhanced formation of Nox-derived ROS, which is generally associated with the up-regulation of different Nox subtypes, has been established in various pathologies, namely cardiovascular diseases, diabetes, obesity, cancer, and neurodegeneration. The detrimental effects of Nox-derived ROS are related to alterations in cell signalling and/or direct irreversible oxidative damage of nucleic acids, proteins, carbohydrates, and lipids. Thus, understanding of transcriptional regulation mechanisms of Nox enzymes have been extensively investigated in an attempt to find ways to counteract the excessive formation of Nox-derived ROS in various pathological states. Despite the numerous existing data, the molecular pathways responsible for Nox up-regulation are not completely understood. This review article summarizes some of the recent advances and concepts related to the regulation of Nox expression in the vascular pathophysiology. It highlights the role of transcription factors and epigenetic mechanisms in this process. Identification of the signalling molecules involved in Nox up-regulation, which is associated with the onset and development of cardiovascular dysfunction may contribute to the development of novel strategies for the treatment of cardiovascular diseases.

  4. Regulation of Nox enzymes expression in vascular pathophysiology: Focusing on transcription factors and epigenetic mechanisms

    Directory of Open Access Journals (Sweden)

    Simona-Adriana Manea

    2015-08-01

    Full Text Available NADPH oxidases (Nox represent a family of hetero-oligomeric enzymes whose exclusive biological function is the generation of reactive oxygen species (ROS. Nox-derived ROS are essential modulators of signal transduction pathways that control key physiological activities such as cell growth, proliferation, migration, differentiation, and apoptosis, immune responses, and biochemical pathways. Enhanced formation of Nox-derived ROS, which is generally associated with the up-regulation of different Nox subtypes, has been established in various pathologies, namely cardiovascular diseases, diabetes, obesity, cancer, and neurodegeneration. The detrimental effects of Nox-derived ROS are related to alterations in cell signalling and/or direct irreversible oxidative damage of nucleic acids, proteins, carbohydrates, and lipids. Thus, understanding of transcriptional regulation mechanisms of Nox enzymes have been extensively investigated in an attempt to find ways to counteract the excessive formation of Nox-derived ROS in various pathological states. Despite the numerous existing data, the molecular pathways responsible for Nox up-regulation are not completely understood. This review article summarizes some of the recent advances and concepts related to the regulation of Nox expression in the vascular pathophysiology. It highlights the role of transcription factors and epigenetic mechanisms in this process. Identification of the signalling molecules involved in Nox up-regulation, which is associated with the onset and development of cardiovascular dysfunction may contribute to the development of novel strategies for the treatment of cardiovascular diseases.

  5. Myogenic factors that regulate expression of muscle-specific microRNAs.

    Science.gov (United States)

    Rao, Prakash K; Kumar, Roshan M; Farkhondeh, Mina; Baskerville, Scott; Lodish, Harvey F

    2006-06-01

    Since their discovery as key regulators of early animal development, microRNAs now are recognized as widespread regulators of gene expression. Despite their abundance, little is known regarding the regulation of microRNA biogenesis. We show that three highly conserved muscle-specific microRNAs, miR-1, miR-133 and miR-206, are robustly induced during the myoblast-myotube transition, both in primary human myoblasts and in the mouse mesenchymal C2C12 stem cell line. These microRNAs were not induced during osteogenic conversion of C2C12 cells. Moreover, both loci encoding miR-1, miR-1-1, and miR-1-2, and two of the three encoding miR-133, miR-133a-1 and miR-133a-2, are strongly induced during myogenesis. Some of the induced microRNAs are in intergenic regions, whereas two are transcribed in the opposite direction to the nonmuscle-specific gene in which they are embedded. By using CHIP analysis, we demonstrate that the myogenic factors Myogenin and MyoD bind to regions upstream of these microRNAs and, therefore, are likely to regulate their expression. Because miR-1 and miR-206 are predicted to repress similar mRNA targets, our work suggests that induction of these microRNAs is important in regulating the expression of muscle-specific proteins.

  6. miR-181b as a key regulator of the oncogenic process and its clinical implications in cancer (Review).

    Science.gov (United States)

    Liu, Juan; Shi, Weifeng; Wu, Changping; Ju, Jingfang; Jiang, Jingting

    2014-01-01

    MicroRNAs (miRNAs or miRs) are small, non-coding, single-stranded RNA molecules that regulate gene expression at the post-transcriptional level to repress protein expression of target genes. Among these, miR-181b has been found to be a critical regulatory miRNA linking inflammation and cancer. The functional significance of miR-181b in various tumors and translational research suggests that it exhibits great potential as a predictive and prognostic biomarker. Extensive efforts are underway to identify mRNA targets and the affected regulatory networks, which may be the key to providing a better understanding of miR-181b-mediated signaling pathways.

  7. Expression profiling reveals Spot 42 small RNA as a key regulator in the central metabolism of Aliivibrio salmonicida

    Directory of Open Access Journals (Sweden)

    Hansen Geir Å

    2012-01-01

    Full Text Available Abstract Background Spot 42 was discovered in Escherichia coli nearly 40 years ago as an abundant, small and unstable RNA. Its biological role has remained obscure until recently, and is today implicated in having broader roles in the central and secondary metabolism. Spot 42 is encoded by the spf gene. The gene is ubiquitous in the Vibrionaceae family of gamma-proteobacteria. One member of this family, Aliivibrio salmonicida, causes cold-water vibriosis in farmed Atlantic salmon. Its genome encodes Spot 42 with 84% identity to E. coli Spot 42. Results We generated a A. salmonicida spf deletion mutant. We then used microarray and Northern blot analyses to monitor global effects on the transcriptome in order to provide insights into the biological roles of Spot 42 in this bacterium. In the presence of glucose, we found a surprisingly large number of ≥ 2X differentially expressed genes, and several major cellular processes were affected. A gene encoding a pirin-like protein showed an on/off expression pattern in the presence/absence of Spot 42, which suggests that Spot 42 plays a key regulatory role in the central metabolism by regulating the switch between fermentation and respiration. Interestingly, we discovered an sRNA named VSsrna24, which is encoded immediately downstream of spf. This new sRNA has an expression pattern opposite to that of Spot 42, and its expression is repressed by glucose. Conclusions We hypothesize that Spot 42 plays a key role in the central metabolism, in part by regulating the pyruvat dehydrogenase enzyme complex via pirin.

  8. Thyroid hormones regulate fibroblast growth factor receptor signaling during chondrogenesis.

    Science.gov (United States)

    Barnard, Joanna C; Williams, Allan J; Rabier, Bénédicte; Chassande, Olivier; Samarut, Jacques; Cheng, Sheue-Yann; Bassett, J H Duncan; Williams, Graham R

    2005-12-01

    Childhood hypothyroidism causes growth arrest with delayed ossification and growth-plate dysgenesis, whereas thyrotoxicosis accelerates ossification and growth. Thyroid hormone (T(3)) regulates chondrocyte proliferation and is essential for hypertrophic differentiation. Fibroblast growth factors (FGFs) are also important regulators of chondrocyte proliferation and differentiation, and activating mutations of FGF receptor-3 (FGFR3) cause achondroplasia. We investigated the hypothesis that T(3) regulates chondrogenesis via FGFR3 in ATDC5 cells, which undergo a defined program of chondrogenesis. ATDC5 cells expressed two FGFR1, four FGFR2, and one FGFR3 mRNA splice variants throughout chondrogenesis, and expression of each isoform was stimulated by T(3) during the first 6-12 d of culture, when T(3) inhibited proliferation by 50%. FGFR3 expression was also increased in cells treated with T(3) for 21 d, when T(3) induced an earlier onset of hypertrophic differentiation and collagen X expression. FGFR3 expression was reduced in growth plates from T(3) receptor alpha-null mice, which exhibit skeletal hypothyroidism, but was increased in T(3) receptor beta(PV/PV) mice, which display skeletal thyrotoxicosis. These findings indicate that FGFR3 is a T(3)-target gene in chondrocytes. In further experiments, T(3) enhanced FGF2 and FGF18 activation of the MAPK-signaling pathway but inhibited their activation of signal transducer and activator of transcription-1. FGF9 did not activate MAPK or signal transducer and activator of transcription-1 pathways in the absence or presence of T(3). Thus, T(3) exerted differing effects on FGFR activation during chondrogenesis depending on which FGF ligand stimulated the FGFR and which downstream signaling pathway was activated. These studies identify novel interactions between T(3) and FGFs that regulate chondrocyte proliferation and differentiation during chondrogenesis.

  9. On the Security of a Two-Factor Authentication and Key Agreement Scheme for Telecare Medicine Information Systems.

    Science.gov (United States)

    Arshad, Hamed; Teymoori, Vahid; Nikooghadam, Morteza; Abbassi, Hassan

    2015-08-01

    Telecare medicine information systems (TMISs) aim to deliver appropriate healthcare services in an efficient and secure manner to patients. A secure mechanism for authentication and key agreement is required to provide proper security in these systems. Recently, Bin Muhaya demonstrated some security weaknesses of Zhu's authentication and key agreement scheme and proposed a security enhanced authentication and key agreement scheme for TMISs. However, we show that Bin Muhaya's scheme is vulnerable to off-line password guessing attacks and does not provide perfect forward secrecy. Furthermore, in order to overcome the mentioned weaknesses, we propose a new two-factor anonymous authentication and key agreement scheme using the elliptic curve cryptosystem. Security and performance analyses demonstrate that the proposed scheme not only overcomes the weaknesses of Bin Muhaya's scheme, but also is about 2.73 times faster than Bin Muhaya's scheme.

  10. Efficient production of optically pure L-lactic acid from food waste at ambient temperature by regulating key enzyme activity.

    Science.gov (United States)

    Li, Xiang; Chen, Yinguang; Zhao, Shu; Chen, Hong; Zheng, Xiong; Luo, Jinyang; Liu, Yanan

    2015-03-01

    Bio-production of optically pure L-lactic acid from food waste has attracted much interest as it can treat organic wastes with simultaneous recovery of valuable by-products. However, the yield of L-lactic acid was very low and no optically pure L-lactic acid was produced in the literature due to (1) the lower activity of enzymes involved in hydrolysis and L-lactic acid generation, and (2) the participation of other enzymes related to D-lactic acid and acetic and propionic acids production. In this paper, a new strategy was reported for effective production of optically pure L-lactic acid from food waste at ambient temperature, i.e. via regulating key enzyme activity by sewage sludge supplement and intermittent alkaline fermentation. It was found that not only optically pure L-lactic acid was produced, but the yield was enhanced by 2.89-fold. The mechanism study showed that the activities of enzymes relevant to food waste hydrolysis and lactic acid production were enhanced, and the key enzymes related to volatile fatty acids and D-lactic acid generations were severally decreased or inhibited. Also, the microbes responsible for L-lactic acid production were selectively proliferated. Finally, the pilot-scale continuous experiment was conducted to testify the feasibility of this new technique.

  11. KEY FACTORS OF PROCESS MATURITY IN ENGLISH-SPEAKING CARIBBEAN FIRMS

    Directory of Open Access Journals (Sweden)

    Delroy Chevers

    2014-05-01

    Full Text Available The information system (IS community has been struggling with the delivery of low quality systems. Software process improvement (SPI has been accepted as one of the remedies to overcome this problem, with process maturity being a key element. However, most studies on process maturity and the determinants of IS quality have been conducted in large firms in developed countries. This study assessed the key determinants of process maturity in small software development firms in the English-speaking Caribbean (ESC. Using the established practices in the capability maturity model integration (CMMI as the baseline for the analysis, it was found that project monitoring & control, and verification & validation are key determinants of process maturity in the ESC. These findings can assist IS professionals in their quest to produce higher quality software products, as well as provide a platform for further refinement of the proposed research model by IS researchers.

  12. Plasmin and Plasminogen induce macrophage reprogramming and regulate key steps of inflammation resolution via Annexin A1.

    Science.gov (United States)

    Sugimoto, Michelle A; Ribeiro, Ana Luíza C; Costa, Bruno R C; Vago, Juliana P; Lima, Kátia M; Carneiro, Fernanda S; Ortiz, Mylena Maira O; Lima, Graziele Letícia N; Carmo, Aline A F; Rocha, Renata M; Perez, Denise A; Reis, Alessandra C; Pinho, Vanessa; Miles, Lindsey A; Garcia, Cristiana C; Teixeira, Mauro M; Sousa, Lirlândia P

    2017-03-20

    Inflammation resolution is an active process that functions to restore tissue homeostasis. Participation of the plasminogen/plasmin (Plg/Pla) system in the productive phase of inflammation is well known, but its involvement in the resolution phase remains unclear. Therefore, we aimed to investigate the potential role of Plg/Pla in key events during the resolution of acute inflammation and its underlying mechanisms. Plg/Pla injection into the pleural cavity of BALB/c mice induced a time-dependent influx of mononuclear cells that were primarily macrophages of anti-inflammatory (M2 - F4/80(high) Gr1(-) CD11b(high)) and proresolving (Mres - F4/80(med) CD11b(low)) phenotypes, without changing the number of macrophages with a pro-inflammatory profile (M1 - F4/80(low) Gr1(+) CD11b(med)). Pleural injection of Plg/Pla also increased M2 markers (CD206 and Arginase-1) and secretory products (TGF-β and IL-6) and decreased the expression of iNOS (M1 marker). During the resolving phase of LPS-induced inflammation, when resolving macrophages predominate, we found increased Plg expression and Pla activity, further supporting a link between the Plg/Pla system and key cellular events in resolution. Indeed, Plg or Pla given at the peak of inflammation promoted resolution by decreasing neutrophil numbers and increasing neutrophil apoptosis and efferocytosis in a serine-protease inhibitor sensitive manner. Next, we confirmed the ability of Plg/Pla to both promote efferocytosis and override the pro-survival effect of LPS, via AnxA1. These findings suggest that Plg/Pla regulate several key steps in inflammation resolution, namely, neutrophil apoptosis, macrophage reprogramming and efferocytosis, which have a major impact on the establishment of an efficient resolution process.

  13. A Comprehensive Test of General Strain Theory: Key Strains, Situational- and Trait-Based Negative Emotions, Conditioning Factors, and Delinquency

    Science.gov (United States)

    Moon, Byongook; Morash, Merry; McCluskey, Cynthia Perez; Hwang, Hye-Won

    2009-01-01

    Using longitudinal data on South Korean youth, the authors addressed limitations of previous tests of general strain theory (GST), focusing on the relationships among key strains, situational- and trait-based negative emotions, conditioning factors, and delinquency. Eight types of strain previously shown most likely to result in delinquency,…

  14. Virtual communities, research groups and projects on IMS Learning Design. State of the art, key factors and forthcoming challenges

    NARCIS (Netherlands)

    Burgos, Daniel; Koper, Rob

    2005-01-01

    Burgos, D., Koper, R. (2005) Virtual communities, research groups and projects on IMS Learning Design. State of the art, key factors and forthcoming challenges. In E-Journal of Educational Research, Assessment and Evaluation, vol. 11, issue 2 [www.uv.es/RELIEVE]. Available at [http://www.uv.es/

  15. Stress-induced nuclear RNA degradation pathways regulate yeast bromodomain factor 2 to promote cell survival.

    Directory of Open Access Journals (Sweden)

    Kevin Roy

    2014-09-01

    Full Text Available Bromodomain proteins are key regulators of gene expression. How the levels of these factors are regulated in specific environmental conditions is unknown. Previous work has established that expression of yeast Bromodomain factor 2 (BDF2 is limited by spliceosome-mediated decay (SMD. Here we show that BDF2 is subject to an additional layer of post-transcriptional control through RNase III-mediated decay (RMD. We found that the yeast RNase III Rnt1p cleaves a stem-loop structure within the BDF2 mRNA to down-regulate its expression. However, these two nuclear RNA degradation pathways play distinct roles in the regulation of BDF2 expression, as we show that the RMD and SMD pathways of the BDF2 mRNA are differentially activated or repressed in specific environmental conditions. RMD is hyper-activated by salt stress and repressed by hydroxyurea-induced DNA damage while SMD is inactivated by salt stress and predominates during DNA damage. Mutations of cis-acting signals that control SMD and RMD rescue numerous growth defects of cells lacking Bdf1p, and show that SMD plays an important role in the DNA damage response. These results demonstrate that specific environmental conditions modulate nuclear RNA degradation pathways to control BDF2 expression and Bdf2p-mediated gene regulation. Moreover, these results show that precise dosage of Bromodomain factors is essential for cell survival in specific environmental conditions, emphasizing their importance for controlling chromatin structure and gene expression in response to environmental stress.

  16. Contribution of thermal and nonthermal factors to the regulation of body temperature in humans

    National Research Council Canada - National Science Library

    Igor B. Mekjavic; Ola Eiken

    2006-01-01

    .... This reciprocal inhibition theory, presumably reflecting the manner in which thermal factors contribute to homeothermy in humans, does not incorporate the effect of nonthermal factors on temperature regulation...

  17. The regulation of alfalfa saponin extract on key genes involved in hepatic cholesterol metabolism in hyperlipidemic rats.

    Directory of Open Access Journals (Sweden)

    Yinghua Shi

    Full Text Available To investigate the cholesterol-lowering effects of alfalfa saponin extract (ASE and its regulation mechanism on some key genes involved in cholesterol metabolism, 40 healthy 7 weeks old male Sprague Dawley (SD rats were randomly divided into four groups with 10 rats in each group: control group, hyperlipidemic group, ASE treatment group, ASE prevention group. The body weight gain, relative liver weight and serum lipid 1evels of rats were determined. Total cholesterol (TC and total bile acids (TBA levels in liver and feces were also measured. Furthermore, the activity and mRNA expressions of Hmgcr, Acat2, Cyp7a1 and Ldlr were investigated. The results showed the following: (1 The abnormal serum lipid levels in hyperlipidemic rats were ameliorated by ASE administration (both ASE prevention group and treatment group (P<0.05. (2 Both ASE administration to hyperlipidemic rats significantly reduced liver TC and increased liver TBA level (P<0.05. TC and TBA levels in feces of hyperlipidemic rats were remarkably elevated by both ASE administration (P<0.05. (3 mRNA expressions of Hmgcr and Acat2 in the liver of hyperlipidemic rats were remarkably down-regulated (P<0.05, as well as mRNA expressions of Cyp7a1 and Ldlr were dramatically up-regulated by both ASE administration (P<0.05. The activities of these enzymes also paralleled the observed changes in mRNA levels. (4 There was no significant difference between ASE treatment and ASE prevention group for most parameters evaluated. Our present study indicated that ASE had cholesterol-lowering effects. The possible mechanism could be attributed to (1 the down-regulation of Hmgcr and Acat2, as well as up-regulation of Cyp7a1 and Ldlr in the liver of hyperlipidemic rats, which was involved in cholesterol biosynthesis, uptake, and efflux pathway; (2 the increase in excretion of cholesterol. The findings in our study suggested ASE had great potential usefulness as a natural agent for treating hyperlipidemia.

  18. GAS6 is a key homeostatic immunological regulator of host-commensal interactions in the oral mucosa.

    Science.gov (United States)

    Nassar, Maria; Tabib, Yaara; Capucha, Tal; Mizraji, Gabriel; Nir, Tsipora; Pevsner-Fischer, Meirav; Zilberman-Schapira, Gili; Heyman, Oded; Nussbaum, Gabriel; Bercovier, Herve; Wilensky, Asaf; Elinav, Eran; Burstyn-Cohen, Tal; Hovav, Avi-Hai

    2017-01-17

    The oral epithelium contributes to innate immunity and oral mucosal homeostasis, which is critical for preventing local inflammation and the associated adverse systemic conditions. Nevertheless, the mechanisms by which the oral epithelium maintains homeostasis are poorly understood. Here, we studied the role of growth arrest specific 6 (GAS6), a ligand of the TYRO3-AXL-MERTK (TAM) receptor family, in regulating oral mucosal homeostasis. Expression of GAS6 was restricted to the outer layers of the oral epithelium. In contrast to protein S, the other TAM ligand, which was constitutively expressed postnatally, expression of GAS6 initiated only 3-4 wk after birth. Further analysis revealed that GAS6 expression was induced by the oral microbiota in a myeloid differentiation primary response gene 88 (MyD88)-dependent fashion. Mice lacking GAS6 presented higher levels of inflammatory cytokines, elevated frequencies of neutrophils, and up-regulated activity of enzymes, generating reactive nitrogen species. We also found an imbalance in Th17/Treg ratio known to control tissue homeostasis, as Gas6-deficient dendritic cells preferentially secreted IL-6 and induced Th17 cells. As a result of this immunological shift, a significant microbial dysbiosis was observed in Gas6(-/-) mice, because anaerobic bacteria largely expanded by using inflammatory byproducts for anaerobic respiration. Using chimeric mice, we found a critical role for GAS6 in epithelial cells in maintaining oral homeostasis, whereas its absence in hematopoietic cells synergized the level of dysbiosis. We thus propose GAS6 as a key immunological regulator of host-commensal interactions in the oral epithelium.

  19. PDE11A regulates social behaviors and is a key mechanism by which social experience sculpts the brain.

    Science.gov (United States)

    Hegde, Shweta; Ji, Hao; Oliver, David; Patel, Neema S; Poupore, Nicolas; Shtutman, Michael; Kelly, Michy P

    2016-10-29

    Despite the fact that appropriate social behaviors are vital to thriving in one's environment, little is understood of the molecular mechanisms controlling social behaviors or how social experience sculpts these signaling pathways. Here, we determine if Phosphodiesterase 11A (PDE11A), an enzyme that is enriched in the ventral hippocampal formation (VHIPP) and that breaks down cAMP and cGMP, regulates social behaviors. PDE11 wild-type (WT), heterozygous (HT), and knockout (KO) mice were tested in various social approach assays and gene expression differences were measured by RNA sequencing. The effect of social isolation on PDE11A4 compartmentalization and subsequent social interactions and social memory was also assessed. Deletion of PDE11A triggered age- and sex-dependent deficits in social approach in specific social contexts but not others. Mice appear to detect altered social behaviors of PDE11A KO mice, because C57BL/6J mice prefer to spend time with a sex-matched PDE11A WT vs. its KO littermate; whereas, a PDE11A KO prefers to spend time with a novel PDE11A KO vs. its WT littermate. Not only is PDE11A required for intact social interactions, we found that 1month of social isolation vs. group housing decreased PDE11A4 protein expression specifically within the membrane fraction of VHIPP. This isolation-induced decrease in PDE11A4 expression appears functional because social isolation impairs subsequent social approach behavior and social memory in a PDE11A genotype-dependent manner. Pathway analyses following RNA sequencing suggests PDE11A is a key regulator of the oxytocin pathway and membrane signaling, consistent with its pivotal role in regulating social behavior.

  20. Local Text Cohesion, Reading Ability and Individual Science Aspirations: Key Factors Influencing Comprehension in Science Classes

    Science.gov (United States)

    Hall, Sophie S.; Kowalski, Rebecca; Paterson, Kevin B.; Basran, Jaskaran; Filik, Ruth; Maltby, John

    2015-01-01

    In response to the concern of the need to improve the scientific skills of school children, this study investigated the influence of text design (in terms of text cohesion) and individual differences, with the aim of identifying pathways to improving science education in early secondary school (Key Stage 3). One hundred and four secondary school…

  1. A comparison study on detection of key geochemical variables and factors through three different types of factor analysis

    Science.gov (United States)

    Hoseinzade, Zohre; Mokhtari, Ahmad Reza

    2017-10-01

    Large numbers of variables have been measured to explain different phenomena. Factor analysis has widely been used in order to reduce the dimension of datasets. Additionally, the technique has been employed to highlight underlying factors hidden in a complex system. As geochemical studies benefit from multivariate assays, application of this method is widespread in geochemistry. However, the conventional protocols in implementing factor analysis have some drawbacks in spite of their advantages. In the present study, a geochemical dataset including 804 soil samples collected from a mining area in central Iran in order to search for MVT type Pb-Zn deposits was considered to outline geochemical analysis through various fractal methods. Routine factor analysis, sequential factor analysis, and staged factor analysis were applied to the dataset after opening the data with (additive logratio) alr-transformation to extract mineralization factor in the dataset. A comparison between these methods indicated that sequential factor analysis has more clearly revealed MVT paragenesis elements in surface samples with nearly 50% variation in F1. In addition, staged factor analysis has given acceptable results while it is easy to practice. It could detect mineralization related elements while larger factor loadings are given to these elements resulting in better pronunciation of mineralization.

  2. The stress-regulated transcription factor CHOP promotes hepatic inflammatory gene expression, fibrosis, and oncogenesis.

    Directory of Open Access Journals (Sweden)

    Diane DeZwaan-McCabe

    Full Text Available Viral hepatitis, obesity, and alcoholism all represent major risk factors for hepatocellular carcinoma (HCC. Although these conditions also lead to integrated stress response (ISR or unfolded protein response (UPR activation, the extent to which these stress pathways influence the pathogenesis of HCC has not been tested. Here we provide multiple lines of evidence demonstrating that the ISR-regulated transcription factor CHOP promotes liver cancer. We show that CHOP expression is up-regulated in liver tumors in human HCC and two mouse models thereof. Chop-null mice are resistant to chemical hepatocarcinogenesis, and these mice exhibit attenuation of both apoptosis and cellular proliferation. Chop-null mice are also resistant to fibrosis, which is a key risk factor for HCC. Global gene expression profiling suggests that deletion of CHOP reduces the levels of basal inflammatory signaling in the liver. Our results are consistent with a model whereby CHOP contributes to hepatic carcinogenesis by promoting inflammation, fibrosis, cell death, and compensatory proliferation. They implicate CHOP as a common contributing factor in the development of HCC in a variety of chronic liver diseases.

  3. Nuclear Factor of Activated T cells (NFAT): key regulator of cardiac hypertrophy and skeletal muscle adaptation

    NARCIS (Netherlands)

    Bourajjaj, M.

    2008-01-01

    Despite significant progress in the prevention and treatment of cardiovascular diseases, heart failure is still a leading cause of morbidity and mortality in industrial countries. Sustained cardiac hypertrophy, which is defined as an increase in heart size resulting from an increase in cardiomyocyte

  4. The E2F transcription factors: key regulators of cell proliferation

    DEFF Research Database (Denmark)

    Müller, H; Helin, K

    2000-01-01

    . It is becoming more and more evident that the regulatory circuits governing the cell cycle are very complex and highly interlinked. Certain aspects of RB-1 function, for instance its role in differentiation, cannot be easily explained by the current models of pRB-E2F interaction. One reason is that pRB has...

  5. Eutrophication development and its key regulating factors in a water-supply reservoir in North China

    Institute of Scientific and Technical Information of China (English)

    Liping Wang; Lusan Liu; Binghui Zheng

    2013-01-01

    Yanghe Reservoir is an important source of drinking water for Qinhuangdao City,North China; however,in recent decades this water source has been eutrophic with recurrent summer cyanobacterial blooms.The trophic grade of the system in summer was mesotrophiceutrophic in 1990 and became hypertrophic in 2011.The nutrient availability is extremely high during the entire year,and the water temperature should be the primary driver of the summer blooms.In May-October of 2010 and 2011,abrupt variations were observed in the Secchi depth (SD) and chlorophyll a (Chl-a),and both the correlated analysis of Chl-a-SD and trophic status indices (TSI) deviation (TSIChI-a-TSISD) showed that algal cell density dominated light attenuation.During the algal bloom outbreak,the microcystin concentration was found to vary between 0.35-2.12 μg/L in 2010 and 0.11-1.86 μg/L in 2011.The maximum microcystin content was more than two times the safety limit required for drinking water.Inflow discharges were most concentrated in the summer,with periods of lower residence time and the largest water level fluctuation over ~e entire year.When a high availability of nutrients promoted a high Chl-a concentration in the whole system,it appeared that the instability caused by the decrease in residence time could not produce effective changes in the cyanobacterial abundance.The results indicated that nutrient enrichment in the aquatic systems of Yanghe Reservoir is the most serious problem and that the status would not been modified effectively by increasing hydrological fluctuations (e.g.,decreasing the residence time).Therefore,decreasing the nutrient concentrations is the only route to improve the water quality of this reservoir.

  6. Nuclear Factor of Activated T cells (NFAT): key regulator of cardiac hypertrophy and skeletal muscle adaptation

    NARCIS (Netherlands)

    Bourajjaj, M.

    2008-01-01

    Despite significant progress in the prevention and treatment of cardiovascular diseases, heart failure is still a leading cause of morbidity and mortality in industrial countries. Sustained cardiac hypertrophy, which is defined as an increase in heart size resulting from an increase in cardiomyocyte

  7. Activating transcription factor 4 regulates osteoclast differentiation in mice

    Science.gov (United States)

    Cao, Huiling; Yu, Shibing; Yao, Zhi; Galson, Deborah L.; Jiang, Yu; Zhang, Xiaoyan; Fan, Jie; Lu, Binfeng; Guan, Youfei; Luo, Min; Lai, Yumei; Zhu, Yibei; Kurihara, Noriyoshi; Patrene, Kenneth; Roodman, G. David; Xiao, Guozhi

    2010-01-01

    Activating transcription factor 4 (ATF4) is a critical transcription factor for osteoblast (OBL) function and bone formation; however, a direct role in osteoclasts (OCLs) has not been established. Here, we targeted expression of ATF4 to the OCL lineage using the Trap promoter or through deletion of Atf4 in mice. OCL differentiation was drastically decreased in Atf4–/– bone marrow monocyte (BMM) cultures and bones. Coculture of Atf4–/– BMMs with WT OBLs or a high concentration of RANKL failed to restore the OCL differentiation defect. Conversely, Trap-Atf4-tg mice displayed severe osteopenia with dramatically increased osteoclastogenesis and bone resorption. We further showed that ATF4 was an upstream activator of the critical transcription factor Nfatc1 and was critical for RANKL activation of multiple MAPK pathways in OCL progenitors. Furthermore, ATF4 was crucial for M-CSF induction of RANK expression on BMMs, and lack of ATF4 caused a shift in OCL precursors to macrophages. Finally, ATF4 was largely modulated by M-CSF signaling and the PI3K/AKT pathways in BMMs. These results demonstrate that ATF4 plays a direct role in regulating OCL differentiation and suggest that it may be a therapeutic target for treating bone diseases associated with increased OCL activity. PMID:20628199

  8. Myeloid Colony Stimulating Factors as Regulators of Macrophage Polarization

    Directory of Open Access Journals (Sweden)

    Thomas A Hamilton

    2014-11-01

    Full Text Available The scope of functional heterogeneity in macrophages has been defined by two polarized end states known as M1 and M2, which exhibit the pro-inflammatory activities necessary for host defense and the tissue repair activities required for tissue repair respectively. Macrophage populations in different tissue locations exist in distinct phenotypic states across this M1/M2 spectrum and the development and abundance of individual subsets result from the local and systemic action of myeloid colony stimulating factors (CSFs including M-CSF and GM-CSF. These factors have relatively non-overlapping roles in the differentiation and maintenance of specific macrophage subsets. Furthermore there is now evidence that CSFs may also regulate macrophage phenotype during challenge. Cell culture studies from multiple laboratories demonstrate that macrophages developed in the presence of GM-CSF exhibit amplified response to M1 polarizing stimuli while M-CSF potentiates responses to M2 stimuli. As a consequence these factors can be important determinants of the magnitude and duration of both acute and chronic inflammatory pathology and may, therefore, be potential targets for therapeutic manipulation in specific human disease settings.

  9. Activating transcription factor 4 regulates osteoclast differentiation in mice.

    Science.gov (United States)

    Cao, Huiling; Yu, Shibing; Yao, Zhi; Galson, Deborah L; Jiang, Yu; Zhang, Xiaoyan; Fan, Jie; Lu, Binfeng; Guan, Youfei; Luo, Min; Lai, Yumei; Zhu, Yibei; Kurihara, Noriyoshi; Patrene, Kenneth; Roodman, G David; Xiao, Guozhi

    2010-08-01

    Activating transcription factor 4 (ATF4) is a critical transcription factor for osteoblast (OBL) function and bone formation; however, a direct role in osteoclasts (OCLs) has not been established. Here, we targeted expression of ATF4 to the OCL lineage using the Trap promoter or through deletion of Atf4 in mice. OCL differentiation was drastically decreased in Atf4-/- bone marrow monocyte (BMM) cultures and bones. Coculture of Atf4-/- BMMs with WT OBLs or a high concentration of RANKL failed to restore the OCL differentiation defect. Conversely, Trap-Atf4-tg mice displayed severe osteopenia with dramatically increased osteoclastogenesis and bone resorption. We further showed that ATF4 was an upstream activator of the critical transcription factor Nfatc1 and was critical for RANKL activation of multiple MAPK pathways in OCL progenitors. Furthermore, ATF4 was crucial for M-CSF induction of RANK expression on BMMs, and lack of ATF4 caused a shift in OCL precursors to macrophages. Finally, ATF4 was largely modulated by M-CSF signaling and the PI3K/AKT pathways in BMMs. These results demonstrate that ATF4 plays a direct role in regulating OCL differentiation and suggest that it may be a therapeutic target for treating bone diseases associated with increased OCL activity.

  10. The transcription factor p8 regulates autophagy during diapause embryo formation in Artemia parthenogenetica.

    Science.gov (United States)

    Lin, Cheng; Jia, Sheng-Nan; Yang, Fan; Jia, Wen-Huan; Yu, Xiao-Jian; Yang, Jin-Shu; Yang, Wei-Jun

    2016-07-01

    Autophagy is an essential homeostatic process by which cytoplasmic components, including macromolecules and organelles, are degraded by lysosome. Increasing evidence suggests that phosphorylated AMP-activated protein kinase (p-AMPK) and target of rapamycin (TOR) play key roles in the regulation of autophagy. However, the regulation of autophagy in quiescent cells remains unclear, despite the fact that autophagy is known to be critical for normal development, regeneration, and degenerative diseases. Here, crustacean Artemia parthenogenetica was used as a model system because they produced and released encysted embryos that enter a state of obligate dormancy in cell quiescence to withstand various environmental threats. We observed that autophagy was increased before diapause stage but dropped to extremely low level in diapause cysts in Artemia. Western blot analyses indicated that the regulation of autophagy was AMPK/TOR independent during diapause embryo formation. Importantly, the level of p8 (Ar-p8), a stress-inducible transcription cofactor, was elevated at the stage just before diapause and was absent in encysted embryos, indicating that Ar-p8 may regulate autophagy. The results of Ar-p8 knockdown revealed that Ar-p8 regulated autophagy during diapause formation in Artemia. Moreover, we observed that activating transcription factors 4 and 6 (ATF4 and ATF6) responded to Ar-p8-regulated autophagy, indicating that autophagy targeted endoplasmic reticulum (ER) during diapause formation in Artemia. Additionally, AMPK/TOR-independent autophagy was validated in human gastric cancer MKN45 cells overexpressing Ar-p8. The findings presented here may provide insights into the role of p8 in regulating autophagy in quiescent cells.

  11. Characterization of key transcription factors as molecular signatures of HPV-positive and HPV-negative oral cancers.

    Science.gov (United States)

    Verma, Gaurav; Vishnoi, Kanchan; Tyagi, Abhishek; Jadli, Mohit; Singh, Tejveer; Goel, Ankit; Sharma, Ankita; Agarwal, Kiran; Prasad, Subhash Chandra; Pandey, Durgatosh; Sharma, Shashi; Mehrotra, Ravi; Singh, Sukh Mahendra; Bharti, Alok Chandra

    2017-02-03

    Prior studies established constitutively active AP-1, NF-κB, and STAT3 signaling in oral cancer. Differential expression/activation of specific members of these transcription factors has been documented in HPV-positive oral lesions that respond better to therapy. We performed a comprehensive analysis of differentially expressed, transcriptionally active members of these pivotal signaling mediators to develop specific signatures of HPV-positive and HPV-negative oral lesions by immunohistochemical method that is applicable in low-resource settings. We examined a total of 31 prospective and 30 formalin-fixed, paraffin-embedded tissues from treatment-naïve, histopathologically and clinically confirmed cases diagnosed as oral or oropharyngeal squamous cell carcinoma (OSCC/OPSCC). Following determination of their HPV status by GP5 + /GP6 +  PCR, the sequential sections of the tissues were evaluated for expression of JunB, JunD, c-Fos, p50, p65, STAT3, and pSTAT3(Y705), along with two key regulatory proteins pEGFR and p16 by IHC. Independent analysis of JunB and p65 showed direct correlation with HPV positivity, whereas STAT3 and pSTAT3 were inversely correlated. A combined analysis of transcription factors revealed a more restrictive combination, characterized by the presence of AP-1 and NF-κB lacking involvement of STAT3 that strongly correlated with HPV-positive tumors. Presence of STAT3/pSTAT3 with NF-κB irrespective of the presence or absence of AP-1 members was present in HPV-negative lesions. Expression of pSTAT3 strongly correlated with all the AP-1/NF-κB members (except JunD), its upstream activator pEGFR(Y)(1092) , and HPV infection-related negative regulator p16. Overall, we show a simple combination of AP-1, NF-κB, and STAT3 members' expression that may serve as molecular signature of HPV-positive lesions or more broadly the tumors that show better prognosis.

  12. Arabidopsis WRKY33 is a key transcriptional regulator of hormonal and metabolic responses toward Botrytis cinerea infection.

    Science.gov (United States)

    Birkenbihl, Rainer P; Diezel, Celia; Somssich, Imre E

    2012-05-01

    The Arabidopsis (Arabidopsis thaliana) transcription factor WRKY33 is essential for defense toward the necrotrophic fungus Botrytis cinerea. Here, we aimed at identifying early transcriptional responses mediated by WRKY33. Global expression profiling on susceptible wrky33 and resistant wild-type plants uncovered massive differential transcriptional reprogramming upon B. cinerea infection. Subsequent detailed kinetic analyses revealed that loss of WRKY33 function results in inappropriate activation of the salicylic acid (SA)-related host response and elevated SA levels post infection and in the down-regulation of jasmonic acid (JA)-associated responses at later stages. This down-regulation appears to involve direct activation of several jasmonate ZIM-domain genes, encoding repressors of the JA-response pathway, by loss of WRKY33 function and by additional SA-dependent WRKY factors. Moreover, genes involved in redox homeostasis, SA signaling, ethylene-JA-mediated cross-communication, and camalexin biosynthesis were identified as direct targets of WRKY33. Genetic studies indicate that although SA-mediated repression of the JA pathway may contribute to the susceptibility of wrky33 plants to B. cinerea, it is insufficient for WRKY33-mediated resistance. Thus, WRKY33 apparently directly targets other still unidentified components that are also critical for establishing full resistance toward this necrotroph.

  13. Stochastic seasonality and nonlinear density-dependent factors regulate population size in an African rodent

    DEFF Research Database (Denmark)

    Leirs, Herwig; Steneth, Nils Chr.; Nichols, James D.

    1997-01-01

    no information on actual demographic rates(9,10). Here we report on both density-dependent and density-independent effects in a murid rodent pest species, the multimammute rat Mastomys natalensis (Smith, 1834), using statistical capture-recapture models, Both effects occur simultaneously, but we also demonstrate......Ecology has long been troubled by the controversy over how populations are regulated(1,2). Some ecologists focus on the role of environmental effects, whereas others argue that density-dependent feedback mechanisms are central(3-6). The relative importance of both processes is still hotly debated......, but clear examples of both processes acting in the same population are rare(7,8). Key-factor analysis (regression of population changes on possible causal factors) and time-series analysis are often used to investigate the presence of density dependence, but such approaches may be biased and provide...

  14. UPF1, a conserved nonsense-mediated mRNA decay factor, regulates cyst wall protein transcripts in Giardia lamblia.

    Directory of Open Access Journals (Sweden)

    Yi-Hsiu Chen

    Full Text Available The Giardia lamblia cyst wall is required for survival outside the host and infection. Three cyst wall protein (cwp genes identified to date are highly up-regulated during encystation. However, little is known of the molecular mechanisms governing their gene regulation. Messenger RNAs containing premature stop codons are rapidly degraded by a nonsense-mediated mRNA decay (NMD system to avoid production of non-functional proteins. In addition to RNA surveillance, NMD also regulates thousands of naturally occurring transcripts through a variety of mechanisms. It is interesting to know the NMD pathway in the primitive eukaryotes. Previously, we have found that the giardial homologue of a conserved NMD factor, UPF1, may be functionally conserved and involved in NMD and in preventing nonsense suppression. In this study, we tested the hypothesis that NMD factors can regulate some naturally occurring transcripts in G. lamblia. We found that overexpression of UPF1 resulted in a significant decrease of the levels of CWP1 and cyst formation and of the endogenous cwp1-3, and myb2 mRNA levels and stability. This indicates that NMD could contribute to the regulation of the cwp1-3 and myb2 transcripts, which are key to G. lamblia differentiation into cyst. Interestingly, we also found that UPF1 may be involved in regulation of eight other endogenous genes, including up-regulation of the translation elongation factor gene, whose product increases translation which is required for NMD. Our results indicate that NMD factor could contribute to the regulation of not only nonsense containing mRNAs, but also mRNAs of the key encystation-induced genes and other endogenous genes in the early-diverging eukaryote, G. lamblia.

  15. AN EXPEDITION IN SEARCH OF A 5TH UNIVERSAL FACTOR - KEY ISSUES IN THE LEXICAL APPROACH

    NARCIS (Netherlands)

    DERAAD, B

    1994-01-01

    It is argued that the fifth factor of the Big Five Model of personality traits cannot yet claim universal status. In order to identify a fifth factor within the lexical approach it is necessary to make full use of the potentialities of the psycholexical principles. Several flaws in the lexical

  16. From Loose Groups to Effective Teams: The Nine Key Factors of the Team Landscape.

    Science.gov (United States)

    Sheard, A. G.; Kakabadse, A. P.

    2002-01-01

    A loose group of individuals working on a task differs from an effective team on nine factors: clearly defined goals, priorities, roles and responsibilities, self-awareness, leadership, group dynamics, communications, content, and infrastructure. Ways to eliminate barriers and speed formation of effective teams could be based on those factors.…

  17. The Promise of Virtual Teams: Identifying Key Factors in Effectiveness and Failure

    Science.gov (United States)

    Horwitz, Frank M.; Bravington, Desmond; Silvis, Ulrik

    2006-01-01

    Purpose: The aim of the investigation is to identify enabling and disenabling factors in the development and operation of virtual teams; to evaluate the importance of factors such as team development, cross-cultural variables, leadership, communication and social cohesion as contributors to virtual team effectiveness. Design/methodology/approach:…

  18. Starting a hospital-based home health agency: Part II--Key success factors.

    Science.gov (United States)

    Montgomery, P

    1993-09-01

    In Part II of a three-part series, the financial, technological and legislative issues of a hospital-based home health-agency are discussed. Beginning a home healthcare service requires intensive research to answer key environmental and operational questions--need, competition, financial projections, initial start-up costs and the impact of delayed depreciation. Assessments involving technology, staffing, legislative and regulatory issues can help project service volume, productivity and cost-control.

  19. The Key Factor for Uniform and Patterned Glow Dielectric Barrier Discharge

    Institute of Scientific and Technical Information of China (English)

    OUYANG Ji-Ting; DUAN Xiao-Xi; XU Shao-Wei; HE Feng

    2012-01-01

    We present the results from 2D fluid modeling of the key roles controlling the glow dielectric barrier discharge (DBD) structure. A uniform DBD can be sustained at lower frequency when the space charge reaches uniformity due to plasma decay, while the patterned structure appears above a critical frequency when the space charge is nonuniform. The patterns start from the electrode edge where the electric field is significantly distorted, characterized by the patterned seed electrons that always form ahead of the surface charges. The formation of the patterned DBD structure is associated with the lateral inhibition of the local increase of space charges. The distribution of the volume seed electrons plays a key role in the DBD structure while the distribution of surface charge is a result of the formed structure.%We present the results from 2D fluid modeling of the key roles controlling the glow dielectric barrier discharge (DBD) structure.A uniform DBD can be sustained at lower frequency when the space charge reaches uniformity due to plasma decay,while the patterned structure appears above a critical frequency when the space charge is nonuniform.The patterns start from the electrode edge where the electric field is significantly distorted,characterized by the patterned seed electrons that always form ahead of the surface charges.The formation of the patterned DBD structure is associated with the lateral inhibition of the local increase of space charges.The distribution of the volume seed electrons plays a key role in the DBD structure while the distribution of surface charge is a result of the formed structure.

  20. The vision of immigrant students about key factors and skills for access to college

    OpenAIRE

    Elena Cano García; Maite Fernández Ferrer

    2015-01-01

    One of the most important challenges in education is working against absenteeism and school dropout. Especially relevant is the case of immigrant students who are a vulnerable group, fact that causes a high difference in results between immigrants and native students, so that only a very small percentage reaches college.For this reason, the study “Competencies and keys for an educational success from the perspective of college students’ children of immigrants” (2009 ARAF1 00010) has sought to...

  1. The E2F-DP1 Transcription Factor Complex Regulates Centriole Duplication in Caenorhabditis elegans.

    Science.gov (United States)

    Miller, Jacqueline G; Liu, Yan; Williams, Christopher W; Smith, Harold E; O'Connell, Kevin F

    2016-01-15

    Centrioles play critical roles in the organization of microtubule-based structures, from the mitotic spindle to cilia and flagella. In order to properly execute their various functions, centrioles are subjected to stringent copy number control. Central to this control mechanism is a precise duplication event that takes place during S phase of the cell cycle and involves the assembly of a single daughter centriole in association with each mother centriole . Recent studies have revealed that posttranslational control of the master regulator Plk4/ZYG-1 kinase and its downstream effector SAS-6 is key to ensuring production of a single daughter centriole. In contrast, relatively little is known about how centriole duplication is regulated at a transcriptional level. Here we show that the transcription factor complex EFL-1-DPL-1 both positively and negatively controls centriole duplication in the Caenorhabditis elegans embryo. Specifically, we find that down regulation of EFL-1-DPL-1 can restore centriole duplication in a zyg-1 hypomorphic mutant and that suppression of the zyg-1 mutant phenotype is accompanied by an increase in SAS-6 protein levels. Further, we find evidence that EFL-1-DPL-1 promotes the transcription of zyg-1 and other centriole duplication genes. Our results provide evidence that in a single tissue type, EFL-1-DPL-1 sets the balance between positive and negative regulators of centriole assembly and thus may be part of a homeostatic mechanism that governs centriole assembly.

  2. Trefoil factor 3 peptide regulates migration via a Twist-dependent pathway in gastric cell.

    Science.gov (United States)

    Zheng, Qianqian; Gao, Jian; Li, Honglin; Guo, Wendong; Mao, Qi; Gao, Enhui; Zhu, Ya-qin

    2013-08-16

    Trefoil factor 3 (TFF3) is a member of the TFF-domain peptide family and essential in regulating cell migration and maintaining mucosal integrity in gastrointestinal tract. However, the role of TFF3 and its downstream regulating mechanisms in cancer cell migration remain unclear. We previously reported that TFF3 prolonged the up-regulation of Twist protein to modulate IL-8 secretion in intestinal epithelial cells. In this study, we investigated the role of Twist protein in TFF3-induced migration of SGC7901 cells. While Twist was activated by TFF3, siRNA-mediated knockdown of Twist abolished TFF3-induced cell migration. Furthermore, the migration related marker CK-8 as well as ZO-1 and MMP-9 was also regulated by TFF3 via a Twist-dependent mechanism. Our study suggests that Twist, as an important potential downstream effector, plays a key role in TFF3-modulated metastasis in gastric cancer and can be a promising therapeutic target against intestinal-type gastric cancer.

  3. Study on the Key Success Factors of the Operation of a Regional Military Logistic Food Material Center

    Directory of Open Access Journals (Sweden)

    Fu-Jin Wang

    2010-01-01

    Full Text Available Problem statement: In order to establish an integrated supply system of the military food material, the study was to discuss the key success factors of operation of the military regional food material logistic center in Taiwan. Approach: The Delphi method, questionnaires and telephone interviews were used to collect and integrate the opinions of experts and scholars. Simultaneously, the Analytic Hierarchy Process (AHP was applied to confirm the evaluative factors of each level, i.e., one goal (to construct key success factors of the operation of a regional military logistic food material center for the first level, two analytical aspects (the external and internal environments for the second level, six evaluative facets (the safety design, strategic management, administrative effect, policy, service and internal and external integration for the third level and 19 evaluative criteria for the fourth level. Results: The 350 questionnaires from the second phase which were sent out to four kinds of respondents, 319 valid ones were returned. Conclusion: After AHP analysis, the results of this study could suggest an evaluation table for the key success factors of operation of the military regional food material logistic center in Taiwan.

  4. Regulation of rDNA transcription in response to growth factors, nutrients and energy.

    Science.gov (United States)

    Kusnadi, Eric P; Hannan, Katherine M; Hicks, Rodney J; Hannan, Ross D; Pearson, Richard B; Kang, Jian

    2015-02-01

    Exquisite control of ribosome biogenesis is fundamental for the maintenance of cellular growth and proliferation. Importantly, synthesis of ribosomal RNA by RNA polymerase I is a key regulatory step in ribosome biogenesis and a major biosynthetic and energy consuming process. Consequently, ribosomal RNA gene transcription is tightly coupled to the availability of growth factors, nutrients and energy. Thus cells have developed an intricate sensing network to monitor the cellular environment and modulate ribosomal DNA transcription accordingly. Critical controllers in these sensing networks, which mediate growth factor activation of ribosomal DNA transcription, include the PI3K/AKT/mTORC1, RAS/RAF/ERK pathways and MYC transcription factor. mTORC1 also responds to amino acids and energy status, making it a key hub linking all three stimuli to the regulation of ribosomal DNA transcription, although this is achieved via overlapping and distinct mechanisms. This review outlines the current knowledge of how cells respond to environmental cues to control ribosomal RNA synthesis. We also highlight the critical points within this network that are providing new therapeutic opportunities for treating cancers through modulation of RNA polymerase I activity and potential novel imaging strategies.

  5. Transcriptome Analysis of Ullrich Congenital Muscular Dystrophy Fibroblasts Reveals a Disease Extracellular Matrix Signature and Key Molecular Regulators.

    Directory of Open Access Journals (Sweden)

    Sonia Paco

    Full Text Available Collagen VI related myopathies encompass a range of phenotypes with involvement of skeletal muscle, skin and other connective tissues. They represent a severe and relatively common form of congenital disease for which there is no treatment. Collagen VI in skeletal muscle and skin is produced by fibroblasts.In order to gain insight into the consequences of collagen VI mutations and identify key disease pathways we performed global gene expression analysis of dermal fibroblasts from patients with Ullrich Congenital Muscular Dystrophy with and without vitamin C treatment. The expression data were integrated using a range of systems biology tools. Results were validated by real-time PCR, western blotting and functional assays.We found significant changes in the expression levels of almost 600 genes between collagen VI deficient and control fibroblasts. Highly regulated genes included extracellular matrix components and surface receptors, including integrins, indicating a shift in the interaction between the cell and its environment. This was accompanied by a significant increase in fibroblasts adhesion to laminin. The observed changes in gene expression profiling may be under the control of two miRNAs, miR-30c and miR-181a, which we found elevated in tissue and serum from patients and which could represent novel biomarkers for muscular dystrophy. Finally, the response to vitamin C of collagen VI mutated fibroblasts significantly differed from healthy fibroblasts. Vitamin C treatment was able to revert the expression of some key genes to levels found in control cells raising the possibility of a beneficial effect of vitamin C as a modulator of some of the pathological aspects of collagen VI related diseases.

  6. Key success factors in managing a conference centre in South Africa ...

    African Journals Online (AJOL)

    South African Journal for Research in Sport, Physical Education and Recreation ... The six factors were activities and layout, marketing, operational aspects, ... for the curricula of tertiary institutions offering event and conference tourism.

  7. Regulation of stem cell factor expression in inflammation and asthma

    Directory of Open Access Journals (Sweden)

    Carla A Da Silva

    2005-03-01

    Full Text Available Stem cell factor (SCF is a major mast cell growth factor, which could be involved in the local increase of mast cell number in the asthmatic airways. In vivo, SCF expression increases in asthmatic patients and this is reversed after treatment with glucocorticoids. In vitro in human lung fibroblasts in culture, IL-1beta, a pro-inflammatory cytokine, confirms this increased SCF mRNA and protein expression implying the MAP kinases p38 and ERK1/2 very early post-treatment, and glucocorticoids confirm this decrease. Surprisingly, glucocorticoids potentiate the IL-1beta-enhanced SCF expression at short term treatment, implying increased SCF mRNA stability and SCF gene transcription rate. This potentiation involves p38 and ERK1/2. Transfection experiments with the SCF promoter including intron1 also confirm this increase and decrease of SCF expression by IL-1beta and glucocorticoids, and the potentiation by glucocorticoids of the IL-1beta-induced SCF expression. Deletion of the GRE or kappaB sites abolishes this potentiation, and the effect of IL-1beta or glucocorticoids alone. DNA binding of GR and NF-kappaB are also demonstrated for these effects. In conclusion, this review concerns new mechanisms of regulation of SCF expression in inflammation that could lead to potential therapeutic strategy allowing to control mast cell number in the asthmatic airways.

  8. Clusters Regarding Key Factors Affecting Changes in Accounting, Finance, Administration and Management Control

    OpenAIRE

    Rodica Gabriela Blidisel; Adina Simona Popa; Raimondo Lo Russo; Maria Moraru

    2010-01-01

    During the last decade, important changes have occurred in public governance, which has evolved in this time from hierarchical bureaucracy to participatory governance, where the role of citizens in public decision-making process is more direct. There were performed reforms in finance, management administration and finances of public sector. Starting from the factors that influenced during the history the accounting, finances, administration and management control, we want to test the factors ...

  9. Exercise, skeletal muscle and inflammation: ARE-binding proteins as key regulators in inflammatory and adaptive networks.

    Science.gov (United States)

    Beiter, Thomas; Hoene, Miriam; Prenzler, Frauke; Mooren, Frank C; Steinacker, Jürgen M; Weigert, Cora; Nieß, Andreas M; Munz, Barbara

    2015-01-01

    The role of inflammation in skeletal muscle adaptation to exercise is complex and has hardly been elucidated so far. While the acute inflammatory response to exercise seems to promote skeletal muscle training adaptation and regeneration, persistent, low-grade inflammation, as seen in a multitude of chronic diseases, is obviously detrimental. The regulation of cytokine production in skeletal muscle cells has been relatively well studied, yet little is known about the compensatory and anti-inflammatory mechanisms that resolve inflammation and restore tissue homeostasis. One important strategy to ensure sequential, timely and controlled resolution of inflammation relies on the regulated stability of mRNAs encoding pro-inflammatory mediators. Many key transcripts in early immune responses are characterized by the presence of AU-rich elements (AREs) in the 3'-untranslated regions of their mRNAs, allowing efficient fine-tuning of gene expression patterns at the post-transcriptional level. AREs exert their function by recruiting particular RNA-binding proteins, resulting, in most cases, in de-stabilization of the target transcripts. The best-characterized ARE-binding proteins are HuR, CUGBP1, KSRP, AUF1, and the three ZFP36 proteins, especially TTP/ZFP36. Here, we give a general introduction into the role of inflammation in the adaptation of skeletal muscle to exercise. Subsequently, we focus on potential roles of ARE-binding proteins in skeletal muscle tissue in general and specifically exercise-induced skeletal muscle remodeling. Finally, we present novel data suggesting a specific function of TTP/ZFP36 in exercise-induced skeletal muscle plasticity.

  10. AMP-activated kinase in human spermatozoa: identification, intracellular localization, and key function in the regulation of sperm motility.

    Science.gov (United States)

    Calle-Guisado, Violeta; de Llera, Ana Hurtado; Martin-Hidalgo, David; Mijares, Jose; Gil, Maria C; Alvarez, Ignacio S; Bragado, Maria J; Garcia-Marin, Luis J

    2016-09-27

    AMP-activated kinase (AMPK), a protein that regulates energy balance and metabolism, has recently been identified in boar spermatozoa where regulates key functional sperm processes essential for fertilization. This work's aims are AMPK identification, intracellular localization, and their role in human spermatozoa function. Semen was obtained from healthy human donors. Sperm AMPK and phospho-Thr172-AMPK were analyzed by Western blotting and indirect immunofluorescence. High- and low-quality sperm populations were separated by a 40%-80% density gradient. Human spermatozoa motility was evaluated by an Integrated Semen Analysis System (ISAS) in the presence or absence of the AMPK inhibitor compound C (CC). AMPK is localized along the human spermatozoa, at the entire acrosome, midpiece and tail with variable intensity, whereas its active form, phospho-Thr172-AMPK, shows a prominent staining at the acrosome and sperm tail with a weaker staining in the midpiece and the postacrosomal region. Interestingly, spermatozoa bearing an excess residual cytoplasm show strong AMPK staining in this subcellular compartment. Both AMPK and phospho-Thr172-AMPK human spermatozoa contents exhibit important individual variations. Moreover, active AMPK is predominant in the high motility sperm population, where shows a stronger intensity compared with the low motility sperm population. Inhibition of AMPK activity in human spermatozoa by CC treatment leads to a significant reduction in any sperm motility parameter analyzed: percent of motile sperm, sperm velocities, progressivity, and other motility coefficients. This work identifies and points out AMPK as a new molecular mechanism involved in human spermatozoa motility. Further AMPK implications in the clinical efficiency of assisted reproduction and in other reproductive areas need to be studied.

  11. Regulation of Adipogenesis and Key Adipogenic Gene Expression by 1, 25-Dihydroxyvitamin D in 3T3-L1 Cells.

    Directory of Open Access Journals (Sweden)

    Shuhan Ji

    Full Text Available The functions of 1, 25-dihydroxyvitamin D (1, 25-(OH2D3 in regulating adipogenesis, adipocyte differentiation and key adipogenic gene expression were studied in 3T3-L1 preadipocytes. Five concentrations (0.01, 0.1, 1, 10, 100 nM of 1, 25-(OH2D3 were studied and lipid accumulation measured by Oil Red O staining and expression of adipogenic genes quantified using quantitative real-time PCR. Adipogenic responses to 1, 25-(OH2D3 were determined on 6, and 12 h, and days 1-10 after induction of adipogenesis by a hormonal cocktail with or without 1, 25-(OH2D3. In response to 1, 25-(OH2D3 (1, 10, and 100 nM, lipid accumulation and the expression of PPARγ, C/EBPα, FABP4 and SCD-1 were inhibited through day 10, and vitamin D receptor expression was inhibited in the early time points. The greatest inhibitory effect was upon expression of FABP4. Expression of SREBP-1c was only affected on day 2. The lowest concentrations of 1, 25-(OH2D3 tested did not affect adipocyte differentiation or adipogenic gene expression. The C/EBPα promoter activity response to 1, 25-(OH2D3 was also tested, with no effect detected. These results indicate that 1, 25-(OH2D3 inhibited adipogenesis via suppressing adipogenic-specific genes, and is invoked either during PPARγ activation or immediately up-stream thereof. Gene expression down-stream of PPARγ especially FABP4 was strongly inhibited, and we suggest that the role of 1, 25-(OH2D3 in regulating adipogenesis will be informed by further studies of adipogenic-specific gene promoter activity.

  12. Human resource development – A key factor for the sustainable development of Albania

    Directory of Open Access Journals (Sweden)

    Perlat Lame

    2004-01-01

    Full Text Available This article deals with the current situation of labor resources in Albania and its trends from the viewpoint of their contributions to the overall country progress. A real partnership between business and public institutions, the efforts to formalize the economy, to promote discipline and better application of international standards are considered key issues for the future country developments. The effective management of human resources and coordination could not be reached without profound structural and economic reforms, without free entrepreneurship initiative encouragement, and without mutual confidence between the employers and the employees.

  13. Functional Characterization of the GATA Transcription Factors GNC and CGA1 Reveals Their Key Role in Chloroplast Development, Growth, and Division in Arabidopsis1[W][OA

    Science.gov (United States)

    Chiang, Yi-Hsuan; Zubo, Yan O.; Tapken, Wiebke; Kim, Hyo Jung; Lavanway, Ann M.; Howard, Louisa; Pilon, Marinus; Kieber, Joseph J.; Schaller, G. Eric

    2012-01-01

    Chloroplasts develop from proplastids in a process that requires the interplay of nuclear and chloroplast genomes, but key steps in this developmental process have yet to be elucidated. Here, we show that the nucleus-localized transcription factors GATA NITRATE-INDUCIBLE CARBON-METABOLISM-INVOLVED (GNC) and CYTOKININ-RESPONSIVE GATA1 (CGA1) regulate chloroplast development, growth, and division in Arabidopsis (Arabidopsis thaliana). GNC and CGA1 are highly expressed in green tissues, and the phytohormone cytokinin regulates their expression. A gnc cga1 mutant exhibits a reduction in overall chlorophyll levels as well as in chloroplast size in the hypocotyl. Ectopic overexpression of either GNC or CGA1 promotes chloroplast biogenesis in hypocotyl cortex and root pericycle cells, based on increases in the number and size of the chloroplasts, and also results in expanded zones of chloroplast production into the epidermis of hypocotyls and cotyledons and into the cortex of roots. Ectopic overexpression also promotes the development of etioplasts from proplastids in dark-grown seedlings, subsequently enhancing the deetiolation process. Inducible expression of GNC demonstrates that GNC-mediated chloroplast biogenesis can be regulated postembryonically, notably so for chloroplast production in cotyledon epidermal cells. Analysis of the gnc cga1 loss-of-function and overexpression lines supports a role for these transcription factors in regulating the effects of cytokinin on chloroplast division. These data support a model in which GNC and CGA1 serve as two of the master transcriptional regulators of chloroplast biogenesis, acting downstream of cytokinin and mediating the development of chloroplasts from proplastids and enhancing chloroplast growth and division in specific tissues. PMID:22811435

  14. Transcription factor KLF7 regulates differentiation of neuroectodermal and mesodermal cell lineages

    Energy Technology Data Exchange (ETDEWEB)

    Caiazzo, Massimiliano, E-mail: caiazzo@igb.cnr.it [Institute of Genetics and Biophysics ' A. Buzzati-Traverso,' CNR, 80131 Naples (Italy); Istituto di diagnosi e cura ' Hermitage Capodimonte,' 80131 Naples (Italy); Colucci-D' Amato, Luca, E-mail: luca.colucci@unina2.it [Institute of Genetics and Biophysics ' A. Buzzati-Traverso,' CNR, 80131 Naples (Italy); Dipartimento di Scienze della Vita, Seconda Universita di Napoli, 81100 Caserta (Italy); Esposito, Maria T., E-mail: maria_teresa.esposito@kcl.ac.uk [CEINGE Biotecnologie Avanzate, 80145 Naples (Italy); Parisi, Silvia, E-mail: parisi@ceinge.unina.it [CEINGE Biotecnologie Avanzate, 80145 Naples (Italy); Stifani, Stefano, E-mail: stefano.stifani@mcgill.ca [Centre for Neuronal Survival, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada H3A 2B4 (Canada); Ramirez, Francesco, E-mail: francesco.ramirez@mssm.edu [Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY 10029 (United States); Porzio, Umberto di, E-mail: diporzio@igb.cnr.it [Institute of Genetics and Biophysics ' A. Buzzati-Traverso,' CNR, 80131 Naples (Italy)

    2010-08-15

    Previous gene targeting studies in mice have implicated the nuclear protein Krueppel-like factor 7 (KLF7) in nervous system development while cell culture assays have documented its involvement in cell cycle regulation. By employing short hairpin RNA (shRNA)-mediated gene silencing, here we demonstrate that murine Klf7 gene expression is required for in vitro differentiation of neuroectodermal and mesodermal cells. Specifically, we show a correlation of Klf7 silencing with down-regulation of the neuronal marker microtubule-associated protein 2 (Map2) and the nerve growth factor (NGF) tyrosine kinase receptor A (TrkA) using the PC12 neuronal cell line. Similarly, KLF7 inactivation in Klf7-null mice decreases the expression of the neurogenic marker brain lipid-binding protein/fatty acid-binding protein 7 (BLBP/FABP7) in neural stem cells (NSCs). We also report that Klf7 silencing is detrimental to neuronal and cardiomyocytic differentiation of embryonic stem cells (ESCs), in addition to altering the adipogenic and osteogenic potential of mouse embryonic fibroblasts (MEFs). Finally, our results suggest that genes that are key for self-renewal of undifferentiated ESCs repress Klf7 expression in ESCs. Together with previous findings, these results provide evidence that KLF7 has a broad spectrum of regulatory functions, which reflect the discrete cellular and molecular contexts in which this transcription factor operates.

  15. Binding Mode Analysis of Zerumbone to Key Signal Proteins in the Tumor Necrosis Factor Pathway

    Directory of Open Access Journals (Sweden)

    Ayesha Fatima

    2015-01-01

    Full Text Available Breast cancer is the second most common cancer among women worldwide. Several signaling pathways have been implicated as causative and progression agents. The tumor necrosis factor (TNF α protein plays a dual role in promoting and inhibiting cancer depending largely on the pathway initiated by the binding of the protein to its receptor. Zerumbone, an active constituent of Zingiber zerumbet, Smith, is known to act on the tumor necrosis factor pathway upregulating tumour necrosis factor related apoptosis inducing ligand (TRAIL death receptors and inducing apoptosis in cancer cells. Zerumbone is a sesquiterpene that is able to penetrate into the hydrophobic pockets of proteins to exert its inhibiting activity with several proteins. We found a good binding with the tumor necrosis factor, kinase κB (IKKβ and the Nuclear factor κB (NF-κB component proteins along the TNF pathway. Our results suggest that zerumbone can exert its apoptotic activities by inhibiting the cytoplasmic proteins. It inhibits the IKKβ kinase that activates the NF-κB and also binds to the NF-κB complex in the TNF pathway. Blocking both proteins can lead to inhibition of cell proliferating proteins to be downregulated and possibly ultimate induction of apoptosis.

  16. Belongingness in Early Secondary School: Key Factors that Primary and Secondary Schools Need to Consider.

    Directory of Open Access Journals (Sweden)

    Sharmila Vaz

    Full Text Available It is unknown if, and how, students redefine their sense of school belongingness after negotiating the transition to secondary school. The current study used longitudinal data from 266 students with, and without, disabilities who negotiated the transition from 52 primary schools to 152 secondary schools. The study presents the 13 most significant personal student and contextual factors associated with belongingness in the first year of secondary school. Student perception of school belongingness was found to be stable across the transition. No variability in school belongingness due to gender, disability or household-socio-economic status (SES was noted. Primary school belongingness accounted for 22% of the variability in secondary school belongingness. Several personal student factors (competence, coping skills and school factors (low-level classroom task-goal orientation, which influenced belongingness in primary school, continued to influence belongingness in secondary school. In secondary school, effort-goal orientation of the student and perception of their school's tolerance to disability were each associated with perception of school belongingness. Family factors did not influence belongingness in secondary school. Findings of the current study highlight the need for primary schools to foster belongingness among their students at an early age, and transfer students' belongingness profiles as part of the hand-over documentation. Most of the factors that influenced school belongingness before and after the transition to secondary are amenable to change.

  17. [PRODUCT OF THE BMI1--A KEY COMPONENT OF POLYCOMB--POSITIVELY REGULATES ADIPOCYTE DIFFERENTIATION OF MOUSE MESENCHYMAL STEM CELLS].

    Science.gov (United States)

    Petrov, N S; Vereschagina, N A; Sushilova, E N; Kropotov, A V; Miheeva, N F; Popov, B V

    2016-01-01

    Bmil is a key component of Polycomb (PcG), which in mammals controls the basic functions of mammalian somatic stem cells (SSC) such as self-renewal and differentiation. Bmi1 supports SSC via transcriptional suppression of genes associated with cell cycle and differentiation. The most studied target genes of Bmi1 are the genes of Ink4 locus, CdkI p16(Ink4a) and p1(Arf), suppression of which due to activating mutations of the BMI1 results in formation of cancer stem cells (CSC) and carcinomas in various tissues. In contrast, inactivation of BMI1 results in cell cycle arrest and cell senescence. Although clinical phenomena of hypo- and hyperactivation of BMI1 are well known, its targets and mechanisms of regulation of tissue specific SSC are still obscure. The goal of this study was to evaluate the regulatory role of BMI1 in adipocyte differentiation (AD) of mouse mesenchymal stem cells (MSC). Induction of AD in mouse MSC of the C3H10T1/2 cell line was associated with an increase in the expression levels of BMI1, the genes of pRb family (RB, p130) and demethylase UTX, but not methyltransferase EZH2, whose products regulate the methylation levels of H3K27. It was observed earlier that H3K27me3 may play the role of the epigenetic switch by promoting AD of human MSC via activating expression of the PPARγ2, the master gene of AD (Hemming et al., 2014). Here we show that inactivation of BMI1 using specific siRNA slows and decreases the levels of AD, but does not abolish it. This is associated with a complete inhibition of the expression of adipogenic marker genes--PPARγ2, ADIPOQ and a decrease in the expression of RB, p130, but not UTX. The results obtained give evidence that the epigenetic mechanism regulating AD differentiation in mouse and human MSC is different.

  18. Issues in the Language Policy of the European Union. Motivation as a Key Factor in Promoting Language Learning

    OpenAIRE

    Komorowska, Hanna

    2007-01-01

    As motivation has been identified by the EU High Level Group on Multilingualism as the key factor in promoting language education, the author, herself member of HLGM, discusses a variety of approaches to motivation and presents guidelines for the promotional activity at national, regional and school levels, concentrating on its aims and procedures, identifying age groups and motives to be targeted, as well as arguments and strategies to be used in the process of eliciting and sustaining le...

  19. Clusters Regarding Key Factors Affecting Changes in Accounting, Finance, Administration and Management Control

    Directory of Open Access Journals (Sweden)

    Rodica Gabriela Blidisel

    2010-01-01

    Full Text Available During the last decade, important changes have occurred in public governance, which has evolved in this time from hierarchical bureaucracy to participatory governance, where the role of citizens in public decision-making process is more direct. There were performed reforms in finance, management administration and finances of public sector. Starting from the factors that influenced during the history the accounting, finances, administration and management control, we want to test the factors that affect the changes of these elements in Romanian environment.

  20. Norepinephrine Regulates Condylar Bone Loss via Comorbid Factors.

    Science.gov (United States)

    Jiao, K; Niu, L; Xu, X; Liu, Y; Li, X; Tay, F R; Wang, M

    2015-06-01

    Degenerative changes of condylar subchondral bone occur frequently in temporomandibular disorders. Although psychologic stresses and occlusal abnormalities have been implicated in temporomandibular disorder, it is not known if these risks represent synergistic comorbid factors that are involved in condylar subchondral bone degradation that is regulated by the sympathetic nervous system. In the present study, chronic immobilization stress (CIS), chemical sympathectomy, and unilateral anterior crossbite (UAC) were sequentially applied in a murine model. Norepinephrine contents in the subjects' serum and condylar subchondral bone were detected by ELISA; bone and cartilage remodeling parameters and related gene expression in the subchondral bone were examined. Subchondral bone loss and increased subchondral bone norepinephrine level were observed in the CIS and UAC groups. These groups exhibited decreased bone mineral density, volume fraction, and bone formation rate; decreased expressions of osterix, collagen I, and osteocalcin; but increased trabecular separation, osteoclast number and surface, and RANKL expression. Combined CIS + UAC produced more severe subchondral bone loss, higher bone norepinephrine level, and decreased chondrocyte density and cartilage thickness when compared to CIS or UAC alone. Sympathectomy simultaneously prevented subchondral bone loss and decreased bone norepinephrine level in all experimental subgroups when compared to the vehicle-treated counterparts. Norepinephrine also decreased mRNA expression of osterix, collagen I, and osteocalcin by mesenchymal stem cells at 7 and 14 d of stimulation and increased the expression of RANKL and RANKL/OPG ratio by mesenchymal stem cells at 2 h. In conclusion, CIS and UAC synergistically promote condylar subchondral bone loss and cartilage degradation; such processes are partially regulated by norepinephrine within subchondral bone.

  1. Vitamin D receptor deficiency and low vitamin D diet stimulate aortic calcification and osteogenic key factor expression in mice.

    Directory of Open Access Journals (Sweden)

    Nadine Schmidt

    Full Text Available Low levels of 25-hydroxy vitamin D (25(OHD are associated with cardiovascular diseases. Herein, we tested the hypothesis that vitamin D deficiency could be a causal factor in atherosclerotic vascular changes and vascular calcification. Aortic root sections of vitamin D receptor knockout (VDR(-/- mice that were stained for vascular calcification and immunostained for osteoblastic differentiation factors showed more calcified areas and a higher expression of the osteogenic key factors Msx2, Bmp2, and Runx2 than the wild-type mice (P<0.01. Data from LDL receptor knockout (LDLR(-/- mice that were fed western diet with either low (50 IU/kg, recommended (1,000 IU/kg, or high (10,000 IU/kg amounts of vitamin D(3 over 16 weeks revealed increasing plasma concentrations of 25(OHD (P<0.001 with increasing intake of vitamin D, whereas levels of calcium and phosphorus in plasma and femur were not influenced by the dietary treatment. Mice treated with the low vitamin D diet had more calcified lesions and a higher expression of Msx2, Bmp2, and Runx2 in aortic roots than mice fed recommended or high amounts of vitamin D (P<0.001. Taken together, these findings indicate vitamin D deficiency as a risk factor for aortic valve and aortic vessel calcification and a stimulator of osteogenic key factor expression in these vascular areas.

  2. Key factors in frame building: how strategic political actors shape news media coverage

    NARCIS (Netherlands)

    Hänggli, R.

    2012-01-01

    In this article, the author focuses on the relationship between political actors and the mass media. The author uses media frames as dependent variables and investigates the factors that influence the presence and frequency of frames applied by journalists (the frames in "news media"). This has come

  3. Key-socio economic factors influencing sustainable land management investments in the West Usambara Highlands, Tanzania

    NARCIS (Netherlands)

    Nyanga, A.W.; Kessler, C.A.; Tenge, A.J.M.

    2016-01-01

    Low investments in sustainable land management (SLM) limit agricultural production in the East African Highlands, leading to increased soil erosion, low productivity of land and food insecurity. Recent studies in the region show that different socio-economic factors influence SLM investments by farm

  4. Key Success Factors of Innovation in Multinational Agri-food Prospector Companies

    NARCIS (Netherlands)

    Fortuin, F.T.J.M.; Batterink, M.H.; Omta, S.W.F.

    2007-01-01

    The Wageningen Innovation Assessment Tool (WIAT) compares the self assessment of the drivers and barriers to innovation at the company level and the critical success and failure factors of innovation at the project level with data of agrifood prospector firms around the world. In total 46 innovation

  5. Genetic risk factors for venous thrombosis : key players or minor risk modifiers?

    NARCIS (Netherlands)

    Vossen, Carolina Yvonne

    2005-01-01

    Venous thrombosis is a common disease, which manifests itself mostly in the deep veins of the leg, with a reported incidence of 1-2 per 1000 individuals per year. Several genetic risk factors have been identified for venous thrombosis. It is, however, difficult to predict the risk of venous

  6. Key Success Factors of Innovation in Multinational Agri-food Prospector Companies

    NARCIS (Netherlands)

    Fortuin, F.T.J.M.; Batterink, M.H.; Omta, S.W.F.

    2007-01-01

    The Wageningen Innovation Assessment Tool (WIAT) compares the self assessment of the drivers and barriers to innovation at the company level and the critical success and failure factors of innovation at the project level with data of agrifood prospector firms around the world. In total 46 innovation

  7. Oxidative stress--a key emerging impact factor in health, ageing, lifestyle and aesthetics.

    Science.gov (United States)

    Kandola, K; Bowman, A; Birch-Machin, M A

    2015-12-01

    Oxidative stress is the resultant damage that arises due to redox imbalances, more specifically an increase in destructive free radicals and reduction in protection from antioxidants and the antioxidant defence pathways. Oxidation of lipids by reactive oxygen species (ROS) can damage cellular structures and result in premature cell death. At low levels, ROS-induced oxidative stress can be prevented through the action of antioxidants, however, when ROS are present in excess, inflammation and cytotoxicity eventually results leading to cellular oxidative stress damage. Increasing evidence for the role of oxidative stress in various diseases including neurological, dermatological, and cardiovascular diseases is now emerging. Mitochondria are the principal source (90%) of ROS in the cell, with superoxide radicals being generated when molecular oxygen is combined with free electrons. Given the key role of mitochondria in the generation of cellular oxidative stress it is worth considering this organelle and the process in more detail and to provide methods of intervention.

  8. Key recovery factors for the August 24, 2014, South Napa Earthquake

    Science.gov (United States)

    Hudnut, Kenneth W.; Brocher, Thomas M.; Prentice, Carol S.; Boatwright, John; Brooks, Benjamin A.; Aagaard, Brad T.; Blair, James Luke; Fletcher, Jon Peter B.; Erdem, Jemile; Wicks, Chuck; Murray, Jessica R.; Pollitz, Fred F.; Langbein, John O.; Svarc, Jerry L.; Schwartz, David P.; Ponti, Daniel J.; Hecker, Suzanne; DeLong, Stephen B.; Rosa, Carla M.; Jones, Brenda; Lamb, Rynn M.; Rosinski, Anne M.; McCrink, Timothy P.; Dawson, Timothy E.; Seitz, Gordon G.; Glennie, Craig; Hauser, Darren; Ericksen, Dodd; Mardock, Dan; Hoirup, Don F.; Bray, Jonathan D.; Rubin, Ron S.

    2014-01-01

    Through discussions between the Federal Emergency Management Agency (FEMA) and the U.S. Geological Survey (USGS) following the South Napa earthquake, it was determined that several key decision points would be faced by FEMA for which additional information should be sought and provided by USGS and its partners. This report addresses the four tasks that were agreed to. These tasks are (1) assessment of ongoing fault movement (called afterslip) especially in the Browns Valley residential neighborhood, (2) assessment of the shaking pattern in the downtown area of the City of Napa, (3) improvement of information on the fault hazards posed by the West Napa Fault System (record of past earthquakes and slip rate, for example), and (4) imagery acquisition and data processing to provide overall geospatial information support to FEMA.

  9. Measles virus nucleocapsid protein, a key contributor to Paget’s disease, increases IL-6 expression via down-regulation of FoxO3/Sirt1signaling

    Science.gov (United States)

    Wang, Feng-Ming; Sarmasik, Aliye; Hiruma, Yuko; Sun, Quanhong; Sammut, Benedicte; Windle, Jolene J.; Roodman, G. David; Galson, Deborah L.

    2012-01-01

    Measles virus plays an important role as an environmental factor in the pathogenesis of Paget’s disease (PD). Previous studies have shown that IL-6 is increased in the bone marrow of Paget’s patients and that measles virus nucleocapsid protein (MVNP) induces IL-6 secretion by pagetic osteoclasts. Further, IL-6 plays a critical role in the development of pagetic osteoclasts and bone lesions induced by PD, but the mechanisms regulating IL-6 production by MVNP remain unclear. Our current studies revealed that MVNP expression in osteoclast precursors down-regulated Sirt1 mRNA and protein, a negative regulator of NF-κB activity, which is a key factor for IL-6 expression. MVNP expression in NIH3T3 cells also elevated Il-6 transcription and impaired the expression of Sirt1 mRNA both under basal conditions and upon activation of the Sirt1 upstream regulator FoxO3 by LY294002 (a PI3K/AKT inhibitor). Luciferase activity assays showed that constitutively active FoxO3 abolished the repressive effect of MVNP on reporters driven by either FoxO3 response elements or the Sirt1 promoter. Further, protein stability assays revealed that FoxO3 was degraded more rapidly in MVNP-expressing cells than in control cells following the addition of cycloheximide. Similarly, co-transfection of MVNP and FoxO3 into HEK293 cells demonstrated that MVNP decreased the protein levels of over-expressed FoxO3 in a dose-dependent manner. Treatment with the proteasome inhibitor, MG132, blocked the MVNP-triggered decrease of FoxO3, and the treatment with the serine/threonine phosphatase inhibitor, Calyculin A, revealed that MVNP increased phosphorylation of FoxO3. Further, over-expression of Sirt1 or treatment with the Sirt1 activator resveratrol blocked the increase in Il-6 transcription by MVNP. Finally, resveratrol reduced the numbers of TRAP positive multi-nuclear cells in bone marrow cultures from TRAP-MVNP transgenic mice to wild type levels. These results indicate that MVNP decreases FoxO3

  10. Soil Surface Structure: A key factor for the degree of soil water repellency

    Science.gov (United States)

    Ahn, S.; Doerr, S. H.; Douglas, P.; Bryant, R.; Hamlett, C.; McHale, G.; Newton, M.; Shirtcliffe, N.

    2012-04-01

    Despite of considerable efforts, the degree of water repellency has not always been fully explained by chemical property of soil (termed hydrophobicity). That might be because the structure of a soil surface was not considered properly, which is another main factor determining the severity of soil water repellency. Surface structure has only recently been considered in soil science, whilst it has been paid attention for several decades in materials science due to its relevance to industrial applications. In this contribution, comparison of critical contact angles measured on different surface structures (made with glass beads, glass shards and beach sands) is presented and the effect of surface structure on manifestation of soil water repellency is discussed in terms of several different variables such as the individual particles shape, and areal and structural factors of the actual surface.

  11. Negative thinking: a key factor in depressive symptoms in Thai adolescents.

    Science.gov (United States)

    Charoensuk, Sukjai

    2007-01-01

    Negative thinking, self-esteem, parental bonding, and everyday stressors are factors related to depressive symptoms in studies conducted in the United States, but they have been rarely explored in Thailand. An understanding of factors influencing depressive symptoms in Thai youth will lead to the development of interventions to decrease depressive symptoms among this age group. The purpose of this study was to examine the effects of parental bonding, everyday stressors, self-esteem, and negative thinking on depressive symptoms among Thai adolescents. A random sample of 812 high school students in Chon Buri, Thailand, participated in the study. The prevalence of depressive symptoms varied from 20-21% depending on the measures used. Negative thinking was the best predictor of depressive symptoms in Thai adolescents. Negative thinking also mediated the effects of parental bonding, everyday stressors, and self-esteem on depressive symptoms.

  12. A structured elicitation method to identify key direct risk factors for the management of natural resources.

    Science.gov (United States)

    Smith, Michael; Wallace, Ken; Lewis, Loretta; Wagner, Christian

    2015-11-01

    The high level of uncertainty inherent in natural resource management requires planners to apply comprehensive risk analyses, often in situations where there are few resources. In this paper, we demonstrate a broadly applicable, novel and structured elicitation approach to identify important direct risk factors. This new approach combines expert calibration and fuzzy based mathematics to capture and aggregate subjective expert estimates of the likelihood that a set of direct risk factors will cause management failure. A specific case study is used to demonstrate the approach; however, the described methods are widely applicable in risk analysis. For the case study, the management target was to retain all species that characterise a set of natural biological elements. The analysis was bounded by the spatial distribution of the biological elements under consideration and a 20-year time frame. Fourteen biological elements were expected to be at risk. Eleven important direct risk factors were identified that related to surrounding land use practices, climate change, problem species (e.g., feral predators), fire and hydrological change. In terms of their overall influence, the two most important risk factors were salinisation and a lack of water which together pose a considerable threat to the survival of nine biological elements. The described approach successfully overcame two concerns arising from previous risk analysis work: (1) the lack of an intuitive, yet comprehensive scoring method enabling the detection and clarification of expert agreement and associated levels of uncertainty; and (2) the ease with which results can be interpreted and communicated while preserving a rich level of detail essential for informed decision making.

  13. Key factors determining success of primary eye care through vision centres in rural India: Patients′ perspectives

    Directory of Open Access Journals (Sweden)

    Vilas Kovai

    2012-01-01

    Full Text Available Aim : This paper intends to discuss the patients′ perspective on the determinants of primary eye care services from vision centers (VC in rural India. Materials and Methods : A retrospective study design and interview method was used on 127 randomly selected patients who accessed the 4 VCs in 2007. Factor analyses and linear regression models were used to predict the associations with patient satisfaction. Results : The three factors derived from factor analyses were: (1-vision technician (VT, (2-location of VC, and (3-access to VC; explaining 60% of the variance in total patients′ satisfaction with VC. The first model (R2 : 0.61; F 1,124=144.36, P <0.001, indicated that respondents who had ′difficulty to travel to the place of VC′ and those who can afford to pay had less satisfaction with VT services. The second model (R2 =0.18; F 1,124=29.5, P <0.001 explained that respondents′ difficulty to identify the building of VC had decreased patients′ satisfaction and the third model (R2 =0.36; F 1,124=45.6, P <0.001 indicated that those who had to travel<5 km to the VC and had 0.38 units of increased satisfaction level with the services of VC. Conclusion : A good VT can enhance patient satisfaction. However, patient expectations are not only confined to the provider but also other factors such as ability to pay and convenient transportation that helps patients reach the location of the VC with ease.

  14. Key Success Factors of Innovation in Multinational Agri-food Prospector Companies

    OpenAIRE

    Fortuin, F.T.J.M.; Batterink, M.H.; Omta, S.W.F. (Onno)

    2007-01-01

    The Wageningen Innovation Assessment Tool (WIAT) compares the self assessment of the drivers and barriers to innovation at the company level and the critical success and failure factors of innovation at the project level with data of agrifood prospector firms around the world. In total 46 innovation projects, 11 successfully concluded and 6 failed projects, as well as 29 running projects in 12 multinational agrifood prospector companies in the Netherlands and France, two innovation consortia ...

  15. Key factors for a successful implementation of personalized e-health services.

    Science.gov (United States)

    Griebel, Lena; Sedlmayr, Brita; Prokosch, Hans-Ulrich; Criegee-Rieck, Manfred; Sedlmayr, Martin

    2013-01-01

    Personalized e-health services hold many promises, e.g. the improvement of health care quality or the reduction of costs. However, such services can't tap their full potential if they will not be used. That's why it is essential to understand what brings potential users to accept them. In the literature many acceptance models exist that predict the usage of innovations, but none of them specifically refers to the adoption of e-health services. Therefore we combined the Unified Theory of Acceptance and Use of Technology (UTAUT) and the e-health literacy concept and enhanced the resulting model with additional factors. MEDLINE® was searched; 75 studies were included for final analysis. Apart from the UTAUT variables and e-health literacy, 10 additional factors were identified: anxiety, trust, attitude toward using, computer self-efficacy, perceived system quality, search strategy, user's condition, health specific knowledge, Internet dependency and satisfaction with medical care. Future research will include the devolvement of an instrument for assessing these factors and testing the initial research model in an international context.

  16. Comparative "-omics" in Mycoplasma pneumoniae Clinical Isolates Reveals Key Virulence Factors.

    Directory of Open Access Journals (Sweden)

    Maria Lluch-Senar

    Full Text Available The human respiratory tract pathogen M. pneumoniae is one of the best characterized minimal bacterium. Until now, two main groups of clinical isolates of this bacterium have been described (types 1 and 2, differing in the sequence of the P1 adhesin gene. Here, we have sequenced the genomes of 23 clinical isolates of M. pneumoniae. Studying SNPs, non-synonymous mutations, indels and genome rearrangements of these 23 strains and 4 previously sequenced ones, has revealed new subclasses in the two main groups, some of them being associated with the country of isolation. Integrative analysis of in vitro gene essentiality and mutation rates enabled the identification of several putative virulence factors and antigenic proteins; revealing recombination machinery, glycerol metabolism and peroxide production as possible factors in the genetics and physiology of these pathogenic strains. Additionally, the transcriptomes and proteomes of two representative strains, one from each of the two main groups, have been characterized to evaluate the impact of mutations on RNA and proteins levels. This study has revealed that type 2 strains show higher expression levels of CARDS toxin, a protein recently shown to be one of the major factors of inflammation. Thus, we propose that type 2 strains could be more toxigenic than type 1 strains of M. pneumoniae.

  17. Academic mobility as a key factor of quality assurance in tertiary education

    Science.gov (United States)

    Voroshilova, Anna A.

    2015-01-01

    Academic mobility of both faculty and students forms a critical element of the international dimension of higher education and is one of the most important factors of quality assurance of higher education institutions worldwide. Internationalization and globalization of Russian higher education system is having one of the major impacts on the quality management and assurance. Faculty and student mobility figures are now one of the core factors for obtaining state accreditation for Russian universities as well as an important indicator showing the university success and prestige. The aim of the paper is a closer look at the perspectives and results of the academic mobility, the factors stimulating and discouraging mobility, and the outcomes of the mobility influencing the education in Russian universities. Siberian State Aerospace University has had more than 10 years experience in organizing student mobility. Most of the problems in carrying out international activities are common for the whole Russia but still there are some peculiarities featuring technical universities situated in the centre of Russia.

  18. Factors affecting the regulation of pacing: current perspectives

    Directory of Open Access Journals (Sweden)

    Mauger AR

    2014-09-01

    Full Text Available Alexis R Mauger Endurance Research Group, School of Sport and Exercise Sciences, Faculty of Science, University of Kent, Chatham, UK Abstract: During prolonged dynamic and rhythmic exercise, muscular pain and discomfort arises as a result of an increased concentration of deleterious metabolites. Sensed by peripheral nociceptors and transmitted via afferent feedback to the brain, this provides important information regarding the physiological state of the muscle. These sensations ultimately contribute to what is termed "exercise-induced pain". Despite being well recognized by athletes and coaches, and suggested to be integral to exercise performance, this construct has largely escaped attention in experimental work. This perspective article highlights the current understanding of pacing in endurance performance, and the causes of exercise-induced pain. A new perspective is described, which proposes how exercise-induced pain may be a contributing factor in helping individuals to regulate their work rate during exercise and thus provides an important construct in pacing. Keywords: pain, exercise-induced pain, discomfort, exercise performance, self-paced

  19. Social Economy as a key factor for enhancing Blue Growth in Greece. A conceptual perspective

    Directory of Open Access Journals (Sweden)

    Dimitris Banousis

    2016-11-01

    Full Text Available In recent years, Blue Economy has been an expanding concept in the EU, both as a tool for development as well as an economy transforming concept while its strategic orientation is reflected in EU’s Blue Growth strategy. On parallel Europe’s 2020 Strategy goals and their translation into targets for the member states, serves as a common ground for -among others- the implementation of Blue Growth goals and the enforcement of the activities of Social Economy Enterprises. Starting from this fact, a survey has been conducted to address: (a the contribution of the Blue Growth goals to the activities of the Greek private and public economic sectors, as well as of the Social Economic one; (b the current state of the art interaction between Blue Economy and Social Economy in Greece, and; (c the current and future trends regarding the contribution of Social Cooperative Enterprises (SCE as a tool for enhancing Blue Growth impact. Key findings include the level of engagement of SCEs with Blue Growth sectors, their potential of future involvement and the reasons for the current skepticism towards the Blue Growth potential. The above mentioned are complemented with a discussion on the viability and compatibility of a Blue Growth Social Concept adapted in the special environment of a heavily maritime related economy such as Greece.

  20. Crystallographic orientation and electrode nature are key factors for electric current generation by Geobacter sulfurreducens.

    Science.gov (United States)

    Maestro, Beatriz; Ortiz, Juan M; Schrott, Germán; Busalmen, Juan P; Climent, Víctor; Feliu, Juan M

    2014-08-01

    We have investigated the influence of electrode material and crystallographic structure on electron transfer and biofilm formation of Geobacter sulfurreducens. Single-crystal gold-Au(110), Au(111), Au(210)-and platinum-Pt(100), Pt(110), Pt(111), Pt(210)-electrodes were tested and compared to graphite rods. G. sulfurreducens electrochemically interacts with all these materials with different attachment kinetics and final current production, although redox species involved in the electron transfer to the anode are virtually the same in all cases. Initial bacterial colonization was fastest on graphite up to the monolayer level, whereas gold electrodes led to higher final current densities. Crystal geometry was shown to have an important influence, with Au(210) sustaining a current density of up to 1442±101μAcm(-2) at the steady state, over Au(111) with 961±94μAcm(-2) and Au(110) with 944±89μAcm(-2). On the other hand, the platinum electrodes displayed the lowest performances, including Pt(210). Our results indicate that both crystal geometry and electrode material are key parameters for the efficient interaction of bacteria with the substrate and should be considered for the design of novel materials and microbial devices to optimize energy production.

  1. Evaluation of thermal steam-explosion key operation factors to optimize biogas production from biological sludge.

    Science.gov (United States)

    Pérez-Elvira, S I; Sapkaite, I; Fdz-Polanco, F

    2015-01-01

    Thermal steam-explosion is the most extended hydrolysis pretreatment to enhance anaerobic digestion of sludge. Thermal hydrolysis key parameters are temperature (T) and time (t), and the generally accepted values reported from full-scale information are: 150-230 °C and 20-60 min. This study assesses the influence of different temperature-time-flash combinations (110-180 °C, 5-60 min, 1-3 re-flashing) on the anaerobic degradation of secondary sludge through biochemical methane potential (BMP) tests. All the conditions tested presented higher methane production compared to the untreated sludge, and both solubilization (after the hydrolysis) and degradation (by anaerobic digestion) increased linearly when increasing the severity (T-t) of the pretreatment, reaching 40% solubilization and degradation of the particulate matter at 180° C-60 min. However, for the 180 °C temperature, the treatment time impacted negatively on the lag phase. No influence of re-flashing the pretreated matter was observed. In conclusion, thermal steam-explosion at short operation times (5 min) and moderate temperatures (145 °C) seems to be very attractive from a degradation point of view thus presenting a methane production enhancement similar to the one obtained at 180°C and without negative influence of the lag phase.

  2. Use of simulink to address key factors for radon mitigation in a Fairbanks home.

    Science.gov (United States)

    Marsik, Tom; Johnson, Ron

    2008-05-01

    Hilly areas around Fairbanks, Alaska, are known to have elevated soil radon concentrations. Due to geological conditions, cold winters, and the resulting stack effect, houses in these areas are prone to higher indoor radon concentrations. Key variables with respect to radon mitigation were addressed in this paper by using a dynamic model implemented in MATLAB Simulink. These variables included the ventilation rate; the foundation flow resistance, which can be affected by sealing the foundation during the construction of a house; and the differential pressure between the subslab and the house interior, which can be affected by using a subslab depressurization system. The model was used for the scenario of a varying differential pressure and then for the scenario of a varying ventilation rate at a Fairbanks home where real-time radon concentrations were measured. The correlation coefficients between the model-predicted and measured radon concentrations were 0.96 and 0.94, for both scenarios respectively, which verified the feasibility of the model for predicting indoor radon concentrations.

  3. Insulin-like growth factor-II regulates bone sialoprotein gene transcription.

    Science.gov (United States)

    Choe, Jin; Sasaki, Yoko; Zhou, Liming; Takai, Hideki; Nakayama, Yohei; Ogata, Yorimasa

    2016-09-01

    Insulin-like growth factor-I and -II (IGF-I and IGF-II) have been found in bone extracts of several different species, and IGF-II is the most abundant growth factor stored in bone. Bone sialoprotein (BSP) is a noncollagenous extracellular matrix glycoprotein associated with mineralized connective tissues. In this study, we have investigated the regulation of BSP transcription by IGF-II in rat osteoblast-like ROS17/2.8 cells. IGF-II (50 ng/ml) increased BSP mRNA and protein levels after 6-h stimulation, and enhanced luciferase activities of the constructs pLUC3 (-116 to +60), pLUC4 (-425 to +60), pLUC5 (-801 to +60) and pLUC6 (-938 to +60). Effects of IGF-II were inhibited by tyrosine kinase, extracellular signal-regulated kinase1/2 and phosphatidylinositol 3-kinase inhibitors, and abrogated by 2-bp mutations in cAMP response element (CRE), FGF2 response element (FRE) and homeodomain protein-binding site (HOX). The results of gel shift assays showed that nuclear proteins binding to CRE, FRE and HOX sites were increased by IGF-II (50 ng/ml) at 3 and 6 h. CREB1, phospho-CREB1, c-Fos and c-Jun antibodies disrupted the formation of the CRE-protein complexes. Dlx5 and Runx2 antibodies disrupted the FRE- and HOX-protein complex formations. These studies therefore demonstrated that IGF-II increased BSP transcription by targeting CRE, FRE and HOX elements in the proximal promoter of the rat BSP gene. Moreover, phospho-CREB1, c-Fos, c-Jun, Dlx5 and Runx2 transcription factors appear to be key regulators of IGF-II effects on BSP transcription.

  4. Identification of trans-acting factors regulating SamDC expression in Oryza sativa

    Energy Technology Data Exchange (ETDEWEB)

    Basu, Supratim, E-mail: supratim_genetics@yahoo.co.in [Department of Crop Soil and Environmental Sciences, University of Arkansas, Fayetteville, AR 72701 (United States); Division of Plant Biology, Bose Institute, Kolkata (India); Roychoudhury, Aryadeep [Post Graduate Department of Biotechnology, St. Xavier' s College (Autonomous), 30, Mother Teresa Sarani, Kolkata - 700016, West Bengal (India); Sengupta, Dibyendu N. [Division of Plant Biology, Bose Institute, Kolkata (India)

    2014-03-07

    Highlights: • Identification of cis elements responsible for SamDC expression by in silico analysis. • qPCR analysis of SamDC expression to abiotic and biotic stress treatments. • Detection of SamDC regulators using identified cis-elements as probe by EMSA. • Southwestern Blot analysis to predict the size of the trans-acting factors. - Abstract: Abiotic stress affects the growth and productivity of crop plants; to cope with the adverse environmental conditions, plants have developed efficient defense machinery comprising of antioxidants like phenolics and flavonoids, and osmolytes like polyamines. SamDC is a key enzyme in the polyamine biosynthesis pathway in plants. In our present communication we have done in silico analysis of the promoter region of SamDC to look for the presence of different cis-regulatory elements contributing to its expression. Based on the presence of different cis-regulatory elements we completed comparative analysis of SamDC gene expression in rice lamina of IR-29 and Nonabokra by qPCR in response to the abiotic stress treatments of salinity, drought, cold and the biotic stress treatments of ABA and light. Additionally, to explore the role of the cis-regulatory elements in regulating the expression of SamDC gene in plants we comparatively analyzed the binding of rice nuclear proteins prepared from IR-29 and Nonabokra undergoing various stress treatments. The intensity of the complex formed was low and inducible in IR-29 in contrast to Nonabokra. Southwestern blot analysis helped in predicting the size of the trans-acting factors binding to these cis-elements. To our knowledge this is the first report on the comprehensive analysis of SamDC gene expression in rice and identification of the trans-acting factors regulating its expression.

  5. Physiologically-based toxicokinetic models help identifying the key factors affecting contaminant uptake during flood events

    Energy Technology Data Exchange (ETDEWEB)

    Brinkmann, Markus; Eichbaum, Kathrin [Department of Ecosystem Analysis, Institute for Environmental Research,ABBt – Aachen Biology and Biotechnology, RWTH Aachen University, Worringerweg 1, 52074 Aachen (Germany); Kammann, Ulrike [Thünen-Institute of Fisheries Ecology, Palmaille 9, 22767 Hamburg (Germany); Hudjetz, Sebastian [Department of Ecosystem Analysis, Institute for Environmental Research,ABBt – Aachen Biology and Biotechnology, RWTH Aachen University, Worringerweg 1, 52074 Aachen (Germany); Institute of Hydraulic Engineering and Water Resources Management, RWTH Aachen University, Mies-van-der-Rohe-Straße 1, 52056 Aachen (Germany); Cofalla, Catrina [Institute of Hydraulic Engineering and Water Resources Management, RWTH Aachen University, Mies-van-der-Rohe-Straße 1, 52056 Aachen (Germany); Buchinger, Sebastian; Reifferscheid, Georg [Federal Institute of Hydrology (BFG), Department G3: Biochemistry, Ecotoxicology, Am Mainzer Tor 1, 56068 Koblenz (Germany); Schüttrumpf, Holger [Institute of Hydraulic Engineering and Water Resources Management, RWTH Aachen University, Mies-van-der-Rohe-Straße 1, 52056 Aachen (Germany); Preuss, Thomas [Department of Environmental Biology and Chemodynamics, Institute for Environmental Research,ABBt- Aachen Biology and Biotechnology, RWTH Aachen University, Worringerweg 1, 52074 Aachen (Germany); and others

    2014-07-01

    Highlights: • A PBTK model for trout was coupled with a sediment equilibrium partitioning model. • The influence of physical exercise on pollutant uptake was studies using the model. • Physical exercise during flood events can increase the level of biliary metabolites. • Cardiac output and effective respiratory volume were identified as relevant factors. • These confounding factors need to be considered also for bioconcentration studies. - Abstract: As a consequence of global climate change, we will be likely facing an increasing frequency and intensity of flood events. Thus, the ecotoxicological relevance of sediment re-suspension is of growing concern. It is vital to understand contaminant uptake from suspended sediments and relate it to effects in aquatic biota. Here we report on a computational study that utilizes a physiologically based toxicokinetic model to predict uptake, metabolism and excretion of sediment-borne pyrene in rainbow trout (Oncorhynchus mykiss). To this end, data from two experimental studies were compared with the model predictions: (a) batch re-suspension experiments with constant concentration of suspended particulate matter at two different temperatures (12 and 24 °C), and (b) simulated flood events in an annular flume. The model predicted both the final concentrations and the kinetics of 1-hydroxypyrene secretion into the gall bladder of exposed rainbow trout well. We were able to show that exhaustive exercise during exposure in simulated flood events can lead to increased levels of biliary metabolites and identified cardiac output and effective respiratory volume as the two most important factors for contaminant uptake. The results of our study clearly demonstrate the relevance and the necessity to investigate uptake of contaminants from suspended sediments under realistic exposure scenarios.

  6. Hydrology and human behavior: two key factors of diarrhea incidence in montane tropical humid areas

    Science.gov (United States)

    Boithias, Laurie; Choisy, Marc; Souliyaseng, Noy; Jourdren, Marine; Quet, Fabrice; Buisson, Yves; Thammahacksa, Chanthamousone; Silvera, Norbert; Latsachack, Keooudone; Sengtaheuanghoung, Oloth; Pierret, Alain; Rochelle-Newall, Emma; Becerra, Sylvia; Ribolzi, Olivier

    2017-04-01

    The global burden of diarrhea is a leading cause of morbidity and mortality worldwide. In montane areas of South-East Asia such as northern Laos, recent changes in land use have induced increased runoff, soil erosion and in-stream suspended sediment loads, and potential pathogen dissemination. In this study we hypothesized that climate factors combined with human behavior control diarrhea incidence, either because higher rainfall, leading to higher stream discharges, suspended sediment loads and Fecal Indicator Bacteria (FIB) counts, are associated with higher numbers of reported diarrhea cases during the rainy season, or because water shortage leads to the use of less safe water sources during the dry season. For this mixed methods approach, we conducted a retrospective time series analysis of meteorological variables (rainfall, air temperature), hydrological variables (discharge, suspended sediments, FIB counts, water temperature) at the outlet of 2 catchments in Northern Lao PDR, and the number of diarrheal disease cases reported in 6 health centers located in the Luang Prabang Province. We also examined the socio-behavioral factors potentially affecting vulnerability to the effect of the climate factors, such as drinking water sources and hygiene habits. We found the FIB Escherichia coli to be present all year long (100-1,000 MPN 100 mL-1) indicating that fecal contamination is ubiquitous and constant. We found that populations switch their water supply from wells to surface water during drought periods, the latter of which appear to be at higher risk of bacterial contamination than municipal water fountains. We thus found that water shortage in the Luang Prabang area triggers diarrhea peaks during the dry and hot season and that rainfall and aquifer refill ends the epidemic during the wet season. We thus found that anthropogenic drivers, such as hygiene practices, were at least as important as environmental drivers in determining the seasonal pattern of a

  7. Systemic inflammation: a key factor in the pathogenesis of cardiovascular complications in obstructive sleep apnoea syndrome?

    LENUS (Irish Health Repository)

    Ryan, S

    2012-02-01

    Obstructive sleep apnoea syndrome (OSAS) is a highly prevalent disease and is recognised as a major public health burden. Large-scale epidemiological studies have demonstrated an independent relationship between OSAS and various cardiovascular disorders. The pathogenesis of cardiovascular complications in OSAS is not completely understood but a multifactorial aetiology is likely. Inflammatory processes have emerged as critical in the pathogenesis of atherosclerosis at all stages of atheroma formation. Increased levels of various circulating markers of inflammation including tumour necrosis factor alpha (TNFalpha), interleukin 6 (IL6), IL-8 and C-reactive protein (CRP) have been reported as associated with future cardiovascular risk. There is increasing evidence of elevated inflammatory markers in OSAS with a significant fall after effective treatment with continuous positive airway pressure. This evidence is particularly strong for TNFalpha, whereas studies on IL6 and CRP have yielded conflicting results possibly due to the confounding effects of obesity. Cell culture and animal studies have significantly contributed to our understanding of the underlying mechanisms of the association between OSAS and inflammation. Intermittent hypoxia, the hallmark of OSAS, results in activation of pro-inflammatory transcription factors such as nuclear factor kappa B (NF-kappaB) and activator protein (AP)-1. These promote activation of various inflammatory cells, particularly lymphocytes and monocytes, with the downstream consequence of expression of pro-inflammatory mediators that may lead to endothelial dysfunction. This review provides a critical analysis of the current evidence for an association between OSAS, inflammation and cardiovascular disease, discusses basic mechanisms that may be responsible for this association and proposes future research possibilities.

  8. Regulation of a transcription factor network by Cdk1 coordinates late cell cycle gene expression.

    Science.gov (United States)

    Landry, Benjamin D; Mapa, Claudine E; Arsenault, Heather E; Poti, Kristin E; Benanti, Jennifer A

    2014-05-02

    To maintain genome stability, regulators of chromosome segregation must be expressed in coordination with mitotic events. Expression of these late cell cycle genes is regulated by cyclin-dependent kinase (Cdk1), which phosphorylates a network of conserved transcription factors (TFs). However, the effects of Cdk1 phosphorylation on many key TFs are not known. We find that elimination of Cdk1-mediated phosphorylation of four S-phase TFs decreases expression of many late cell cycle genes, delays mitotic progression, and reduces fitness in budding yeast. Blocking phosphorylation impairs degradation of all four TFs. Consequently, phosphorylation-deficient mutants of the repressors Yox1 and Yhp1 exhibit increased promoter occupancy and decreased expression of their target genes. Interestingly, although phosphorylation of the transcriptional activator Hcm1 on its N-terminus promotes its degradation, phosphorylation on its C-terminus is required for its activity, indicating that Cdk1 both activates and inhibits a single TF. We conclude that Cdk1 promotes gene expression by both activating transcriptional activators and inactivating transcriptional repressors. Furthermore, our data suggest that coordinated regulation of the TF network by Cdk1 is necessary for faithful cell division.

  9. Steroidogenic Factor 1 in the Ventromedial Nucleus of the Hypothalamus Regulates Age-Dependent Obesity

    Science.gov (United States)

    Kinyua, Ann W.; Yang, Dong Joo; Chang, Inik; Kim, Ki Woo

    2016-01-01

    The ventromedial nucleus of the hypothalamus (VMH) is important for the regulation of whole body energy homeostasis and lesions in the VMH are reported to result in massive weight gain. The nuclear receptor steroidogenic factor 1 (SF-1) is a known VMH marker as it is exclusively expressed in the VMH region of the brain. SF-1 plays a critical role not only in the development of VMH but also in its physiological functions. In this study, we generated prenatal VMH-specific SF-1 KO mice and investigated age-dependent energy homeostasis regulation by SF-1. Deletion of SF-1 in the VMH resulted in dysregulated insulin and leptin homeostasis and late onset obesity due to increased food intake under normal chow and high fat diet conditions. In addition, SF-1 ablation was accompanied by a marked reduction in energy expenditure and physical activity and this effect was significantly pronounced in the aged mice. Taken together, our data indicates that SF-1 is a key component in the VMH-mediated regulation of energy homeostasis and implies that SF-1 plays a protective role against metabolic stressors including aging and high fat diet. PMID:27598259

  10. A Brief Discussion on the Key Factors of Developing and Implementing College Student's ICC

    Institute of Scientific and Technical Information of China (English)

    YANG Xi; WANG Yan-ru

    2015-01-01

    Language and culture are interrelated with each other, to learn a foreign language is not only about learning language it⁃self, but achieving a mutual understanding and appreciating of other cultures. The need for the people of intercultural communica⁃tive competence (ICC) in various work fields is consistently increasing. The development and implementation of intercultural com⁃municative competence has become the major goal of college English teaching. This paper mainly discusses the main factors in de⁃veloping and implementing ICC to find out their possible benefits and constrains in order to give some suggestions for the further development of Chinese college English teachers.

  11. KEY FACTORS OF TRANSFORMATION OF THE INTERNATIONAL MARKET AT THE PRESENT STAGE OF GLOBAL ECONOMY

    Directory of Open Access Journals (Sweden)

    A. Starostina

    2013-11-01

    Full Text Available The main conditions of transformation of the world market in modern conditions of globalization are determined. The main transformation’s factors of the international services market at the present stage of the world’s economy development are singled out. The impacts of the global market for the growth of productivity are investigated. The features for increase of export potential of developing countries in international trade in services are explored. The main characteristic features of the subject structure of the modern world market are showed.

  12. Identification of key factors that reduce the variability of the single photon response.

    Science.gov (United States)

    Caruso, Giovanni; Bisegna, Paolo; Andreucci, Daniele; Lenoci, Leonardo; Gurevich, Vsevolod V; Hamm, Heidi E; DiBenedetto, Emmanuele

    2011-05-10

    Rod photoreceptors mediate vision in dim light. Their biological function is to discriminate between distinct, very low levels of illumination, i.e., they serve as reliable photon counters. This role requires high reproducibility of the response to a particular number of photons. Indeed, single photon responses demonstrate unexpected low variability, despite the stochastic nature of the individual steps in the transduction cascade. We analyzed individual system mechanisms to identify their contribution to variability suppression. These include: (i) cooperativity of the regulation of the second messengers; (ii) diffusion of cGMP and Ca(2+) in the cytoplasm; and (iii) the effect of highly localized cGMP hydrolysis by activated phosphodiesterase resulting in local saturation. We find that (i) the nonlinear relationships between second messengers and current at the plasma membrane, and the cGMP hydrolysis saturation effects, play a major role in stabilizing the system; (ii) the presence of a physical space where the second messengers move by Brownian motion contributes to stabilization of the photoresponse; and (iii) keeping Ca(2+) at its dark level has only a minor effect on the variability of the system. The effects of diffusion, nonlinearity, and saturation synergize in reducing variability, supporting the notion that the observed high fidelity of the photoresponse is the result of global system function of phototransduction.

  13. Key Factors for Determining Risk of Groundwater Impacts Due to Leakage from Geologic Carbon Sequestration Reservoirs

    Energy Technology Data Exchange (ETDEWEB)

    Carroll, Susan [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Keating, Elizabeth [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Mansoor, Kayyum [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Dai, Zhenue [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Sun, Yunwei [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Trainor-Guitton, Whitney [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Brown, Chris [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Bacon, Diana [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2014-01-06

    The National Risk Assessment Partnership (NRAP) is developing a science-based toolset for the analysis of potential impacts to groundwater chemistry from CO2 injection (www.netldoe.gov/nrap). The toolset adopts a stochastic approach in which predictions address uncertainties in shallow underwater and leakage scenarios. It is derived from detailed physics and chemistry simulation results that are used to train more computationally efficient models,l referred to here as reduced-order models (ROMs), for each component system. In particular, these tools can be used to help regulators and operators understand the expected sizes and longevity of plumes in pH, TDS, and dissolved metals that could result from a leakage of brine and/or CO2 from a storage reservoir into aquifers. This information can inform, for example, decisions on monitoring strategies that are both effective and efficient. We have used this approach to develop predictive reduced-order models for two common types of reservoirs, but the approach could be used to develop a model for a specific aquifer or other common types of aquifers. In this paper we describe potential impacts to groundwater quality due to CO2 and brine leakage, discuss an approach to calculate thresholds under which "no impact" to groundwater occurs, describe the time scale for impact on groundwater, and discuss the probability of detecting a groundwater plume should leakage occur.

  14. LEAFY COTYLEDON1-CASEIN KINASE I-TCP15-PHYTOCHROME INTERACTING FACTOR4 Network Regulates Somatic Embryogenesis by Regulating Auxin Homeostasis1[OPEN

    Science.gov (United States)

    Min, Ling; Hu, Qin; Li, Yaoyao; Xu, Jiao; Ma, Yizan; Zhu, Longfu; Yang, Xiyan; Zhang, Xianlong

    2015-01-01

    Somatic embryogenesis (SE) is an efficient tool for the propagation of plant species and also, a useful model for studying the regulatory networks in embryo development. However, the regulatory networks underlying the transition from nonembryogenic callus to somatic embryos during SE remain poorly understood. Here, we describe an upland cotton (Gossypium hirsutum) CASEIN KINASE I gene, GhCKI, which is a unique key regulatory factor that strongly affects SE. Overexpressing GhCKI halted the formation of embryoids and plant regeneration because of a block in the transition from nonembryogenic callus to somatic embryos. In contrast, defective GhCKI in plants facilitated SE. To better understand the mechanism by which GhCKI regulates SE, the regulatory network was analyzed. A direct upstream negative regulator protein, cotton LEAFY COTYLEDON1, was identified to be targeted to a cis-element, CTTTTC, in the promoter of GhCKI. Moreover, GhCKI interacted with and phosphorylated cotton CINCINNATA-like TEOSINTE BRANCHED1-CYCLOIDEA-PCF transcription factor15 by coordinately regulating the expression of cotton PHYTOCHROME INTERACTING FACTOR4, finally disrupting auxin homeostasis, which led to increased cell proliferation and aborted somatic embryo formation in GhCKI-overexpressing somatic cells. Our results show a complex process of SE that is negatively regulated by GhCKI through a complex regulatory network. PMID:26491146

  15. LEAFY COTYLEDON1-CASEIN KINASE I-TCP15-PHYTOCHROME INTERACTING FACTOR4 Network Regulates Somatic Embryogenesis by Regulating Auxin Homeostasis.

    Science.gov (United States)

    Min, Ling; Hu, Qin; Li, Yaoyao; Xu, Jiao; Ma, Yizan; Zhu, Longfu; Yang, Xiyan; Zhang, Xianlong

    2015-12-01

    Somatic embryogenesis (SE) is an efficient tool for the propagation of plant species and also, a useful model for studying the regulatory networks in embryo development. However, the regulatory networks underlying the transition from nonembryogenic callus to somatic embryos during SE remain poorly understood. Here, we describe an upland cotton (Gossypium hirsutum) CASEIN KINASE I gene, GhCKI, which is a unique key regulatory factor that strongly affects SE. Overexpressing GhCKI halted the formation of embryoids and plant regeneration because of a block in the transition from nonembryogenic callus to somatic embryos. In contrast, defective GhCKI in plants facilitated SE. To better understand the mechanism by which GhCKI regulates SE, the regulatory network was analyzed. A direct upstream negative regulator protein, cotton LEAFY COTYLEDON1, was identified to be targeted to a cis-element, CTTTTC, in the promoter of GhCKI. Moreover, GhCKI interacted with and phosphorylated cotton CINCINNATA-like TEOSINTE BRANCHED1-CYCLOIDEA-PCF transcription factor15 by coordinately regulating the expression of cotton PHYTOCHROME INTERACTING FACTOR4, finally disrupting auxin homeostasis, which led to increased cell proliferation and aborted somatic embryo formation in GhCKI-overexpressing somatic cells. Our results show a complex process of SE that is negatively regulated by GhCKI through a complex regulatory network.

  16. Identification and transcript profiles of citrus growth-regulating factor genes involved in the regulation of leaf and fruit development.

    Science.gov (United States)

    Liu, Xiao; Guo, Ling-Xia; Jin, Long-Fei; Liu, Yong-Zhong; Liu, Tao; Fan, Yu-Hua; Peng, Shu-Ang

    2016-10-01

    Growth-regulating factor (GRF) is an important protein in GA-mediated response, with key roles in plant growth and development. However, it is not known whether or how the GRF proteins in citrus to regulate organ size. In this study, nine citrus GRF genes (CsGRF1-9) were validated from the 'Anliu' sweet orange (AL, Citrus sinensis cv. Anliu) by PCR amplification. They all contain two conserved motifs (QLQ and WRC) and have 3-4 exons. The transcript levels of genes were detected by qRT-PCR. Transcript analysis showed that (1) CsGRF 1, 2, 5, 6, 7, and 9 expressed predominantly in young leaf, CsGRF 3 and 4 expressed predominantly in fruit immature juice sacs and CsGRF 8 expressed predominantly in root; (2) all citrus GRF genes had significantly higher expression in young leaves than mature leaf; (3) in juice sacs, the transcript levels of CsGRF1, 4, 5, 6, and 8 increased significantly while the transcript levels of CsGRF2, 3, 7, and 9 had no significant change from 80 DAF to 100 DAF. Besides, GA3 treatment did not affect the transcript levels of CsGRF5 and CsGRF6 but significantly increased the transcript levels of the other seven CsGRF genes in young leaves. These results suggested that all CsGRF genes involve in the leaf development, CsGRF1, 4, 5, 6, and 8 act developmentally whilst CsGRF2, 3, 7, and 9 play fundamental roles in fruit cell enlargement, which may be through GA pathway or GA-independent pathway.

  17. THE CLASSIFICATION OF UNCERTAINTY OF THE KEY FACTORS PRICING IN TOURISM SPHERE

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    N. Sagalakova

    2015-10-01

    Full Text Available Specific characteristics of non-productive processes in the sphere of tourism and their difference from processes of the production sphere are investigated. Features of the pricing process at the tourism enterprise are analyzed. The main problems at implementation of model of the optimum price formation of a tourism product are identified. Classification of factors of pricing at the tourism enterprise is constructed. For the comparative analysis all factors of influence on pricing process, it is possible to divide into groups on the following classification signs: controllability (controllable and uncontrollable; accessory to system (internal and external; quantification (quantitative and qualitative; stability (stable and unstable. Interpretation to the main types of uncertain parameters, which exert impact on the price of a tourism product, is given. The accounting of uncertainty of the price when forming a tourism product will allow to construct adequate forecasts on the basis of which effective decisions concerning management of the pricing process at the tourism enterprise will be made.

  18. Organisation as a key factor in Localised Agri-Food Systems (LAFS

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    Corrado Giacomini

    2015-05-01

    Full Text Available Most studies of Localised Agri-Food Systems (LAFS focus on the localised concentration of members and firms, and pay less attention to organisational factors, particularly those of an exogenous nature. This paper focuses on the role of organisation in a LAFS, assessing the efficacy of EU organisational measures aimed at strengthening the concentration of supply from the recent CAP reform 2014-2020. The paper has three sections. Part One describes the evolution of the concept of LAFS. Part Two examines the leading role played by institutions in organising relationships between firms in a LAFS. The example provided is that of the measures affecting the organisation of supply introduced by the recent CAP reform, 2014-2020. It makes particular reference to the Distretto del pomodoro da industria – Nord Italia (‘Industrial Tomato District – Northern Italy’. Part Three describes how organisational factors can lead to the creation of a LAFS, while the criterion of proximity is necessary but not sufficient.

  19. The Extent of Satisfaction on the Key Factors that Affect Learner Motivation

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    Ambreen Shahriar

    2011-10-01

    Full Text Available This paper is based on a small-scale research conducted at the Institute of English, University of Sindh, Pakistan. The research participants include the students of B.A. (Hons. Part- II, whohad studied English language as a subject during B.A. (Hons. Part- I as well. The data was collected through questionnaires, which asked questions related to English language learners’ satisfaction on their language teacher, teaching learning environment, syllabus, and testing and assessment system, which are considered as the most factors that can affect and enhance learner motivation. The extent of their satisfaction, that they showed, in turn explains their motivation towards learning English language. The findings of the research include learning of English for both integrative and instrumental reasons with for getting importance as the most commonly chosen reason. 100% students showed willingness to attend the language class, yet a number of them find it boring and gave suggestions related to improvement. Students showed a lot less satisfaction towards their teacher and the teaching method and suggested proper teacher training along with some other things.Suggestions are also given on the improvement of the content of syllabus, yet it needs further investigation. The most dissatisfying factor brought forward by this research is the assessment system, so the research definitely calls for the introduction of a proper improved assessment system. This research paves way for future research as it raises a number of issues and questions for researchers to address.

  20. Effects of specific key environmental factors on the life expectancy of optical data carriers

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    Drago Kunej

    2011-01-01

    Full Text Available In recent years, the concept of content preservation rather than carrier preservation has become the norm with regard to long-term digital preservation. Nonetheless, the life expectancy of digital carriers is important because, in addition to other digital system parameters, it determines the migration time of digital content. In general, a cleaner,cooler, drier, and more stable environment extends the life expectancy, and appropriate protection of individual types of carriers is based on understanding the vulnerability of the carrier and consequently on providing optimal storage conditions and appropriate handling. This paper presents the effects of specific environmental factors (i.e., temperature, humidity, and light on the life expectancy of physical digital recording media, with an emphasis on optical media. Although optical discs are just one of the various methods of digital data storage today, they continue to be a popular archive medium. It should be noted that optical discs are not permanent recording media, as is often wrongly believed, and that their life expectancy is significantly influenced by environmental factors. At the ZRC SAZU Institute of Ethnomusicology, an experiment was conducted to analyze the durability of digital records saved on CD-Rs that were exposed to light in everyday working conditions. The results showed that exposing recordable optical discs to light, especially direct sunlight, can result in complete destruction of the data recorded within a few days or weeks. This confirmed the importance of careful handling, appropriate storage, and regular testing of digital carriers.

  1. Developing Talented Soccer Players: An Analysis of Socio-Spatial Factors as Possible Key Constraints

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    Serra-Olivares Jaime

    2016-12-01

    Full Text Available Most studies on the identification and development of soccer talent have been one-dimensional in nature. Although some multi-dimensional analyses have been conducted, few research studies have assessed in any depth the socio-spatial factors influencing talent development. The aim of this particular study was to analyse variations in the international representation of clubs (n = 821 and countries (n = 59 in the development of players who took part in the 2014 FIFA Soccer World Cup. Clubs and countries were ranked and divided into quartiles according to the number of players developed between the ages of 15 and 21 (clubs and countries that developed players for at least three years between these ages and the number of official league matches played by these players up to the age of 23. Significant variations were observed between clubs in terms of the number of developed players who took part in the World Cup and the number of official league matches played by these players up to the age of 23 (p < .05, and also between countries (p < .05. The findings reveal the need to carry out more in-depth studies into the type of training and competition engaged in by elite players in the period of development between the ages of 15 and 21. It may be the case that these factors are potentially decisive socio-spatial constraints in the development of soccer talent.

  2. Use of wild–caught individuals as a key factor for success in vertebrate translocations

    Energy Technology Data Exchange (ETDEWEB)

    Rummel, L.; MartInez-AbraIn, A.; Mayol, J.; Ruiz-Olmo, J.; Mañas, F.; Jimenez, J.; Gomez, J.A.; Oro, D.

    2016-07-01

    Success of vertebrate translocations is crucial to improve efficacy and efficiency of conservation actions but it is often difficult to assess because negative results (failed translocations) are seldom published. We developed surveys and sent them to heads of conservation services in three major Spanish Mediterranean regions. The purpose of our surveys was to determine which methodological factor, that could easily be implemented in practice, was more influential for translocation success. These factors included the origin of translocated individuals (captive or wild) and translocation effort (propagule size and program duration). After analyzing 83 programs, corresponding to 34 different vertebrate species, by means of generalized linear mixed modelling, we found that ‘origin’ was more relevant for translocation success than ‘effort’, although we could not rule out some role of translocation effort. Variance in success of translocation programs involving individuals from wild sources was smaller and consequently results more predictable. Origin interacted with taxa so that success was higher when using wild birds and especially wild fish and mammals, but not when releasing reptiles. Hence, we suggest that, for any given effort, translocation results will be better for most vertebrate taxa if individuals from wild sources are used. When this is not feasible, managers should release captive–reared individuals for a long number of years rather than a short number of years. (Author)

  3. An Analysis of Key Factors for the Success of the Communal Management of Knowledge

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    Bourdon, Isabelle

    2008-01-01

    This paper explores the links between Knowledge Management and new community-based models of the organization from both a theoretical and an empirical perspective. From a theoretical standpoint, we look at Communities of Practice (CoPs) and Knowledge Management (KM) and explore the links between the two as they relate to the use of information systems to manage knowledge. We begin by reviewing technologically supported approaches to KM and introduce the idea of "Systemes d'Aide a la Gestion des Connaissances" SAGC (Systems to aid the Management of Knowledge). Following this we examine the contribution that communal structures such as CoPs can make to intraorganizational KM and highlight some of 'success factors' for this approach to KM that are found in the literature. From an empirical standpoint, we present the results of a survey involving the Chief Knowledge Officers (CKOs) of twelve large French businesses; the objective of this study was to identify the factors that might influence the success of such a...

  4. The HIV/AIDS Epidemic in the Dominican Republic: Key Contributing Factors.

    Science.gov (United States)

    Rojas, Patria; Malow, Robert; Ruffin, Beverly; Rothe, Eugenio M; Rosenberg, Rhonda

    2011-01-01

    This article reviews HIV/AIDS epidemiological data and recent research conducted in the Dominican Republic, with a focus on explaining the variability in estimated seroincidence and prevalence within the country. HIV seroprevalence estimates range from 1.0% (in the general population) to 11.0% among men who have sex with men (MSM). Some have indicated that the highest HIV seroprevalence occurs in Haitian enclaves called bateyes (US Agency for International Development [USAID], 2008), which are migrant worker shantytowns primarily serving the sugar industry in the Dominican Republic. Others report higher or comparable rates to the bateyes in areas related to the tourism and sex industries. As in other Caribbean and Latin American countries, reported HIV transmission in the Dominican Republic is predominantly due to unprotected heterosexual sex and the infection rate has been increasing disproportionally among women. The Dominican Republic represents two thirds of the Hispaniola island; the western one third is occupied by Haiti, the nation with the highest HIV prevalence in the western hemisphere. Although data is limited, it shows important differences in seroprevalence and incidence between these two countries, but commonalities such as poverty, gender inequalities, and stigma appear to be pivotal factors driving the epidemic. This article will discuss these and other factors that may contribute to the HIV epidemic in the Dominican Republic, as well as highlight the gaps in the literature and provide recommendations to guide further work in this area, particularly in the role of governance in sustainable HIV prevention.

  5. Appraising the e-readiness of online learning facilitators: key human factors

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    L. Vermeulen

    2008-07-01

    Full Text Available Higher education institutions in South Africa have undergone a number of changes over the past few years. These changes brought about inter alia changed work environments and job demands. One of the new job demands is the need to incorporate technology in teaching and learning, viz. e-learning. Not all job incumbents, however, adapted successfully to these changes, particularly with regard to e-readiness. Such a lack in e-readiness is likely to influence the effectiveness with which an academic employee will fulfil his/her online learning duties. Therefore, it is important to find solutions to overcome the lack of e-readiness. This article will focus on the role of human resource appraisal, in order to assess the e-readiness of online learning facilitators with a view to improving their online skills and capacity. A number of human factors that can play a role in employee performance and motivation, namely learning styles, personal profile patterns, and pace and style of technology adoption will be briefly outlined, in order to determine the role that these factors could play in assessing the e-readiness of online learning facilitators.

  6. KEY FACTORS AND TIMING PATTERNS IN THE TENNIS FOREHAND OF DIFFERENT SKILL LEVELS

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    Johannes Landlinger

    2010-12-01

    Full Text Available The main purpose of the present study was to quantify and compare selected kinematic variables and their timing during the tennis forehand of different skill levels. An eight-camera 400 Hz, Vicon motion analysis system recorded kinematic data of six ATP- professionals (elite and seven high performance (HP players when shots were played cross court and down the line. Timing of the maximum angles, linear and angular velocities was measured prior to and after impact. A total of twelve strokes per subject were analyzed from the beginning to the end of horizontal racquet movement. Significant differences (p < 0.01 and large effect sizes were observed between elite and HP players in the timing of maximum pelvis (-0.075 ± 0.008 vs. -0.093 ± 0.012 s and trunk angular velocities (-0.057 ± 0.004 vs. -0.075 ± 0.011 s before impact. The elite group showed a tendency (p < 0.05 towards higher peak horizontal shoulder (3.0 ± 0.4 vs. 2.5 ± 0.4 m·s-1 and racquet velocities (33.1 ± 2.4 vs. 31.1 ± 1.9 m·s-1 compared to the HP players. Depending on the situation (cross court vs. down the line, different peak hip, racquet and separation angles were found for both groups. Similar peak values were detected between groups for maximum angular velocities and displacement of key variables that had been selected for analysis. The findings of this study can be vital for successful player development, improved performance or injury prevention. The later occurrence of maximum angular pelvis and trunk rotations were the main reasons for the tendency towards higher horizontal shoulder and racquet velocities in the elite group.

  7. Quorum sensing is a key regulator for the antifungal and biocontrol activity of chitinase-producing Chromobacterium sp. C61.

    Science.gov (United States)

    Kim, In Seon; Yang, Si Young; Park, Seur Kee; Kim, Young Cheol

    2017-01-01

    Chromobacterium sp. strain C61 has strong biocontrol activity; however, the genetic and biochemical determinants of its plant disease suppression activity are not well understood. Here, we report the identification and characterization of two new determinants of its biocontrol activity. Transposon mutagenesis was used to identify mutants that were deficient in fungal suppression. One of these mutants had an insertion in a homologue of depD, a structural gene in the dep operon, that encodes a protein involved in non-ribosomal peptide synthesis. In the second mutant, the insertion was in a homologue of the luxI gene, which encodes a homoserine lactone synthase. The luxI(-) and depD(-) mutants had no antifungal activity in vitro and a dramatically reduced capacity to suppress various plant diseases in planta. Antifungal production and biocontrol were restored by complementation of the luxI(-) mutant. Other phenotypes associated with effective biological control, including motility and lytic enzyme secretion, were also affected by the luxI mutation. Biochemical analysis of ethyl acetate extracts of culture filtrates of the mutant and wild-type strains showed that a key antifungal compound, chromobactomycin, was produced by wild-type C61 and the complemented luxI(-) mutant, but not by the luxI(-) or depD(-) mutant. These data suggest that multiple biocontrol-related phenotypes are regulated by homoserine lactones in C61. Thus, quorum sensing plays an essential role in the biological control potential of diverse bacterial lineages. © 2016 BSPP and John Wiley & Sons Ltd.

  8. Circadian transcription factor BMAL1 regulates innate immunity against select RNA viruses.

    Science.gov (United States)

    Majumdar, Tanmay; Dhar, Jayeeta; Patel, Sonal; Kondratov, Roman; Barik, Sailen

    2017-02-01

    BMAL1 (brain and muscle ARNT-like protein 1, also known as MOP3 or ARNT3) belongs to the family of the basic helix-loop-helix (bHLH)-PAS domain-containing transcription factors, and is a key component of the molecular oscillator that generates circadian rhythms. Here, we report that BMAL1-deficient cells are significantly more susceptible to infection by two major respiratory viruses of the Paramyxoviridae family, namely RSV and PIV3. Embryonic fibroblasts from Bmal1(-/-) mice produced nearly 10-fold more progeny virus than their wild type controls. These results were supported by animal studies whereby pulmonary infection of RSV produced a more severe disease and morbidity in Bmal1(-/-)mice. These results show that BMAL1 can regulate cellular innate immunity against specific RNA viruses.

  9. IFN regulatory factor 8 is a key constitutive determinant of the morphological and molecular properties of microglia in the CNS.

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    Carsten Minten

    Full Text Available IFN regulatory factor (IRF 8 is a transcription factor that has a key role in the cellular response to IFN-γ and is pivotal in myeloid cell differentiation. Whether IRF8 plays a role in the development and function of microglia, the tissue-resident myeloid cells of the brain, is unknown. Here, we show IRF8 is a constitutively produced nuclear factor in microglia, which suggested that IRF8 might also be a key homeostatic transcriptional determinant of the microglial cell phenotype. In support of this, in mice with a targeted disruption of the IRF8 gene, microglia were increased in number and showed gross alterations in morphology and surface area. In situ analysis of some key myeloid markers revealed that IRF8-deficient microglia had significantly reduced levels of Iba1, but increased levels of CD206 (mannose receptor and F4/80 as well as increased tomato lectin binding. Analysis of microglia ex vivo revealed IRF8-deficient microglia had significantly increased levels of CD45, CD11b and F4/80, but significantly decreased levels of the chemokine receptors CCR2, CCR5 and CX3CR1. The known involvement of some of these molecular markers in membrane dynamics and phagocytosis led us to examine the phagocytic capacity of cultured IRF8-deficient microglia, however, this was found to be similar to wild type microglia. We conclude IRF8 is a constitutively produced nuclear factor in resident microglia of the CNS being a crucial transcriptional determinant of the phenotype of these cells in the healthy brain.

  10. Solution structure of the LIM-homeodomain transcription factor complex Lhx3/Ldb1 and the effects of a pituitary mutation on key Lhx3 interactions.

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    Mugdha Bhati

    Full Text Available Lhx3 is a LIM-homeodomain (LIM-HD transcription factor that regulates neural cell subtype specification and pituitary development in vertebrates, and mutations in this protein cause combined pituitary hormone deficiency syndrome (CPHDS. The recently published structures of Lhx3 in complex with each of two key protein partners, Isl1 and Ldb1, provide an opportunity to understand the effect of mutations and posttranslational modifications on key protein-protein interactions. Here, we use small-angle X-ray scattering of an Ldb1-Lhx3 complex to confirm that in solution the protein is well represented by our previously determined NMR structure as an ensemble of conformers each comprising two well-defined halves (each made up of LIM domain from Lhx3 and the corresponding binding motif in Ldb1 with some flexibility between the two halves. NMR analysis of an Lhx3 mutant that causes CPHDS, Lhx3(Y114C, shows that the mutation does not alter the zinc-ligation properties of Lhx3, but appears to cause a structural rearrangement of the hydrophobic core of the LIM2 domain of Lhx3 that destabilises the domain and/or reduces the affinity of Lhx3 for both Ldb1 and Isl1. Thus the mutation would affect the formation of Lhx3-containing transcription factor complexes, particularly in the pituitary gland where these complexes are required for the production of multiple pituitary cell types and hormones.

  11. [Change in the activity of the key gluconeogenesis enzymes in the rat liver and kidneys during the action of subextreme and extreme factors on the body].

    Science.gov (United States)

    Panin, L E; Kolosova, I E; Nechaev, Iu S

    1979-06-01

    The activity of glucogenesis key enzymes (phosphoenolpyruvate carboxinase, fructoso-1,6-siphosphatase, glucoso-6-phosphatase) of the rat liver and kidneys was studied simultaneously under the effect of extreme and subextreme factors on the organism. The low initial phosphoenolpyruvate carboxikinase activity in the liver and its high inductivity under extreme conditions suggest a role of this enzyme as limiting link in glyconeogenesis. The activity of phosphoenolpyruvate carboxinase in the kidneys is comparable to that of fructoso-1,6-diphosphatase; it is considerably higher than the activity of glucoso-6-phosphatase. The phosphoenolpyruvate carboxinase activity in the kidneys is 5--6 times higher than in the liver. The activity of phosphoenolpyruvate carboxinase and glucoso-6-phosphatase is increased under the effect of extreme factors, and that of fructoso-1,6-diphosphatase remains unchanged. The lack of clear synchronous changes in the activity of glucogenesis key enzymes in the liver and kidneys indicates that the cells of these organs do not provide the united operon for phosphoenolpyruvate carboxinase, fructoso-1,6-diphosphatase and glucoso-6-phosphatase with common regulation mechanism.

  12. KEY FACTORS THAT INFLUENCE THE PERFORMANCE PROPERTIES OF ARP/MCU SALTSTONE MIXES

    Energy Technology Data Exchange (ETDEWEB)

    Harbour, J.; Edwards, T.; Williams, V.

    2009-10-05

    At the Saltstone Production Facility (SPF), decontaminated salt solution (DSS) is combined with premix (a cementitious mixture of portland cement (PC), blast furnace slag (BFS) and Class F fly ash (FA)) in a Readco mixer to produce fresh (uncured) Saltstone. After transfer to the Saltstone Disposal Facility (SDF) the hydration reactions initiated during the contact of the premix and salt solution continue during the curing period to produce the hardened waste form product. The amount of heat generated from hydration and the resultant temperature increase in the vaults depend on the composition of the decontaminated salt solution being dispositioned as well as the grout formulation (mix design). This report details the results from Task 3 of the Saltstone Variability Study for FY09 which was performed to identify, and quantify when possible, those factors that drive the performance properties of the projected ARP/MCU Batches. A baseline ARP/MCU mix (at 0.60 water to cementitious materials (w/cm) ratio) was established and consisted of the normal premix composition and a salt solution that was an average of the projected compositions of the last three ARP/MCU batches developed by T. A. Le. This task introduced significant variation in (1) wt % slag, w/cm ratio, and wt % portland cement about the baseline mix and (2) the temperature of curing in order to better assess the dependence of the performance properties on these factors. Two separate campaigns, designated Phase 10 and Phase 11, were carried out under Task 3. Experimental designs and statistical analyses were used to search for correlation among properties and to develop linear models to predict property values based on factors such as w/cm ratio, slag concentration, and portland cement concentration. It turns out that the projected salt compositions contained relatively high amounts of aluminate (0.22 M) even though no aluminate was introduced due to caustic aluminate removal from High Level Waste. Previous

  13. Syntactic computation in the human brain: the degree of merger as a key factor.

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    Shinri Ohta

    Full Text Available Our goal of this study is to characterize the functions of language areas in most precise terms. Previous neuroimaging studies have reported that more complex sentences elicit larger activations in the left inferior frontal gyrus (L. F3op/F3t, although the most critical factor still remains to be identified. We hypothesize that pseudowords with grammatical particles and morphosyntactic information alone impose a construction of syntactic structures, just like normal sentences, and that "the Degree of Merger" (DoM in recursively merged sentences parametrically modulates neural activations. Using jabberwocky sentences with distinct constructions, we fitted various parametric models of syntactic, other linguistic, and nonlinguistic factors to activations measured with functional magnetic resonance imaging. We demonstrated that the models of DoM and "DoM+number of Search (searching syntactic features" were the best to explain activations in the L. F3op/F3t and supramarginal gyrus (L. SMG, respectively. We further introduced letter strings, which had neither lexical associations nor grammatical particles, but retained both matching orders and symbol orders of sentences. By directly contrasting jabberwocky sentences with letter strings, localized activations in L. F3op/F3t and L. SMG were indeed independent of matching orders and symbol orders. Moreover, by using dynamic causal modeling, we found that the model with a inhibitory modulatory effect for the bottom-up connectivity from L. SMG to L. F3op/F3t was the best one. For this best model, the top-down connection from L. F3op/F3t to L. SMG was significantly positive. By using diffusion-tensor imaging, we confirmed that the left dorsal pathway of the superior longitudinal and arcuate fasciculi consistently connected these regions. Lastly, we established that nonlinguistic order-related and error-related factors significantly activated the right (R. lateral premotor cortex and R. F3op/F3t

  14. Hepatocyte nuclear factor 4 alpha is a key factor related to depression and physiological homeostasis in the mouse brain.

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    Kyosuke Yamanishi

    Full Text Available Major depressive disorder (MDD is a common psychiatric disorder that involves marked disabilities in global functioning, anorexia, and severe medical comorbidities. MDD is associated with not only psychological and sociocultural problems, but also pervasive physical dysfunctions such as metabolic, neurobiological and immunological abnormalities. Nevertheless, the mechanisms underlying the interactions between these factors have yet to be determined in detail. The aim of the present study was to identify the molecular mechanisms responsible for the interactions between MDD and dysregulation of physiological homeostasis, including immunological function as well as lipid metabolism, coagulation, and hormonal activity in the brain. We generated depression-like behavior in mice using chronic mild stress (CMS as a model of depression. We compared the gene expression profiles in the prefrontal cortex (PFC of CMS and control mice using microarrays. We subsequently categorized genes using two web-based bioinformatics applications: Ingenuity Pathway Analysis and The Database for Annotation, Visualization, and Integrated Discovery. We then confirmed significant group-differences by analyzing mRNA and protein expression levels not only in the PFC, but also in the thalamus and hippocampus. These web tools revealed that hepatocyte nuclear factor 4 alpha (Hnf4a may exert direct effects on various genes specifically associated with amine synthesis, such as genes involved in serotonin metabolism and related immunological functions. Moreover, these genes may influence lipid metabolism, coagulation, and hormonal activity. We also confirmed the significant effects of Hnf4a on both mRNA and protein expression levels in the brain. These results suggest that Hnf4a may have a critical influence on physiological homeostasis under depressive states, and may be associated with the mechanisms responsible for the interactions between MDD and the dysregulation of

  15. INFORMATION AND COMMUNICATION TECHNOLOGIES AS A KEY FACTOR OF INNOVATIVE DEVELOPMENT OF HIGHER EDUCATION: GLOBAL DIMENSION

    Directory of Open Access Journals (Sweden)

    Oleksii S. Voronkin

    2016-10-01

    Full Text Available The paper presents the review of the most common indexes, characterizing the level of ICTs development in Ukraine: Global Competitiveness Index, Networked Readiness Index, Digital Opportunity Index, Global Opportunity Index, ICT Development Index, as well as the indicators like the number of Internet users, consumer prices for services of home Internet. Based on this analysis the level of ICTs development in Ukraine has been analyzed. The factors hindering the general ICTs development and the problems that accompany the use of ICT in higher education in Ukraine have been defined and systemized. Prospects of further development of ICT in education have been determined. The paper emphasizes that the authoritative international ratings should be used by the State in order to analyze the problematic aspects of the current policy, address and resolve these aspects, provide appropriate training of future professionals, and monitor the progress in this area.

  16. Olive (Olea europaea L.) tree nitrogen status is a key factor for olive oil quality.

    Science.gov (United States)

    Erel, Ran; Kerem, Zohar; Ben-Gal, Alon; Dag, Arnon; Schwartz, Amnon; Zipori, Isaac; Basheer, Loai; Yermiyahu, Uri

    2013-11-27

    The influence of macronutrient status on olive oil properties was studied for three years. Data were analyzed by a multivariate model considering N, P, K, and fruiting year as explanatory factors. Oil quality parameters were primarily associated with N concentration in leaves and fruits which increased with N in irrigation solution. The effect of P on oil quality was mainly indirect since increased P availability increased N accumulation. The potassium level had negligible effects. The oil phenolic content decreased linearly as a function of increased leaf N, indicating protein-phenol competition in leaves. The overall saturation level of the fatty acids decreased with fruit N, resulting in increased polyunsaturated fatty acids. Free fatty acids increased with increased levels of fruit N. High fruit load tended to reduce fruit N and subsequently improve oil quality. The effect of N on oil properties depended solely on its concentration in leaves or fruits, regardless of the cause.

  17. The Key Factors Affecting Tuber Development of Potato in vitro and the Relation with Protein Fractions

    Institute of Scientific and Technical Information of China (English)

    WANG Da-yong; LIAN Yong; ZHU De-wei

    2002-01-01

    According to previous analysis, some properties bounding up with tuber yield were investigated.The results showed that tuber average weight, plastid Mg2+ -ATPase activity, plastid Ca2+ -ATPase activity,mitochondria Mg2+-ATPase activity, total soluble protein content, tuber average diameter, and Q-enzyme activity were important factors determining the tuber yield. The linear regression equation was:Y = 0.5211 +0.0595X(1) + 0.8389X(2) + 0.0882X(3) - 0. 0073X(4) + 0. 1449X(5) + 0. 3510X(6) + 0. 0031X(7) -0.00003X(8) + 0.3412X(9)+ 0.0127X(10) + 0.2904X(11) + 0.0570X(12) + 0.0159X(13) + 0.3585X(14)+ 0.0134X(15) -0.1012X(16). At the same time, the relation between several important properties and soluble protein fractions were analyzed.

  18. Study on the Key Factor Parameters to Increase Productivity in Construction and Manufacturing Industries.

    Science.gov (United States)

    Almazyed, K.; Alaswad, A.; Olabi, A. G.

    2016-02-01

    Proper management of human and non-human resources in construction and manufacturing projects can give-in considerable savings in time and cost. Construction and Manufacturing industry faces issues in connection with problems related with productivity and the problems are usually connected with performance of employees. The performance of employees is affected by many factors. In this paper a survey was made on respondents who are employed various projects of Saudi Arabia. The researcher developed a theoretical framework from the existing research which was used as a Model to collect and analyze the field data to test the hypothesis. In this research activity three predictors (commitment, job satisfaction and job performance) for determining the change in productivity. The results highlight that commitment and job performance (respectively) are the two predictors which are explaining 37% of variation in the productivity of the companies. The results also show that Job Satisfaction has no role in the prediction of productivity.

  19. KEY FACTORS IN THE MANAGEMENT OF HORIZONTALLY INTEGRATED STRUCTURE OF MEDICAL SERVICES COMPANIES

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    Ivan Doshkov

    2017-02-01

    Full Text Available Marketing management in the sphere of health services is an activity, which has to do with evaluation of the potential (economic, demographic, morbidity etc. in a given geographical region and with outlining the framework of a competitive and profitable business. For the provision of effective management, a thorough economic analysis of the healthcare activities is necessary. With view to optimization of the results, economic evaluation at different levels needs to be made, including systematic consideration of the factors, which influence the decision for directing the resources to a given alternative use at the expense of other use. The management of a healthcare enterprise is successful, only if the management of its individual units is successful and if they work in line with one another for the achievement of the common targets of the organization.

  20. Motivation and engagement in computer-based learning tasks: investigating key contributing factors

    Directory of Open Access Journals (Sweden)

    Michela Ott, Mauro Tavella

    2010-04-01

    Full Text Available This paper, drawing on a research project concerning the educational use of digital mind games with primary school students, aims at giving a contribution to the understanding of which are the main factors influencing student motivation during computer-based learning activities. It puts forward some ideas and experience based reflections, starting by considering digital games that are widely recognized as the most promising ICT tools to enhance student motivation. The project results suggest that student genuine engagement in learning activities is mainly related to the actual possession of the skills and of the cognitive capacities needed to perform the task. In this perspective, cognitive overload should be regarded as one of the main reasons contributing to hinder student motivation and, consequently, should be avoided. Other elements such as game attractiveness and experimental setting constraints resulted to have a lower effect on student motivation.

  1. Merkel Cell Carcinoma: An Update of Key Imaging Techniques, Prognostic Factors, Treatment, and Follow-up.

    Science.gov (United States)

    Llombart, B; Kindem, S; Chust, M

    2017-03-01

    Merkel cell carcinoma, though rare, is one of the most aggressive tumors a dermatologist faces. More than a third of patients with this diagnosis die from the disease. Numerous researchers have attempted to identify clinical and pathologic predictors to guide prognosis, but their studies have produced inconsistent results. Because the incidence of Merkel cell carcinoma is low and it appears in patients of advanced age, prospective studies have not been done and no clear treatment algorithm has been developed. This review aims to provide an exhaustive, up-to-date account of Merkel cell carcinoma for the dermatologist. We describe prognostic factors and the imaging techniques that are most appropriate for evaluating disease spread. We also discuss current debates on treating Merkel cell carcinoma. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

  2. POSITIONING KNOWLEDGE MANAGEMENT AS KEY SUCCESS FACTOR IN THE GROWTH OF COOPERATIVES IN MALAYSIA

    Directory of Open Access Journals (Sweden)

    Yeop Hussin Bidin

    2007-01-01

    Full Text Available Economic and business challenges in the new millennium have shaped the manner cooperative movement in Malaysia charts its future outlook. After almost 82 years, a national policy was launched by the Government on January 2004 to assist in the comprehensive development of the cooperative movement. The National CooperativePolicy (NCP will ensure that the huge resources of the cooperatives can be harnessed to generate and contribute to the economic growth of the country. However, in the light of many issues such as weak structure and the absence of good corporate governance in some cooperatives, the present Cooperative Act 1993 is being reviewed and several new provisions would be added to increase supervision, monitoring and enforcement against existing cooperatives in alaysia. It is quite imperative that by regulating the operation of cooperatives will require also the managing of intellectual and human capital assets that exist in the movement. Through establishing a framework and terms of reference such that fundamental elements of knowledge management can be instilled areprerequisites to developing innovativeness in this growing economic sector. The sharing of knowledge among the cooperatives will eventually produce better and more educated human resources that are able to experience greater control over the works and the administration of their quality working life. Structural analysis of the cooperative movement indicates the significant influence of knowledge management in sustaining its future growth given the timely introduction of the NCP. Thus, measures taken to underline this influence will also be addressed to represent the cooperative movement's readiness to face economic and business challenges in Malaysia.

  3. Hydrophobic environment is a key factor for the stability of thermophilic proteins.

    Science.gov (United States)

    Gromiha, M Michael; Pathak, Manish C; Saraboji, Kadhirvel; Ortlund, Eric A; Gaucher, Eric A

    2013-04-01

    The stability of thermophilic proteins has been viewed from different perspectives and there is yet no unified principle to understand this stability. It would be valuable to reveal the most important interactions for designing thermostable proteins for such applications as industrial protein engineering. In this work, we have systematically analyzed the importance of various interactions by computing different parameters such as surrounding hydrophobicity, inter-residue interactions, ion-pairs and hydrogen bonds. The importance of each interaction has been determined by its predicted relative contribution in thermophiles versus the same contribution in mesophilic homologues based on a dataset of 373 protein families. We predict that hydrophobic environment is the major factor for the stability of thermophilic proteins and found that 80% of thermophilic proteins analyzed showed higher hydrophobicity than their mesophilic counterparts. Ion pairs, hydrogen bonds, and interaction energy are also important and favored in 68%, 50%, and 62% of thermophilic proteins, respectively. Interestingly, thermophilic proteins with decreased hydrophobic environments display a greater number of hydrogen bonds and/or ion pairs. The systematic elimination of mesophilic proteins based on surrounding hydrophobicity, interaction energy, and ion pairs/hydrogen bonds, led to correctly identifying 95% of the thermophilic proteins in our analyses. Our analysis was also applied to another, more refined set of 102 thermophilic-mesophilic pairs, which again identified hydrophobicity as a dominant property in 71% of the thermophilic proteins. Further, the notion of surrounding hydrophobicity, which characterizes the hydrophobic behavior of residues in a protein environment, has been applied to the three-dimensional structures of elongation factor-Tu proteins and we found that the thermophilic proteins are enriched with a hydrophobic environment. The results obtained in this work highlight the

  4. A Key Role for Leukemia Inhibitory Factor in C26 Cancer Cachexia*

    Science.gov (United States)

    Seto, Danielle N.; Kandarian, Susan C.; Jackman, Robert W.

    2015-01-01

    Cachexia is an exacerbating event in many types of cancer that is strongly associated with a poor prognosis. We have identified cytokine, signaling, and transcription factors that are required for cachexia in the mouse C26 colon carcinoma model of cancer. C2C12 myotubes treated with conditioned medium from C26 cancer cells induced atrophy and activated a STAT-dependent reporter gene but not reporter genes dependent on SMAD, FOXO, C/EBP, NF-κB, or AP-1. Of the gp130 family members IL-11, IL-6, oncostatin M (OSM), and leukemia inhibitory factor (LIF), only OSM and LIF were sufficient to activate the STAT reporter in myotubes. LIF was elevated in C26 conditioned medium (CM), but IL-6, OSM, TNFα, and myostatin were not. A LIF-blocking antibody abolished C26 CM-induced STAT reporter activation, STAT3 phosphorylation, and myotube atrophy but blocking antibodies to IL-6 or OSM did not. JAK2 inhibitors also blocked C26 CM-induced STAT reporter activation, STAT3 phosphorylation, and atrophy in myotubes. LIF at levels found in the C26 CM was sufficient for STAT reporter activation and atrophy in myotubes. In vivo, an increase in serum LIF preceded the increase in IL-6 in mice with C26 tumors. Overexpression of a dominant negative Stat3Cβ-EGFP gene in myotubes and in mouse muscle blocked the atrophy caused by C26 CM or C26 tumors, respectively. Taken together, these data support an important role of LIF-JAK2-STAT3 in C26 cachexia and point to a therapeutic approach for at least some types of cancer cachexia. PMID:26092726

  5. A Key Role for Leukemia Inhibitory Factor in C26 Cancer Cachexia.

    Science.gov (United States)

    Seto, Danielle N; Kandarian, Susan C; Jackman, Robert W

    2015-08-07

    Cachexia is an exacerbating event in many types of cancer that is strongly associated with a poor prognosis. We have identified cytokine, signaling, and transcription factors that are required for cachexia in the mouse C26 colon carcinoma model of cancer. C2C12 myotubes treated with conditioned medium from C26 cancer cells induced atrophy and activated a STAT-dependent reporter gene but not reporter genes dependent on SMAD, FOXO, C/EBP, NF-κB, or AP-1. Of the gp130 family members IL-11, IL-6, oncostatin M (OSM), and leukemia inhibitory factor (LIF), only OSM and LIF were sufficient to activate the STAT reporter in myotubes. LIF was elevated in C26 conditioned medium (CM), but IL-6, OSM, TNFα, and myostatin were not. A LIF-blocking antibody abolished C26 CM-induced STAT reporter activation, STAT3 phosphorylation, and myotube atrophy but blocking antibodies to IL-6 or OSM did not. JAK2 inhibitors also blocked C26 CM-induced STAT reporter activation, STAT3 phosphorylation, and atrophy in myotubes. LIF at levels found in the C26 CM was sufficient for STAT reporter activation and atrophy in myotubes. In vivo, an increase in serum LIF preceded the increase in IL-6 in mice with C26 tumors. Overexpression of a dominant negative Stat3Cβ-EGFP gene in myotubes and in mouse muscle blocked the atrophy caused by C26 CM or C26 tumors, respectively. Taken together, these data support an important role of LIF-JAK2-STAT3 in C26 cachexia and point to a therapeutic approach for at least some types of cancer cachexia.

  6. Sexual Education of Young University Students: Some Key Factors and Challenges

    Directory of Open Access Journals (Sweden)

    María Luisa Preinfalk-Fernández

    2015-09-01

    Full Text Available In general terms, higher education institutions not only face the challenge of teaching some discipline to their students, but also of strengthening their life skills. Since university students are majorly young, the desire to provide them with comprehensive training is particularly relevant, since it is at this stage of life when they model their behavior for adulthood. In this training challenge, sex education plays a decisive role. This research paper aims to show that factors such as information gaps, unsafe sexual practices, myths, prejudices and stereotypes persist in the university student population and do not allow them to live sexuality safely and pleasurable. Moreover, these factors show Costa Rica’s need for higher education institutions to strengthen their actions in sex education. A brief tour is made from various angles through the sexual experiences of the university student population, namely: their perceptions about the training requirements they face, their main concerns, their unsafe sexual practices, their inability to negotiate sexual and reproductive health care, their knowledge and preventive practices in terms of sexual and reproductive health, the existence of forms of violence within university life, among others. The findings set out are part of a larger research, based on contributions from the theory of gender and social constructionism. Such data derives from the application of a questionnaire to a sample stratified by unequal conglomerates composed of 766 regular students of undergraduate courses, enrolled in the first cycle of 2011, at Universidad Nacional de Costa Rica. The margin of error is 1.5% and the confidence level, 95%. The data was tabulated using the software CSPRO and analyzed with software R. After obtaining the results of the instrument’s application, a focus group was created with the participation of professionals who teach sexuality courses in this university, and two other groups with

  7. Key factors controlling microbial community response after a fire: importance of severity and recurrence

    Science.gov (United States)

    Lombao, Alba; Barreiro, Ana; Martín, Ángela; Díaz-Raviña, Montserrat

    2015-04-01

    Microorganisms play an important role in forest ecosystems, especially after fire when vegetation is destroyed and soil is bared. Fire severity and recurrence might be one of main factors controlling the microbial response after a wildfire but information about this topic is scarce. The aim of this study is to evaluate the influence of fire regimen (recurrence and severity) on soil microbial community structure by means of the analysis of phospholipid fatty acid (PLFA). The study was performed with unburned and burned samples collected from the top layer of a soil affected by a high severity fire (Laza, NW Spain) heated under laboratory conditions at different temperatures (50°C, 75°C, 100°C, 125°C, 150°C, 175°C, 200°C, 300°C) to simulate different fire intensities; the process was repeated after further soil recovery (1 month incubation) to simulate fire recurrence. The soil temperature was measured with thermocouples and used to calculate the degree-hours as estimation of the amount of heat supplied to the samples (fire severity). The PLFA analysis was used to estimate total biomass and the biomass of specific groups (bacteria, fungi, gram-positive bacteria and gram-negative bacteria) as well as microbial community structure (PLFA pattern) and PLFA data were analyzed by means of principal component analysis (PCA) in order to identify main factors determining microbial community structure. The results of PCA, performed with the whole PLFA data set, showed that first component explained 35% of variation and clearly allow us to differentiate unburned samples from the corresponding burned samples, while the second component, explaining 16% of variation, separated samples according the heating temperature. A marked impact of fire regimen on soil microorganisms was detected; the microbial community response varied depending on previous history of soil heating and the magnitude of changes in the PLFA pattern was related to the amount of heat supplied to the

  8. Forkhead transcription factor foxe1 regulates chondrogenesis in zebrafish.

    Science.gov (United States)

    Nakada, Chisako; Iida, Atsumi; Tabata, Yoko; Watanabe, Sumiko

    2009-12-15

    Forkhead transcription factor (Fox) e1 is a causative gene for Bamforth-Lazarus syndrome, which is characterized by hypothyroidism and cleft palate. Applying degenerate polymerase chain reaction using primers specific for the conserved forkhead domain, we identified zebrafish foxe1 (foxe1). Foxe1 is expressed in the thyroid, pharynx, and pharyngeal skeleton during development; strongly expressed in the gill and weakly expressed in the brain, eye, and heart in adult zebrafish. A loss of function of foxe1 by morpholino antisense oligo (MO) exhibited abnormal craniofacial development, shortening of Meckel's cartilage and the ceratohyals, and suppressed chondrycytic proliferation. However, at 27 hr post fertilization, the foxe1 MO-injected embryos showed normal dlx2, hoxa2, and hoxb2 expression, suggesting that the initial steps of pharyngeal skeletal development, including neural crest migration and specification of the pharyngeal arch occurred normally. In contrast, at 2 dpf, a severe reduction in the expression of sox9a, colIIaI, and runx2b, which play roles in chondrocytic proliferation and differentiation, was observed. Interestingly, fgfr2 was strongly upregulated in the branchial arches of the foxe1 MO-injected embryos. Unlike Foxe1-null mice, normal thyroid development in terms of morphology and thyroid-specific marker expression was observed in foxe1 MO-injected zebrafish embryos. Taken together, our results indicate that Foxe1 plays an important role in chondrogenesis during development of the pharyngeal skeleton in zebrafish, probably through regulation of fgfr2 expression. Furthermore, the roles reported for FOXE1 in mammalian thyroid development may have been acquired during evolution.

  9. Key factors in work engagement and job motivation of teaching faculty at a university medical centre.

    Science.gov (United States)

    van den Berg, B A M; Bakker, Arnold B; Ten Cate, Th J

    2013-11-01

    This study reports about teacher motivation and work engagement in a Dutch University Medical Centre (UMC). We examined factors affecting the motivation for teaching in a UMC, the engagement of UMC Utrecht teaching faculty in their work, and their engagement in teaching compared with engagement in patient care and research. Based on a pilot study within various departments at the UMCU, a survey on teaching motivation and work engagement was developed and sent to over 600 UMCU teachers. About 50 % responded. Work engagement was measured by the Utrecht Work Engagement Scale, included in this survey. From a list of 22 pre-defined items, 5 were marked as most motivating: teaching about my own speciality, noticeable appreciation for teaching by my direct superior, teaching small groups, feedback on my teaching performance, and freedom to determine what I teach. Feedback on my teaching performance showed the strongest predictive value for teaching engagement. Engagement scores were relatively favourable, but engagement with patient care was higher than with research and teaching. Task combinations appear to decrease teaching engagement. Our results match with self-determination theory and the job demands-resources model, and challenge the policy to combine teaching with research and patient care.

  10. Endogenous Purification Reveals GREB1 as a Key Estrogen Receptor Regulatory Factor

    Directory of Open Access Journals (Sweden)

    Hisham Mohammed

    2013-02-01

    Full Text Available Estrogen receptor-α (ER is the driving transcription factor in most breast cancers, and its associated proteins can influence drug response, but direct methods for identifying interacting proteins have been limited. We purified endogenous ER using an approach termed RIME (rapid immunoprecipitation mass spectrometry of endogenous proteins and discovered the interactome under agonist- and antagonist-liganded conditions in breast cancer cells, revealing transcriptional networks in breast cancer. The most estrogen-enriched ER interactor is GREB1, a potential clinical biomarker with no known function. GREB1 is shown to be a chromatin-bound ER coactivator and is essential for ER-mediated transcription, because it stabilizes interactions between ER and additional cofactors. We show a GREB1-ER interaction in three xenograft tumors, and using a directed protein-protein approach, we find GREB1-ER interactions in half of ER+ primary breast cancers. This finding is supported by histological expression of GREB1, which shows that GREB1 is expressed in half of ER+ cancers, and predicts good clinical outcome. These findings reveal an unexpected role for GREB1 as an estrogen-specific ER cofactor that is expressed in drug-sensitive contexts.

  11. Illiteracy, Financial Insecurity and Loneliness as Key Factors for Depression in Elderly Population of Punjab

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    R. Kaur

    2014-06-01

    Full Text Available Geriatric depression is a common phenomenon in most of the elderly people worldwide as they all experience the same range of normal emotions. Current study is an endeavor in this context as studies on geriatric depression in Punjabi population are not available at all. A total of 210 elderly people above 60 years of age willingly participated in this study. Demographic data was collected by personal interview (after taking written consent from subjects under study. Statistical computations revealed that 11.43% elderly people suffered from severe depression. The statistical t-value (2.49 shows that there are significant differences in depression score between the rural areas and urban areas elderly population. Differences in depression between rural areas and old age homes are non-significant (t-value of 0.20 and difference in depression scores between urban and old age homes are again significant with t-value of 2.29.Results concluded that elderly people living in old age homes and rural areas are more depressed as compared to urban areas residents. Financial insecurity, loneliness, widow(er hood and illiteracy are major contributing factors in geriatric depression in Punjabi population of India.

  12. Health, Islam and Alternative Capitalism. Three possible Key Factors in Developing Somaliland

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    Daria Zizzola

    2012-02-01

    Full Text Available The main aim of this paper is to investigate the socio, political and economic dynamics that have occurred in Somaliland in the last decades. Even though this country is still unrecognized by the international community, Somaliland’s economy has undertaken an enduring growth, above all in the private entrepreneurial sector. The author argues that religion has had an important role in the Somali cultural and social identification. According to this assumption, the article analyzes the Islamic factor by showing how it has led to the creation of many alternative connections supported by mutual trust and religious solidarity among involved communities. These connections are somehow fulfilling the absence of political legitimacy while progressively substituting conventional routes of intra-national negotiation, like diplomacy. To confirm this tendency, specific arguments are drawn from Somaliland’s health sector. The health care system is considered a preferential index to evaluate the level of national development. Above all, the private non-profit sector gives some evidence of the Somali capacity of running competitive private businesses while multiplying simultaneously their resources and suppliers with a consequent increase in autonomy and efficiency. This successful compromise bears the fruits of Somali engagement and can be identified by their inexhaustible adaptability to adverse conditions and their ability to avoid, not deny, the rational rules imposed by external actors and their ostensible, insurmountable interests.

  13. Protein Adsorption Patterns and Analysis on IV Nanoemulsions—The Key Factor Determining the Organ Distribution

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    Mirko Jansch

    2012-12-01

    Full Text Available Intravenous nanoemulsions have been on the market for parenteral nutrition since the 1950s; meanwhile, they have also been used successfully for IV drug delivery. To be well tolerable, the emulsions should avoid uptake by the MPS cells of the body; for drug delivery, they should be target-specific. The organ distribution is determined by the proteins adsorbing them after injection from the blood (protein adsorption pattern, typically analyzed by two-dimensional polyacrylamide gel electrophoresis, 2-D PAGE. The article reviews the 2-D PAGE method, the analytical problems to be faced and the knowledge available on how the composition of emulsions affects the protein adsorption patterns, e.g., the composition of the oil phase, stabilizer layer and drug incorporation into the interface or oil core. Data were re-evaluated and compared, and the implications for the in vivo distribution are discussed. Major results are that the interfacial composition of the stabilizer layer is the main determining factor and that this composition can be modulated by simple processes. Drug incorporation affects the pattern depending on the localization of the drug (oil core versus interface. The data situation regarding in vivo effects is very limited; mainly, it has to be referred to in the in vivo data of polymeric nanoparticles. As a conclusion, determination of the protein adsorption patterns can accelerate IV nanoemulsion formulation development regarding optimized organ distribution and related pharmacokinetics.

  14. Thermal physical properties and key influence factors of phase change emulsion

    Institute of Scientific and Technical Information of China (English)

    XU Hui; YANG Rui; ZHANG Yinping; HUANG Zhe; LIN Jia; WANG Xin

    2005-01-01

    Latent functionally thermal fluids (LFTF) are a novel kind of heat storage and heat transfer fluids that include phase change microcapsule slurry and phase change emulsion (PCE). They have much greater apparent specific heats and higher heat transfer abilities in the phase change temperature range than conventional single-phase heat transfer fluids such as water. Thus they are advantageous in the field of the convective heat transfer enhancement and energy transport. In this paper, some thermal physical properties such as viscosity, fusion heat and apparent specific heat (cp) are measured, and the influences of some factors (such as selection of surfactants, preparation method, temperature, mixing ratio of surfactants and mass concentration of phase change material) on them are discussed. The study shows that: 1) the viscosity of the PCE prepared in the present work is lower than that reported in the literature; 2) its apparent specific heat value for the phase change temperature region is high and proportionally increases with the concentration of phase change material.

  15. THE QUALITY OF THE TOURIST DESTINATIONS A KEY FACTOR FOR INCREASING THEIR ATTRACTIVENESS

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    Daliborka Blazeska

    2015-12-01

    Full Text Available Taking into consideration that the tourism is extremely important for any country including Republic of Macedonia, it is necessary to pay attention to the quality of the tourist destinations and increasing of their attractiveness. So winners in the field of tourism will be those countries that have attractive tourist destination that will attract a lot of visitors. In this paper is defined the relationship between the factors of attractiveness of the destination and the achieving of competitiveness. In order to become competitive in the global market, the tourist destination has to be innovative and to continually search for new competitive advantages. Those kind of competitive advantages enable stable and long-term sustainable development of the tourist destination. In this paper special emphasis is put to the monitoring of the quality of the tourist destination with constant inquiries of the tourists (domestic and foreign regarding the most important segments of the quality of the tourist product which they are using, in order to perceive the satisfaction or the eventual dissatisfaction in order to be taken concrete strategies for the following period. The obtained results clearly confirm the dissatisfaction with the road infrastructure and signalization, the price of the services and the conditions for the stay, as well as the additional attractions that were expected to get.

  16. Pharmacy patronage: identifying key factors in the decision making process using the determinant attribute approach.

    Science.gov (United States)

    Franic, Duska M; Haddock, Sarah M; Tucker, Leslie Tootle; Wooten, Nathan

    2008-01-01

    To use the determinant attribute approach, a research method commonly used in marketing to identify the wants of various consumer groups, to evaluate consumer pharmacy choice when having a prescription order filled in different pharmacy settings. Cross sectional. Community independent, grocery store, community chain, and discount store pharmacies in Georgia between April 2005 and April 2006. Convenience sample of adult pharmacy consumers (n = 175). Survey measuring consumer preferences on 26 attributes encompassing general pharmacy site features (16 items), pharmacist characteristics (5 items), and pharmacy staff characteristics (5 items). 26 potential determinant attributes for pharmacy selection. 175 consumers were surveyed at community independent (n = 81), grocery store (n = 44), community chain (n = 27), or discount store (n = 23) pharmacy settings. The attributes of pharmacists and staff at all four pharmacy settings were shown to affect pharmacy patronage motives, although consumers frequenting non-community independent pharmacies were also motivated by secondary convenience factors, e.g., hours of operation, and prescription coverage. Most consumers do not perceive pharmacies as merely prescription-distribution centers that vary only by convenience. Prescriptions are not just another economic good. Pharmacy personnel influence pharmacy selection; therefore, optimal staff selection and training is likely the greatest asset and most important investment for ensuring pharmacy success.

  17. Epidermal growth factor receptor:a key manipulator in molecular pathways of malignant glioma

    Institute of Scientific and Technical Information of China (English)

    Changshu Ke

    2016-01-01

    The epidermal growth factor receptor (EGFR) is a member of the ErbB/EGFR family, including EGFR/Her1, ErbB2/Her2, ErbB-3/Her3, and ErbB-4/Her4. EGFR exerts its efects through the receptor tyrosine kinase phosphorylation and activation of important downstream signaling pathways in normal and neoplastic cels, mainly the Ras GTPase/MAP kinase (MAPK), STAT3, and phosphatidylinositide 3 kinase-AKT pathways. EGFR deregulation is common in malignant glioma, especialy primary glioblastoma, and exists in three forms: gene overexpression (amplification), autocrine efects of EGFR activation, and activating receptor mutation (EGFRvIII). However, some EGFR abnormalities have also been found in low-grade gliomas, including the nuclear localization of EGFR, expression in the microfoci of anaplastic transformation, and association with neovascularization in the mesenchyma of the glioma, which suggests that some unknown EGFR-related mechanisms are possibly responsible for its central role in the initiation and progression of malignant glioma. Uncovering these mechanisms wil have potential value in the development of radio-therapy, chemotherapy, and EGFR-targeted therapy for glioma.

  18. DCLK1 regulates pluripotency and angiogenic factors via microRNA-dependent mechanisms in pancreatic cancer.

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    Sripathi M Sureban

    Full Text Available Stem cell pluripotency, angiogenesis and epithelial-mesenchymal transition (EMT have been shown to be significantly upregulated in pancreatic ductal adenocarcinoma (PDAC and many other aggressive cancers. The dysregulation of these processes is believed to play key roles in tumor initiation, progression, and metastasis, and is contributory to PDAC being the fourth leading cause of cancer-related deaths in the US. The tumor suppressor miRNA miR-145 downregulates critical pluripotency factors and oncogenes and results in repressed metastatic potential in PDAC. Additionally, the miR-200 family regulates several angiogenic factors which have been linked to metastasis in many solid tumors. We have previously demonstrated that downregulation of DCLK1 can upregulate critical miRNAs in both in vitro and in vivo cancer models and results in downregulation of c-MYC, KRAS, NOTCH1 and EMT-related transcription factors. A recent report has also shown that Dclk1 can distinguish between normal and tumor stem cells in Apc (min/+ mice and that ablation of Dclk1(+ cells resulted in regression of intestinal polyps without affecting homeostasis. Here we demonstrate that the knockdown of DCLK1 using poly(lactide-co-glycolide-encapsulated-DCLK1-siRNA results in AsPC1 tumor growth arrest. Examination of xenograft tumors revealed, (a increased miR-145 which results in decreased pluripotency maintenance factors OCT4, SOX2, NANOG, KLF4 as well as KRAS and RREB1; (b increased let-7a which results in decreased pluripotency factor LIN28B; and (c increased miR-200 which results in decreased VEGFR1, VEGFR2 and EMT-related transcription factors ZEB1, ZEB2, SNAIL and SLUG. Specificity of DCLK1 post-transcriptional regulation of the downstream targets of miR-145, miR-200 and let-7a was accomplished utilizing a luciferase-based reporter assay. We conclude that DCLK1 plays a significant master regulatory role in pancreatic tumorigenesis through the regulation of multiple tumor

  19. The routine utilization of dental care during pregnancy in eastern China and the key underlying factors: a Hangzhou City study.

    Directory of Open Access Journals (Sweden)

    Wei Sun

    Full Text Available OBJECTIVES: Oral diseases are associated with adverse pregnancy outcomes. The routine utilization of dental care (RUDC during pregnancy is an effective way to improve pregnant women's oral health, and thus safeguard the health of their babies. As