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Sample records for regulated enhancers uncovers

  1. 77 FR 12227 - Long Term 2 Enhanced Surface Water Treatment Rule: Uncovered Finished Water Reservoirs; Public...

    Science.gov (United States)

    2012-02-29

    ... Water Treatment Rule: Uncovered Finished Water Reservoirs; Public Meeting AGENCY: Environmental... review of the uncovered finished water reservoir requirement in the Long Term 2 Enhanced Surface Water... uncovered finished water reservoir requirement and the agency's Six Year Review process. EPA also plans to...

  2. Uncovering transcriptional regulation of metabolism by using metabolic network topology

    DEFF Research Database (Denmark)

    Patil, Kiran Raosaheb; Nielsen, Jens

    2005-01-01

    in the metabolic network that follow a common transcriptional response. Thus, the algorithm enables identification of so-called reporter metabolites (metabolites around which the most significant transcriptional changes occur) and a set of connected genes with significant and coordinated response to genetic......Cellular response to genetic and environmental perturbations is often reflected and/or mediated through changes in the metabolism, because the latter plays a key role in providing Gibbs free energy and precursors for biosynthesis. Such metabolic changes are often exerted through transcriptional...... therefore developed an algorithm that is based on hypothesis-driven data analysis to uncover the transcriptional regulatory architecture of metabolic networks. By using information on the metabolic network topology from genome-scale metabolic reconstruction, we show that it is possible to reveal patterns...

  3. Uncovering packaging features of co-regulated modules based on human protein interaction and transcriptional regulatory networks

    Directory of Open Access Journals (Sweden)

    He Weiming

    2010-07-01

    Full Text Available Abstract Background Network co-regulated modules are believed to have the functionality of packaging multiple biological entities, and can thus be assumed to coordinate many biological functions in their network neighbouring regions. Results Here, we weighted edges of a human protein interaction network and a transcriptional regulatory network to construct an integrated network, and introduce a probabilistic model and a bipartite graph framework to exploit human co-regulated modules and uncover their specific features in packaging different biological entities (genes, protein complexes or metabolic pathways. Finally, we identified 96 human co-regulated modules based on this method, and evaluate its effectiveness by comparing it with four other methods. Conclusions Dysfunctions in co-regulated interactions often occur in the development of cancer. Therefore, we focussed on an example co-regulated module and found that it could integrate a number of cancer-related genes. This was extended to causal dysfunctions of some complexes maintained by several physically interacting proteins, thus coordinating several metabolic pathways that directly underlie cancer.

  4. Mapping posttranscriptional regulation of the human glycome uncovers microRNA defining the glycocode

    OpenAIRE

    Agrawal, Praveen; Kurcon, Tomasz; Pilobello, Kanoelani T.; Rakus, John F.; Koppolu, Sujeethraj; Liu, Zhongyin; Batista, Bianca S.; Eng, William S.; Hsu, Ku-Lung; Liang, Yaxuan; Mahal, Lara K.

    2014-01-01

    Carbohydrates (glycans) are complex cell surface molecules that control multiple aspects of cell biology, including cell–cell communication, cancer metastasis, and inflammation. Glycan biosynthesis requires the coordination of many enzymes, but how this is regulated is not well understood. Herein we show that microRNA (miRNA), small noncoding RNA, are a major regulator of cell surface glycosylation. We map miRNA expression onto carbohydrate signatures obtained by using lectin microarrays, a g...

  5. Uncovering transcriptional regulation of glycerol metabolism in Aspergilli through genome-wide gene expression data anlysis

    DEFF Research Database (Denmark)

    Salazar, Margarita Pena; Vongsangnak, Wanwipa; Panagiotou, Gianni

    2009-01-01

    Glycerol is catabolized by a wide range of microorganisms including Aspergillus species. To identify the transcriptional regulation of glycerol metabolism in Aspergillus, we analyzed data from triplicate batch fermentations of three different Aspergilli (Aspergillus nidulans, Aspergillus oryzae...... and Aspergillus niger) with glucose and glycerol as carbon sources. Protein comparisons and cross-analysis with gene expression data of all three species resulted in the identification of 88 genes having a conserved response across the three Aspergilli. A promoter analysis of the up-regulated genes led...... to the identification of a conserved binding site for a putative regulator to be 5′-TGCGGGGA-3′, a binding site that is similar to the binding site for Adr1 in yeast and humans. We show that this Adr1 consensus binding sequence was over-represented on promoter regions of several genes in A. nidulans, A. oryzae and A...

  6. Musical Intensity in Affect Regulation: Uncovering Hope and Resilience Through Heavy Music

    OpenAIRE

    Hereld, Diana Christine

    2016-01-01

    This thesis discusses the nature of music’s impact on identity, subjectivity, and the self. To better understand music’s role in promoting hope and resilience, I pinpoint how heavy, intense, and highly emotive music applied over distinct listening practices impacts the regulation of affect and self-destructive impulses in individuals who suffer from trauma, mental illness, or self-destructive behavior. This research also investigates the characteristic of intensity often found in heavy music ...

  7. Characterization of the serine acetyltransferase gene family of Vitis vinifera uncovers differences in regulation of OAS synthesis in woody plants

    Science.gov (United States)

    Tavares, Sílvia; Wirtz, Markus; Beier, Marcel P.; Bogs, Jochen; Hell, Rüdiger; Amâncio, Sara

    2015-01-01

    In higher plants cysteine biosynthesis is catalyzed by O-acetylserine(thiol)lyase (OASTL) and represents the last step of the assimilatory sulfate reduction pathway. It is mainly regulated by provision of O-acetylserine (OAS), the nitrogen/carbon containing backbone for fixation of reduced sulfur. OAS is synthesized by Serine acetyltransferase (SERAT), which reversibly interacts with OASTL in the cysteine synthase complex (CSC). In this study we identify and characterize the SERAT gene family of the crop plant Vitis vinifera. The identified four members of the VvSERAT protein family are assigned to three distinct groups upon their sequence similarities to Arabidopsis SERATs. Expression of fluorescently labeled VvSERAT proteins uncover that the sub-cellular localization of VvSERAT1;1 and VvSERAT3;1 is the cytosol and that VvSERAT2;1 and VvSERAT2;2 localize in addition in plastids and mitochondria, respectively. The purified VvSERATs of group 1 and 2 have higher enzymatic activity than VvSERAT3;1, which display a characteristic C-terminal extension also present in AtSERAT3;1. VvSERAT1;1 and VvSERAT2;2 are evidenced to form the CSC. CSC formation activates VvSERAT2;2, by releasing CSC-associated VvSERAT2;2 from cysteine inhibition. Thus, subcellular distribution of SERAT isoforms and CSC formation in cytosol and mitochondria is conserved between Arabidopsis and grapevine. Surprisingly, VvSERAT2;1 lack the canonical C-terminal tail of plant SERATs, does not form the CSC and is almost insensitive to cysteine inhibition (IC50 = 1.9 mM cysteine). Upon sulfate depletion VvSERAT2;1 is strongly induced at the transcriptional level, while transcription of other VvSERATs is almost unaffected in sulfate deprived grapevine cell suspension cultures. Application of abiotic stresses to soil grown grapevine plants revealed isoform-specific induction of VvSERAT2;1 in leaves upon drought, whereas high light- or temperature- stress hardly trigger VvSERAT2;1 transcription. PMID:25741355

  8. The bacterial two-hybrid system uncovers the involvement of acetylation in regulating of Lrp activity in Salmonella Typhimurium

    Directory of Open Access Journals (Sweden)

    Ran Qin

    2016-11-01

    Full Text Available Nε-lysine acetylation is an abundant and important Post-translational modification in bacteria. We used the bacterial two-hybrid system to screen the genome library of the Salmonella Typhimurium to identify potential proteins involved in acetyltransferase Pat - or deacetylase CobB-mediated acetylation. Then, the in vitro (deacetylation assays were used to validate the potential targets, such as STM14_1074, NrdF, RhaR. Lrp, a leucine-responsive regulatory protein and global regulator, was shown to interact with Pat. We further demonstrate that Lrp could be acetylated by Pat and deacetylated by NAD+-dependent CobB in vitro. Specifically, the conserved lysine residue 36 (K36 in helix-turn-helix (HTH DNA-binding domain of Lrp was acetylated. Acetylation of K36 impaired the function of Lrp through altering the affinity with the target promoter. The mutation of K36 in chromosome mimicking acetylation enhanced the transcriptional level of itself and attenuated the mRNA levels of Lrp-regulated genes including fimA, which was confirmed by yeast agglutination assay. These findings demonstrate that the acetylation regulates the DNA-binding activity of Lrp, suggesting that acetylation modification of transcription factors is a conserved regulatory manner to modulate gene expression in bacteria and eukaryotes.

  9. Choosing to regulate: does choice enhance craving regulation?

    Science.gov (United States)

    Mobasser, Arian; Zeithamova, Dagmar; Pfeifer, Jennifer H

    2018-01-01

    Abstract Goal-directed behavior and lifelong well-being often depend on the ability to control appetitive motivations, such as cravings. Cognitive reappraisal is an effective way to modulate emotional states, including cravings, but is often studied under explicit instruction to regulate. Despite the strong prediction from Self-Determination Theory that choice should enhance task engagement and regulation success, little is known empirically about whether and how regulation is different when participants choose (vs are told) to exert control. To investigate how choice affects neural activity and regulation success, participants reappraised their responses to images of personally-craved foods while undergoing functional neuroimaging. Participants were either instructed to view or reappraise (‘no-choice’) or chose freely to view or reappraise (‘yes-choice’). Choice increased activity in the frontoparietal control network. We expected this activity would be associated with increased task engagement, resulting in better regulation success. However, contrary to this prediction, choice slightly reduced regulation success. Follow-up multivariate functional neuroimaging analyses indicated that choice likely disrupted allocation of limited cognitive resources during reappraisal. While unexpected, these results highlight the importance of studying upstream processes such as regulation choice, as they may affect the ability to regulate cravings and other emotional states. PMID:29462475

  10. Additional file 10: Figure S3. of Uncovering co-expression gene network modules regulating fruit acidity in diverse apples

    OpenAIRE

    Bai, Yang; Dougherty, Laura; Cheng, Lailiang; Zhong, Gan-Yuan; Xu, Kenong

    2015-01-01

    Other regulators from modules Turquoise and Brown and their assigned tight clusters. Elements and their contents, formats and messages are same as those noted in Fig. 8a. (A) Regulator M239684 and Cluster 41 of 68 genes. (B) Regulator M239684 and Cluster 5 of 14 genes. (C) Regulator M239684 and Cluster 7 of 14 genes. (D) Regulator M753318 and Cluster 23 of 11 genes. (E) Regulator M753318 and Cluster 32 of 11 genes. (F) Regulator M175481 and Cluster 2 of 16 genes. (G) Regulator M134341 and Cl...

  11. Environmental regulations handbook for enhanced oil recovery

    International Nuclear Information System (INIS)

    Madden, M.P.; Blatchford, R.P.; Spears, R.B.

    1991-12-01

    This handbook is intended to assist owners and operators of enhanced oil recovery (EOR) operations in acquiring some introductory knowledge of the various state agencies, the US Environmental Protection Agency, and the many environmental laws, rules and regulations which can have jurisdiction over their permitting and compliance activities. It is a compendium of summarizations of environmental rules. It is not intended to give readers specific working details of what is required from them, nor can it be used in that manner. Readers of this handbook are encouraged to contact environmental control offices nearest to locations of interest for current regulations affecting them

  12. Environmental regulations handbook for enhanced oil recovery

    Energy Technology Data Exchange (ETDEWEB)

    Madden, M.P. [National Inst. for Petroleum and Energy Research, Bartlesville, OK (United States); Blatchford, R.P.; Spears, R.B. [Spears and Associates, Inc., Tulsa, OK (United States)

    1991-12-01

    This handbook is intended to assist owners and operators of enhanced oil recovery (EOR) operations in acquiring some introductory knowledge of the various state agencies, the US Environmental Protection Agency, and the many environmental laws, rules and regulations which can have jurisdiction over their permitting and compliance activities. It is a compendium of summarizations of environmental rules. It is not intended to give readers specific working details of what is required from them, nor can it be used in that manner. Readers of this handbook are encouraged to contact environmental control offices nearest to locations of interest for current regulations affecting them.

  13. Functional analysis of Arabidopsis immune-related MAPKs uncovers a role for MPK3 as negative regulator of inducible defences

    KAUST Repository

    Frei dit Frey, Nicolas

    2014-06-30

    Background Mitogen-activated protein kinases (MAPKs) are key regulators of immune responses in animals and plants. In Arabidopsis, perception of microbe-associated molecular patterns (MAMPs) activates the MAPKs MPK3, MPK4 and MPK6. Increasing information depicts the molecular events activated by MAMPs in plants, but the specific and cooperative contributions of the MAPKs in these signalling events are largely unclear. Results In this work, we analyse the behaviour of MPK3, MPK4 and MPK6 mutants in early and late immune responses triggered by the MAMP flg22 from bacterial flagellin. A genome-wide transcriptome analysis reveals that 36% of the flg22-upregulated genes and 68% of the flg22-downregulated genes are affected in at least one MAPK mutant. So far MPK4 was considered as a negative regulator of immunity, whereas MPK3 and MPK6 were believed to play partially redundant positive functions in defence. Our work reveals that MPK4 is required for the regulation of approximately 50% of flg22-induced genes and we identify a negative role for MPK3 in regulating defence gene expression, flg22-induced salicylic acid accumulation and disease resistance to Pseudomonas syringae. Among the MAPK-dependent genes, 27% of flg22-upregulated genes and 76% of flg22-downregulated genes require two or three MAPKs for their regulation. The flg22-induced MAPK activities are differentially regulated in MPK3 and MPK6 mutants, both in amplitude and duration, revealing a highly interdependent network. Conclusions These data reveal a new set of distinct functions for MPK3, MPK4 and MPK6 and indicate that the plant immune signalling network is choreographed through the interplay of these three interwoven MAPK pathways.

  14. Functional analysis of Arabidopsis immune-related MAPKs uncovers a role for MPK3 as negative regulator of inducible defences

    KAUST Repository

    Frei dit Frey, Nicolas; Garcia, Ana; Bigeard, Jean; Zaag, Rim; Bueso, Eduardo; Garmier, Marie; Pateyron, Sté phanie; de Tauzia-Moreau, Marie-Ludivine; Brunaud, Vé ronique; Balzergue, Sandrine; Colcombet, Jean; Aubourg, Sé bastien; Martin-Magniette, Marie-Laure; Hirt, Heribert

    2014-01-01

    -induced genes and we identify a negative role for MPK3 in regulating defence gene expression, flg22-induced salicylic acid accumulation and disease resistance to Pseudomonas syringae. Among the MAPK-dependent genes, 27% of flg22-upregulated genes and 76

  15. Characterization of the serine acetyltransferase gene family of Vitis vinifera uncovers differences in regulation of OAS synthesis in woody plants

    OpenAIRE

    Silvia eTavares; Silvia eTavares; Markus eWirtz; Marcel Pascal Beier; Jochen eBogs; Jochen eBogs; Jochen eBogs; Ruediger eHell; Sara eAmâncio

    2015-01-01

    In higher plants cysteine biosynthesis is catalyzed by O-acetylserine(thiol)lyase (OASTL) and represents the last step of the assimilatory sulfate reduction pathway. It is mainly regulated by provision of O-acetylserine (OAS), the nitrogen/carbon containing backbone for fixation of reduced sulfur. OAS is synthesized by Serine acetyltransferase (SERAT), which reversibly interacts with OASTL in the cysteine synthase complex (CSC). In this study we identify and characterize the SERAT protein fam...

  16. Characterization of the serine acetyltransferase gene family of Vitis vinifera uncovers differences in regulation of OAS synthesis in woody plants

    OpenAIRE

    Tavares, Sílvia; Wirtz, Markus; Beier, Marcel P.; Bogs, Jochen; Hell, Rüdiger; Amâncio, Sara

    2015-01-01

    In higher plants cysteine biosynthesis is catalyzed by O-acetylserine(thiol)lyase (OASTL) and represents the last step of the assimilatory sulfate reduction pathway. It is mainly regulated by provision of O-acetylserine (OAS), the nitrogen/carbon containing backbone for fixation of reduced sulfur. OAS is synthesized by Serine acetyltransferase (SERAT), which reversibly interacts with OASTL in the cysteine synthase complex (CSC). In this study we identify and characterize the SERAT gene family...

  17. A fast, open source implementation of adaptive biasing potentials uncovers a ligand design strategy for the chromatin regulator BRD4

    OpenAIRE

    Dickson, Bradley M.; de Waal, Parker W; Ramjan, Zachary H; Xu, H Eric; Rothbart, Scott B.

    2016-01-01

    In this communication we introduce an efficient implementation of adaptive biasing that greatly improves the speed of free energy computation in molecular dynamics simulations. We investigated the use of accelerated simulations to inform on compound design using a recently reported and clinically relevant inhibitor of the chromatin regulator BRD4 (bromodomain-containing protein 4). Benchmarking on our local compute cluster, our implementation achieves up to 2.5 times more force calls per day ...

  18. Additional file 9: Figure S2. of Uncovering co-expression gene network modules regulating fruit acidity in diverse apples

    OpenAIRE

    Bai, Yang; Dougherty, Laura; Cheng, Lailiang; Zhong, Gan-Yuan; Xu, Kenong

    2015-01-01

    Regulator M190273 and its other five assigned tight clusters. Elements and their contents, formats and messages are same as those noted in Fig. 8a. (A) Cluster 8 of 31 genes. (B) Cluster 9 of 28 genes. (C) Cluster 40 of 55 genes. (D) Cluster 21 of 11 genes. (E) Cluster 45 of 10 genes. (PPTX 238 kb)

  19. Uncovering iron regulation with species-specific transcriptome patterns in Atlantic and coho salmon during a Caligus rogercresseyi infestation.

    Science.gov (United States)

    Valenzuela-Muñoz, V; Boltaña, S; Gallardo-Escárate, C

    2017-09-01

    Salmon species cultured in Chile evidence different levels of susceptibility to the sea louse Caligus rogercresseyi. These differences have mainly been associated with specific immune responses. Moreover, iron regulation seems to be an important mechanism to confer immunity during the host infestation. This response called nutritional immunity has been described in bacterial infections, despite that no comprehensive studies involving in marine ectoparasites infestation have been reported. With this aim, we analysed the transcriptome profiles of Atlantic and coho salmon infected with C. rogercresseyi to evidence modulation of the iron metabolism as a proxy of nutritional immune responses. Whole transcriptome sequencing was performed in samples of skin and head kidney from Atlantic and coho salmon infected with sea lice. RNA-seq analyses revealed significant upregulation of transcripts in both salmon species at 7 and 14 dpi in skin and head kidney, respectively. However, iron regulation transcripts were differentially modulated, evidencing species-specific expression profiles. Genes related to heme degradation and iron transport such as hepcidin, transferrin and haptoglobin were primary upregulated in Atlantic salmon; meanwhile, in coho salmon, genes associated with heme biosynthesis were strongly transcribed. In summary, Atlantic salmon, which are more susceptible to infestation, presented molecular mechanisms to deplete cellular iron availability, suggesting putative mechanisms of nutritional immunity. In contrast, resistant coho salmon were less affected by sea lice, mainly activating pro-inflammatory mechanisms to cope with infestation. © 2017 John Wiley & Sons Ltd.

  20. A fast, open source implementation of adaptive biasing potentials uncovers a ligand design strategy for the chromatin regulator BRD4

    Science.gov (United States)

    Dickson, Bradley M.; de Waal, Parker W.; Ramjan, Zachary H.; Xu, H. Eric; Rothbart, Scott B.

    2016-10-01

    In this communication we introduce an efficient implementation of adaptive biasing that greatly improves the speed of free energy computation in molecular dynamics simulations. We investigated the use of accelerated simulations to inform on compound design using a recently reported and clinically relevant inhibitor of the chromatin regulator BRD4 (bromodomain-containing protein 4). Benchmarking on our local compute cluster, our implementation achieves up to 2.5 times more force calls per day than plumed2. Results of five 1 μs-long simulations are presented, which reveal a conformational switch in the BRD4 inhibitor between a binding competent and incompetent state. Stabilization of the switch led to a -3 kcal/mol improvement of absolute binding free energy. These studies suggest an unexplored ligand design principle and offer new actionable hypotheses for medicinal chemistry efforts against this druggable epigenetic target class.

  1. Uncovering the Role of Erythrocyte-Derived Extracellular Vesicles in Malaria: From Immune Regulation to Cell Communication

    Directory of Open Access Journals (Sweden)

    Johan Ankarklev

    2014-05-01

    Full Text Available Investigation of the involvement of extracellular vesicles (EVs in parasite biology has burgeoned in recent years. Human infecting protozoan parasites, such as Trypanosoma cruzi, Lesihmania sp . and Trichomonas vaginalis , have all demonstrated the utilization of EVs as virulence factors in order to activate or hamper host immunity. Novel findings have provided evidence that the deployment of EVs by Plasmodium sp . has a major impact in disease outcomes and serves as an integral part in controlling stage switching in its life cycle. Clinical studies have highlighted elevated levels of EVs in patients with severe malaria disease and EVs have been linked to increased sequestration of infected red blood cells to the endothelium, causing obstruction of blood flow. It has also been found that EVs produced during malaria disease activate innate immunity. Intriguingly, recent discoveries indicate that Plasmodium sp . “highjack” the erythrocyte microvesiculation system in order to cross-communicate. Both the transfer of DNA and parasite density regulation has been suggested as key mechanisms of EVs in malaria biology.

  2. Single-molecule tracking of small GTPase Rac1 uncovers spatial regulation of membrane translocation and mechanism for polarized signaling

    Science.gov (United States)

    Das, Sulagna; Yin, Taofei; Yang, Qingfen; Zhang, Jingqiao; Wu, Yi I.; Yu, Ji

    2015-01-01

    Polarized Rac1 signaling is a hallmark of many cellular functions, including cell adhesion, motility, and cell division. The two steps of Rac1 activation are its translocation to the plasma membrane and the exchange of nucleotide from GDP to GTP. It is, however, unclear whether these two processes are regulated independent of each other and what their respective roles are in polarization of Rac1 signaling. We designed a single-particle tracking (SPT) method to quantitatively analyze the kinetics of Rac1 membrane translocation in living cells. We found that the rate of Rac1 translocation was significantly elevated in protrusions during cell spreading on collagen. Furthermore, combining FRET sensor imaging with SPT measurements in the same cell, the recruitment of Rac1 was found to be polarized to an extent similar to that of the nucleotide exchange process. Statistical analysis of single-molecule trajectories and optogenetic manipulation of membrane lipids revealed that Rac1 membrane translocation precedes nucleotide exchange, and is governed primarily by interactions with phospholipids, particularly PI(3,4,5)P3, instead of protein factors. Overall, the study highlights the significance of membrane translocation in spatial Rac1 signaling, which is in addition to the traditional view focusing primarily on GEF distribution and exchange reaction. PMID:25561548

  3. 76 FR 7522 - Federal Acquisition Regulation; Enhancing Contract Transparency

    Science.gov (United States)

    2011-02-10

    ... transparency while retaining the protection of information that should be considered in the contracting process... the need for transparency in Government contracting information and believe these recommendations... Regulation; Enhancing Contract Transparency AGENCY: Department of Defense (DoD), General Services...

  4. Genetic analysis of pathway regulation for enhancing branched-chain amino acid biosynthesis in plants

    KAUST Repository

    Chen, Hao

    2010-08-01

    The branched-chain amino acids (BCAAs) valine, leucine and isoleucine are essential amino acids that play critical roles in animal growth and development. Animals cannot synthesize these amino acids and must obtain them from their diet. Plants are the ultimate source of these essential nutrients, and they synthesize BCAAs through a conserved pathway that is inhibited by its end products. This feedback inhibition has prevented scientists from engineering plants that accumulate high levels of BCAAs by simply over-expressing the respective biosynthetic genes. To identify components critical for this feedback regulation, we performed a genetic screen for Arabidopsis mutants that exhibit enhanced resistance to BCAAs. Multiple dominant allelic mutations in the VALINE-TOLERANT 1 (VAT1) gene were identified that conferred plant resistance to valine inhibition. Map-based cloning revealed that VAT1 encodes a regulatory subunit of acetohydroxy acid synthase (AHAS), the first committed enzyme in the BCAA biosynthesis pathway. The VAT1 gene is highly expressed in young, rapidly growing tissues. When reconstituted with the catalytic subunit in vitro, the vat1 mutant-containing AHAS holoenzyme exhibits increased resistance to valine. Importantly, transgenic plants expressing the mutated vat1 gene exhibit valine tolerance and accumulate higher levels of BCAAs. Our studies not only uncovered regulatory characteristics of plant AHAS, but also identified a method to enhance BCAA accumulation in crop plants that will significantly enhance the nutritional value of food and feed. © 2010 Blackwell Publishing Ltd.

  5. Environmental regulations handbook for enhanced oil recovery. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, T.D.

    1980-08-01

    A guide to environmental laws and regulations which have special significance for enhanced oil recovery (EOR) is presented. The Clean Air Act, the Clean Water Act, the Safe Drinking Water Act, Resource Conservation and Recovery Act, federal regulations, and state regulations are discussed. This handbook has been designed as a planning tool and a convenient reference source. The 16 states included comprise the major oil-producing states in various regions of the state. The major topics covered are: general guidelines for complying with environmental laws and regulations; air pollution control; water pollution control; protecting drinking water: underground injection control; hazardous waste management; and federal laws affecting siting or operation of EOR facilities. (DMC)

  6. Transcriptome analysis uncovers Arabidopsis F-BOX STRESS INDUCED 1 as a regulator of jasmonic acid and abscisic acid stress gene expression.

    Science.gov (United States)

    Gonzalez, Lauren E; Keller, Kristen; Chan, Karen X; Gessel, Megan M; Thines, Bryan C

    2017-07-17

    The ubiquitin 26S proteasome system (UPS) selectively degrades cellular proteins, which results in physiological changes to eukaryotic cells. F-box proteins are substrate adaptors within the UPS and are responsible for the diversity of potential protein targets. Plant genomes are enriched in F-box genes, but the vast majority of these have unknown roles. This work investigated the Arabidopsis F-box gene F-BOX STRESS INDUCED 1 (FBS1) for its effects on gene expression in order elucidate its previously unknown biological function. Using publically available Affymetrix ATH1 microarray data, we show that FBS1 is significantly co-expressed in abiotic stresses with other well-characterized stress response genes, including important stress-related transcriptional regulators. This gene suite is most highly expressed in roots under cold and salt stresses. Transcriptome analysis of fbs1-1 knock-out plants grown at a chilling temperature shows that hundreds of genes require FBS1 for appropriate expression, and that these genes are enriched in those having roles in both abiotic and biotic stress responses. Based on both this genome-wide expression data set and quantitative real-time PCR (qPCR) analysis, it is apparent that FBS1 is required for elevated expression of many jasmonic acid (JA) genes that have established roles in combatting environmental stresses, and that it also controls a subset of JA biosynthesis genes. FBS1 also significantly impacts abscisic acid (ABA) regulated genes, but this interaction is more complex, as FBS1 has both positive and negative effects on ABA-inducible and ABA-repressible gene modules. One noteworthy effect of FBS1 on ABA-related stress processes, however, is the restraint it imposes on the expression of multiple class I LIPID TRANSFER PROTEIN (LTP) gene family members that have demonstrated protective effects in water deficit-related stresses. FBS1 impacts plant stress responses by regulating hundreds of genes that respond to the plant

  7. A response regulator from a soil metagenome enhances resistance to the β-lactam antibiotic carbenicillin in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Heather K Allen

    Full Text Available Functional metagenomic analysis of soil metagenomes is a method for uncovering as-yet unidentified mechanisms for antibiotic resistance. Here we report an unconventional mode by which a response regulator derived from a soil metagenome confers resistance to the β-lactam antibiotic carbenicillin in Escherichia coli. A recombinant clone (βlr16 harboring a 5,169 bp DNA insert was selected from a metagenomic library previously constructed from a remote Alaskan soil. The βlr16 clone conferred specific resistance to carbenicillin, with limited increases in resistance to other tested antibiotics, including other β-lactams (penicillins and cephalosporins, rifampin, ciprofloxacin, erythromycin, chloramphenicol, nalidixic acid, fusidic acid, and gentamicin. Resistance was more pronounced at 24°C than at 37°C. Zone-of-inhibition assays suggested that the mechanism of carbenicillin resistance was not due to antibiotic inactivation. The DNA insert did not encode any genes known to confer antibiotic resistance, but did have two putative open reading frames (ORFs that were annotated as a metallopeptidase and a two-component response regulator. Transposon mutagenesis and subcloning of the two ORFs followed by phenotypic assays showed that the response regulator gene was necessary and sufficient to confer the resistance phenotype. Quantitative reverse transcriptase PCR showed that the response regulator suppressed expression of the ompF porin gene, independently of the small RNA regulator micF, and enhanced expression of the acrD, mdtA, and mdtB efflux pump genes. This work demonstrates that antibiotic resistance can be achieved by the modulation of gene regulation by heterologous DNA. Functional analyses such as these can be important for making discoveries in antibiotic resistance gene biology and ecology.

  8. Uncovering Black Womanhood in Engineering

    Science.gov (United States)

    Gibson, Sheree L.; Espino, Michelle M.

    2016-01-01

    Despite the growing research that outlines the experiences of Blacks and women undergraduates in engineering, little is known about Black women in this field. The purpose of this qualitative study was to uncover how eight Black undergraduate women in engineering understood their race and gender identities in a culture that can be oppressive to…

  9. Enhancement of Self-Regulation, Assertiveness, and Empathy.

    Science.gov (United States)

    Sanz de Acedo Lizarraga, M. Luisa; Ugarte, M. Dolores; Cardelle-Elawar, Maria; Iriarte, M. Dolores; Sanz de Acedo Baquedano, M. Teresa

    2003-01-01

    Examined the effects of teaching self-regulation strategies and social skills to 40 middle school students who presented difficulties in self-reflection, self-inquiry, assertiveness, and empathy. Significant gains were observed in the experimental group in self-regulation of learning, self-control of behavior, assertiveness, empathy, and…

  10. Enhancing forest tenure reforms through more responsive regulations

    Directory of Open Access Journals (Sweden)

    Anne M Larson

    2012-01-01

    Full Text Available Forest tenure reforms have offered new opportunities for communities to obtain formal rights to forests and forest benefits, but at the same time a variety of limitations are placed on livelihood options. This article draws on several case studies of reforms in Africa, Asia and Latin America to analyse the regulations accompanying reforms. It identifies three types of regulations, namely rules that limit areas available to local communities; rules that delineate conservation areas and impose related limits on use; and bureaucratic requirements for permits and management plans, which restrict the commercial use and marketing of valuable forest products. It discusses problems with these regulations, and proposes a simple framework for identifying ways to promote regulations that work for forest conservation but are more responsive to the needs of communities and forests.

  11. The ultra-sensitive Nodewalk technique identifies stochastic from virtual, population-based enhancer hubs regulating MYC in 3D: Implications for the fitness of cancer cells

    KAUST Repository

    Sumida, Noriyuki

    2018-03-27

    The relationship between stochastic transcriptional bursts and dynamic 3D chromatin states is not well understood due to poor sensitivity and/or resolution of current chromatin structure-based assays. Consequently, it is not well established if enhancers operate individually and/or in clusters to coordinate gene transcription. In the current study, we introduce Nodewalk, which uniquely combines high sensitivity with high resolution to enable the analysis of chromatin networks in minute input material. The >10,000-fold increase in sensitivity over other many-to-all competing methods uncovered that active chromatin hubs identified in large input material, corresponding to 10 000 cells, flanking the MYC locus are primarily virtual. Thus, the close agreement between chromatin interactomes generated from aliquots corresponding to less than 10 cells with randomly re-sampled interactomes, we find that numerous distal enhancers positioned within flanking topologically associating domains (TADs) converge on MYC in largely mutually exclusive manners. Moreover, when comparing with several enhancer baits, the assignment of the MYC locus as the node with the highest dynamic importance index, indicates that it is MYC targeting its enhancers, rather than vice versa. Dynamic changes in the configuration of the boundary between TADs flanking MYC underlie numerous stochastic encounters with a diverse set of enhancers to depict the plasticity of its transcriptional regulation. Such an arrangement might increase the fitness of the cancer cell by increasing the probability of MYC transcription in response to a wide range of environmental cues encountered by the cell during the neoplastic process.

  12. The ultra-sensitive Nodewalk technique identifies stochastic from virtual, population-based enhancer hubs regulating MYC in 3D: Implications for the fitness of cancer cells

    KAUST Repository

    Sumida, Noriyuki; Sifakis, Emmanouil; Scholz, Barbara A; Fernandez Woodbridge, Alejandro; Kiani, Narsis A.; Gomez-Cabrero, David; Svensson, J Peter; Tegner, Jesper; Gondor, Anita; Ohlsson, Rolf

    2018-01-01

    The relationship between stochastic transcriptional bursts and dynamic 3D chromatin states is not well understood due to poor sensitivity and/or resolution of current chromatin structure-based assays. Consequently, it is not well established if enhancers operate individually and/or in clusters to coordinate gene transcription. In the current study, we introduce Nodewalk, which uniquely combines high sensitivity with high resolution to enable the analysis of chromatin networks in minute input material. The >10,000-fold increase in sensitivity over other many-to-all competing methods uncovered that active chromatin hubs identified in large input material, corresponding to 10 000 cells, flanking the MYC locus are primarily virtual. Thus, the close agreement between chromatin interactomes generated from aliquots corresponding to less than 10 cells with randomly re-sampled interactomes, we find that numerous distal enhancers positioned within flanking topologically associating domains (TADs) converge on MYC in largely mutually exclusive manners. Moreover, when comparing with several enhancer baits, the assignment of the MYC locus as the node with the highest dynamic importance index, indicates that it is MYC targeting its enhancers, rather than vice versa. Dynamic changes in the configuration of the boundary between TADs flanking MYC underlie numerous stochastic encounters with a diverse set of enhancers to depict the plasticity of its transcriptional regulation. Such an arrangement might increase the fitness of the cancer cell by increasing the probability of MYC transcription in response to a wide range of environmental cues encountered by the cell during the neoplastic process.

  13. Enhanced current and voltage regulators for stand-alone applications

    DEFF Research Database (Denmark)

    Federico, de Bosio; Pastorelli, Michele; Antonio DeSouza Ribeiro, Luiz

    2016-01-01

    State feedback decoupling permits to achieve a better dynamic response for Voltage Source in stand-alone applications. The design of current and voltage regulators is performed in the discrete-time domain since it provides better accuracy and allows direct pole placement. As the attainable...... bandwidth of the current loop is mainly limited by computational and PWM delays, a lead compensator structure is proposed to overcome this limitation. The design of the voltage regulator is based on the Nyquist criterion, verifying to guarantee a high sensitivity peak. Discrete-time domain implementation...

  14. Regulation of hepatitis B virus ENI enhancer activity by hepatocyte-enriched transcription factor HNF3.

    Science.gov (United States)

    Chen, M; Hieng, S; Qian, X; Costa, R; Ou, J H

    1994-11-15

    Hepatitis B virus (HBV) ENI enhancer can activate the expression of HBV and non-HBV genes in a liver-specific manner. By performing the electrophoretic mobility-shift assays, we demonstrated that the three related, liver-enriched, transcription factors, HNF3 alpha, HNF3 beta, and HNF3 gamma could all bind to the 2c site of HBV ENI enhancer. Mutations introduced in the 2c site to abolish the binding by HNF3 reduced the enhancer activity approximately 15-fold. Moreover, expression of HNF3 antisense sequences to suppress the expression of HNF3 in Huh-7 hepatoma cells led to reduction of the ENI enhancer activity. These results indicate that HNF3 positively regulates the ENI enhancer activity and this regulation is most likely mediated through the 2c site. The requirement of HNF3 for the ENI enhancer activity could explain the liver specificity of this enhancer element.

  15. 76 FR 77115 - Amendments to the Export Administration Regulations: Facilitating Enhanced Public Understanding...

    Science.gov (United States)

    2011-12-12

    ..., and 774 [Docket No. 110627356-1475-01] RIN 0694-AF29 Amendments to the Export Administration Regulations: Facilitating Enhanced Public Understanding of the Provisions That Implement the Comprehensive U.S... rule, the Bureau of Industry and Security (BIS) amends the Export Administration Regulations (EAR) by...

  16. Climate regulation enhances the value of second generation biofuel technology

    Science.gov (United States)

    Hertel, T. W.; Steinbuks, J.; Tyner, W.

    2014-12-01

    Commercial scale implementation of second generation (2G) biofuels has long been 'just over the horizon - perhaps a decade away'. However, with recent innovations, and higher oil prices, we appear to be on the verge of finally seeing commercial scale implementations of cellulosic to liquid fuel conversion technologies. Interest in this technology derives from many quarters. Environmentalists see this as a way of reducing our carbon footprint, however, absent a global market for carbon emissions, private firms will not factor this into their investment decisions. Those interested in poverty and nutrition see this as a channel for lessening the biofuels' impact on food prices. But what is 2G technology worth to society? How valuable are prospective improvements in this technology? And how are these valuations affected by future uncertainties, including climate regulation, climate change impacts, and energy prices? This paper addresses all of these questions. We employ FABLE, a dynamic optimization model for the world's land resources which characterizes the optimal long run path for protected natural lands, managed forests, crop and livestock land use, energy extraction and biofuels over the period 2005-2105. By running this model twice for each future state of the world - once with 2G biofuels technology available and once without - we measure the contribution of the technology to global welfare. Given the uncertainty in how these technologies are likely to evolve, we consider a range cost estimates - from optimistic to pessimistic. In addition to technological uncertainty, there is great uncertainty in the conditions characterizing our baseline for the 21st century. For each of the 2G technology scenarios, we therefore also consider a range of outcomes for key drivers of global land use, including: population, income, oil prices, climate change impacts and climate regulation. We find that the social valuation of 2G technologies depends critically on climate change

  17. 78 FR 60169 - Federal Acquisition Regulation; Pilot Program for Enhancement of Contractor Employee...

    Science.gov (United States)

    2013-09-30

    ... 9000-AM56 Federal Acquisition Regulation; Pilot Program for Enhancement of Contractor Employee... program enhancing whistleblower protections for contractor employees. DATES: Effective: September 30, 2013... contractor employees at FAR subpart 3.9. The pilot program is mandated by section 828, entitled ``Pilot...

  18. Cognitive emotion regulation enhances aversive prediction error activity while reducing emotional responses.

    Science.gov (United States)

    Mulej Bratec, Satja; Xie, Xiyao; Schmid, Gabriele; Doll, Anselm; Schilbach, Leonhard; Zimmer, Claus; Wohlschläger, Afra; Riedl, Valentin; Sorg, Christian

    2015-12-01

    Cognitive emotion regulation is a powerful way of modulating emotional responses. However, despite the vital role of emotions in learning, it is unknown whether the effect of cognitive emotion regulation also extends to the modulation of learning. Computational models indicate prediction error activity, typically observed in the striatum and ventral tegmental area, as a critical neural mechanism involved in associative learning. We used model-based fMRI during aversive conditioning with and without cognitive emotion regulation to test the hypothesis that emotion regulation would affect prediction error-related neural activity in the striatum and ventral tegmental area, reflecting an emotion regulation-related modulation of learning. Our results show that cognitive emotion regulation reduced emotion-related brain activity, but increased prediction error-related activity in a network involving ventral tegmental area, hippocampus, insula and ventral striatum. While the reduction of response activity was related to behavioral measures of emotion regulation success, the enhancement of prediction error-related neural activity was related to learning performance. Furthermore, functional connectivity between the ventral tegmental area and ventrolateral prefrontal cortex, an area involved in regulation, was specifically increased during emotion regulation and likewise related to learning performance. Our data, therefore, provide first-time evidence that beyond reducing emotional responses, cognitive emotion regulation affects learning by enhancing prediction error-related activity, potentially via tegmental dopaminergic pathways. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Enhancing socially shared regulation in collaborative learning groups: designing for CSCL regulation tools

    NARCIS (Netherlands)

    Järvelä, Sanna; Kirschner, Paul A.; Panadero, Ernesto; Malmberg, Jonna; Phielix, Chris; Jaspers, Jos; Koivuniemi, Marieke; Järvenoja, Hanna

    2016-01-01

    For effective computer supported collaborative learning (CSCL), socially shared regulation of learning (SSRL) is necessary. To this end, this article extends the idea first posited by Ja¨rvela¨ and Hadwin (Educ Psychol 48(1):25–39, 2013) that successful collaboration in CSCL contexts requires

  20. Measuring ability to enhance and suppress emotional expression: The Flexible Regulation of Emotional Expression (FREE) Scale.

    Science.gov (United States)

    Burton, Charles L; Bonanno, George A

    2016-08-01

    Flexibility in self-regulatory behaviors has proved to be an important quality for adjusting to stressful life events and requires individuals to have a diverse repertoire of emotion regulation abilities. However, the most commonly used emotion regulation questionnaires assess frequency of behavior rather than ability, with little evidence linking these measures to observable capacity to enact a behavior. The aim of the current investigation was to develop and validate a Flexible Regulation of Emotional Expression (FREE) Scale that measures a person's ability to enhance and suppress displayed emotion across an array of hypothetical contexts. In Studies 1 and 2, a series of confirmatory factor analyses revealed that the FREE Scale consists of 4 first-order factors divided by regulation and emotional valence type that can contribute to 2 higher order factors: expressive enhancement ability and suppression ability. In Study 1, we also compared the FREE Scale to other commonly used emotion regulation measures, which revealed that suppression ability is conceptually distinct from suppression frequency. In Study 3, we compared the FREE Scale with a composite of traditional frequency-based indices of expressive regulation to predict performance in a previously validated emotional modulation paradigm. Participants' enhancement and suppression ability scores on the FREE Scale predicted their corresponding performance on the laboratory task, even when controlling for baseline expressiveness. These studies suggest that the FREE Scale is a valid and flexible measure of expressive regulation ability. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  1. Effects of sulekang capsule in enhancement of resistance to radiation and regulating immunological function in mice

    International Nuclear Information System (INIS)

    Zhao Naikun; Zhou Ouliang; Du Weixia

    1990-01-01

    The effects of Sulekang capsule in enhancing the resistance to radiation and regulating the immunological function in mice were described. The results show that Sulekang capsule may lengthen the survival time (p 60 Co gamma rays. The experimental results of ANAE reaction show that the activety of T cells of normal or exposed mice may be enhanced by Sulekang capsule, which can control the decrease of both ANAE-positive cells and T cells in exposed mice. So it may enhance the immunological function on exposed animals

  2. 75 FR 26916 - Federal Acquisition Regulation: FAR Case 2009-004, Enhancing Contract Transparency

    Science.gov (United States)

    2010-05-13

    ... Regulation: FAR Case 2009-004, Enhancing Contract Transparency AGENCY: Department of Defense (DoD), General... commercial or financial information. This transparency effort is intended to promote efficiency in Government... the Administration's memorandum entitled Transparency and Open Government (January 21, 2009...

  3. 78 FR 59851 - Defense Federal Acquisition Regulation Supplement: Enhancement of Contractor Employee...

    Science.gov (United States)

    2013-09-30

    ...-AH97 Defense Federal Acquisition Regulation Supplement: Enhancement of Contractor Employee... contractor and subcontractor employees. DATES: Effective date: September 30, 2013. In accordance with FAR 1... Whistleblower Protections for Contractor Employees) made extensive changes to 10 U.S.C. 2409, entitled...

  4. Does Using E-Portfolios for Reflective Writing Enhance High School Students' Self-Regulated Learning?

    Science.gov (United States)

    Chang, Chi-Cheng; Liang, Chaoyun; Shu, Kuen-Ming; Tseng, Kuo-Hung; Lin, Chun-Yu

    2016-01-01

    The study aims to examine whether reflective writing using e-portfolios enhances high school students' self-regulated learning. Participants included two classes of eighth-graders majoring in Information Processing and taking a course called "Website Design" at a vocational high school in Taiwan. There were 41 students, with 18 males and…

  5. Active and Inactive Enhancers Cooperate to Exert Localized and Long-Range Control of Gene Regulation.

    Science.gov (United States)

    Proudhon, Charlotte; Snetkova, Valentina; Raviram, Ramya; Lobry, Camille; Badri, Sana; Jiang, Tingting; Hao, Bingtao; Trimarchi, Thomas; Kluger, Yuval; Aifantis, Iannis; Bonneau, Richard; Skok, Jane A

    2016-06-07

    V(D)J recombination relies on the presence of proximal enhancers that activate the antigen receptor (AgR) loci in a lineage- and stage-specific manner. Unexpectedly, we find that both active and inactive AgR enhancers cooperate to disseminate their effects in a localized and long-range manner. Here, we demonstrate the importance of short-range contacts between active enhancers that constitute an Igk super-enhancer in B cells. Deletion of one element reduces the interaction frequency between other enhancers in the hub, which compromises the transcriptional output of each component. Furthermore, we establish that, in T cells, long-range contact and cooperation between the inactive Igk enhancer MiEκ and the active Tcrb enhancer Eβ alters enrichment of CBFβ binding in a manner that impacts Tcrb recombination. These findings underline the complexities of enhancer regulation and point to a role for localized and long-range enhancer-sharing between active and inactive elements in lineage- and stage-specific control. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  6. Active and Inactive Enhancers Cooperate to Exert Localized and Long-Range Control of Gene Regulation

    Directory of Open Access Journals (Sweden)

    Charlotte Proudhon

    2016-06-01

    Full Text Available V(DJ recombination relies on the presence of proximal enhancers that activate the antigen receptor (AgR loci in a lineage- and stage-specific manner. Unexpectedly, we find that both active and inactive AgR enhancers cooperate to disseminate their effects in a localized and long-range manner. Here, we demonstrate the importance of short-range contacts between active enhancers that constitute an Igk super-enhancer in B cells. Deletion of one element reduces the interaction frequency between other enhancers in the hub, which compromises the transcriptional output of each component. Furthermore, we establish that, in T cells, long-range contact and cooperation between the inactive Igk enhancer MiEκ and the active Tcrb enhancer Eβ alters enrichment of CBFβ binding in a manner that impacts Tcrb recombination. These findings underline the complexities of enhancer regulation and point to a role for localized and long-range enhancer-sharing between active and inactive elements in lineage- and stage-specific control.

  7. Enhancing well-being at work: The role of emotion regulation skills as personal resources.

    Science.gov (United States)

    Buruck, Gabriele; Dörfel, Denise; Kugler, Joachim; Brom, Sarah Susanne

    2016-10-01

    Dealing with negative emotions is a crucial work demand, particularly for employees in health care. Job resources (e.g., autonomy, social support, or reward) but also personal resources (such as emotion regulation strategies) might reduce job stress and support well-being. Following this, the present study focused on strengthening emotion regulation as 1 way of dealing with high job demands. The aim of this study was to evaluate the impact of a standardized emotion regulation training (Affect Regulation Training [ART]; Berking, 2010) to improve emotion regulation skills and well-being of employees in elderly health care. Therefore, 96 elderly care workers filled out an established questionnaire of emotion regulation skills as well as a measure of well-being at pretreatment, posttreatment and at 6-month follow-up. The findings show that the ART fosters emotion regulation skills. In particularly, acceptance, tolerance, and modification of negative emotions was enhanced in the training groups in comparison to a control-group. Modification, meaning the ability to actively change emotions, improved even more over the follow-up-period. Simultaneously, well-being of participants increased over all measurement time points in the ART-group compared with the control-group. Additionally, the improvement in emotion regulation skills from pre to posttreatment was related to well-being at follow-up. In summary, our results support the ART as an effective intervention for dealing with negative emotions and to enhance well-being among employees in elderly care. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  8. Uncovering Transcriptional Regulatory Networks by Sparse Bayesian Factor Model

    Directory of Open Access Journals (Sweden)

    Qi Yuan(Alan

    2010-01-01

    Full Text Available Abstract The problem of uncovering transcriptional regulation by transcription factors (TFs based on microarray data is considered. A novel Bayesian sparse correlated rectified factor model (BSCRFM is proposed that models the unknown TF protein level activity, the correlated regulations between TFs, and the sparse nature of TF-regulated genes. The model admits prior knowledge from existing database regarding TF-regulated target genes based on a sparse prior and through a developed Gibbs sampling algorithm, a context-specific transcriptional regulatory network specific to the experimental condition of the microarray data can be obtained. The proposed model and the Gibbs sampling algorithm were evaluated on the simulated systems, and results demonstrated the validity and effectiveness of the proposed approach. The proposed model was then applied to the breast cancer microarray data of patients with Estrogen Receptor positive ( status and Estrogen Receptor negative ( status, respectively.

  9. A transient-enhanced NMOS low dropout voltage regulator with parallel feedback compensation

    International Nuclear Information System (INIS)

    Wang Han; Tan Lin

    2016-01-01

    This paper presents a transient-enhanced NMOS low-dropout regulator (LDO) for portable applications with parallel feedback compensation. The parallel feedback structure adds a dynamic zero to get an adequate phase margin with a load current variation from 0 to 1 A. A class-AB error amplifier and a fast charging/discharging unit are adopted to enhance the transient performance. The proposed LDO has been implemented in a 0.35 μm BCD process. From experimental results, the regulator can operate with a minimum dropout voltage of 150 mV at a maximum 1 A load and I Q of 165 μA. Under the full range load current step, the voltage undershoot and overshoot of the proposed LDO are reduced to 38 mV and 27 mV respectively. (paper)

  10. Spatial diversification of agroecosystems to enhance biological control and other regulating services: An agroecological perspective.

    Science.gov (United States)

    Hatt, Séverin; Boeraeve, Fanny; Artru, Sidonie; Dufrêne, Marc; Francis, Frédéric

    2018-04-15

    Spatial diversification of crop and non-crop habitats in farming systems is promising for enhancing natural regulation of insect pests. Nevertheless, results from recent syntheses show variable effects. One explanation is that the abundance and diversity of pests and natural enemies are affected by the composition, design and management of crop and non-crop habitats. Moreover, interactions between both local and landscape elements and practices carried out at different spatial scales may affect the regulation of insect pests. Hence, research is being conducted to understand these interdependencies. However, insects are not the only pests and pests are not the only elements to regulate in agroecosystems. Broadening the scope could allow addressing multiple issues simultaneously, but also solving them together by enhancing synergies. Indeed, spatial diversification of crop and non-crop habitats can allow addressing the issues of weeds and pathogens, along with being beneficial to several other regulating services like pollination, soil conservation and nutrient cycling. Although calls rise to develop multifunctional landscapes that optimize the delivery of multiple ecosystem services, it still represents a scientific challenge today. Enhancing interdisciplinarity in research institutions and building interrelations between scientists and stakeholders may help reach this goal. Despite obstacles, positive results from research based on such innovative approaches are encouraging for engaging science in this path. Hence, the aim of the present paper is to offer an update on these issues by exploring the most recent findings and discussing these results to highlight needs for future research. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Emotion Regulation through Movement: Unique Sets of Movement Characteristics are Associated with and Enhance Basic Emotions.

    Science.gov (United States)

    Shafir, Tal; Tsachor, Rachelle P; Welch, Kathleen B

    2015-01-01

    We have recently demonstrated that motor execution, observation, and imagery of movements expressing certain emotions can enhance corresponding affective states and therefore could be used for emotion regulation. But which specific movement(s) should one use in order to enhance each emotion? This study aimed to identify, using Laban Movement Analysis (LMA), the Laban motor elements (motor characteristics) that characterize movements whose execution enhances each of the basic emotions: anger, fear, happiness, and sadness. LMA provides a system of symbols describing its motor elements, which gives a written instruction (motif) for the execution of a movement or movement-sequence over time. Six senior LMA experts analyzed a validated set of video clips showing whole body dynamic expressions of anger, fear, happiness and sadness, and identified the motor elements that were common to (appeared in) all clips expressing the same emotion. For each emotion, we created motifs of different combinations of the motor elements common to all clips of the same emotion. Eighty subjects from around the world read and moved those motifs, to identify the emotion evoked when moving each motif and to rate the intensity of the evoked emotion. All subjects together moved and rated 1241 motifs, which were produced from 29 different motor elements. Using logistic regression, we found a set of motor elements associated with each emotion which, when moved, predicted the feeling of that emotion. Each emotion was predicted by a unique set of motor elements and each motor element predicted only one emotion. Knowledge of which specific motor elements enhance specific emotions can enable emotional self-regulation through adding some desired motor qualities to one's personal everyday movements (rather than mimicking others' specific movements) and through decreasing motor behaviors which include elements that enhance negative emotions.

  12. Emotion regulation through movement: Unique sets of movement characteristics are associated with and enhance basic emotions

    Directory of Open Access Journals (Sweden)

    Tal eShafir

    2016-01-01

    Full Text Available We have recently demonstrated that motor execution, observation and imagery of movements expressing certain emotions can enhance corresponding affective states and therefore could be used for emotion regulation. But which specific movement(s should one use in order to enhance each emotion? This study aimed to identify, using Laban Movement Analysis (LMA, the Laban motor elements (motor characteristics that characterize movements whose execution enhances each of the basic emotions: anger, fear happiness, and sadness. LMA provides a system of symbols describing its motor elements, which gives a written instruction (motif for the execution of a movement or movement-sequence over time. Six senior LMA experts analyzed a validated set of video clips showing whole body dynamic expressions of anger, fear, happiness and sadness, and identified the motor elements that were common to (appeared in all clips expressing the same emotion. For each emotion, we created motifs of different combinations of the motor elements common to all clips of the same emotion. Eighty subjects from around the world read and moved those motifs, to identify the emotion evoked when moving each motif and to rate the intensity of the evoked emotion. All subjects together moved and rated 1241 motifs, which were produced from 29 different motor elements. Using logistic regression, we found a set of motor elements associated with each emotion which, when moved, predicted the feeling of that emotion. Each emotion was predicted by a unique set of motor elements and each motor element predicted only one emotion. Knowledge of which specific motor elements enhance specific emotions can enable emotional self-regulation through adding some desired motor qualities to one’s personal everyday movements (rather than mimicking others’ specific movements and through decreasing motor behaviors which include elements that enhance negative emotions.

  13. Regulation of the neuropathy-associated Pmp22 gene by a distal super-enhancer.

    Science.gov (United States)

    Pantera, Harrison; Moran, John J; Hung, Holly A; Pak, Evgenia; Dutra, Amalia; Svaren, John

    2018-05-16

    Peripheral nerve myelination is adversely affected in the most common form of the hereditary peripheral neuropathy called Charcot-Marie-Tooth Disease. This form, classified as CMT1A, is caused by a 1.4 Mb duplication on chromosome 17, which includes the abundantly expressed Schwann cell myelin gene, Peripheral Myelin Protein 22 (PMP22). This is one of the most common copy number variants causing neurological disease. Overexpression of Pmp22 in rodent models recapitulates several aspects of neuropathy, and reduction of Pmp22 in such models results in amelioration of the neuropathy phenotype. Recently we identified a potential super-enhancer approximately 90-130 kb upstream of the Pmp22 transcription start sites. This super-enhancer encompasses a cluster of individual enhancers that have the acetylated histone H3K27 active enhancer mark, and coincides with smaller duplications identified in patients with milder CMT1A-like symptoms, where the PMP22 coding region itself was not part of the duplication. In this study, we have utilized genome editing to create a deletion of this super-enhancer to determine its role in Pmp22 regulation. Our data show a significant decrease in Pmp22 transcript expression using allele-specific internal controls. Moreover, the P2 promoter of the Pmp22 gene, which is used in other cell types, is affected, but we find that the Schwann cell-specific P1 promoter is disproportionately more sensitive to loss of the super-enhancer. These data show for the first time the requirement of these upstream enhancers for full Pmp22 expression.

  14. Memory Enhancement by Targeting Cdk5 Regulation of NR2B

    Science.gov (United States)

    Plattner, Florian; Hernandéz, Adan; Kistler, Tara M.; Pozo, Karine; Zhong, Ping; Yuen, Eunice Y.; Tan, Chunfeng; Hawasli, Ammar H.; Cooke, Sam F.; Nishi, Akinori; Guo, Ailan; Wiederhold, Thorsten; Yan, Zhen; Bibb, James A.

    2014-01-01

    SUMMARY Many psychiatric and neurological disorders are characterized by learning and memory deficits, for which cognitive enhancement is considered a valid treatment strategy. The N-methyl-D-aspartate receptor (NMDAR) is a prime target for the development of cognitive enhancers due to its fundamental role in learning and memory. In particular, the NMDAR subunit NR2B improves synaptic plasticity and memory when over-expressed in neurons. However, NR2B regulation is not well understood and no therapies potentiating NMDAR function have been developed. Here, we show that serine 1116 of NR2B is phosphorylated by cyclin-dependent kinase 5 (Cdk5). Cdk5-dependent NR2B phosphorylation is regulated by neuronal activity and controls the receptor’s cell surface expression. Disrupting NR2B-Cdk5 interaction using a small interfering peptide (siP) increases NR2B surface levels, facilitates synaptic transmission, and improves memory formation in vivo. Our results reveal a novel regulatory mechanism critical to NR2B function that can be targeted for the development of cognitive enhancers. PMID:24607229

  15. Study on influence over approaching a market in the international trade by enhancing the international environmental regulation

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Sang In; Park, Joon Young [Korea Environment Institute, Seoul (Korea)

    1999-12-01

    The focal point of connecting trade and environment is what kind of influence over a national competitiveness of a national economy can be brought by enhancing environmental regulations. Traditionally it was accepted that the enhancement of environmental policy had a negative impact on competitiveness. However, recent study results show that the enhancement of environmental policy can strengthen industrial competitiveness for a long term. This study analyzes the significance of enhancing the international environmental regulation from a developing country's standpoint in association with this. 27 refs., 8 tabs.

  16. Study on influence over approaching a market in the international trade by enhancing the international environmental regulation

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Sang In; Park, Joon Young [Korea Environment Institute, Seoul (Korea)

    1999-12-01

    The focal point of connecting trade and environment is what kind of influence over a national competitiveness of a national economy can be brought by enhancing environmental regulations. Traditionally it was accepted that the enhancement of environmental policy had a negative impact on competitiveness. However, recent study results show that the enhancement of environmental policy can strengthen industrial competitiveness for a long term. This study analyzes the significance of enhancing the international environmental regulation from a developing country's standpoint in association with this. 27 refs., 8 tabs.

  17. Enhancing Social Responsibility within Global Supply Chains: Is Legal Regulation the Optimal Solution?

    Directory of Open Access Journals (Sweden)

    Katerina Peterková

    2011-03-01

    Full Text Available This paper was presented at the first meeting of the NSU study group “Conceptions of ethical and social values in post-secular society: Towards a new ethical imagination in a cosmopolitan world society”, held on January 28-30, 2011 at Copenhagen Business School. First, this paper examines the voluntary (ethical v. mandatory (legal basis of corporate social responsibility (CSR. Second, it examines the relationship between CSR, law and business ethics. Third, it tries to answer the question if there is a need for a hard[2] legal regulation of CSR within international supply relationships or if ethical norms, e.g. expressed in the form of self-regulation, may better serve the purpose. And finally, it suggests possible ways for the future development of suitable regulatory methods for enhancing social standards within international supply chains. The questions are approached solely from the perspectives of legal theory and socio-legal analysis.

  18. Graphene quantum dots as enhanced plant growth regulators: effects on coriander and garlic plants.

    Science.gov (United States)

    Chakravarty, Disha; Erande, Manisha B; Late, Dattatray J

    2015-10-01

    We report investigations on the use of graphene quantum dots for growth enhancement in coriander (Coriandrum sativam L.) and garlic (Allium sativum) plants. The as-received seeds of coriander and garlic were treated with 0.2 mg mL(-1) of graphene quantum dots for 3 h before planting. Graphene quantum dots enhanced the growth rate in coriander and garlic plants, including leaves, roots, shoots, flowers and fruits, when the seeds were treated with graphene quantum dots. Our investigations open up the opportunity to use graphene quantum dots as plant growth regulators that can be used in a variety of other food plants for high yield. © 2015 Society of Chemical Industry.

  19. Identification of sumoylation sites in CCDC6, the first identified RET partner gene in papillary thyroid carcinoma, uncovers a mode of regulating CCDC6 function on CREB1 transcriptional activity.

    Directory of Open Access Journals (Sweden)

    Chiara Luise

    Full Text Available CCDC6 was originally identified in chimeric genes as caused by chromosomal translocation involving the RET protooncogene in some thyroid tumors. Recognised as a 65 kDa pro-apoptotic phosphoprotein, CCDC6 has been enrolled as an ATM substrate that contribute to protect genome integrity by modulating PP4c activity in response to genotoxic stress. Recently, CCDC6 has been identified as a repressor of CREB1-dependent transcription. Sumoylation has emerged as an important mechanism in transcriptional control. Here, we report the identification and characterization of three sites of sumoylation in CCDC6 (K74, K266 and K424 which are highly conserved in vertebrates. We demonstrate that the post-translational modifications by SUMO2 constrain most of the CCDC6 protein in the cytosol and affect its functional interaction with CREB1 with a decrease of CCDC6 repressive function on CREB1 transcriptional activity. Indeed, the impairment of functional outcome of sumoylated CCDC6 is obtained knocking down all three the sumoylation sites. Interestingly, in thyroid cells the SUMO2-mediated CCDC6 post-translational modifications are induced by Forskolin, a cAMP analog. Signal transduction via the cAMP pathway is known to be ubiquitous and represents a major line of communication between many organisms and their environment. We believe that CCDC6 could be an important player in the dynamics of cAMP signaling by fine regulating CREB1 transcriptional activity in normal and transformed thyroid cells.

  20. Urea uptake enhances barrier function and antimicrobial defense in humans by regulating epidermal gene expression

    Science.gov (United States)

    Grether-Beck, Susanne; Felsner, Ingo; Brenden, Heidi; Kohne, Zippora; Majora, Marc; Marini, Alessandra; Jaenicke, Thomas; Rodriguez-Martin, Marina; Trullas, Carles; Hupe, Melanie; Elias, Peter M.; Krutmann, Jean

    2012-01-01

    Urea is an endogenous metabolite, known to enhance stratum corneum hydration. Yet, topical urea anecdotally also improves permeability barrier function, and it appears to exhibit antimicrobial activity. Hence, we hypothesized that urea is not merely a passive metabolite, but a small-molecule regulator of epidermal structure and function. In 21 human volunteers, topical urea improved barrier function in parallel with enhanced antimicrobial peptide (LL-37 and β-defensin-2) expression. Urea both stimulates expression of, and is transported into keratinocytes by two urea transporters, UT-A1 and UT-A2, and by aquaporin 3, 7 and 9. Inhibitors of these urea transporters block the downstream biological effects of urea, which include increased mRNA and protein levels for: (i) transglutaminase-1, involucrin, loricrin and filaggrin; (ii) epidermal lipid synthetic enzymes, and (iii) cathelicidin/LL-37 and β-defensin-2. Finally, we explored the potential clinical utility of urea, showing that topical urea applications normalized both barrier function and antimicrobial peptide expression in a murine model of atopic dermatitis (AD). Together, these results show that urea is a small-molecule regulator of epidermal permeability barrier function and antimicrobial peptide expression after transporter uptake, followed by gene regulatory activity in normal epidermis, with potential therapeutic applications in diseased skin. PMID:22418868

  1. DNA breaks and chromatin structural changes enhance the transcription of autoimmune regulator target genes.

    Science.gov (United States)

    Guha, Mithu; Saare, Mario; Maslovskaja, Julia; Kisand, Kai; Liiv, Ingrid; Haljasorg, Uku; Tasa, Tõnis; Metspalu, Andres; Milani, Lili; Peterson, Pärt

    2017-04-21

    The autoimmune regulator (AIRE) protein is the key factor in thymic negative selection of autoreactive T cells by promoting the ectopic expression of tissue-specific genes in the thymic medullary epithelium. Mutations in AIRE cause a monogenic autoimmune disease called autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. AIRE has been shown to promote DNA breaks via its interaction with topoisomerase 2 (TOP2). In this study, we investigated topoisomerase-induced DNA breaks and chromatin structural alterations in conjunction with AIRE-dependent gene expression. Using RNA sequencing, we found that inhibition of TOP2 religation activity by etoposide in AIRE-expressing cells had a synergistic effect on genes with low expression levels. AIRE-mediated transcription was not only enhanced by TOP2 inhibition but also by the TOP1 inhibitor camptothecin. The transcriptional activation was associated with structural rearrangements in chromatin, notably the accumulation of γH2AX and the exchange of histone H1 with HMGB1 at AIRE target gene promoters. In addition, we found the transcriptional up-regulation to co-occur with the chromatin structural changes within the genomic cluster of carcinoembryonic antigen-like cellular adhesion molecule genes. Overall, our results suggest that the presence of AIRE can trigger molecular events leading to an altered chromatin landscape and the enhanced transcription of low-expressed genes. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. ABT737 enhances cholangiocarcinoma sensitivity to cisplatin through regulation of mitochondrial dynamics

    International Nuclear Information System (INIS)

    Fan, Zhongqi; Yu, Huimei; Cui, Ni; Kong, Xianggui; Liu, Xiaomin; Chang, Yulei; Wu, Yao; Sun, Liankun; Wang, Guangyi

    2015-01-01

    Cholangiocarcinoma responses weakly to cisplatin. Mitochondrial dynamics participate in the response to various stresses, and mainly involve mitophagy and mitochondrial fusion and fission. Bcl-2 family proteins play critical roles in orchestrating mitochondrial dynamics, and are involved in the resistance to cisplatin. Here we reported that ABT737, combined with cisplatin, can promote cholangiocarcinoma cells to undergo apoptosis. We found that the combined treatment decreased the Mcl-1 pro-survival form and increased Bak. Cells undergoing cisplatin treatment showed hyperfused mitochondria, whereas fragmentation was dominant in the mitochondria of cells exposed to the combined treatment, with higher Fis1 levels, decreased Mfn2 and OPA1 levels, increased ratio of Drp1 60 kD to 80 kD form, and more Drp1 located on mitochondria. More p62 aggregates were observed in cells with fragmented mitochondria, and they gradually translocated to mitochondria. Mitophagy was induced by the combined treatment. Knockdown p62 decreased the Drp1 ratio, increased Tom20, and increased cell viability. Our data indicated that mitochondrial dynamics play an important role in the response of cholangiocarcinoma to cisplatin. ABT737 might enhance cholangiocarcinoma sensitivity to cisplatin through regulation of mitochondrial dynamics and the balance within Bcl-2 family proteins. Furthermore, p62 seems to be critical in the regulation of mitochondrial dynamics. - Highlights: • Cholangiocarcinoma may adapt to cisplatin through mitochondrial fusion. • ABT737 sensitizes cholangiocarcinoma to cisplatin by promoting fission and mitophagy. • p62 might participate in the regulation of mitochondrial fission and mitophagy

  3. MiR-155 Enhances Insulin Sensitivity by Coordinated Regulation of Multiple Genes in Mice

    Science.gov (United States)

    Lin, Taoyan; Lin, Xia; Chen, Li; Zeng, Hui; Han, Yanjiang; Wu, Lihong; Huang, Shun; Wang, Meng; Huang, Shenhao; Xie, Raoying; Liang, Liqi; Liu, Yu; Liu, Ruiyu; Zhang, Tingting; Li, Jing; Wang, Shengchun; Sun, Penghui; Huang, Wenhua; Yao, Kaitai; Xu, Kang; Du, Tao; Xiao, Dong

    2016-01-01

    miR-155 plays critical roles in numerous physiological and pathological processes, however, its function in the regulation of blood glucose homeostasis and insulin sensitivity and underlying mechanisms remain unknown. Here, we reveal that miR-155 levels are downregulated in serum from type 2 diabetes (T2D) patients, suggesting that miR-155 might be involved in blood glucose control and diabetes. Gain-of-function and loss-of-function studies in mice demonstrate that miR-155 has no effects on the pancreatic β-cell proliferation and function. Global transgenic overexpression of miR-155 in mice leads to hypoglycaemia, improved glucose tolerance and insulin sensitivity. Conversely, miR-155 deficiency in mice causes hyperglycemia, impaired glucose tolerance and insulin resistance. In addition, consistent with a positive regulatory role of miR-155 in glucose metabolism, miR-155 positively modulates glucose uptake in all cell types examined, while mice overexpressing miR-155 transgene show enhanced glycolysis, and insulin-stimulated AKT and IRS-1 phosphorylation in liver, adipose tissue or skeletal muscle. Furthermore, we reveal these aforementioned phenomena occur, at least partially, through miR-155-mediated repression of important negative regulators (i.e. C/EBPβ, HDAC4 and SOCS1) of insulin signaling. Taken together, these findings demonstrate, for the first time, that miR-155 is a positive regulator of insulin sensitivity with potential applications for diabetes treatment. PMID:27711113

  4. Dioscin enhances methotrexate absorption by down-regulating MDR1 in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Lijuan, E-mail: jlwang1979@163.com [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning (China); Wang, Changyuan, E-mail: wangcyuan@163.com [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian, Liaoning (China); Peng, Jinyong, E-mail: jinyongpeng2005@163.com [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian, Liaoning (China); Liu, Qi, E-mail: llaqii@yahoo.com.cn [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian, Liaoning (China); Meng, Qiang, E-mail: mengq531@yahoo.cn [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian, Liaoning (China); Sun, Huijun, E-mail: sunhuijun@hotmail.com [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian, Liaoning (China); Huo, Xiaokui, E-mail: huoxiaokui@163.com [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian, Liaoning (China); and others

    2014-06-01

    The purpose of this study was to investigate the enhancing effect of dioscin on the absorption of methotrexate (MTX) and clarify the molecular mechanism involved in vivo and in vitro. Dioscin increased MTX chemosensitivity and transepithelial flux in the absorptive direction, significantly inhibiting multidrug resistance 1 (MDR1) mRNA and protein expression and MDR1 promoter and nuclear factor κ-B (NF-κB) activities in Caco-2 cells. Moreover, inhibitor κB-α (IκB-α) degradation was inhibited by dioscin. Dioscin enhanced the intracellular concentration of MTX by down-regulating MDR1 expression through a mechanism that involves NF-κB signaling pathway inhibition in Caco-2 cells. Dioscin strengthened MTX absorption by inhibiting MDR1 expression in rat intestine. In addition, even though MTX is absorbed into the enterocytes, there was no increase in toxicity observed, and that, in fact, decreased toxicity was seen. - Highlights: • Dioscin raised MTX concentration by inhibiting MDR1 in Caco-2 cells. • Dioscin suppresses MDR1 by inhibiting NF-κB signaling pathway in Caco-2 cells. • Dioscin can enhance MTX absorption via inhibiting MDR1 in vivo and in vitro. • Dioscin did not increase MTX-induced gastrointestinal mucosal toxicity.

  5. EGCG Enhances Cisplatin Sensitivity by Regulating Expression of the Copper and Cisplatin Influx Transporter CTR1 in Ovary Cancer.

    Directory of Open Access Journals (Sweden)

    Xuemin Wang

    Full Text Available Cisplatin is one of the first-line platinum-based chemotherapeutic agents for treatment of many types of cancer, including ovary cancer. CTR1 (copper transporter 1, a transmembrane solute carrier transporter, has previously been shown to increase the cellular uptake and sensitivity of cisplatin. It is hypothesized that increased CTR1 expression would enhance the sensitivity of cancer cells to cisplatin (cDDP. The present study demonstrates for the first time that (--epigallocatechin-3-gallate (EGCG, a major polyphenol from green tea, can enhance CTR1 mRNA and protein expression in ovarian cancer cells and xenograft mice. EGCG inhibits the rapid degradation of CTR1 induced by cDDP. The combination of EGCG and cDDP increases the accumulation of cDDP and DNA-Pt adducts, and subsequently enhances the sensitivity of ovarian cancer SKOV3 and OVCAR3 cells to the chemotherapeutic agent. In the OVCAR3 ovarian cancer xenograft nude mice model, the combination of the lower concentration of cDDP and EGCG strongly repressed the tumor growth and exhibited protective effect on the nephrotoxicity induced by cisplatin. Overall, these findings uncover a novel chemotherapy mechanism of EGCG as an adjuvant for the treatment of ovarian cancer.

  6. Deepwater Horizon: Experience the Events That Led to This Accident, Follow the Investigation as They Uncover the Human Factors

    International Nuclear Information System (INIS)

    Bannerman, T.

    2016-01-01

    With the Key themes of leadership, culture, reputation and risk, process safety and the human and organizational factors inside partnership and joint ventures, this session run by AKT immerses you into the situation on board the Deepwater Horizon drilling rig in the Gulf of Mexico on the day of the disaster 20 April 2010. The sequence of events are acted out and then we follow the investigation as they uncover negligence, poor regulation, inadequate maintenance, and catastrophic decision making and what the US authorities called “a reckless disregard for safety”. This session will show how this type of workshop event has been used in different organizations, and the actors run the session to show how the facts of the disaster can be used to enhance knowledge of managers and senior leaders of factors that can trigger a major event. (author)

  7. Uncovering student ideas in physical science

    CERN Document Server

    Keeley, Page

    2014-01-01

    If you and your students can't get enough of a good thing, Volume 2 of Uncovering Student Ideas in Physical Science is just what you need. The book offers 39 new formative assessment probes, this time with a focus on electric charge, electric current, and magnets and electromagnetism. It can help you do everything from demystify electromagnetic fields to explain the real reason balloons stick to the wall after you rub them on your hair.

  8. Familial Brugada syndrome uncovered by hyperkalaemic diabetic ketoacidosis

    NARCIS (Netherlands)

    Postema, Pieter G.; Vlaar, Alexander P. J.; DeVries, J. Hans; Tan, Hanno L.

    2011-01-01

    We describe a case of diabetic ketoacidosis with concomitant hyperkalaemia that uncovered a typical Brugada syndrome electrocardiogram (ECG). Further provocation testing in the patient and his son confirmed familial Brugada syndrome. Diabetic ketoacidosis with hyperkalaemia may uncover an

  9. Enhancing Decision-Making in STSE Education by Inducing Reflection and Self-Regulated Learning

    Science.gov (United States)

    Gresch, Helge; Hasselhorn, Marcus; Bögeholz, Susanne

    2017-02-01

    Thoughtful decision-making to resolve socioscientific issues is central to science, technology, society, and environment (STSE) education. One approach for attaining this goal involves fostering students' decision-making processes. Thus, the present study explores whether the application of decision-making strategies, combined with reflections on the decision-making processes of others, enhances decision-making competence. In addition, this study examines whether this process is supported by elements of self-regulated learning, i.e., self-reflection regarding one's own performance and the setting of goals for subsequent tasks. A computer-based training program which involves the resolution of socioscientific issues related to sustainable development was developed in two versions: with and without elements of self-regulated learning. Its effects on decision-making competence were analyzed using a pre test-post test follow-up control-group design ( N = 242 high school students). Decision-making competence was assessed using an open-ended questionnaire that focused on three facets: consideration of advantages and disadvantages, metadecision aspects, and reflection on the decision-making processes of others. The findings suggest that students in both training groups incorporated aspects of metadecision into their statements more often than students in the control group. Furthermore, both training groups were more successful in reflecting on the decision-making processes of others. The students who received additional training in self-regulated learning showed greater benefits in terms of metadecision aspects and reflection, and these effects remained significant two months later. Overall, our findings demonstrate that the application of decision-making strategies, combined with reflections on the decision-making process and elements of self-regulated learning, is a fruitful approach in STSE education.

  10. Selective Regulation of Oocyte Meiotic Events Enhances Progress in Fertility Preservation Methods

    Directory of Open Access Journals (Sweden)

    Onder Celik

    2015-01-01

    Full Text Available Following early embryonic germ cell migration, oocytes are surrounded by somatic cells and remain arrested at diplotene stage until luteinizing hormone (LH surge. Strict regulation of both meiotic arrest and meiotic resumption during dormant stage are critical for future fertility. Intercellular signaling system between the somatic compartment and oocyte regulates these meiotic events and determines the follicle quality. As well as the collected number of eggs, their qualities are also important for in vitro fertilization (IVF outcome. In spontaneous and IVF cycles, germinal vesicle (GV–stage oocytes, premature GV breakdown, and persistence of first meiotic arrest limit the reproductive performance. Likewise, both women with premature ovarian aging and young cancer women are undergoing chemoradiotherapy under the risk of follicle loss because of unregulated meiotic events. Understanding of oocyte meiotic events is therefore critical for the prevention of functional ovarian reserve. High levels of cyclic guanosine monophophate (cGMP, cyclic adenosine monophophate (cAMP and low phosphodiesterase (PDE 3A enzyme activity inside the oocyte are responsible for maintaining of meiotic arrest before the LH surge. cGMP is produced in the somatic compartment, and natriuretic peptide precursor C (Nppc and natriuretic peptide receptor 2 (Npr2 regulate its production. cGMP diffuses into the oocyte and reduces the PDE3A activity, which inhibits the conversion of cAMP to the 5′AMP, and cAMP levels are enhanced. In addition, oocyte itself has the ability to produce cAMP. Taken together, accumulation of cAMP inside the oocyte induces protein kinase activity, which leads to the inhibition of maturation-promoting factor and meiotic arrest also continues. By stimulating the expression of epidermal growth factor, LH inhibits the Nppc/Npr2 system, blocks cGMP synthesis, and initiates meiotic resumption. Oocytes lacking the functional of this pathway may lead to

  11. Interactive, technology-enhanced self-regulated learning tools in healthcare education: a literature review.

    Science.gov (United States)

    Petty, Julia

    2013-01-01

    Learning technology is increasingly being implemented for programmes of blended learning within nurse education. With a growing emphasis on self-directed study particularly in post-basic education, there is a need for learners to be guided in their learning away from practice and limited classroom time. Technology-enabled (TE) tools which engage learners actively can play a part in this. The effectiveness and value of interactive TE learning strategies within healthcare is the focus of this paper. To identify literature that explores the effectiveness of interactive, TE tools on knowledge acquisition and learner satisfaction within healthcare with a view to evaluating their use for post-basic nurse education. A Literature Review was performed focusing on papers exploring the comparative value and perceived benefit of TE tools compared to traditional modes of learning within healthcare. The Databases identified as most suitable due to their relevance to healthcare were accessed through EBSCOhost. Primary, Boolean and advanced searches on key terms were undertaken. Inclusion and exclusion criteria were applied which resulted in a final selection of 11 studies for critique. Analysis of the literature found that knowledge acquisition in most cases was enhanced and measured learner satisfaction was generally positive for interactive, self-regulated TE tools. However, TE education may not suit all learners and this is critiqued in the light of the identified limitations. Interactive self regulation and/or testing can be a valuable learning strategy that can be incorporated into self-directed programmes of study for post-registration learners. Whilst acknowledging the learning styles not suited to such tools, the concurrent use of self-directed TE tools with those learning strategies necessitating a more social presence can work together to support enhancement of knowledge required to deliver rationale for nursing practice. Copyright © 2012 Elsevier Ltd. All rights

  12. Performance enhancement of microbial fuel cell by applying transient-state regulation

    International Nuclear Information System (INIS)

    Liang, Peng; Zhang, Changyong; Jiang, Yong; Bian, Yanhong; Zhang, Helan; Sun, Xueliang; Yang, Xufei; Zhang, Xiaoyuan; Huang, Xia

    2017-01-01

    Highlights: • MFC was operated with transient-state regulation to enhance its performance. • Effects of the TSR parameters on MFC performance were thoroughly investigated. • Long-term operation of MFC in TSR mode allowed 32.7% higher power production. • Anode capacitance helped reduce the MFC’s internal impedance in the TSR mode. - Abstract: A binder-free, pseudocapacitive anode was fabricated by coating reduced graphene oxide (rGO) and manganese oxide (MnO_2) nanoparticles on stainless steel fibre felt (SS). Microbial fuel cell (MFC) equipped with this novel anode yielded a maximum power density of 1045 mW m"−"2, 20 times higher than that of a similar MFC with a bare SS anode (46 mW m"−"2). Transient-state regulation (TSR) was implemented to further improve the MFC’s power generation. The optimal TSR duty cycle ranged from 67% to 95%, and the MFC’s power density increased with TSR frequency. A maximum power density output of 1238 mW m"−"2 was achieved at the TSR duty cycle of 75% and the frequency of 1 Hz, 18.4% greater than that obtained from the steady state operation. The TSR mode delivered better MFC performance especially when the external resistance was small. Long-term operation tests revealed that the current density and power density yielded in the TSR mode were on average 15.0% and 32.7% greater than those in the steady state mode, respectively. The TSR mode was believed to reduce the internal resistance of the MFC while enhance substrate mass transfer and electron transfer within the anode matrix, thereby improving the MFC performance.

  13. Dexamethasone Treatment Leads to Enhanced Fear Extinction and Dynamic Fkbp5 Regulation in Amygdala.

    Science.gov (United States)

    Sawamura, Takehito; Klengel, Torsten; Armario, Antonio; Jovanovic, Tanja; Norrholm, Seth D; Ressler, Kerry J; Andero, Raül

    2016-02-01

    Posttraumatic stress disorder (PTSD) is both a prevalent and debilitating trauma-related disorder associated with dysregulated fear learning at the core of many of its signs and symptoms. Improvements in the currently available psychological and pharmacological treatments are needed in order to improve PTSD treatment outcomes and to prevent symptom relapse. In the present study, we used a putative animal model of PTSD that included presentation of immobilization stress (IMO) followed by fear conditioning (FC) a week later. We then investigated the acute effects of GR receptor activation on the extinction (EXT) of conditioned freezing, using dexamethasone administered systemically which is known to result in suppression of the HPA axis. In our previous work, IMO followed by tone-shock-mediated FC was associated with impaired fear EXT. In this study, we administered dexamethasone 4 h before EXT training and then examined EXT retention (RET) 24 h later to determine whether dexamethasone suppression rescued EXT deficits. Dexamethasone treatment produced dose-dependent enhancement of both EXT and RET. Dexamethasone was also associated with reduced amygdala Fkbp5 mRNA expression following EXT and after RET. Moreover, DNA methylation of the Fkbp5 gene occurred in a dose-dependent and time course-dependent manner within the amygdala. Additionally, we found dynamic changes in epigenetic regulation, including Dnmt and Tet gene pathways, as a function of both fear EXT and dexamethasone suppression of the HPA axis. Together, these data suggest that dexamethasone may serve to enhance EXT by altering Fkbp5-mediated glucocorticoid sensitivity via epigenetic regulation of Fkbp5 expression.

  14. Challenges for tree officers to enhance the provision of regulating ecosystem services from urban forests.

    Science.gov (United States)

    Davies, Helen J; Doick, Kieron J; Hudson, Malcolm D; Schreckenberg, Kate

    2017-07-01

    Urbanisation and a changing climate are leading to more frequent and severe flood, heat and air pollution episodes in Britain's cities. Interest in nature-based solutions to these urban problems is growing, with urban forests potentially able to provide a range of regulating ecosystem services such as stormwater attenuation, heat amelioration and air purification. The extent to which these benefits are realized is largely dependent on urban forest management objectives, the availability of funding, and the understanding of ecosystem service concepts within local governments, the primary delivery agents of urban forests. This study aims to establish the extent to which British local authorities actively manage their urban forests for regulating ecosystem services, and identify which resources local authorities most need in order to enhance provision of ecosystem services by Britain's urban forests. Interviews were carried out with staff responsible for tree management decisions in fifteen major local authorities from across Britain, selected on the basis of their urban nature and high population density. Local authorities have a reactive approach to urban forest management, driven by human health and safety concerns and complaints about tree disservices. There is relatively little focus on ensuring provision of regulating ecosystem services, despite awareness by tree officers of the key role that urban forests can play in alleviating chronic air pollution, flood risk and urban heat anomalies. However, this is expected to become a greater focus in future provided that existing constraints - lack of understanding of ecosystem services amongst key stakeholders, limited political support, funding constraints - can be overcome. Our findings suggest that the adoption of a proactive urban forest strategy, underpinned by quantified and valued urban forest-based ecosystem services provision data, and innovative private sector funding mechanisms, can facilitate a change to a

  15. Do phosphoinositides regulate membrane water permeability of tobacco protoplasts by enhancing the aquaporin pathway?

    Science.gov (United States)

    Ma, Xiaohong; Shatil-Cohen, Arava; Ben-Dor, Shifra; Wigoda, Noa; Perera, Imara Y; Im, Yang Ju; Diminshtein, Sofia; Yu, Ling; Boss, Wendy F; Moshelion, Menachem; Moran, Nava

    2015-03-01

    Enhancing the membrane content of PtdInsP 2 , the already-recognized protein-regulating lipid, increased the osmotic water permeability of tobacco protoplasts, apparently by increasing the abundance of active aquaporins in their membranes. While phosphoinositides are implicated in cell volume changes and are known to regulate some ion channels, their modulation of aquaporins activity has not yet been reported for any organism. To examine this, we compared the osmotic water permeability (P f) of protoplasts isolated from tobacco (Nicotiana tabacum) cultured cells (NT1) with different (genetically lowered or elevated relative to controls) levels of inositol trisphosphate (InsP3) and phosphatidyl inositol [4,5] bisphosphate (PtdInsP2). To achieve this, the cells were transformed with, respectively, the human InsP3 5-phosphatase ('Ptase cells') or human phosphatidylinositol (4) phosphate 5-kinase ('PIPK cells'). The mean P f of the PIPK cells was several-fold higher relative to that of controls and Ptase cells. Three results favor aquaporins over the membrane matrix as underlying this excessive P f: (1) transient expression of the maize aquaporin ZmPIP2;4 in the PIPK cells increased P f by 12-30 μm s(-1), while in the controls only by 3-4 μm s(-1). (2) Cytosol acidification-known to inhibit aquaporins-lowered the P f in the PIPK cells down to control levels. (3) The transcript of at least one aquaporin was elevated in the PIPK cells. Together, the three results demonstrate the differences between the PIPK cells and their controls, and suggest a hitherto unobserved regulation of aquaporins by phosphoinositides, which could occur through direct interaction or indirect phosphoinositides-dependent cellular effects.

  16. Arctigenin enhances swimming endurance of sedentary rats partially by regulation of antioxidant pathways.

    Science.gov (United States)

    Wu, Ruo-ming; Sun, Yan-yan; Zhou, Ting-ting; Zhu, Zhi-yuan; Zhuang, Jing-jing; Tang, Xuan; Chen, Jing; Hu, Li-hong; Shen, Xu

    2014-10-01

    Arctigenin, a phenylpropanoid dibenzylbutyrolactone lignan found in traditional Chinese herbs, has been determined to exhibit a variety of pharmacological activities, including anti-tumor, anti-inflammation, neuroprotection, and endurance enhancement. In the present study, we investigated the antioxidation and anti-fatigue effects of arctigenin in rats. Rat L6 skeletal muscle cell line was exposed to H2O2 (700 μmol/L), and ROS level was assayed using DCFH-DA as a probe. Male SD rats were injected with arctigenin (15 mg·kg(-1)·d(-1), ip) for 6 weeks, and then the weight-loaded forced swimming test (WFST) was performed to evaluate their endurance. The levels of antioxidant-related genes in L6 cells and the skeletal muscles of rats were analyzed using real-time RT-PCR and Western blotting. Incubation of L6 cells with arctigenin (1, 5, 20 μmol/L) dose-dependently decreased the H2O2-induced ROS production. WFST results demonstrated that chronic administration of arctigenin significantly enhanced the endurance of rats. Furthermore, molecular biology studies on L6 cells and skeletal muscles of the rats showed that arctigenin effectively increased the expression of the antioxidant-related genes, including superoxide dismutase (SOD), glutathione reductase (Gsr), glutathione peroxidase (GPX1), thioredoxin (Txn) and uncoupling protein 2 (UCP2), through regulation of two potential antioxidant pathways: AMPK/PGC-1α/PPARα in mitochondria and AMPK/p53/Nrf2 in the cell nucleus. Arctigenin efficiently enhances rat swimming endurance by elevation of the antioxidant capacity of the skeletal muscles, which has thereby highlighted the potential of this natural product as an antioxidant in the treatment of fatigue and related diseases.

  17. Arctigenin enhances swimming endurance of sedentary rats partially by regulation of antioxidant pathways

    Science.gov (United States)

    Wu, Ruo-ming; Sun, Yan-yan; Zhou, Ting-ting; Zhu, Zhi-yuan; Zhuang, Jing-jing; Tang, Xuan; Chen, Jing; Hu, Li-hong; Shen, Xu

    2014-01-01

    Aim: Arctigenin, a phenylpropanoid dibenzylbutyrolactone lignan found in traditional Chinese herbs, has been determined to exhibit a variety of pharmacological activities, including anti-tumor, anti-inflammation, neuroprotection, and endurance enhancement. In the present study, we investigated the antioxidation and anti-fatigue effects of arctigenin in rats. Methods: Rat L6 skeletal muscle cell line was exposed to H2O2 (700 μmol/L), and ROS level was assayed using DCFH-DA as a probe. Male SD rats were injected with arctigenin (15 mg·kg−1·d−1, ip) for 6 weeks, and then the weight-loaded forced swimming test (WFST) was performed to evaluate their endurance. The levels of antioxidant-related genes in L6 cells and the skeletal muscles of rats were analyzed using real-time RT-PCR and Western blotting. Results: Incubation of L6 cells with arctigenin (1, 5, 20 μmol/L) dose-dependently decreased the H2O2-induced ROS production. WFST results demonstrated that chronic administration of arctigenin significantly enhanced the endurance of rats. Furthermore, molecular biology studies on L6 cells and skeletal muscles of the rats showed that arctigenin effectively increased the expression of the antioxidant-related genes, including superoxide dismutase (SOD), glutathione reductase (Gsr), glutathione peroxidase (GPX1), thioredoxin (Txn) and uncoupling protein 2 (UCP2), through regulation of two potential antioxidant pathways: AMPK/PGC-1α/PPARα in mitochondria and AMPK/p53/Nrf2 in the cell nucleus. Conclusion: Arctigenin efficiently enhances rat swimming endurance by elevation of the antioxidant capacity of the skeletal muscles, which has thereby highlighted the potential of this natural product as an antioxidant in the treatment of fatigue and related diseases. PMID:25152028

  18. CCAAT/Enhancer Binding Protein β Regulates Expression of Indian Hedgehog during Chondrocytes Differentiation

    Science.gov (United States)

    Ushijima, Takahiro; Okazaki, Ken; Tsushima, Hidetoshi; Ishihara, Kohei; Doi, Toshio; Iwamoto, Yukihide

    2014-01-01

    Background CCAAT/enhancer binding protein β (C/EBPβ) is a transcription factor that promotes hypertrophic differentiation of chondrocytes. Indian hedgehog (Ihh) also stimulates the hypertrophic transition of chondrocytes. Furthermore, runt-related transcription factor-2 (RUNX2) was reported to regulate chondrocyte maturation during skeletal development and to directly regulate transcriptional activity of Ihh. In this study, we investigated whether the interaction of C/EBPβ and RUNX2 regulates the expression of Ihh during chondrocyte differentiation. Methodology/Results Immunohistochemistry of embryonic growth plate revealed that both C/EBPβ and Ihh were strongly expressed in pre-hypertrophic and hypertrophic chondrocytes. Overexpression of C/EBPβ by adenovirus vector in ATDC5 cells caused marked stimulation of Ihh and Runx2. Conversely, knockdown of C/EBPβ by lentivirus expressing shRNA significantly repressed Ihh and Runx2 in ATDC5 cells. A reporter assay revealed that C/EBPβ stimulated transcriptional activity of Ihh. Deletion and mutation analysis showed that the C/EBPβ responsive element was located between −214 and −210 bp in the Ihh promoter. An electrophoretic mobility shift assay (EMSA) and a chromatin immunoprecipitation (ChIP) assay also revealed the direct binding of C/EBPβ to this region. Moreover, reporter assays demonstrated that RUNX2 failed to stimulate the transcriptional activity of the Ihh promoter harboring a mutation at the C/EBPβ binding site. EMSA and ChIP assays showed that RUNX2 interacted to this element with C/EBPβ. Immunoprecipitation revealed that RUNX2 and C/EBPβ formed heterodimer complex with each other in the nuclei of chondrocytes. These data suggested that the C/EBPβ binding element is also important for RUNX2 to regulate the expression of Ihh. Ex vivo organ culture of mouse limbs transfected with C/EBPβ showed that the expression of Ihh and RUNX2 was increased upon ectopic C/EBPβ expression. Conclusions C

  19. CCAAT/enhancer binding protein β regulates expression of Indian hedgehog during chondrocytes differentiation.

    Directory of Open Access Journals (Sweden)

    Takahiro Ushijima

    Full Text Available CCAAT/enhancer binding protein β (C/EBPβ is a transcription factor that promotes hypertrophic differentiation of chondrocytes. Indian hedgehog (Ihh also stimulates the hypertrophic transition of chondrocytes. Furthermore, runt-related transcription factor-2 (RUNX2 was reported to regulate chondrocyte maturation during skeletal development and to directly regulate transcriptional activity of Ihh. In this study, we investigated whether the interaction of C/EBPβ and RUNX2 regulates the expression of Ihh during chondrocyte differentiation.Immunohistochemistry of embryonic growth plate revealed that both C/EBPβ and Ihh were strongly expressed in pre-hypertrophic and hypertrophic chondrocytes. Overexpression of C/EBPβ by adenovirus vector in ATDC5 cells caused marked stimulation of Ihh and Runx2. Conversely, knockdown of C/EBPβ by lentivirus expressing shRNA significantly repressed Ihh and Runx2 in ATDC5 cells. A reporter assay revealed that C/EBPβ stimulated transcriptional activity of Ihh. Deletion and mutation analysis showed that the C/EBPβ responsive element was located between -214 and -210 bp in the Ihh promoter. An electrophoretic mobility shift assay (EMSA and a chromatin immunoprecipitation (ChIP assay also revealed the direct binding of C/EBPβ to this region. Moreover, reporter assays demonstrated that RUNX2 failed to stimulate the transcriptional activity of the Ihh promoter harboring a mutation at the C/EBPβ binding site. EMSA and ChIP assays showed that RUNX2 interacted to this element with C/EBPβ. Immunoprecipitation revealed that RUNX2 and C/EBPβ formed heterodimer complex with each other in the nuclei of chondrocytes. These data suggested that the C/EBPβ binding element is also important for RUNX2 to regulate the expression of Ihh. Ex vivo organ culture of mouse limbs transfected with C/EBPβ showed that the expression of Ihh and RUNX2 was increased upon ectopic C/EBPβ expression.C/EBPβ and RUNX2 cooperatively stimulate

  20. What Teachers Think about Self-Regulated Learning: Investigating Teacher Beliefs and Teacher Behavior of Enhancing Students’ Self-Regulation

    OpenAIRE

    Dignath-van Ewijk, Charlotte; van der Werf, Greetje

    2012-01-01

    In order to foster self-regulated learning (SRL), teachers should provide students with learning strategies, as well as with constructivist learning environments that allow them to self-regulate their learning. These two components complement each other. When investigating teachers’ promotion of SRL, not only teacher behavior, but also teachers’ beliefs as well as their knowledge about SRL are relevant aspects to consider. Therefore, this study seeks to examine teachers’ knowledge and beliefs...

  1. A single enhancer regulating the differential expression of duplicated red-sensitive opsin genes in zebrafish.

    Directory of Open Access Journals (Sweden)

    Taro Tsujimura

    2010-12-01

    Full Text Available A fundamental step in the evolution of the visual system is the gene duplication of visual opsins and differentiation between the duplicates in absorption spectra and expression pattern in the retina. However, our understanding of the mechanism of expression differentiation is far behind that of spectral tuning of opsins. Zebrafish (Danio rerio have two red-sensitive cone opsin genes, LWS-1 and LWS-2. These genes are arrayed in a tail-to-head manner, in this order, and are both expressed in the long member of double cones (LDCs in the retina. Expression of the longer-wave sensitive LWS-1 occurs later in development and is thus confined to the peripheral, especially ventral-nasal region of the adult retina, whereas expression of LWS-2 occurs earlier and is confined to the central region of the adult retina, shifted slightly to the dorsal-temporal region. In this study, we employed a transgenic reporter assay using fluorescent proteins and P1-artificial chromosome (PAC clones encompassing the two genes and identified a 0.6-kb "LWS-activating region" (LAR upstream of LWS-1, which regulates expression of both genes. Under the 2.6-kb flanking upstream region containing the LAR, the expression pattern of LWS-1 was recapitulated by the fluorescent reporter. On the other hand, when LAR was directly conjugated to the LWS-2 upstream region, the reporter was expressed in the LDCs but also across the entire outer nuclear layer. Deletion of LAR from the PAC clones drastically lowered the reporter expression of the two genes. These results suggest that LAR regulates both LWS-1 and LWS-2 by enhancing their expression and that interaction of LAR with the promoters is competitive between the two genes in a developmentally restricted manner. Sharing a regulatory region between duplicated genes could be a general way to facilitate the expression differentiation in duplicated visual opsins.

  2. New International Initiatives on Enhancement of Biosafety and Biosecurity Regulations for Laboratories Handling Infectious Agents

    International Nuclear Information System (INIS)

    Netesov, S. V.; Drozdov, I. G.

    2007-01-01

    . Establishing international associations of biosafety experts from different countries and regions in order to improve the international integration of efforts in this field and harmonization of said rules and regulations; 4. Continued development of international codes and rules of ethics for scientists and experts handling dangerous pathogens. In Russia these new initiatives were met with complete understanding, and some of them were considered as being extremely important. In particular, a decision was made to revise and enhance the current inventory procedures and regulations, those of inventory monitoring, and transportation of specimens and strains of extremely hazardous infections; and develop special additional regulatory documents in this area. At the same time, a significant amount of work should still be done to implement the above-mentioned proposals and approaches in biosafety and biosecurity taking into account the current situation in this field in Russia. (author)

  3. Interleukin-3 enhances the migration of human mesenchymal stem cells by regulating expression of CXCR4.

    Science.gov (United States)

    Barhanpurkar-Naik, Amruta; Mhaske, Suhas T; Pote, Satish T; Singh, Kanupriya; Wani, Mohan R

    2017-07-14

    subcutaneously implanted matrigel-releasing-SDF-1α in immunocompromised mice. The present study demonstrates for the first time that IL-3 has an important role in enhancing the migration of human MSCs through regulation of the CXCR4/SDF-1α axis. These findings suggest a potential role of IL-3 in improving the efficacy of MSCs in regenerative cell therapy.

  4. Municipalities as facilitators, regulators and energy consumers for enhancing the dissemination of biogas technology in Denmark

    Directory of Open Access Journals (Sweden)

    Rikke Lybæk

    2015-06-01

    Full Text Available Biogas provides many potential benefits as far as renewable energy production, environmental protection and job creation etc. Insufficient initiatives from government/municipalities however hamper more biogas plants to be established, and hence that the large manure potential, and other types of digestible organic waste materials, are being utilized for energy purposes. By looking at municipalities as energy consumer’s, that constitutes a local market for biogas, as regulator’s, enforcing new requirements and regulations on the biogas sector, and finally as facilitator’s, assisting and helping involved stakeholders, the development of the biogas sector could be enhanced. We suggest to: Slim the documentation needed; Require that a part of the municipal heat are provided by biogas; Identify alternative heat markets for sale of non-upgraded biogas; Map new types of gas boosters, etc. We conclude that the role of municipalities as facilitator’s is the most important support that local governments can provide to support biogas.

  5. Self-Regulated Learning Strategies of Engineering College Students While Learning Electric Circuit Concepts with Enhanced Guided Notes

    Science.gov (United States)

    Lawanto, Oenardi; Santoso, Harry

    2013-01-01

    The current study evaluated engineering college students' self-regulated learning (SRL) strategies while learning electric circuit concepts using enhanced guided notes (EGN). Our goal was to describe how students exercise SRL strategies and how their grade performance changes after using EGN. Two research questions guided the study: (1) To what…

  6. Emotion Regulation Enhancement of Cognitive Behavior Therapy for College Student Problem Drinkers: A Pilot Randomized Controlled Trial

    Science.gov (United States)

    Ford, Julian D.; Grasso, Damion J.; Levine, Joan; Tennen, Howard

    2018-01-01

    This pilot randomized clinical trial tested an emotion regulation enhancement to cognitive behavior therapy (CBT) with 29 college student problem drinkers with histories of complex trauma and current clinically significant traumatic stress symptoms. Participants received eight face-to-face sessions of manualized Internet-supported CBT for problem…

  7. Active and inactive enhancers co-operate to exert localized and long-range control of gene regulation

    Science.gov (United States)

    Proudhon, Charlotte; Snetkova, Valentina; Raviram, Ramya; Lobry, Camille; Badri, Sana; Jiang, Tingting; Hao, Bingtao; Trimarchi, Thomas; Kluger, Yuval; Aifantis, Iannis; Bonneau, Richard; Skok, Jane A

    2016-01-01

    V(D)J recombination relies on the presence of proximal enhancers that activate the antigen receptor (AgR) loci in a lineage and stage specific manner. Unexpectedly we find that both active and inactive AgR enhancers co-operate to disseminate their effects in a localized and long-range manner. Here we demonstrate the importance of short-range contacts between active enhancers that constitute an Igk super-enhancer in B cells. Deletion of one element reduces the interaction frequency between other enhancers in the hub, which compromises the transcriptional output of each component. We further establish that in T cells long-range contact and co-operation between the inactive Igk enhancer, MiEκ and the active Tcrb enhancer, Eβ, alters enrichment of CBFβ binding in a manner that impacts Tcrb recombination. These findings underline the complexities of enhancer regulation and point to a role for localized and long-range enhancer-sharing between active and inactive elements in lineage and stage specific control. PMID:27239026

  8. Uncovering client retention antecedents in service organizations

    Directory of Open Access Journals (Sweden)

    Mari Jansen van Rensburg

    2014-01-01

    Full Text Available This paper develops a multi-dimensional model of retention to provide a more complete and integrated view of client retention and its determinants in service contexts. To uncover the antecedents of client retention, social and economic exchanges were reviewed under the fundamental ideas of the Social Exchange Theory. Findings from a survey of senior South African advertising executives suggest that client retention is the result of evaluative as well as relational factors that can influence client responses. Despite contractual obligations, advertisers are willing to pay the costs and make the sacrifices of switching should their expectations be unmet. An important contribution of this study is the use of multi-item scales to measure retention. The model developed provides valuable insight to agencies on client retention management and the optimal allocation of resources for maximum customer equity. This model may also be applied to other service organisations to provide insight to client retention.

  9. Hepatitis C virus host cell interactions uncovered

    DEFF Research Database (Denmark)

    Gottwein, Judith; Bukh, Jens

    2007-01-01

      Insights into virus-host cell interactions as uncovered by Randall et al. (1) in a recent issue of PNAS further our understanding of the hepatitis C virus (HCV) life cycle, persistence, and pathogenesis and might lead to the identification of new therapeutic targets. HCV persistently infects 180...... million individuals worldwide, causing chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The only approved treatment, combination therapy with IFN- and ribavirin, targets cellular pathways (2); however, a sustained virologic response is achieved only in approximately half of the patients...... treated. Therefore, there is a pressing need for the identification of novel drugs against hepatitis C. Although most research focuses on the development of HCV-specific antivirals, such as protease and polymerase inhibitors (3), cellular targets could be pursued and might allow the development of broad...

  10. Technologically enhanced naturally occurring radioactive material (TENORM) and its regulation. Aspects at issue

    International Nuclear Information System (INIS)

    Menon, Shankar

    2001-01-01

    It has been known for quite a long time that mankind lives in a naturally radioactive world. However, it is only during the last decade that it has become generally registered that naturally occurring radioactive material (NORM) is artificially concentrated ('technologically enhanced') in many non- nuclear industries. This concentration, termed TENORM, can be in the products, the by- products or the wastes arising from these industries. The emergence of the NORM/TENORM issue has been of great significance for the discussions on clearance regulations in the nuclear industry. A task group of the OECD/NEA Co-operative Programme on Decommissioning has found that TENORM arisings occur in huge quantities; two to three orders of magnitude larger than those used in European studies on release of material from the nuclear industry. The activity levels in TENORM arisings are generally the same as in very low level nuclear waste. Their occurrence in a large number of industries, as well as their activity levels and quantities, have not been generally known, even to regulatory authorities, until fairly recently. Thus the regulation of TENORM is in its early stages. Ra 226 with a half-life of 1,600 years is by far the most important radionuclide. These data are only shown to give an idea of quantities and activity levels. Other industries with significant radioactive waste streams are petroleum processing, geothermal plants and paper mills. Studies by the European Commission have shown that more or less comparable quantities of TENORM arise in Europe, with similar concentrations of radioactivity. Two of the largest source industries of TENORM are the coal and fertiliser industries. According to UNSCEAR, 280 million tons of coal ash arise globally every year. 40 million tons are used in the production of bricks and cement and 'a great deal' is utilised as road stabiliser, road fill, asphalt mix and fertiliser. Annual doses to residents can be up to several mSv. These doses are

  11. Endothelial cell SHP-2 negatively regulates neutrophil adhesion and promotes transmigration by enhancing ICAM-1-VE-cadherin interaction.

    Science.gov (United States)

    Yan, Meiping; Zhang, Xinhua; Chen, Ao; Gu, Wei; Liu, Jie; Ren, Xiaojiao; Zhang, Jianping; Wu, Xiaoxiong; Place, Aaron T; Minshall, Richard D; Liu, Guoquan

    2017-11-01

    Intercellular adhesion molecule-1 (ICAM-1) mediates the firm adhesion of leukocytes to endothelial cells and initiates subsequent signaling that promotes their transendothelial migration (TEM). Vascular endothelial (VE)-cadherin plays a critical role in endothelial cell-cell adhesion, thereby controlling endothelial permeability and leukocyte transmigration. This study aimed to determine the molecular signaling events that originate from the ICAM-1-mediated firm adhesion of neutrophils that regulate VE-cadherin's role as a negative regulator of leukocyte transmigration. We observed that ICAM-1 interacts with Src homology domain 2-containing phosphatase-2 (SHP-2), and SHP-2 down-regulation via silencing of small interfering RNA in endothelial cells enhanced neutrophil adhesion to endothelial cells but inhibited neutrophil transmigration. We also found that VE-cadherin associated with the ICAM-1-SHP-2 complex. Moreover, whereas the activation of ICAM-1 leads to VE-cadherin dissociation from ICAM-1 and VE-cadherin association with actin, SHP-2 down-regulation prevented ICAM-1-VE-cadherin association and promoted VE-cadherin-actin association. Furthermore, SHP-2 down-regulation in vivo promoted LPS-induced neutrophil recruitment in mouse lung but delayed neutrophil extravasation. These results suggest that SHP-2- via association with ICAM-1-mediates ICAM-1-induced Src activation and modulates VE-cadherin switching association with ICAM-1 or actin, thereby negatively regulating neutrophil adhesion to endothelial cells and enhancing their TEM.-Yan, M., Zhang, X., Chen, A., Gu, W., Liu, J., Ren, X., Zhang, J., Wu, X., Place, A. T., Minshall, R. D., Liu, G. Endothelial cell SHP-2 negatively regulates neutrophil adhesion and promotes transmigration by enhancing ICAM-1-VE-cadherin interaction. © FASEB.

  12. Solution scanning as a key policy tool: identifying management interventions to help maintain and enhance regulating ecosystem services

    Directory of Open Access Journals (Sweden)

    William J. Sutherland

    2014-06-01

    Full Text Available The major task of policy makers and practitioners when confronted with a resource management problem is to decide on the potential solution(s to adopt from a range of available options. However, this process is unlikely to be successful and cost effective without access to an independently verified and comprehensive available list of options. There is currently burgeoning interest in ecosystem services and quantitative assessments of their importance and value. Recognition of the value of ecosystem services to human well-being represents an increasingly important argument for protecting and restoring the natural environment, alongside the moral and ethical justifications for conservation. As well as understanding the benefits of ecosystem services, it is also important to synthesize the practical interventions that are capable of maintaining and/or enhancing these services. Apart from pest regulation, pollination, and global climate regulation, this type of exercise has attracted relatively little attention. Through a systematic consultation exercise, we identify a candidate list of 296 possible interventions across the main regulating services of air quality regulation, climate regulation, water flow regulation, erosion regulation, water purification and waste treatment, disease regulation, pest regulation, pollination and natural hazard regulation. The range of interventions differs greatly between habitats and services depending upon the ease of manipulation and the level of research intensity. Some interventions have the potential to deliver benefits across a range of regulating services, especially those that reduce soil loss and maintain forest cover. Synthesis and applications: Solution scanning is important for questioning existing knowledge and identifying the range of options available to researchers and practitioners, as well as serving as the necessary basis for assessing cost effectiveness and guiding implementation strategies. We

  13. What Teachers Think about Self-Regulated Learning: Investigating Teacher Beliefs and Teacher Behavior of Enhancing Students’ Self-Regulation

    Directory of Open Access Journals (Sweden)

    Charlotte Dignath-van Ewijk

    2012-01-01

    Full Text Available In order to foster self-regulated learning (SRL, teachers should provide students with learning strategies, as well as with constructivist learning environments that allow them to self-regulate their learning. These two components complement each other. When investigating teachers’ promotion of SRL, not only teacher behavior, but also teachers’ beliefs as well as their knowledge about SRL are relevant aspects to consider. Therefore, this study seeks to examine teachers’ knowledge and beliefs on promoting SRL, as well as their predictive value on teachers’ promotion of SRL in the classroom. Forty-seven primary school teachers completed questionnaires on knowledge and beliefs towards both components of the promotion of SRL: strategy instruction and a constructivist learning environment. In addition, teachers had to answer open-ended questions on their understanding of SRL, as well as their implementation of SRL in their classroom. The results show that teachers are more positive towards constructivist than towards SRL (teacher beliefs, and most teachers mentioned characteristics of constructivist learning environments, while only few teachers addressed strategy instruction when being asked about their understanding of SRL (teacher knowledge. Moreover, teacher beliefs are the only predictor for teacher behavior. The results indicate how teacher education could support teachers to learn how to promote SRL effectively.

  14. Sustained response with ixekizumab treatment of moderate-to-severe psoriasis with scalp involvement: results from three phase 3 trials (UNCOVER-1, UNCOVER-2, UNCOVER-3).

    Science.gov (United States)

    Reich, Kristian; Leonardi, Craig; Lebwohl, Mark; Kerdel, Francisco; Okubo, Yukari; Romiti, Ricardo; Goldblum, Orin; Dennehy, Ellen B; Kerr, Lisa; Sofen, Howard

    2017-06-01

    Scalp is a frequently affected and difficult-to-treat area in psoriasis patients. We assessed the efficacy of ixekizumab in the treatment of patients with scalp psoriasis over 60 weeks using the Psoriasis Scalp Severity Index (PSSI). In three Phase 3, multicenter, double-blind, placebo-controlled trials, patients with moderate-to-severe psoriasis in UNCOVER-1 (N = 1296), UNCOVER-2 (N = 1224) and UNCOVER-3 (N = 1346) were randomized to subcutaneous 80 mg ixekizumab every two weeks (Q2W) or every four weeks (Q4W) after a 160 mg starting dose, or placebo through Week 12. Additional UNCOVER-2 and UNCOVER-3 cohorts were randomized to 50 mg bi-weekly etanercept through Week 12. Patients entering the open-label long-term extension (LTE) (UNCOVER-3) received ixekizumab Q4W; UNCOVER-1 and UNCOVER-2 included a blinded maintenance period in which static physician global assessment (sPGA) 0/1 responders were re-randomized to placebo, ixekizumab Q4W, or 80 mg ixekizumab every 12 weeks (Q12W) through Week 60. In patients with moderate-to-severe psoriasis with baseline scalp involvement, PSSI 90 and 100 were achieved at Week 12 in higher percentages of patients treated with ixekizumab Q2W (81.7% and 74.6%) or ixekizumab Q4W (75.6% and 68.9%) compared with patients treated with placebo (7.6% and 6.7%; p psoriasis in patients with moderate-to-severe psoriasis, with most patients achieving complete or near-complete resolution of scalp psoriasis and maintaining this response over 60 weeks.

  15. Hydraulic behaviour of a partially uncovered core

    International Nuclear Information System (INIS)

    Fischer, K.; Hafner, W.

    1989-10-01

    A critical review of experimental data and theoretical models relevant to the thermohydraulic processes in a partially uncovered core has been performed. Presently available optimized thermohydraulic codes should be able to predict swell level elevations within an error band of ± 0.5 m. Rod temperature rising velocities could be predicted within an error bandwidth of ± 10%, provided the correct rod heat capacity is given. A general statement about the accuracy of predicted rod temperatures is not possible because the errors increase with simulation time. Highest errors are expected for long transients with low heating rates and low steam velocities. As a result, three areas for additional research are suggested: - a high-pressure test at 120 bar to complete the void correlation data base, - a low steam flow - low power experiment to improve heat transfer correlations, - a numerical investigation of three-dimensional effects in the reactor core with unequally heated rod bundles. For the present state of 1-dimensional experiments and models, suggestions for a satisfactory modeling have been derived. The suggested further work could improve the modelling capabilities and the code reliability for some limiting cases like high pressure boil-off, low-power long-term steam cooling, and unequal heating of neighbouring bundles considerably

  16. Uncovering Indicators of Commercial Sexual Exploitation.

    Science.gov (United States)

    Bounds, Dawn; Delaney, Kathleen R; Julion, Wrenetha; Breitenstein, Susan

    2017-07-01

    It is estimated that annually 100,000 to 300,000 youth are at risk for sex trafficking; a commercial sex act induced by force, fraud, or coercion, or any such act where the person induced to perform such an act is younger than 18 years of age. Increasingly, such transactions are occurring online via Internet-based sites that serve the commercial sex industry. Commercial sex transactions involving trafficking are illegal; thus, Internet discussions between those involved must be veiled. Even so, transactions around sex trafficking do occur. Within these transactions are innuendos that provide one avenue for detecting potential activity. The purpose of this study is to identify linguistic indicators of potential commercial sexual exploitation within the online comments of men posted on an Internet site. Six hundred sixty-six posts from five Midwest cities and 363 unique members were analyzed via content analysis. Three main indicators were found: the presence of youth or desire for youthfulness, presence of pimps, and awareness of vulnerability. These findings begin a much-needed dialogue on uncovering online risks of commercial sexual exploitation and support the need for further research on Internet indicators of sex trafficking.

  17. Uncovering missing links with cold ends

    Science.gov (United States)

    Zhu, Yu-Xiao; Lü, Linyuan; Zhang, Qian-Ming; Zhou, Tao

    2012-11-01

    To evaluate the performance of prediction of missing links, the known data are randomly divided into two parts, the training set and the probe set. We argue that this straightforward and standard method may lead to terrible bias, since in real biological and information networks, missing links are more likely to be links connecting low-degree nodes. We therefore study how to uncover missing links with low-degree nodes, namely links in the probe set are of lower degree products than a random sampling. Experimental analysis on ten local similarity indices and four disparate real networks reveals a surprising result that the Leicht-Holme-Newman index [E.A. Leicht, P. Holme, M.E.J. Newman, Vertex similarity in networks, Phys. Rev. E 73 (2006) 026120] performs the best, although it was known to be one of the worst indices if the probe set is a random sampling of all links. We further propose an parameter-dependent index, which considerably improves the prediction accuracy. Finally, we show the relevance of the proposed index to three real sampling methods: acquaintance sampling, random-walk sampling and path-based sampling.

  18. Enhancing cellulase production by overexpression of xylanase regulator protein gene, xlnR, in Talaromyces cellulolyticus cellulase hyperproducing mutant strain.

    Science.gov (United States)

    Okuda, Naoyuki; Fujii, Tatsuya; Inoue, Hiroyuki; Ishikawa, Kazuhiko; Hoshino, Tamotsu

    2016-10-01

    We obtained strains with the xylanase regulator gene, xlnR, overexpressed (HXlnR) and disrupted (DXlnR) derived from Talaromyces cellulolyticus strain C-1, which is a cellulase hyperproducing mutant. Filter paper degrading enzyme activity and cellobiohydrolase I gene expression was the highest in HXlnR, followed by C-1 and DXlnR. These results indicate that the enhancement of cellulase productivity was succeeded by xlnR overexpression.

  19. Active Learning and Self-Regulation Enhance Student Teachers' Professional Competences

    Science.gov (United States)

    Virtanen, Päivi; Niemi, Hannele M.; Nevgi, Anne

    2017-01-01

    The study identifies the relationships between active learning, student teachers' self-regulated learning and professional competences. Further, the aim is to investigate how active learning promotes professional competences of student teachers with different self-regulation profiles. Responses from 422 student teachers to an electronic survey…

  20. Using Self-Regulated Learning Strategies in Enhancing Language Proficiency with a Focus on Reading Comprehension

    Science.gov (United States)

    Abbasian, Gholam-Reza; Hartoonian, Anahid

    2014-01-01

    Self-regulated learning strategies have recently received a remarkable attention by researchers. The aim of this study was to explore the relationship between self-regulated learning strategies and students' language proficiency as well as their reading comprehension. To do so, 115 Iranian EFL university students were selected. First, a TOEFL test…

  1. Activated Integrin-Linked Kinase Negatively Regulates Muscle Cell Enhancement Factor 2C in C2C12 Cells

    Directory of Open Access Journals (Sweden)

    Zhenguo Dong

    2015-01-01

    Full Text Available Our previous study reported that muscle cell enhancement factor 2C (MEF2C was fully activated after inhibition of the phosphorylation activity of integrin-linked kinase (ILK in the skeletal muscle cells of goats. It enhanced the binding of promoter or enhancer of transcription factor related to proliferation of muscle cells and then regulated the expression of these genes. In the present investigation, we explored whether ILK activation depended on PI3K to regulate the phosphorylation and transcriptional activity of MEF2C during C2C12 cell proliferation. We inhibited PI3K activity in C2C12 with LY294002 and then found that ILK phosphorylation levels and MEF2C phosphorylation were decreased and that MCK mRNA expression was suppressed significantly. After inhibiting ILK phosphorylation activity with Cpd22 and ILK-shRNA, we found MEF2C phosphorylation activity and MCK mRNA expression were increased extremely significantly. In the presence of Cpd22, PI3K activity inhibition increased MEF2C phosphorylation and MCK mRNA expression indistinctively. We conclude that ILK negatively and independently of PI3K regulated MEF2C phosphorylation activity and MCK mRNA expression in C2C12 cells. The results provide new ideas for the study of classical signaling pathway of PI3K-ILK-related proteins and transcription factors.

  2. Enhancing offspring hypothalamic-pituitary-adrenal (HPA regulation via systematic neonatal novelty exposure: the influence of maternal HPA function

    Directory of Open Access Journals (Sweden)

    Sarah M. Dinces

    2014-06-01

    Full Text Available In the rat, repeated brief exposures to novelty early in life can induce long-lasting enhancements in adult cognitive, social, emotional, and neuroendocrine function. Family-to-family variations in these intervention effects on adult offspring are predicted by the mother’s ability to mount a rapid corticosterone (CORT response to the onset of an acute stressor. Here, in Long-Evans rats, we investigated whether neonatal and adulthood novelty exposure, each individually and in combination, can enhance offspring HPA regulation. Using a 2x2 within-litter design, one half of each litter were exposed to a relatively novel non-home environment for 3-min (Neo_Novel daily during infancy (PND1-21 and the other half of the litter remained in the home cage (Neo_Home; we further exposed half of these two groups to early adulthood (PND54-63 novelty exposure in an open field and the remaining siblings stayed in their home cages. Two aspects of HPA regulation were assessed: the ability to maintain a low level of resting CORT (CORTB and the ability to mount a large rapid CORT response (CORTE to the onset of an acute stressor. Assessment of adult offspring’s ability to regulate HPA regulation began at 370 days of age. We further investigated whether the novelty exposure effects on offspring HPA regulation are sensitive to the context of maternal HPA regulation by assessing maternal HPA regulation similarly beginning 7 days after her pups were weaned. We found that at the population level, rats receiving neonatal, but not early adulthood exposure or both, showed a greater rapid CORTE than their home-staying siblings. At the individual family level, these novelty effects are positively associated with maternal CORTE. These results suggest that early experience of novelty can enhance the offspring’s ability to mount a rapid response to environmental challenge and the success of such early life intervention is critically dependent upon the context of maternal

  3. Consolidity: Mystery of inner property of systems uncovered

    Directory of Open Access Journals (Sweden)

    Hassen T. Dorrah

    2012-10-01

    Full Text Available This paper uncovers the mystery of consolidity, an inner property of systems that was amazingly hidden. Consolidity also reveals the secrecy of why strong stable and highly controllable systems are not invulnerable of falling and collapsing. Consolidity is measured by its Consolidity Index, defined as the ratio of overall changes of output parameters over combined changes of input and system parameters, all operating in fully fuzzy environment. Under this notion, systems are classified into consolidated, quasi-consolidated, neutrally consolidated, unconsolidated, quasi-unconsolidated and mixed types. The strategy for the implementation of consolidity is elaborated for both natural and man-made existing systems as well as the new developed ones. An important critique arises that the by-product consolidity of natural or built-as-usual system could lead to trapping such systems into a completely undesired unconsolidity. This suggests that the ample number of conventional techniques that do not take system consolidity into account should gradually be changed, and adjusted with improved consolidity-based techniques. Four Golden Rules are highlighted for handling system consolidity, and applied to several illustrative case studies. These case studies cover the consolidity analysis of the Drug Concentration problem, Predator-Prey Population problem, Spread of Infectious Disease problem, AIDS Epidemic problem and Arm Race model. It is demonstrated that consolidity changes are contrary (opposite in sign to changes of both stability and controllability. This is a very significant result showing that our present practice of stressing on building strong stable and highly controllable systems could have already jeopardized the consolidity behavior of an ample family of existing real life systems. It is strongly recommended that the four Golden Rules of consolidity should be enforced as future strict regulations of systems modeling, analysis, design and

  4. Active Learning and Self-Regulation Enhance Student Teachers’ Professional Competences

    OpenAIRE

    Virtanen, Päivi; Niemi, Hannele M.; Nevgi, Anne

    2017-01-01

    The study identifies the relationships between active learning, student teachers’ self-regulated learning and professional competences. Further, the aim is to investigate how active learning promotes professional competences of student teachers with different self-regulation profiles. Responses from 422 student teachers to an electronic survey were analysed using statistical methods. It was found that the use of active learning methods, such as goal-oriented and intentional learning as well a...

  5. An ultra-low power output capacitor-less low-dropout regulator with slew-rate-enhanced circuit

    Science.gov (United States)

    Cheng, Xin; Zhang, Yu; Xie, Guangjun; Yang, Yizhong; Zhang, Zhang

    2018-03-01

    An ultra-low power output-capacitorless low-dropout (LDO) regulator with a slew-rate-enhanced (SRE) circuit is introduced. The increased slew rate is achieved by sensing the transient output voltage of the LDO and then charging (or discharging) the gate capacitor quickly. In addition, a buffer with ultra-low output impedance is presented to improve line and load regulations. This design is fabricated by SMIC 0.18 μm CMOS technology. Experimental results show that, the proposed LDO regulator only consumes an ultra-low quiescent current of 1.2 μA. The output current range is from 10 μA to 200 mA and the corresponding variation of output voltage is less than 40 mV. Moreover, the measured line regulation and load regulation are 15.38 mV/V and 0.4 mV/mA respectively. Project supported by the National Natural Science Foundation of China (Nos. 61401137, 61404043, 61674049).

  6. Cognitive enhancement by self-regulation of endogenous oscillations with neurofeedback

    NARCIS (Netherlands)

    Enriquez Geppert, Stefanie; Huster, René J; Ros, Tomas; Wood, Guilherme; Colzato, Lorenza

    2017-01-01

    In the last years, innovations in technology and methodology, as well as increased knowledge about cortical oscillations have significantly impacted the advancement of new neurofeedback approaches. As such, sham-controlled studies, showing evidence for enhanced performance of cognition after

  7. Enhancing Student Success in Online Learning Experiences through the Use of Self-Regulation Strategies

    Science.gov (United States)

    Sharp, Laurie A.; Sharp, Jason H.

    2016-01-01

    Online learning experiences have greatly changed the landscape of instruction. Many courses in postsecondary environments incorporate some type of technological enhancement, which holds benefits for both postsecondary institutions and learners. However, online learning experiences require different pedagogical characteristics than traditional…

  8. Does enhanced regulation improve EIA report quality? Lessons from South Africa

    Energy Technology Data Exchange (ETDEWEB)

    Sandham, L.A., E-mail: luke.sandham@nwu.ac.za [Environmental Assessment Research Group, School of Geo and Spatial Sciences, North-West University, Private Bag X6001, Potchefstroom, 2520 (South Africa); Heerden, A.J. van [Environmental Assessment Research Group, School of Geo and Spatial Sciences, North-West University, Private Bag X6001, Potchefstroom, 2520 (South Africa); Jones, C.E. [School of Environment and Development, University of Manchester, Oxford Road, Manchester, M13 9PL (United Kingdom); Retief, F.P.; Morrison-Saunders, A.N. [Environmental Assessment Research Group, School of Geo and Spatial Sciences, North-West University, Private Bag X6001, Potchefstroom, 2520 (South Africa)

    2013-01-15

    Recently, various EIA systems have been subjected to system review processes with a view to improve performance. Many of these reviews resulted in some form of legislative reform. The South African Environmental Impact Assessment (EIA) regulations were modified in 2006 with the express intent to improve EIA effectiveness. In order to evaluate to what extent the desired outcome was achieved, the quality of EIA reports produced under the 2006 regulations was investigated for comparative analysis with the preceding regime. A sample of EIA reports from the two legislative regimes was reviewed using an adapted version of a well established method known colloquially as the 'Lee and Colley' review package. Despite some improvements in certain aspects, overall report quality has decreased slightly from the 1997 EIA regime. It therefore appears that the modifications to the regulations, often heralded as the solution to improvements in performance have not resulted in improved quality of EIA reports. - Highlights: Black-Right-Pointing-Pointer EIA regulations in South Africa were revised and became more comprehensive in 2006. Black-Right-Pointing-Pointer The report quality of a sample of EIAs was reviewed using the Lee and Colley review package. Black-Right-Pointing-Pointer Report quality showed a slight decline from the previous regulatory regime. Black-Right-Pointing-Pointer EIA good practice needs flexibility rather than over-detailed regulation.

  9. Does enhanced regulation improve EIA report quality? Lessons from South Africa

    International Nuclear Information System (INIS)

    Sandham, L.A.; Heerden, A.J. van; Jones, C.E.; Retief, F.P.; Morrison-Saunders, A.N.

    2013-01-01

    Recently, various EIA systems have been subjected to system review processes with a view to improve performance. Many of these reviews resulted in some form of legislative reform. The South African Environmental Impact Assessment (EIA) regulations were modified in 2006 with the express intent to improve EIA effectiveness. In order to evaluate to what extent the desired outcome was achieved, the quality of EIA reports produced under the 2006 regulations was investigated for comparative analysis with the preceding regime. A sample of EIA reports from the two legislative regimes was reviewed using an adapted version of a well established method known colloquially as the “Lee and Colley” review package. Despite some improvements in certain aspects, overall report quality has decreased slightly from the 1997 EIA regime. It therefore appears that the modifications to the regulations, often heralded as the solution to improvements in performance have not resulted in improved quality of EIA reports. - Highlights: ► EIA regulations in South Africa were revised and became more comprehensive in 2006. ► The report quality of a sample of EIAs was reviewed using the Lee and Colley review package. ► Report quality showed a slight decline from the previous regulatory regime. ► EIA good practice needs flexibility rather than over-detailed regulation.

  10. CRP-Mediated Carbon Catabolite Regulation of Yersinia pestis Biofilm Formation Is Enhanced by the Carbon Storage Regulator Protein, CsrA.

    Directory of Open Access Journals (Sweden)

    Stephan P Willias

    Full Text Available The natural transmission of Yersinia pestis is reliant upon biofilm blockage of the flea vector. However, the environmentally-responsive adaptive regulators which facilitate Y. pestis biofilm production in accordance with the flea midgut milieu are not well understood. We seek to establish the impact of available carbon source metabolism and storage upon Y. pestis biofilm production. Our findings demonstrate that Y. pestis biofilm production is subject to carbon catabolite regulation in which the presence of glucose impairs biofilm production; whereas, the sole metabolism of alternate carbon sources promotes robust biofilm formation. This observation is facilitated by the cAMP receptor protein, CRP. In accordance with a stark growth defect, deletion of crp in both CO92 and KIM6+ Y. pestis strains significantly impaired biofilm production when solely utilizing alternate carbon sources. Media supplementation with cAMP, a small-molecule activator of CRP, did not significantly alter Y. pestis biofilm production. Furthermore, CRP did not alter mRNA abundance of previously-characterized hms biofilm synthesis and regulation factors. Therefore, our findings indicate CRP does not confer a direct stimulatory effect, but may indirectly promote Y. pestis biofilm production by facilitating the alternate carbon source expression profile. Additionally, we assessed the impact of the carbon storage regulator protein, CsrA, upon Y. pestis biofilm production. Contrary to what has been described for E. coli, Y. pestis biofilm formation was found to be enhanced by CsrA. Regardless of media composition and available carbon source, deletion of csrA significantly impaired Y. pestis biofilm production. CsrA was found to promote Y. pestis biofilm production independent of glycogen regulation. Loss of csrA did not significantly alter relative hmsH, hmsP, or hmsT mRNA abundance. However, deletion of hmsP in the csrA-deficient mutant enabled excessive biofilm production

  11. Role of Dlx6 in regulation of an endothelin-1-dependent, dHAND branchial arch enhancer

    Science.gov (United States)

    Charité, Jeroen; McFadden, David G.; Merlo, Giorgio; Levi, Giovanni; Clouthier, David E.; Yanagisawa, Masashi; Richardson, James A.; Olson, Eric N.

    2001-01-01

    Neural crest cells play a key role in craniofacial development. The endothelin family of secreted polypeptides regulates development of several neural crest sublineages, including the branchial arch neural crest. The basic helix–loop–helix transcription factor dHAND is also required for craniofacial development, and in endothelin-1 (ET-1) mutant embryos, dHAND expression in the branchial arches is down-regulated, implicating it as a transcriptional effector of ET-1 action. To determine the mechanism that links ET-1 signaling to dHAND transcription, we analyzed the dHAND gene for cis-regulatory elements that control transcription in the branchial arches. We describe an evolutionarily conserved dHAND enhancer that requires ET-1 signaling for activity. This enhancer contains four homeodomain binding sites that are required for branchial arch expression. By comparing protein binding to these sites in branchial arch extracts from endothelin receptor A (EdnrA) mutant and wild-type mouse embryos, we identified Dlx6, a member of the Distal-less family of homeodomain proteins, as an ET-1-dependent binding factor. Consistent with this conclusion, Dlx6 was down-regulated in branchial arches from EdnrA mutant mice. These results suggest that Dlx6 acts as an intermediary between ET-1 signaling and dHAND transcription during craniofacial morphogenesis. PMID:11711438

  12. Regulation of the Drosophila Enhancer of split and invected-engrailed gene complexes by sister chromatid cohesion proteins.

    Directory of Open Access Journals (Sweden)

    Cheri A Schaaf

    2009-07-01

    Full Text Available The cohesin protein complex was first recognized for holding sister chromatids together and ensuring proper chromosome segregation. Cohesin also regulates gene expression, but the mechanisms are unknown. Cohesin associates preferentially with active genes, and is generally absent from regions in which histone H3 is methylated by the Enhancer of zeste [E(z] Polycomb group silencing protein. Here we show that transcription is hypersensitive to cohesin levels in two exceptional cases where cohesin and the E(z-mediated histone methylation simultaneously coat the entire Enhancer of split and invected-engrailed gene complexes in cells derived from Drosophila central nervous system. These gene complexes are modestly transcribed, and produce seven of the twelve transcripts that increase the most with cohesin knockdown genome-wide. Cohesin mutations alter eye development in the same manner as increased Enhancer of split activity, suggesting that similar regulation occurs in vivo. We propose that cohesin helps restrain transcription of these gene complexes, and that deregulation of similarly cohesin-hypersensitive genes may underlie developmental deficits in Cornelia de Lange syndrome.

  13. Self-regulation strategies may enhance the acute effect of exercise on smoking delay.

    Science.gov (United States)

    Hatzigeorgiadis, Antonis; Pappa, Vassiliki; Tsiami, Anastasia; Tzatzaki, Theodora; Georgakouli, Kalliopi; Zourbanos, Nikos; Goudas, Marios; Chatzisarantis, Nikos; Theodorakis, Yannis

    2016-06-01

    The present study examined the acute effect of a moderate intensity aerobic exercise session combined with self-regulation on smoking delay in physically inactive smokers. Participants were 11 adults (5 males and 6 females) that completed three experimental conditions: control, exercise, and exercise using self-regulation strategies (SR). Following the experimental treatment smoking for the two exercise conditions delayed significantly more than for the control condition; in addition exercise SR delayed smoking marginally more that the plain exercise condition. Findings supported previous research that acute exercise reduces cravings to smoke, and suggests that the use of self-regulation strategies may strengthen exercise for smoking cessation interventions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Waste management regulations and approaches in the EU: potential areas for enhancement or harmonization

    International Nuclear Information System (INIS)

    Salzer, Peter; Butler, Gregg; McGlynn, Grace; Chapman, Neil; McCombie, Charles

    2007-01-01

    This paper describes the results of a survey and study performed for the European Commission on 'Regulations Governing Radioactive Waste Disposal in EU Countries'. Its main purposes were to provide a survey of the regulations governing the disposal of all forms of radioactive waste in all EU Members States and, based on this study, to consider the potential for harmonization in different regulatory areas. Three key parts of the study are presented and the results discussed: collection and assessment of national data, including its verification by national stakeholders, application of multi-attribute analysis methodology to identify optimal waste classification scheme and a workshop of national authorities regulating disposal of radioactive waste. For five determined regulatory issues, the workshop carried out a 'strengths, weaknesses, opportunities and threats' (SWOT) analysis of the impacts of harmonization. (authors)

  15. Self-regulated and technology-enhanced learning: a European perspective

    NARCIS (Netherlands)

    Mooij, Ton; Steffens, Karl; Andrade, Maureen Snow

    2014-01-01

    Self-regulation of learning, learning to learn, and their potential stimulation by specific Information and Communication Technologies (ICTs), are main topics in European policy. This issue of the ‘European Educational Research Journal’ (EERJ) focuses on research to develop, integrate, and evaluate

  16. Self-regulated and technology-enhanced learning: a European perspective

    NARCIS (Netherlands)

    Mooij, Ton; Steffens, Karl; Andrade, Maureen Snow

    2015-01-01

    Self-regulation of learning, learning to learn, and their potential stimulation by specific Information and Communication Technologies (ICTs), are main topics in European policy. This issue of the ‘European Educational Research Journal’ (EERJ) focuses on research to develop, integrate, and evaluate

  17. A Framework for Evaluating and Enhancing Alignment in Self-Regulated Learning Research

    Science.gov (United States)

    Dent, Amy L.; Hoyle, Rick H.

    2015-01-01

    We discuss the articles of this special issue with reference to an important yet previously only implicit dimension of study quality: alignment across the theoretical and methodological decisions that collectively define an approach to self-regulated learning. Integrating and extending work by leaders in the field, we propose a framework for…

  18. Enhancer-derived lncRNAs regulate genome architecture: fact or fiction?

    CSIR Research Space (South Africa)

    Fanucchi, Stephanie

    2017-06-01

    Full Text Available How does the non-coding portion of the genome contribute to the regulation of genome architecture? A recent paper by Tan et al. focuses on the relationship between cis-acting complex-trait-associated lincRNAs and the formation of chromosomal...

  19. Enhancing E. coli tolerance towards oxidative stress via engineering its global regulator cAMP receptor protein (CRP.

    Directory of Open Access Journals (Sweden)

    Souvik Basak

    Full Text Available Oxidative damage to microbial hosts often occurs under stressful conditions during bioprocessing. Classical strain engineering approaches are usually both time-consuming and labor intensive. Here, we aim to improve E. coli performance under oxidative stress via engineering its global regulator cAMP receptor protein (CRP, which can directly or indirectly regulate redox-sensing regulators SoxR and OxyR, and other ~400 genes in E. coli. Error-prone PCR technique was employed to introduce modifications to CRP, and three mutants (OM1~OM3 were identified with improved tolerance via H(2O(2 enrichment selection. The best mutant OM3 could grow in 12 mM H(2O(2 with the growth rate of 0.6 h(-1, whereas the growth of wild type was completely inhibited at this H(2O(2 concentration. OM3 also elicited enhanced thermotolerance at 48°C as well as resistance against cumene hydroperoxide. The investigation about intracellular reactive oxygen species (ROS, which determines cell viability, indicated that the accumulation of ROS in OM3 was always lower than in WT with or without H(2O(2 treatment. Genome-wide DNA microarray analysis has shown not only CRP-regulated genes have demonstrated great transcriptional level changes (up to 8.9-fold, but also RpoS- and OxyR-regulated genes (up to 7.7-fold. qRT-PCR data and enzyme activity assay suggested that catalase (katE could be a major antioxidant enzyme in OM3 instead of alkyl hydroperoxide reductase or superoxide dismutase. To our knowledge, this is the first work on improving E. coli oxidative stress resistance by reframing its transcription machinery through its native global regulator. The positive outcome of this approach may suggest that engineering CRP can be successfully implemented as an efficient strain engineering alternative for E. coli.

  20. Regulation of the glucocorticoid receptor via a BET-dependent enhancer drives antiandrogen resistance in prostate cancer.

    Science.gov (United States)

    Shah, Neel; Wang, Ping; Wongvipat, John; Karthaus, Wouter R; Abida, Wassim; Armenia, Joshua; Rockowitz, Shira; Drier, Yotam; Bernstein, Bradley E; Long, Henry W; Freedman, Matthew L; Arora, Vivek K; Zheng, Deyou; Sawyers, Charles L

    2017-09-11

    In prostate cancer, resistance to the antiandrogen enzalutamide (Enz) can occur through bypass of androgen receptor (AR) blockade by the glucocorticoid receptor (GR). In contrast to fixed genomic alterations, here we show that GR-mediated antiandrogen resistance is adaptive and reversible due to regulation of GR expression by a tissue-specific enhancer. GR expression is silenced in prostate cancer by a combination of AR binding and EZH2-mediated repression at the GR locus, but is restored in advanced prostate cancers upon reversion of both repressive signals. Remarkably, BET bromodomain inhibition resensitizes drug-resistant tumors to Enz by selectively impairing the GR signaling axis via this enhancer. In addition to revealing an underlying molecular mechanism of GR-driven drug resistance, these data suggest that inhibitors of broadly active chromatin-readers could have utility in nuanced clinical contexts of acquired drug resistance with a more favorable therapeutic index.

  1. Self-Regulated Learning: A Touchstone for Technology-Enhanced Classrooms

    Science.gov (United States)

    McQuirter Scott, Ruth; Meeussen, Nancy

    2017-01-01

    Technology-enhanced classrooms offer dynamic possibilities for teachers and students. The teacher's role can shift from being an expert in control of the class to being a coach who challenges students to use technology to explore the world and share their findings in innovative ways. Such redefining of roles, however, involves risk and often…

  2. Regulating Prostate Cancer Sensitivity to Chemotherapy through Translational Control of CCAAT Enhancer Binding Proteins

    Science.gov (United States)

    2015-08-01

    were washed and incubated in permeabilization buffer (TBS, 2% BSA, 0.5% Triton-X 100, 0.1% sodium azide). After blocking, cells were incubated with...implications for establishment of early pregnancy . Cell cycle 2006; 5: 922–925. 15 Boruk M, Savory JG, Hache RJ. AF-2-dependent potentiation of CCAAT enhancer

  3. An improved direct feedback linearization technique for transient stability enhancement and voltage regulation of power generators

    Energy Technology Data Exchange (ETDEWEB)

    Kenne, Godpromesse [Laboratoire d' Automatique et d' Informatique Appliquee (LAIA), Departement de Genie Electrique, Universite de Dschang, B.P. 134 Bandjoun, Cameroun; Goma, Raphael; Lamnabhi-Lagarrigue, Francoise [Laboratoire des Signaux et Systemes (L2S), CNRS-SUPELEC, Universite Paris XI, 3 Rue Joliot Curie, 91192 Gif-sur-Yvette (France); Nkwawo, Homere [Departement GEII, Universite Paris XIII, IUT Villetaneuse, 99 Avenue Jean Baptiste Clement, 93430 Villetaneuse (France); Arzande, Amir; Vannier, Jean Claude [Departement Energie, Ecole Superieure d' Electricite-SUPELEC, 3 Rue Joliot Curie, 91192 Gif-sur-Yvette (France)

    2010-09-15

    In this paper, a simple improved direct feedback linearization design method for transient stability and voltage regulation of power systems is discussed. Starting with the classical direct feedback linearization technique currently applied to power systems, an adaptive nonlinear excitation control of synchronous generators is proposed, which is new and effective for engineering. The power angle and mechanical power input are not assumed to be available. The proposed method is based on a standard third-order model of a synchronous generator which requires only information about the physical available measurements of angular speed, active electric power and generator terminal voltage. Experimental results of a practical power system show that fast response, robustness, damping, steady-state and transient stability as well as voltage regulation are all achieved satisfactorily. (author)

  4. Choir singing and creative writing enhance emotion regulation in adults with chronic mental health conditions.

    Science.gov (United States)

    Dingle, Genevieve A; Williams, Elyse; Jetten, Jolanda; Welch, Jonathon

    2017-11-01

    Adults with mental health conditions commonly experience difficulties with emotion regulation which affect their social functioning. Arts-based groups provide opportunities for shared emotional experiences and emotion regulation. This study explores emotion regulation strategies and the emotional effects of arts-based group participation in adults with mental health problems and in controls. The 62 participants included 39 adults with chronic mental health problems who were members of arts-based groups (ABG) and 23 comparison choir (CC) members who were not specifically experiencing mental health problems. The repeated measures design included self-reports of emotion upon waking (T1), the hour before group (T2), end of the group (T3), and evening (T4), as well as participant notes to explain their emotion ratings at each time. They also completed measures of individual and interpersonal emotion regulation. The ABG participants engaged marginally more in affect worsening strategies than CC (p = .057 and .08), but there were no other group differences. All participants reported a significant increase in positive emotions, F (3, 180) = 28.044, p emotions during the arts-based activity: F (2.637, 155.597) = 21.09, p emotions was short-lived, while the effect on negative emotions lasted until evening. Findings show that participation in arts-based groups benefits the emotions of both healthy adults and those experiencing mental health conditions through individual and interpersonal processes. Individuals with chronic mental health conditions often experience difficulties in emotion processing Participation in arts-based groups was associated with significant increases in positive emotions although these were short-lived Negative emotion was significantly decreased during arts-based group activities, and sustained to the evening assessment Adults with chronic mental health conditions were equally able to derive emotional benefits as healthy adults. © 2017 The

  5. Enhancing Global Competitiveness: Benchmarking Airline Operational Performance in Highly Regulated Environments

    Science.gov (United States)

    Bowen, Brent D.; Headley, Dean E.; Kane, Karisa D.

    1998-01-01

    Enhancing competitiveness in the global airline industry is at the forefront of attention with airlines, government, and the flying public. The seemingly unchecked growth of major airline alliances is heralded as an enhancement to global competition. However, like many mega-conglomerates, mega-airlines will face complications driven by size regardless of the many recitations of enhanced efficiency. Outlined herein is a conceptual model to serve as a decision tool for policy-makers, managers, and consumers of airline services. This model is developed using public data for the United States (U.S.) major airline industry available from the U/S. Department of Transportation, Federal Aviation Administration, the National Aeronautics and Space Administration, the National Transportation Safety Board, and other public and private sector sources. Data points include number of accidents, pilot deviations, operational performance indicators, flight problems, and other factors. Data from these sources provide opportunity to develop a model based on a complex dot product equation of two vectors. A row vector is weighted for importance by a key informant panel of government, industry, and consumer experts, while a column vector is established with the factor value. The resulting equation, known as the national Airline Quality Rating (AQR), where Q is quality, C is weight, and V is the value of the variables, is stated Q=C[i1-19] x V[i1-19]. Looking at historical patterns of AQR results provides the basis for establishment of an industry benchmark for the purpose of enhancing airline operational performance. A 7 year average of overall operational performance provides the resulting benchmark indicator. Applications from this example can be applied to the many competitive environments of the global industry and assist policy-makers faced with rapidly changing regulatory challenges.

  6. Hepatocyte growth factor enhances death receptor-induced apoptosis by up-regulating DR5

    International Nuclear Information System (INIS)

    Li, Yang; Fan, Xing; Goodwin, C Rory; Laterra, John; Xia, Shuli

    2008-01-01

    Hepatocyte growth factor (HGF) and its receptor c-MET are commonly expressed in malignant gliomas and embryonic neuroectodermal tumors including medulloblastoma and appear to play an important role in the growth and dissemination of these malignancies. Dependent on cell context and the involvement of specific downstream effectors, both pro- and anti-apoptotic effects of HGF have been reported. Human medulloblastoma cells were treated with HGF for 24–72 hours followed by death receptor ligand TRAIL (Tumor necrosis factor-related apoptosis-inducing ligand) for 24 hours. Cell death was measured by MTT and Annexin-V/PI flow cytometric analysis. Changes in expression levels of targets of interest were measured by Northern blot analysis, quantitative reverse transcription-PCR, Western blot analysis as well as immunoprecipitation. In this study, we show that HGF promotes medulloblastoma cell death induced by TRAIL. TRAIL alone triggered apoptosis in DAOY cells and death was enhanced by pre-treating the cells with HGF for 24–72 h prior to the addition of TRAIL. HGF (100 ng/ml) enhanced TRAIL (10 ng/ml) induced cell death by 36% (P < 0.001). No cell death was associated with HGF alone. Treating cells with PHA-665752, a specific c-Met receptor tyrosine kinase inhibitor, significantly abrogated the enhancement of TRAIL-induced cell death by HGF, indicating that its death promoting effect requires activation of its canonical receptor tyrosine kinase. Cell death induced by TRAIL+HGF was predominately apoptotic involving both extrinsic and intrinsic pathways as evidenced by the increased activation of caspase-3, 8, 9. Promotion of apoptosis by HGF occurred via the increased expression of the death receptor DR5 and enhanced formation of death-inducing signal complexes (DISC). Taken together, these and previous findings indicate that HGF:c-Met pathway either promotes or inhibits medulloblastoma cell death via pathway and context specific mechanisms

  7. Identification of Drugs that Regulate Dermal Stem Cells and Enhance Skin Repair

    Directory of Open Access Journals (Sweden)

    Sibel Naska

    2016-01-01

    Full Text Available Here, we asked whether we could identify pharmacological agents that enhance endogenous stem cell function to promote skin repair, focusing on skin-derived precursors (SKPs, a dermal precursor cell population. Libraries of compounds already used in humans were screened for their ability to enhance the self-renewal of human and rodent SKPs. We identified and validated five such compounds, and showed that two of them, alprostadil and trimebutine maleate, enhanced the repair of full thickness skin wounds in middle-aged mice. Moreover, SKPs isolated from drug-treated skin displayed long-term increases in self-renewal when cultured in basal growth medium without drugs. Both alprostadil and trimebutine maleate likely mediated increases in SKP self-renewal by moderate hyperactivation of the MEK-ERK pathway. These findings identify candidates for potential clinical use in human skin repair, and provide support for the idea that pharmacological activation of endogenous tissue precursors represents a viable therapeutic strategy.

  8. CCAAT/enhancer-binding proteins regulate expression of the human steroidogenic acute regulatory protein (StAR) gene.

    Science.gov (United States)

    Christenson, L K; Johnson, P F; McAllister, J M; Strauss, J F

    1999-09-10

    Two putative CCAAT/enhancer-binding protein (C/EBP) response elements were identified in the proximal promoter of the human steroidogenic acute regulatory protein (StAR) gene, which encodes a key protein-regulating steroid hormone synthesis. Expression of C/EBPalpha and -beta increased StAR promoter activity in COS-1 and HepG2 cells. Cotransfection of C/EBPalpha or -beta and steroidogenic factor 1, a transcription factor required for cAMP regulation of StAR expression, into COS-1 augmented 8-bromoadenosine 3':5'-cyclic monophosphate (8-Br-cAMP)-stimulated promoter activity. When the putative C/EBP response elements were mutated, individually or together, a pronounced decline in basal StAR promoter activity in human granulosa-lutein cells resulted, but the fold stimulation of promoter activity by 8-Br-cAMP was unaffected. Recombinant C/EBPalpha and -beta bound to the two identified sequences but not the mutated elements. Human granulosa-lutein cell nuclear extracts also bound these elements but not the mutated sequences. An antibody to C/EBPbeta, but not C/EBPalpha, supershifted the nuclear protein complex associated with the more distal element. The complex formed by nuclear extracts with the proximal element was not supershifted by either antibody. Western blot analysis revealed the presence of C/EBPalpha and C/EBPbeta in human granulosa-lutein cell nuclear extracts. C/EBPbeta levels were up-regulated 3-fold by 8-Br-cAMP treatment. Our studies demonstrate a role for C/EBPbeta as well as yet to be identified proteins, which can bind to C/EBP response elements, in the regulation of StAR gene expression and suggest a mechanism by which C/EBPbeta participates in the cAMP regulation of StAR gene transcription.

  9. International cooperation for the development of consistent and stable transportation regulations to promote and enhance safety and security

    International Nuclear Information System (INIS)

    Strosnider, J.

    2004-01-01

    International commerce of radioactive materials crosses national boundaries, linking separate regulatory institutions with a common purpose and making it necessary for these institutions to work together in order to achieve common safety goals in a manner that does not place an undue burden on industry and commerce. Widespread and increasing use of radioactive materials across the world has led to increases in the transport of radioactive materials. The demand for consistency in the oversight of international transport has also increased to prevent unnecessary delays and costs associated with incongruent or redundant regulatory requirements by the various countries through which radioactive material is transported. The International Atomic Energy Agency (IAEA) is the authority for international regulation of transportation of radioactive materials responsible for promulgation of regulations and guidance for the establishment of acceptable methods of transportation for the international community. As such, the IAEA is seen as the focal point for consensus building between its Member States to develop consistency in transportation regulations and reviews and to ensure the safe and secure transport of radioactive material. International cooperation is also needed to ensure stability in our regulatory processes. Changes to transportation regulations should be based on an anticipated safety benefit supported by risk information and insights gained from continuing experience, evaluation, and research studies. If we keep safety as the principle basis for regulatory changes, regulatory stability will be enhanced. Finally, as we endeavour to maintain consistency and stability in our international regulations, we must be mindful of the new security challenges that lay before the international community as a result of a changing terrorist environment. Terrorism is a problem of global concern that also requires international cooperation and support, as we look for ways to

  10. Regulation

    International Nuclear Information System (INIS)

    Ballereau, P.

    1999-01-01

    The different regulations relative to nuclear energy since the first of January 1999 are given here. Two points deserve to be noticed: the decree of the third august 1999 authorizing the national Agency for the radioactive waste management to install and exploit on the commune of Bures (Meuse) an underground laboratory destined to study the deep geological formations where could be stored the radioactive waste. The second point is about the uranium residues and the waste notion. The judgment of the administrative tribunal of Limoges ( 9. july 1998) forbidding the exploitation of a storage installation of depleted uranium considered as final waste and qualifying it as an industrial waste storage facility has been annulled bu the Court of Appeal. It stipulated that, according to the law number 75663 of the 15. july 1965, no criteria below can be applied to depleted uranium: production residue (possibility of an ulterior enrichment), abandonment of a personal property or simple intention to do it ( future use aimed in the authorization request made in the Prefecture). This judgment has devoted the primacy of the waste notion on this one of final waste. (N.C.)

  11. Hypocretin-1 receptors regulate the reinforcing and reward-enhancing effects of cocaine: Pharmacological and behavioral genetics evidence

    Directory of Open Access Journals (Sweden)

    Jonathan eHollander

    2012-07-01

    Full Text Available Considerable evidence suggests that transmission at hypocretin-1 (orexin-1 receptors (Hcrt-R1 plays an important role in the reinstatement of extinguished cocaine-seeking behaviors in rodents. However, far less is known about the role for hypocretin transmission in regulating ongoing cocaine-taking behavior. Here, we investigated the effects of the selective Hcrt-R1 antagonist SB-334867 on cocaine intake, as measured by intravenous (IV cocaine self-administration in rats. The stimulatory effects of cocaine on brain reward systems contribute to the establishment and maintenance of cocaine-taking behaviors. Therefore, we also assessed the effects of SB-334867 on the reward-enhancing properties of cocaine, as measured by cocaine-induced lowering of intracranial self-stimulation (ICSS thresholds. Finally, to definitively establish a role for Hcrt-R1 in regulating cocaine intake, we assessed IV cocaine self-administration in Hcrt-R1 knockout mice. We found that SB-334867 (1-4 mg/kg dose-dependently decreased cocaine (0.5 mg/kg/infusion self-administration in rats but did not alter responding for food rewards under the same schedule of reinforcement. This suggests that SB-334867 decreased cocaine reinforcement without negatively impacting operant performance. SB-334867 (1-4 mg/kg also dose-dependently attenuated the stimulatory effects of cocaine (10 mg/kg on brain reward systems, as measured by reversal of cocaine-induced lowering of ICSS thresholds in rats. Finally, we found that Hcrt-R1 knockout mice self-administered far less cocaine than wildtype mice across the entire dose-response function. These data demonstrate that Hcrt-R1 play an important role in regulating the reinforcing and reward-enhancing properties of cocaine, and suggest that hypocretin transmission is likely essential for establishing and maintaining the cocaine habit in human addicts.

  12. Dissecting and engineering of the TetR family regulator SACE_7301 for enhanced erythromycin production in Saccharopolyspora erythraea.

    Science.gov (United States)

    Wu, Hang; Chen, Meng; Mao, Yongrong; Li, Weiwei; Liu, Jingtao; Huang, Xunduan; Zhou, Ying; Ye, Bang-Ce; Zhang, Lixin; Weaver, David T; Zhang, Buchang

    2014-11-13

    Saccharopolyspora erythraea was extensively utilized for the industrial-scale production of erythromycin A (Er-A), a macrolide antibiotic commonly used in human medicine. Yet, S. erythraea lacks regulatory genes in the erythromycin biosynthetic gene (ery) cluster, hampering efforts to enhance Er-A production via the engineering of regulatory genes. By the chromosome gene inactivation technique based on homologous recombination with linearized DNA fragments, we have inactivated a number of candidate TetR family transcriptional regulators (TFRs) and identified one TFR (SACE_7301) positively controlling erythromycin biosynthesis in S. erythraea A226. qRT-PCR and EMSA analyses demonstrated that SACE_7301 activated the transcription of erythromycin biosynthetic gene eryAI and the resistance gene ermE by interacting with their promoter regions with low affinities, similar to BldD (SACE_2077) previously identified to regulate erythromycin biosynthesis and morphological differentiation. Therefore, we designed a strategy for overexpressing SACE_7301 with 1 to 3 extra copies under the control of PermE* in A226. Following up-regulated transcriptional expression of SACE_7301, eryAI and ermE, the SACE_7301-overexpressed strains all increased Er-A production over A226 proportional to the number of copies. Likewise, when SACE_7301 was overexpressed in an industrial S. erythraea WB strain, Er-A yields of the mutants WB/7301, WB/2×7301 and WB/3×7301 were respectively increased by 17%, 29% and 42% relative to that of WB. In a 5 L fermentor, Er-A accumulation increased to 4,230 mg/L with the highest-yield strain WB/3×7301, an approximately 27% production improvement over WB (3,322 mg/L). We have identified and characterized a TFR, SACE_7301, in S. erythraea that positively regulated erythromycin biosynthesis, and overexpression of SACE_7301 in wild-type and industrial S. erythraea strains enhanced Er-A yields. This study markedly improves our understanding of the unusual

  13. CmWRKY1 Enhances the Dehydration Tolerance of Chrysanthemum through the Regulation of ABA-Associated Genes.

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    Qingqing Fan

    Full Text Available WRKY transcription factors serve as antagonistic or synergistic regulators in a variety of abiotic stress responses in plants. Here, we show that CmWRKY1, a member of the group IIb WRKY family isolated from Chrysanthemum morifolium, exhibits no transcriptional activation in yeast cells. The subcellular localization examination showed that CmWRKY1 localizes to the nucleus in vivo. Furthermore, CmWRKY1-overexpressing transgenic lines exhibit enhanced dehydration tolerance in response to polyethylene glycol (PEG treatment compared with wild-type plants. We further confirmed that the transgenic plants exhibit suppressed expression levels of genes negatively regulated by ABA, such as PP2C, ABI1 and ABI2, and activated expression levels of genes positively regulated by ABA, such as PYL2, SnRK2.2, ABF4, MYB2, RAB18, and DREB1A. Taken together, our results indicate that CmWRKY1 plays an important role in the response to drought in chrysanthemum through an ABA-mediated pathway.

  14. GmCLC1 Confers Enhanced Salt Tolerance through Regulating Chloride Accumulation in Soybean

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    Peipei Wei

    2016-07-01

    Full Text Available The family of chloride channel proteins that mediate Cl- transportation play vital roles in plant nutrient supply, cellular action potential and turgor pressure adjustment, stomatal movement, hormone signal recognition and transduction, Cl- homeostasis, and abiotic and biotic stress tolerance. The anionic toxicity, mainly caused by chloride ions (Cl-, on plants under salt stress remains poorly understood. In this work, we investigated the function of soybean Cl-/H+ antiporter GmCLC1 under salt stress in transgenic Arabidopsis thaliana, soybean, and yeast. We found that GmCLC1 enhanced salt tolerance in transgenic A. thaliana by reducing the Cl- accumulation in shoots and hence released the negative impact of salt stress on plant growth. Overexpression of GmCLC1 in the hairy roots of soybean sequestered more Cl- in their roots and transferred less Cl- to their shoots, leading to lower relative electrolyte leakage values in the roots and leaves. When either the soybean GmCLC1 or the yeast chloride transporter gene, GEF1, was transformed into the yeast gef1 mutant, and then treated with different chloride salts (MnCl2, KCl, NaCl, enhanced survival rate was observed. The result indicates that GmCLC1 and GEF1 exerted similar effects on alleviating the stress of diverse chloride salts on the yeast gef1 mutant. Together, this work suggests a protective function of GmCLC1 under Cl- stress.

  15. High-pass filtering and dynamic gain regulation enhance vertical bursts transmission along the mossy fiber pathway of cerebellum

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    Jonathan Mapelli

    2010-05-01

    Full Text Available Signal elaboration in the cerebellum mossy fiber input pathway presents controversial aspects, especially concerning gain regulation and the spot-like (rather than beam-like appearance of granular-to-molecular layer transmission. By using voltage-sensitive dye (VSD imaging in rat cerebellar slices (Mapelli et al., 2010, we found that mossy fiber bursts optimally excited the granular layer above ~50 Hz and the overlaying molecular layer above ~100 Hz, thus generating a cascade of high-pass filters. NMDA receptors enhanced transmission in the granular, while GABA-A receptors depressed transmission in both the granular and molecular layer. Burst transmission gain was controlled through a dynamic frequency-dependent involvement of these receptors. Moreover, while high-frequency transmission was enhanced along vertical lines connecting the granular to molecular layer, no high-frequency enhancement was observed along the parallel fiber axis in the molecular layer. This was probably due to the stronger effect of Purkinje cell GABA-A receptor-mediated inhibition occurring along the parallel fibers than along the granule cell axon ascending branch. The consequent amplification of burst responses along vertical transmission lines could explain the spot-like activation of Purkinje cells observed following punctuate stimulation in vivo .

  16. Structural insight to mutation effects uncover a common allosteric site in class C GPCRs

    DEFF Research Database (Denmark)

    Harpsøe, Kasper; Boesgaard, Michael W; Munk, Christian

    2017-01-01

    MOTIVATION: Class C G protein-coupled receptors (GPCRs) regulate important physiological functions and allosteric modulators binding to the transmembrane domain constitute an attractive and, due to a lack of structural insight, a virtually unexplored potential for therapeutics and the food industry....... Combining pharmacological site-directed mutagenesis data with the recent class C GPCR experimental structures will provide a foundation for rational design of new therapeutics. RESULTS: We uncover one common site for both positive and negative modulators with different amino acid layouts that can...

  17. An HPLC tracing of the enhancer regulation in selected discrete brain areas of food-deprived rats.

    Science.gov (United States)

    Miklya, I; Knoll, B; Knoll, J

    2003-05-09

    The recent discovery of the enhancer regulation in the mammalian brain brought a different perspective to the brain-organized realization of goal-oriented behavior, which is the quintessence of plastic behavioral descriptions such as drive or motivation. According to this new approach, 'drive' means that special endogenous enhancer substances enhance the impulse-propagation-mediated release of transmitters in a proper population of enhancer-sensitive neurons, and keep these neurons in the state of enhanced excitability until the goal is reached. However, to reach any goal needs the participation of the catecholaminergic machinery, the engine of the brain. We developed a method to detect the specific enhancer effect of synthetic enhancer substances [(-)-deprenyl, (-)-PPAP, (-)-BPAP] by measuring the release of transmitters from freshly isolated selected discrete brain areas (striatum, substantia nigra, tuberculum olfactorium, locus coeruleus, raphe) by the aid of HPLC with electrochemical detection. To test the validity of the working hypothesis that in any form of goal-seeking behavior the catecholaminergic and serotonergic neurons work on a higher activity level, we compared the amount of norepinephrine, dopamine, and serotonin released from selected discrete brain areas isolated from the brain of sated and food-deprived rats. Rats were deprived of food for 48 and 72 hours, respectively, and the state of excitability of their catecholaminergic and serotonergic neurons in comparison to that of sated rats was measured. We tested the orienting-searching reflex activity of the rats in a special open field, isolated thereafter selected discrete brain areas and measured the release of norepinephrine, dopamine, and serotonin from the proper tissue samples into the organ bath. The orienting-searching reflex activity of the rats increased proportionally to the time elapsed from the last feed and the amount of dopamine released from the striatum, substantia nigra and

  18. Uncovering ecosystem service bundles through social preferences.

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    Berta Martín-López

    Full Text Available Ecosystem service assessments have increasingly been used to support environmental management policies, mainly based on biophysical and economic indicators. However, few studies have coped with the social-cultural dimension of ecosystem services, despite being considered a research priority. We examined how ecosystem service bundles and trade-offs emerge from diverging social preferences toward ecosystem services delivered by various types of ecosystems in Spain. We conducted 3,379 direct face-to-face questionnaires in eight different case study sites from 2007 to 2011. Overall, 90.5% of the sampled population recognized the ecosystem's capacity to deliver services. Formal studies, environmental behavior, and gender variables influenced the probability of people recognizing the ecosystem's capacity to provide services. The ecosystem services most frequently perceived by people were regulating services; of those, air purification held the greatest importance. However, statistical analysis showed that socio-cultural factors and the conservation management strategy of ecosystems (i.e., National Park, Natural Park, or a non-protected area have an effect on social preferences toward ecosystem services. Ecosystem service trade-offs and bundles were identified by analyzing social preferences through multivariate analysis (redundancy analysis and hierarchical cluster analysis. We found a clear trade-off among provisioning services (and recreational hunting versus regulating services and almost all cultural services. We identified three ecosystem service bundles associated with the conservation management strategy and the rural-urban gradient. We conclude that socio-cultural preferences toward ecosystem services can serve as a tool to identify relevant services for people, the factors underlying these social preferences, and emerging ecosystem service bundles and trade-offs.

  19. Uncovering Ecosystem Service Bundles through Social Preferences

    Science.gov (United States)

    Martín-López, Berta; Iniesta-Arandia, Irene; García-Llorente, Marina; Palomo, Ignacio; Casado-Arzuaga, Izaskun; Amo, David García Del; Gómez-Baggethun, Erik; Oteros-Rozas, Elisa; Palacios-Agundez, Igone; Willaarts, Bárbara; González, José A.; Santos-Martín, Fernando; Onaindia, Miren; López-Santiago, Cesar; Montes, Carlos

    2012-01-01

    Ecosystem service assessments have increasingly been used to support environmental management policies, mainly based on biophysical and economic indicators. However, few studies have coped with the social-cultural dimension of ecosystem services, despite being considered a research priority. We examined how ecosystem service bundles and trade-offs emerge from diverging social preferences toward ecosystem services delivered by various types of ecosystems in Spain. We conducted 3,379 direct face-to-face questionnaires in eight different case study sites from 2007 to 2011. Overall, 90.5% of the sampled population recognized the ecosystem’s capacity to deliver services. Formal studies, environmental behavior, and gender variables influenced the probability of people recognizing the ecosystem’s capacity to provide services. The ecosystem services most frequently perceived by people were regulating services; of those, air purification held the greatest importance. However, statistical analysis showed that socio-cultural factors and the conservation management strategy of ecosystems (i.e., National Park, Natural Park, or a non-protected area) have an effect on social preferences toward ecosystem services. Ecosystem service trade-offs and bundles were identified by analyzing social preferences through multivariate analysis (redundancy analysis and hierarchical cluster analysis). We found a clear trade-off among provisioning services (and recreational hunting) versus regulating services and almost all cultural services. We identified three ecosystem service bundles associated with the conservation management strategy and the rural-urban gradient. We conclude that socio-cultural preferences toward ecosystem services can serve as a tool to identify relevant services for people, the factors underlying these social preferences, and emerging ecosystem service bundles and trade-offs. PMID:22720006

  20. Hippocampal histone acetylation regulates object recognition and the estradiol-induced enhancement of object recognition.

    Science.gov (United States)

    Zhao, Zaorui; Fan, Lu; Fortress, Ashley M; Boulware, Marissa I; Frick, Karyn M

    2012-02-15

    Histone acetylation has recently been implicated in learning and memory processes, yet necessity of histone acetylation for such processes has not been demonstrated using pharmacological inhibitors of histone acetyltransferases (HATs). As such, the present study tested whether garcinol, a potent HAT inhibitor in vitro, could impair hippocampal memory consolidation and block the memory-enhancing effects of the modulatory hormone 17β-estradiol E2. We first showed that bilateral infusion of garcinol (0.1, 1, or 10 μg/side) into the dorsal hippocampus (DH) immediately after training impaired object recognition memory consolidation in ovariectomized female mice. A behaviorally effective dose of garcinol (10 μg/side) also significantly decreased DH HAT activity. We next examined whether DH infusion of a behaviorally subeffective dose of garcinol (1 ng/side) could block the effects of DH E2 infusion on object recognition and epigenetic processes. Immediately after training, ovariectomized female mice received bilateral DH infusions of vehicle, E2 (5 μg/side), garcinol (1 ng/side), or E2 plus garcinol. Forty-eight hours later, garcinol blocked the memory-enhancing effects of E2. Garcinol also reversed the E2-induced increase in DH histone H3 acetylation, HAT activity, and levels of the de novo methyltransferase DNMT3B, as well as the E2-induced decrease in levels of the memory repressor protein histone deacetylase 2. Collectively, these findings suggest that histone acetylation is critical for object recognition memory consolidation and the beneficial effects of E2 on object recognition. Importantly, this work demonstrates that the role of histone acetylation in memory processes can be studied using a HAT inhibitor.

  1. Angiogenin enhances cell migration by regulating stress fiber assembly and focal adhesion dynamics.

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    Saisai Wei

    Full Text Available Angiogenin (ANG acts on both vascular endothelial cells and cancer cells, but the underlying mechanism remains elusive. In this study, we carried out a co-immunoprecipitation assay in HeLa cells and identified 14 potential ANG-interacting proteins. Among these proteins, β-actin, α-actinin 4, and non-muscle myosin heavy chain 9 are stress fiber components and involved in cytoskeleton organization and movement, which prompted us to investigate the mechanism of action of ANG in cell migration. Upon confirmation of the interactions between ANG and the three proteins, further studies revealed that ANG co-localized with β-actin and α-actinin 4 at the leading edge of migrating cells. Down-regulation of ANG resulted in fewer but thicker stress fibers with less dynamics, which was associated with the enlargements of focal adhesions. The focal adhesion kinase activity and cell migration capacity were significantly decreased in ANG-deficient cells. Taken together, our data demonstrated that the existence of ANG in the cytoplasm optimizes stress fiber assembly and focal adhesion formation to accommodate cell migration. The finding that ANG promoted cancer cell migration might provide new clues for tumor metastasis research.

  2. Obestatin enhances in vitro generation of pancreatic islets through regulation of developmental pathways.

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    Alessandra Baragli

    Full Text Available Availability of large amounts of in vitro generated β-cells may support replacement therapy in diabetes. However, methods to obtain β-cells from stem/progenitor cells are limited by inefficient endocrine differentiation. We have recently shown that the ghrelin gene product obestatin displays beneficial effects on pancreatic β-cell survival and function. Obestatin prevents β-cell apoptosis, preserves β-cell mass and stimulates insulin secretion in vitro and in vivo, in both normal and diabetic conditions. In the present study, we investigated whether obestatin may promote in vitro β-cell generation from mouse pancreatic islet-derived precursor cells. Treatment of cultured islets of Langerhans with obestatin (i enriched cells expressing the mesenchymal/neuronal marker nestin, which is associated with pancreatic precursors; (ii increased cell survival and reduced apoptosis during precursor selection; (iii promoted the generation of islet-like cell clusters (ICCs with increased insulin gene expression and C-peptide secretion. Furthermore, obestatin modulated the expression of fibroblast growth factor receptors (FGFRs, Notch receptors and neurogenin 3 (Ngn3 during islet-derived precursor cell selection and endocrine differentiation. These results indicate that obestatin improves the generation of functional β-cells/ICCs in vitro, suggesting implications for cell-based replacement therapy in diabetes. Moreover, obestatin may play a role in regulating pathways involved in pancreas development and regeneration.

  3. Solution processed ternary blend nano-composite charge regulation layer to enhance inverted OLED performances

    Science.gov (United States)

    Kaçar, Rifat; Mucur, Selin Pıravadılı; Yıldız, Fikret; Dabak, Salih; Tekin, Emine

    2018-04-01

    Inverted bottom-emission organic light emitting diodes (IBOLEDs) have attracted increasing attention due to their exceptional air stability and applications in active-matrix displays. For gaining high IBOLED device efficiencies, it is crucial to develop an effective strategy to make the bottom electrode easy for charge injection and transport. Charge selectivity, blocking the carrier flow towards the unfavourable side, plays an important role in determining charge carrier balance and accordingly radiative recombination efficiency. It is therefore highly desirable to functionalize an interfacial layer which will perform many different tasks simultaneously. Here, we contribute to the hole-blocking ability of the zinc oxide/polyethyleneimine (ZnO:PEI) nano-composite (NC) interlayer with the intention of increasing the OLED device efficiency. With this purpose in mind, a small amount of 1,3,5-tris(N-phenylbenzimidazol-2-yl)benzene (TPBi) was added as a hole-blocking molecule into the binary blend of ZnO and PEI solution. The device with a ternary ZnO:PEI:TPBi NC interlayer achieved a maximum current efficiency of 38.20 cd A-1 and a power efficiency of 34.29 lm W-1 with a luminance of 123 200 cd m-2, which are high performance parameters for inverted device architecture. The direct comparisons of device performances incorporating ZnO only, ZnO/PEI bilayers, and ZnO:PEI binary NC counterparts were also performed, which shed light on the origin of device performance enhancement.

  4. Cytolethal Distending Toxin Enhances Radiosensitivity in Prostate Cancer Cells by Regulating Autophagy

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    Hwai-Jeng Lin

    2017-06-01

    Full Text Available Cytolethal distending toxin (CDT produced by Campylobacter jejuni contains three subunits: CdtA, CdtB, and CdtC. Among these three toxin subunits, CdtB is the toxic moiety of CDT with DNase I activity, resulting in DNA double-strand breaks (DSB and, consequently, cell cycle arrest at the G2/M stage and apoptosis. Radiation therapy is an effective modality for the treatment of localized prostate cancer (PCa. However, patients often develop radioresistance. Owing to its particular biochemical properties, we previously employed CdtB as a therapeutic agent for sensitizing radioresistant PCa cells to ionizing radiation (IR. In this study, we further demonstrated that CDT suppresses the IR-induced autophagy pathway in PCa cells by attenuating c-Myc expression and therefore sensitizes PCa cells to radiation. We further showed that CDT prevents the formation of autophagosomes via decreased high-mobility group box 1 (HMGB1 expression and the inhibition of acidic vesicular organelle (AVO formation, which are associated with enhanced radiosensitivity in PCa cells. The results of this study reveal the detailed mechanism of CDT for the treatment of radioresistant PCa.

  5. Ectomycorrhizal fungi enhance nitrogen and phosphorus nutrition of Nothofagus dombeyi under drought conditions by regulating assimilative enzyme activities.

    Science.gov (United States)

    Alvarez, Maricel; Huygens, Dries; Olivares, Erick; Saavedra, Isabel; Alberdi, Miren; Valenzuela, Eduardo

    2009-08-01

    Drought stress conditions (DC) reduce plant growth and nutrition, restraining the sustainable reestablishment of Nothofagus dombeyi in temperate south Chilean forest ecosystems. Ectomycorrhizal symbioses have been documented to enhance plant nitrogen (N) and phosphorus (P) uptake under drought, but the regulation of involved assimilative enzymes remains unclear. We studied 1-year-old N. dombeyi (Mirb.) Oerst. plants in association with the ectomycorrhizal fungi Pisolithus tinctorius (Pers.) Coker & Couch. and Descolea antartica Sing. In greenhouse experiments, shoot and root dry weights, mycorrhizal colonization, foliar N and P concentrations, and root enzyme activities [glutamate synthase (glutamine oxoglutarate aminotransferase (GOGAT), EC 1.4.1.13-14), glutamine synthetase (GS, EC 6.3.1.2), glutamate dehydrogenase (GDH, EC 1.4.1.2-4), nitrate reductase (NR, EC 1.6.6.1), and acid phosphomonoesterase (PME, EC 3.1.3.1-2)] were determined as a function of soil-water content. Inoculation of N. dombeyi with P. tinctorius and D. antartica significantly stimulated plant growth and increased plant foliar N and P concentrations, especially under DC. Ectomycorrhizal inoculation increased the activity of all studied enzymes relative to non-mycorrhizal plants under drought. We speculate that GDH is a key enzyme involved in the enhancement of ectomycorrhizal carbon (C) availability by fuelling the tricarboxylic acid (TCA) cycle under conditions of drought-induced carbon deficit. All studied assimilative enzymes of the ectomycorrhizal associations, involved in C, N, and P transfers, are closely interlinked and interdependent. The up-regulation of assimilative enzyme activities by ectomycorrhizal fungal root colonizers acts as a functional mechanism to increase seedling endurance to drought. We insist upon incorporating ectomycorrhizal inoculation in existing Chilean afforestation programs.

  6. miR-34b/c Regulates Wnt1 and Enhances Mesencephalic Dopaminergic Neuron Differentiation

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    Roberto De Gregorio

    2018-04-01

    Full Text Available Summary: The differentiation of dopaminergic neurons requires concerted action of morphogens and transcription factors acting in a precise and well-defined time window. Very little is known about the potential role of microRNA in these events. By performing a microRNA-mRNA paired microarray screening, we identified miR-34b/c among the most upregulated microRNAs during dopaminergic differentiation. Interestingly, miR-34b/c modulates Wnt1 expression, promotes cell cycle exit, and induces dopaminergic differentiation. When combined with transcription factors ASCL1 and NURR1, miR-34b/c doubled the yield of transdifferentiated fibroblasts into dopaminergic neurons. Induced dopaminergic (iDA cells synthesize dopamine and show spontaneous electrical activity, reversibly blocked by tetrodotoxin, consistent with the electrophysiological properties featured by brain dopaminergic neurons. Our findings point to a role for miR-34b/c in neuronal commitment and highlight the potential of exploiting its synergy with key transcription factors in enhancing in vitro generation of dopaminergic neurons. : In this article, Bellenchi and colleagues show that the microRNA miR-34b/c is expressed in FACS-purified Pitx3-GFP+ neurons and promotes dopaminergic differentiation by negative modulating Wnt1 and the downstream WNT signaling pathway. Induced dopaminergic cells, expressing miR-34b/c, synthesize dopamine and show the electrophysiological properties featured by brain dopaminergic neurons. Keywords: microRNA, dopamine, mESC, miR34b/c, epiSC, transdifferentiation, Wnt1, Wnt pathway, reprogramming

  7. Enhanced Mucosal Defense and Reduced Tumor Burden in Mice with the Compromised Negative Regulator IRAK-M

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    Daniel E. Rothschild

    2017-02-01

    Full Text Available Aberrant inflammation is a hallmark of inflammatory bowel disease (IBD and colorectal cancer. IRAK-M is a critical negative regulator of TLR signaling and overzealous inflammation. Here we utilize data from human studies and Irak-m−/− mice to elucidate the role of IRAK-M in the modulation of gastrointestinal immune system homeostasis. In human patients, IRAK-M expression is up-regulated during IBD and colorectal cancer. Further functional studies in mice revealed that Irak-m−/− animals are protected against colitis and colitis associated tumorigenesis. Mechanistically, our data revealed that the gastrointestinal immune system of Irak-m−/− mice is highly efficient at eliminating microbial translocation following epithelial barrier damage. This attenuation of pathogenesis is associated with expanded areas of gastrointestinal associated lymphoid tissue (GALT, increased neutrophil migration, and enhanced T-cell recruitment. Further evaluation of Irak-m−/− mice revealed a splice variant that robustly activates NF-κB signaling. Together, these data identify IRAK-M as a potential target for future therapeutic intervention.

  8. A novel mammal-specific three partite enhancer element regulates node and notochord-specific Noto expression.

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    Leonie Alten

    Full Text Available The vertebrate organizer and notochord have conserved, essential functions for embryonic development and patterning. The restricted expression of developmental regulators in these tissues is directed by specific cis-regulatory modules (CRMs whose sequence conservation varies considerably. Some CRMs have been conserved throughout vertebrates and likely represent ancestral regulatory networks, while others have diverged beyond recognition but still function over a wide evolutionary range. Here we identify and characterize a mammalian-specific CRM required for node and notochord specific (NNC expression of NOTO, a transcription factor essential for node morphogenesis, nodal cilia movement and establishment of laterality in mouse. A 523 bp enhancer region (NOCE upstream the Noto promoter was necessary and sufficient for NNC expression from the endogenous Noto locus. Three subregions in NOCE together mediated full activity in vivo. Binding sites for known transcription factors in NOCE were functional in vitro but dispensable for NOCE activity in vivo. A FOXA2 site in combination with a novel motif was necessary for NOCE activity in vivo. Strikingly, syntenic regions in non-mammalian vertebrates showed no recognizable sequence similarities. In contrast to its activity in mouse NOCE did not drive NNC expression in transgenic fish. NOCE represents a novel, mammal-specific CRM required for the highly restricted Noto expression in the node and nascent notochord and thus regulates normal node development and function.

  9. A novel mammal-specific three partite enhancer element regulates node and notochord-specific Noto expression.

    Science.gov (United States)

    Alten, Leonie; Schuster-Gossler, Karin; Eichenlaub, Michael P; Wittbrodt, Beate; Wittbrodt, Joachim; Gossler, Achim

    2012-01-01

    The vertebrate organizer and notochord have conserved, essential functions for embryonic development and patterning. The restricted expression of developmental regulators in these tissues is directed by specific cis-regulatory modules (CRMs) whose sequence conservation varies considerably. Some CRMs have been conserved throughout vertebrates and likely represent ancestral regulatory networks, while others have diverged beyond recognition but still function over a wide evolutionary range. Here we identify and characterize a mammalian-specific CRM required for node and notochord specific (NNC) expression of NOTO, a transcription factor essential for node morphogenesis, nodal cilia movement and establishment of laterality in mouse. A 523 bp enhancer region (NOCE) upstream the Noto promoter was necessary and sufficient for NNC expression from the endogenous Noto locus. Three subregions in NOCE together mediated full activity in vivo. Binding sites for known transcription factors in NOCE were functional in vitro but dispensable for NOCE activity in vivo. A FOXA2 site in combination with a novel motif was necessary for NOCE activity in vivo. Strikingly, syntenic regions in non-mammalian vertebrates showed no recognizable sequence similarities. In contrast to its activity in mouse NOCE did not drive NNC expression in transgenic fish. NOCE represents a novel, mammal-specific CRM required for the highly restricted Noto expression in the node and nascent notochord and thus regulates normal node development and function.

  10. Multinuclear giant cell formation is enhanced by down-regulation of Wnt signaling in gastric cancer cell line, AGS

    International Nuclear Information System (INIS)

    Kim, Shi-Mun; Kim, Rockki; Ryu, Jae-Hyun; Jho, Eek-Hoon; Song, Ki-Joon; Jang, Shyh-Ing; Kee, Sun-Ho

    2005-01-01

    AGS cells, which were derived from malignant gastric adenocarcinoma tissue, lack E-cadherin-mediated cell adhesion but have a high level of nuclear β-catenin, which suggests altered Wnt signal. In addition, approximately 5% of AGS cells form multinuclear giant cells in the routine culture conditions, while taxol treatment causes most AGS cells to become giant cells. The observation of reduced nuclear β-catenin levels in giant cells induced by taxol treatment prompted us to investigate the relationship between Wnt signaling and giant cell formation. After overnight serum starvation, the shape of AGS cells became flattened, and this morphological change was accompanied by decrease in Myc expression and an increase in the giant cell population. Lithium chloride treatment, which inhibits GSK3β activity, reversed these serum starvation effects, which suggests an inverse relationship between Wnt signaling and giant cell formation. Furthermore, the down-regulation of Wnt signaling caused by the over-expression of ICAT, E-cadherin, and Axin enhanced giant cell formation. Therefore, down-regulation of Wnt signaling may be related to giant cell formation, which is considered to be a survival mechanism against induced cell death

  11. Strength Enhancement of Car Front Bumper for Slow Speed Impact by FEA Method as per IIHS Regulation

    Science.gov (United States)

    Sonawane, Chandrakant Rameshchandra; Shelar, Ajit Lavaji

    2017-05-01

    Low speed collisions happen significantly due to on road slow moving heavy traffic as well as during parking of vehicles. The bumpers are provided in front and back side of a vehicle has two main purposes: first is to absorb the energy generated during these kinds of slow speed impacts and secondly to protect the expensive parts like main engine parts, radiators and connected engine cooling mechanism, headlights, taillights, etc, by slowing down the vehicles. The problem often in various cars bumper is that they doesn't line-up vertically during low speed impact and leads to damage of various parts which are costly to repair. Many a times bumper design does not have sufficient capacity to absorb the energy generated during these impact. Guideline by International Institute Highway Safety (IIHS) regulation provides useful insight for such low speed impact study. In this paper, slow speed impact test were conducted as per IIHS regulation in three positions namely central impact, left hand corner impact and right hand corner impact. Parameters including bumper material, shape, thickness and impact condition are analyzed using fine element analysis (FEA) to enhance crashworthiness design in low speed impact. Then the vehicle front structure has been modified suitably. It has been observed that lining up the front metal bumper with suitable stiffness provides the best result which ultimately reduces the damage to the vehicle parts.

  12. Inhibition of apoptosis signal-regulating kinase 1 alters the wound epidermis and enhances auricular cartilage regeneration.

    Directory of Open Access Journals (Sweden)

    Qian-Shi Zhang

    Full Text Available Why regeneration does not occur in mammals remains elusive. In lower vertebrates, epimorphic regeneration of the limb is directed by the wound epidermis, which controls blastema formation to promote regrowth of the appendage. Herein, we report that knockout (KO or inhibition of Apoptosis Signal-regulated Kinase-1 (ASK1, also known as mitogen-activated protein kinase kinase kinase 5 (MAP3K5, after full thickness ear punch in mice prolongs keratinocyte activation within the wound epidermis and promotes regeneration of auricular cartilage. Histological analysis showed the ASK1 KO ears displayed enhanced protein markers associated with blastema formation, hole closure and regeneration of auricular cartilage. At seven days after punch, the wound epidermis morphology was markedly different in the KO, showing a thickened stratum corneum with rounded cell morphology and a reduction of both the granular cell layer and decreased expression of filament aggregating protein. In addition, cytokeratin 6 was expressed in the stratum spinosum and granulosum. Topical application of inhibitors of ASK1 (NQDI-1, the upstream ASK1 activator, calcium activated mitogen kinase 2 (KN93, or the downstream target, c-Jun N-terminal kinase (SP600125 also resulted in enhanced regeneration; whereas inhibition of the other downstream target, the p38 α/β isoforms, (SB203580 had no effect. The results of this investigation indicate ASK1 inhibition prolongs keratinocyte and blastemal cell activation leading to ear regeneration.

  13. Inhibition of apoptosis signal-regulating kinase 1 alters the wound epidermis and enhances auricular cartilage regeneration

    Science.gov (United States)

    Zhang, Qian-Shi; Kurpad, Deepa S.; Mahoney, My G.; Steinbeck, Marla J.

    2017-01-01

    Why regeneration does not occur in mammals remains elusive. In lower vertebrates, epimorphic regeneration of the limb is directed by the wound epidermis, which controls blastema formation to promote regrowth of the appendage. Herein, we report that knockout (KO) or inhibition of Apoptosis Signal-regulated Kinase-1 (ASK1), also known as mitogen-activated protein kinase kinase kinase 5 (MAP3K5), after full thickness ear punch in mice prolongs keratinocyte activation within the wound epidermis and promotes regeneration of auricular cartilage. Histological analysis showed the ASK1 KO ears displayed enhanced protein markers associated with blastema formation, hole closure and regeneration of auricular cartilage. At seven days after punch, the wound epidermis morphology was markedly different in the KO, showing a thickened stratum corneum with rounded cell morphology and a reduction of both the granular cell layer and decreased expression of filament aggregating protein. In addition, cytokeratin 6 was expressed in the stratum spinosum and granulosum. Topical application of inhibitors of ASK1 (NQDI-1), the upstream ASK1 activator, calcium activated mitogen kinase 2 (KN93), or the downstream target, c-Jun N-terminal kinase (SP600125) also resulted in enhanced regeneration; whereas inhibition of the other downstream target, the p38 α/β isoforms, (SB203580) had no effect. The results of this investigation indicate ASK1 inhibition prolongs keratinocyte and blastemal cell activation leading to ear regeneration. PMID:29045420

  14. Dioxinodehydroeckol Enhances the Differentiation of Osteoblasts by Regulating the Expression of Phospho-Smad1/5/8

    Directory of Open Access Journals (Sweden)

    Byul-Nim Ahn

    2016-09-01

    Full Text Available Lack of bone formation-related health problems are a major problem for the aging population in the modern world. As a part of the ongoing trend of developing natural substances that attenuate osteoporotic bone loss conditions, dioxinodehydroeckol (DHE from edible brown alga Ecklonia cava was tested for its effects on osteoblastogenic differentiation in MC3T3-E1 pre-osteoblasts. DHE was observed to successfully enhance osteoblast differentiation, as indicated by elevated cell proliferation, alkaline phosphatase activity, intracellular cell mineralization, along with raised levels of osteoblastogenesis indicators at the concentration of 20 μM. Results suggested a possible intervening of DHE on the bone morphogenetic protein (BMP signaling pathway, according to elevated protein levels of BMP-2, collagen-I, and Smads. In addition, the presence of DHE was also able to raise the phosphorylated extracellular signal–regulated kinase (ERK and c-Jun N-terminal kinase (JNK levels which are also activated by the BMP signaling pathway. In conclusion, DHE is suggested to be a potential bioactive compound against bone loss that could enhance osteoblastogenesis with a suggested BMP pathway interaction.

  15. Enhanced

    Directory of Open Access Journals (Sweden)

    Martin I. Bayala

    2014-06-01

    Full Text Available Land Surface Temperature (LST is a key parameter in the energy balance model. However, the spatial resolution of the retrieved LST from sensors with high temporal resolution is not accurate enough to be used in local-scale studies. To explore the LST–Normalised Difference Vegetation Index relationship potential and obtain thermal images with high spatial resolution, six enhanced image sharpening techniques were assessed: the disaggregation procedure for radiometric surface temperatures (TsHARP, the Dry Edge Quadratic Function, the Difference of Edges (Ts∗DL and three models supported by the relationship of surface temperature and water stress of vegetation (Normalised Difference Water Index, Normalised Difference Infrared Index and Soil wetness index. Energy Balance Station data and in situ measurements were used to validate the enhanced LST images over a mixed agricultural landscape in the sub-humid Pampean Region of Argentina (PRA, during 2006–2010. Landsat Thematic Mapper (TM and Moderate Resolution Imaging Spectroradiometer (EOS-MODIS thermal datasets were assessed for different spatial resolutions (e.g., 960, 720 and 240 m and the performances were compared with global and local TsHARP procedures. Results suggest that the Ts∗DL technique is the most adequate for simulating LST to high spatial resolution over the heterogeneous landscape of a sub-humid region, showing an average root mean square error of less than 1 K.

  16. Retinoic acid-loaded polymeric nanoparticles enhance vascular regulation of neural stem cell survival and differentiation after ischaemia

    Science.gov (United States)

    Ferreira, R.; Fonseca, M. C.; Santos, T.; Sargento-Freitas, J.; Tjeng, R.; Paiva, F.; Castelo-Branco, M.; Ferreira, L. S.; Bernardino, L.

    2016-04-01

    Stroke is one of the leading causes of death and disability worldwide. However, current therapies only reach a small percentage of patients and may cause serious side effects. We propose the therapeutic use of retinoic acid-loaded nanoparticles (RA-NP) to safely and efficiently repair the ischaemic brain by creating a favourable pro-angiogenic environment that enhances neurogenesis and neuronal restitution. Our data showed that RA-NP enhanced endothelial cell proliferation and tubule network formation and protected against ischaemia-induced death. To evaluate the effect of RA-NP on vascular regulation of neural stem cell (NSC) survival and differentiation, endothelial cell-conditioned media (EC-CM) were collected. EC-CM from healthy RA-NP-treated cells reduced NSC death and promoted proliferation while EC-CM from ischaemic RA-NP-treated cells decreased cell death, increased proliferation and neuronal differentiation. In parallel, human endothelial progenitor cells (hEPC), which are part of the endogenous repair response to vascular injury, were collected from ischaemic stroke patients. hEPC treated with RA-NP had significantly higher proliferation, which further highlights the therapeutic potential of this formulation. To conclude, RA-NP protected endothelial cells from ischaemic death and stimulated the release of pro-survival, proliferation-stimulating factors and differentiation cues for NSC. RA-NP were shown to be up to 83-fold more efficient than free RA and to enhance hEPC proliferation. These data serve as a stepping stone to use RA-NP as vasculotrophic and neurogenic agents for vascular disorders and neurodegenerative diseases with compromised vasculature.

  17. The uncovered parity properties of the Czech Koruna

    Czech Academy of Sciences Publication Activity Database

    Derviz, Alexis

    2002-01-01

    Roč. 11, č. 1 (2002), s. 17-37 ISSN 1210-0455 R&D Projects: GA AV ČR KSK1019101 Institutional research plan: CEZ:AV0Z1075907 Keywords : uncovered parity * asset prices * international consumption-based capital asset pricing model Subject RIV: AH - Economics

  18. Uncovering the Density of Matter from Multiplicity Distribution

    International Nuclear Information System (INIS)

    Bialas, A.

    2010-01-01

    Multiplicity distributions in the form of superposition of Poisson distributions which are observed in multiparticle production are interpreted as reflection of a two-step nature of this process: the creation and evolution of the strongly interacting fluid, followed by its uncorrelated decay into observed hadrons. A method to uncover the density of the fluid from the observed multiplicity distribution is described. (author)

  19. Deoxycholate-Enhanced Shigella Virulence Is Regulated by a Rare π-Helix in the Type Three Secretion System Tip Protein IpaD.

    Science.gov (United States)

    Bernard, Abram R; Jessop, T Carson; Kumar, Prashant; Dickenson, Nicholas E

    2017-12-12

    Type three secretion systems (T3SS) are specialized nanomachines that support infection by injecting bacterial proteins directly into host cells. The Shigella T3SS has uniquely evolved to sense environmental levels of the bile salt deoxycholate (DOC) and upregulate virulence in response to DOC. In this study, we describe a rare i + 5 hydrogen bonding secondary structure element (π-helix) within the type three secretion system tip protein IpaD that plays a critical role in DOC-enhanced virulence. Specifically, engineered mutations within the π-helix altered the pathogen's response to DOC, with one mutant construct in particular exhibiting an unprecedented reduction in virulence following DOC exposure. Fluorescence polarization binding assays showed that these altered DOC responses are not the result of differences in affinity between IpaD and DOC, but rather differences in the DOC-dependent T3SS tip maturation resulting from binding of IpaD to translocator/effector protein IpaB. Together, these findings begin to uncover the complex mechanism of DOC-enhanced Shigella virulence while identifying an uncommon structural element that may provide a much needed target for non-antibiotic treatment of Shigella infection.

  20. Cognitive enhancement therapy improves fronto-limbic regulation of emotion in alcohol and/or cannabis misusing schizophrenia: a preliminary study

    Directory of Open Access Journals (Sweden)

    Jessica Ann Wojtalik

    2016-01-01

    Full Text Available Individuals with schizophrenia who misuse substances are burdened with impairments in emotion regulation. Cognitive Enhancement Therapy (CET may address these problems by enhancing prefrontal brain function. A small sample of outpatients with schizophrenia and alcohol and/or cannabis substance use problems participating in an 18-month randomized trial of CET (n = 10 or usual care (n = 4 completed post-treatment functional neuroimaging using an emotion regulation task. General linear models explored CET effects on brain activity in emotional neurocircuitry. Individuals treated with CET had significantly greater activation in broad regions of the prefrontal cortex, limbic and striatal systems implicated in emotion regulation compared to usual care. Differential activation favoring CET in prefrontal regions and the insula mediated behavioral improvements in emotional processing. Our data lend preliminary support of CET effects on neuroplasticity in fronto-limbic and striatal circuitries which mediate emotion regulation in people with schizophrenia and comorbid substance misuse problems.

  1. Down-regulation of LncRNA TUG1 enhances radiosensitivity in bladder cancer via suppressing HMGB1 expression.

    Science.gov (United States)

    Jiang, Huijuan; Hu, Xigang; Zhang, Hongzhi; Li, Wenbo

    2017-04-04

    Long non-coding RNAs (lncRNAs) have been reported to regulate the sensitivity of different cancer cells to chemoradiotherapy. Aberrant expression of lncRNA Taurine-upregulated gene 1 (TUG1) has been found to be involved in the development of bladder cancer, however, its function and underlying mechanism in the radioresistance of bladder cancer remains unclear. Quantitative real-time PCR (qRT-PCR) was conducted to measure the expression of TUG1 and HMGB1 mRNA in bladder cancer tissues and cell lines. HMGB1 protein levels were tested by western blot assays. Different doses of X-ray were used for radiation treatment of bladder cancer cells. Colony survival and cell viability were detected by clonogenic assay and CCK-8 Kit, respectively. Cell apoptosis was determined by flow cytometry. A xenograft mouse model was constructed to observe the effect of TUG1 on tumor growth in vivo. The levels of TUG1 and HMGB1 were remarkably increased in bladder cancer tissues and cell lines. Radiation treatment markedly elevated the expression of TUG1 and HMGB1. TUG1 knockdown inhibited cell proliferation, promoted cell apoptosis and decreased colony survival in SW780 and BIU87 cells under radiation. Moreover, TUG1 depletion suppressed the HMGB1 mRNA and protein levels. Furthermore, overexpression of HMGB1 reversed TUG1 knockdown-induced effect in bladder cancer cells. Radiation treatment dramatically reduced the tumor volume and weight in xenograft model, and this effect was more obvious when combined with TUG1 silencing. LncRNA TUG1 knockdown enhances radiosensitivity of bladder cancer by suppressing HMGB1 expression. TUG1 acts as a potential regulator of radioresistance of bladder cancer, and it may represent a promising therapeutic target for bladder cancer patients.

  2. Down-regulation of DNA mismatch repair enhances initiation and growth of neuroblastoma and brain tumour multicellular spheroids.

    Directory of Open Access Journals (Sweden)

    Samuel L Collins

    Full Text Available Multicellular tumour spheroid (MCTS cultures are excellent model systems for simulating the development and microenvironmental conditions of in vivo tumour growth. Many documented cell lines can generate differentiated MCTS when cultured in suspension or in a non-adhesive environment. While physiological and biochemical properties of MCTS have been extensively characterized, insight into the events and conditions responsible for initiation of these structures is lacking. MCTS are formed by only a small subpopulation of cells during surface-associated growth but the processes responsible for this differentiation are poorly understood and have not been previously studied experimentally. Analysis of gene expression within spheroids has provided clues but to date it is not known if the observed differences are a cause or consequence of MCTS growth. One mechanism linked to tumourigenesis in a number of cancers is genetic instability arising from impaired DNA mismatch repair (MMR. This study aimed to determine the role of MMR in MCTS initiation and development. Using surface-associated N2a and CHLA-02-ATRT culture systems we have investigated the impact of impaired MMR on MCTS growth. Analysis of the DNA MMR genes MLH1 and PMS2 revealed both to be significantly down-regulated at the mRNA level compared with non-spheroid-forming cells. By using small interfering RNA (siRNA against these genes we show that silencing of MLH1 and PMS2 enhances both MCTS initiation and subsequent expansion. This effect was prolonged over several passages following siRNA transfection. Down-regulation of DNA MMR can contribute to tumour initiation and progression in N2a and CHLA-02-ATRT MCTS models. Studies of surface-associated MCTS differentiation may have broader applications in studying events in the initiation of cancer foci.

  3. Keratin-6 driven ODC expression to hair follicle keratinocytes enhances stemness and tumorigenesis by negatively regulating Notch

    Energy Technology Data Exchange (ETDEWEB)

    Arumugam, Aadithya; Weng, Zhiping; Chaudhary, Sandeep C.; Afaq, Farrukh [Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294-0019 (United States); Elmets, Craig A. [Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294-0019 (United States); Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Athar, Mohammad, E-mail: mathar@uab.edu [Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294-0019 (United States); Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL 35294 (United States)

    2014-08-29

    Highlights: • Targeting ODC to hair follicle augments skin carcinogenesis and invasive SCCs. • Hair follicle ODC expands stem cell compartment carrying CD34{sup +}/K15{sup +}/p63{sup +} keratinocytes. • Negatively regulated Notch1 is associated with expansion of stem cell compartment. - Abstract: Over-expression of ornithine decarboxylase (ODC) is known to be involved in the epidermal carcinogenesis. However, the mechanism by which it enhances skin carcinogenesis remains undefined. Recently, role of stem cells localized in various epidermal compartments has been shown in the pathogenesis of skin cancer. To direct ODC expression in distinct epidermal compartments, we have developed keratin 6 (K6)-ODC/SKH-1 and keratin 14 (K14)-ODC/SKH-1 mice and employed them to investigate the role of ODC directed to these epidermal compartments on UVB-induced carcinogenesis. K6-driven ODC over-expression directed to outer root sheath (ORS) of hair follicle was more effective in augmenting tumorigenesis as compared to mice where K14-driven ODC expression was directed to inter-follicular epidermal keratinocytes. Chronically UVB-irradiated K6-ODC/SKH-1 developed 15 ± 2.5 tumors/mouse whereas K14-ODC/SKH-1 developed only 6.8 ± 1.5 tumors/mouse. K6-ODC/SKH-1 showed augmented UVB-induced proliferation and much higher pro-inflammatory responses than K14-ODC/SKH-1 mice. Tumors induced in K6-ODC/SKH-1 were rapidly growing, invasive and ulcerative squamous cell carcinoma (SCC) showing decreased expression of epidermal polarity marker E-cadherin and enhanced mesenchymal marker, fibronectin. Interestingly, the number of CD34/CK15/p63 positive stem-like cells was significantly higher in chronically UVB-irradiated K6-ODC/SKH-1 as compared to K14-ODC/SKH-1 mice. Reduced Notch1 expression was correlated with the expansion of stem cell compartment in these animals. However, other signaling pathways such as DNA damage response or mTOR signaling pathways were not significantly different in

  4. Keratin-6 driven ODC expression to hair follicle keratinocytes enhances stemness and tumorigenesis by negatively regulating Notch

    International Nuclear Information System (INIS)

    Arumugam, Aadithya; Weng, Zhiping; Chaudhary, Sandeep C.; Afaq, Farrukh; Elmets, Craig A.; Athar, Mohammad

    2014-01-01

    Highlights: • Targeting ODC to hair follicle augments skin carcinogenesis and invasive SCCs. • Hair follicle ODC expands stem cell compartment carrying CD34 + /K15 + /p63 + keratinocytes. • Negatively regulated Notch1 is associated with expansion of stem cell compartment. - Abstract: Over-expression of ornithine decarboxylase (ODC) is known to be involved in the epidermal carcinogenesis. However, the mechanism by which it enhances skin carcinogenesis remains undefined. Recently, role of stem cells localized in various epidermal compartments has been shown in the pathogenesis of skin cancer. To direct ODC expression in distinct epidermal compartments, we have developed keratin 6 (K6)-ODC/SKH-1 and keratin 14 (K14)-ODC/SKH-1 mice and employed them to investigate the role of ODC directed to these epidermal compartments on UVB-induced carcinogenesis. K6-driven ODC over-expression directed to outer root sheath (ORS) of hair follicle was more effective in augmenting tumorigenesis as compared to mice where K14-driven ODC expression was directed to inter-follicular epidermal keratinocytes. Chronically UVB-irradiated K6-ODC/SKH-1 developed 15 ± 2.5 tumors/mouse whereas K14-ODC/SKH-1 developed only 6.8 ± 1.5 tumors/mouse. K6-ODC/SKH-1 showed augmented UVB-induced proliferation and much higher pro-inflammatory responses than K14-ODC/SKH-1 mice. Tumors induced in K6-ODC/SKH-1 were rapidly growing, invasive and ulcerative squamous cell carcinoma (SCC) showing decreased expression of epidermal polarity marker E-cadherin and enhanced mesenchymal marker, fibronectin. Interestingly, the number of CD34/CK15/p63 positive stem-like cells was significantly higher in chronically UVB-irradiated K6-ODC/SKH-1 as compared to K14-ODC/SKH-1 mice. Reduced Notch1 expression was correlated with the expansion of stem cell compartment in these animals. However, other signaling pathways such as DNA damage response or mTOR signaling pathways were not significantly different in tumors induced

  5. Selective Enhancement of Synaptic Inhibition by Hypocretin (Orexin) in Rat Vagal Motor Neurons: Implications for Autonomic Regulation

    Science.gov (United States)

    Davis, Scott F.; Williams, Kevin W.; Xu, Weiye; Glatzer, Nicholas R.; Smith, Bret N.

    2012-01-01

    The hypocretins (orexins) are hypothalamic neuropeptides implicated in feeding, arousal, and autonomic regulation. These studies were designed to determine the actions of hypocretin peptides on synaptic transmission in the dorsal motor nucleus of the vagus nerve (DMV). Whole-cell patch-clamp recordings were made from DMV neurons in transverse slices of rat brainstem. Some of the neurons were identified as gastric-related by retrograde labeling after inoculation of the stomach wall with pseudorabies virus 152, a viral label that reports enhanced green fluorescent protein. Consistent with previous findings, hypocretins caused an inward current (6–68 pA) in most neurons at holding potentials near rest. In addition, the frequency of spontaneous IPSCs was increased in a concentration-related manner (up to 477%), with little change in EPSCs. This effect was preserved in the presence of tetrodotoxin, suggesting a presynaptic site of action. Hypocretins increased the amplitude of IPSCs evoked by electrical stimulation of the nucleus tractus solitarius (NTS) but not evoked EPSCs. Hypocretin-induced increases in the frequency of IPSCs evoked by photoactivation of caged glutamate within the NTS were also observed. Identical effects of the peptides were observed in identified gastric-related and unlabeled DMV neurons. In contrast to some previous studies, which have reported primarily excitatory actions of the hypocretins in many regions of the CNS, these data support a role for hypocretin in preferentially enhancing synaptic inhibition, including inhibitory inputs arising from neurons in the NTS. These findings indicate that the hypocretins can modulate and coordinate visceral autonomic output by acting directly on central vagal circuits. PMID:12736355

  6. The Uncovered Interest Parity in the Foreign Exchange (FX Markets

    Directory of Open Access Journals (Sweden)

    Silvio Ricardo Micheloto

    2004-12-01

    Full Text Available This work verifies the uncovered interest rates parity (UIP in the FX (foreign exchange emerging markets by using the panel cointegration technique. The data involves several developing countries that compose the EMBI+ Global Index. We compare the results of several panel estimators: OLS (ordinary list square, DOLS (dynamic OLS and FMOLS (fully modified OLS. This new panel technique can handle problems of either non-stationary series (spurious regression or small problem. This latter problem has being considered one of the main causes for distorting the UIP empirical results. By using this approach, we check the UIP in the FX (foreign exchange emerging markets. These markets are more critical because they have been subjected to changing FX regimes and speculative attacks. Our results do not corroborate the uncovered interest parity for the developing countries in the recent years. Thus, the forward premium puzzle may hold in the FX emergent markets.

  7. IL-4 enhances IL-10 production in Th1 cells: implications for Th1 and Th2 regulation.

    Science.gov (United States)

    Mitchell, Ruth E; Hassan, Masriana; Burton, Bronwen R; Britton, Graham; Hill, Elaine V; Verhagen, Johan; Wraith, David C

    2017-09-12

    IL-10 is an immunomodulatory cytokine with a critical role in limiting inflammation in immune-mediated pathologies. The mechanisms leading to IL-10 expression by CD4 + T cells are being elucidated, with several cytokines implicated. We explored the effect of IL-4 on the natural phenomenon of IL-10 production by a chronically stimulated antigen-specific population of differentiated Th1 cells. In vitro, IL-4 blockade inhibited while addition of exogenous IL-4 to Th1 cultures enhanced IL-10 production. In the in vivo setting of peptide immunotherapy leading to a chronically stimulated Th1 phenotype, lack of IL-4Rα inhibited the induction of IL-10. Exploring the interplay of Th1 and Th2 cells through co-culture, Th2-derived IL-4 promoted IL-10 expression by Th1 cultures, reducing their pathogenicity in vivo. Co-culture led to upregulated c-Maf expression with no decrease in the proportion of T-bet + cells in these cultures. Addition of IL-4 also reduced the encephalitogenic capacity of Th1 cultures. These data demonstrate that IL-4 contributes to IL-10 production and that Th2 cells modulate Th1 cultures towards a self-regulatory phenotype, contributing to the cross-regulation of Th1 and Th2 cells. These findings are important in the context of Th1 driven diseases since they reveal how the Th1 phenotype and function can be modulated by IL-4.

  8. Down-regulation of Fusarium oxysporum endogenous genes by Host-Delivered RNA interference enhances disease resistance

    Directory of Open Access Journals (Sweden)

    Zongli eHu

    2015-01-01

    Full Text Available Fusarium oxysporum is a devastating pathogen causing extensive yield losses in a variety of crops and development of sustainable, environmentally friendly methods to improve crop resistance is crucial. We have used Host-Derived RNA interference (HD-RNAi technology to partially silence three different genes (FOW2, FRP1 and OPR in the hemi-biotrophic fungus Fusarium oxysporum f. sp. conglutinans. Expression of double stranded RNA molecules targeting fungal pathogen genes was achieved in a number of transgenic Arabidopsis lines. F. oxysporum infecting the transgenic lines displayed substantially reduced mRNA levels on all three targeted genes, with an average of 75%, 83% and 72% reduction for FOW2, FRP1 and OPR respectively. The silencing of pathogen genes had a clear positive effect on the ability of the transgenic lines to fight infection. All transgenic lines displayed enhanced resistance to F. oxysporum with delayed disease symptom development, especially FRP1 and OPR lines. Survival rates after fungal infection were higher in the transgenic lines compared to control wild type plants which consistently showed survival rates of 10%, with FOW2 lines showing 25% survival; FRP1 lines 30-50% survival and FOW2 between 45-70% survival. The down-regulation effect was specific for the targeted genes without unintended effects in related genes. In addition to producing resistant crops, HD-RNAi can provide a useful tool to rapidly screen candidate fungal pathogenicity genes without the need to produce fungal knockout mutants.

  9. Down-regulation of Fusarium oxysporum endogenous genes by Host-Delivered RNA interference enhances disease resistance

    Science.gov (United States)

    Hu, Zongli; Parekh, Urvi; Maruta, Natsumi; Trusov, Yuri; Botella, Jimmy

    2015-01-01

    Fusarium oxysporum is a devastating pathogen causing extensive yield losses in a variety of crops and development of sustainable, environmentally friendly methods to improve crop resistance is crucial. We have used Host-Derived RNA interference (HD-RNAi) technology to partially silence three different genes (FOW2, FRP1 and OPR) in the hemi-biotrophic fungus Fusarium oxysporum f. sp. conglutinans. Expression of double stranded RNA molecules targeting fungal pathogen genes was achieved in a number of transgenic Arabidopsis lines. F. oxysporum infecting the transgenic lines displayed substantially reduced mRNA levels on all three targeted genes, with an average of 75%, 83% and 72% reduction for FOW2, FRP1 and OPR respectively. The silencing of pathogen genes had a clear positive effect on the ability of the transgenic lines to fight infection. All transgenic lines displayed enhanced resistance to F. oxysporum with delayed disease symptom development, especially FRP1 and OPR lines. Survival rates after fungal infection were higher in the transgenic lines compared to control wild type plants which consistently showed survival rates of 10%, with FOW2 lines showing 25% survival; FRP1 lines 30-50% survival and FOW2 between 45-70% survival. The down-regulation effect was specific for the targeted genes without unintended effects in related genes. In addition to producing resistant crops, HD-RNAi can provide a useful tool to rapidly screen candidate fungal pathogenicity genes without the need to produce fungal knockout mutants.

  10. Uncovering Student Ideas in Astronomy 45 Formative Assessment Probes

    CERN Document Server

    Keeley, Page

    2012-01-01

    What do your students know-or think they know-about what causes night and day, why days are shorter in winter, and how to tell a planet from a star? Find out with this book on astronomy, the latest in NSTA's popular Uncovering Student Ideas in Science series. The 45 astronomy probes provide situations that will pique your students' interest while helping you understand how your students think about key ideas related to the universe and how it operates.

  11. Enhancing Self-Regulation and Approaches to Learning in First-Year College Students: A Narrative-Based Programme Assessed in the Iberian Peninsula

    Science.gov (United States)

    Rosario, Pedro; Nunez, Jose C.; Gonzalez-Pienda, Julio; Valle, Antonio; Trigo, Luisa; Guimaraes, Carina

    2010-01-01

    A programme to enhance first-year college students' self-regulated learning strategies is proposed and assessed in two samples, one from the University of Oviedo (Spain) and the other from the University of Minho (Portugal). Each sample was divided into two groups (experimental and control). The Spanish sample comprised 44 students in the…

  12. Malignant Gastroduodenal Obstruction: Treatment with Self-Expanding Uncovered Wallstent

    International Nuclear Information System (INIS)

    Gutzeit, Andreas; Binkert, Christoph A.; Schoch, Eric; Sautter, Thomas; Jost, Res; Zollikofer, Christoph L.

    2009-01-01

    Purpose: To retrospectively evaluate the clinical effectiveness of a self-expanding uncovered Wallstent in patients with malignant gastroduodenal obstruction. Materials and Methods: Under combined endoscopic and fluoroscopic guidance, 29 patients with a malignant gastroduodenal stenosis were treated with a self-expanding uncovered metallic Wallstent. A dysphagia score was assessed before and after the intervention to measure the success of this palliative therapy. The dysphagia score ranged between grade 0 to grade 4: grade 0 = able to tolerate solid food, grade 1 = able to tolerate soft food, grade 2 = able to tolerate thick liquids, grade 3 = able to tolerate water or clear fluids, and grade 4 = unable to tolerate anything perorally. Stent patency and patients survival rates were calculated. Results: The insertion of the gastroduodenal stent was technically successful in 28 patients (96.5%). After stenting, 25 patients (86.2%) showed clinical improvement by at least one score point. During follow-up, 22 (78.5%) of 28 patients showed no stent occlusion until death and did not have to undergo any further intervention. In six patients (20.6%), all of whom were treated with secondary stent insertions, occlusion with tumor ingrowth and/or overgrowth was observed after the intervention. The median period of primary stent patency in our study was 240 days. Conclusion: Placement of an uncovered Wallstent is clinically effective in patients with malignant gastroduodenal obstruction. Stent placement is associated with high technical success, good palliation effect, and high durability of stent function.

  13. Overexpression of microRNA-132 enhances the radiosensitivity of cervical cancer cells by down-regulating Bmi-1.

    Science.gov (United States)

    Liu, Gui-Feng; Zhang, Shu-Hua; Li, Xue-Feng; Cao, Li-Yan; Fu, Zhan-Zhao; Yu, Shao-Nan

    2017-10-06

    We examined the effects of microRNA-132 (miR-132) on Bmi-1 expression and radiosensitivity in HeLa, SiHa, and C33A cervical cancer (CC) cells and 104 CC patients. MiR-132 expression was decreased and Bmi-1 expression was increased in tumor tissues compared to adjacent normal tissues and in radiotherapy-resistant patients compared to radiotherapy-sensitive patients. MiR-132 expression and Bmi-1 mRNA expression were also negatively correlated in tumor tissues. HeLa, SiHa, and C33A cells were divided into blank, miR-132 negative control (NC), miR-132 inhibitor, miR-132 mimics, siBmi-1, and miR-132 inhibitor + siBmi-1 groups, after which expression of miR-132 and Bmi-1, and the interaction between them and cell survival, proliferation, and apoptosis were examined. Bmi-1 was confirmed as a target of miRNA-132. Survival was higher and apoptosis lower in the miR-132 inhibitor group than the blank group after various doses of radiation. By contrast, survival was lower and apoptosis higher in the miRNA-132 mimics and siBmi-1 groups than in the blank group. Moreover, miR-132 expression increased and Bmi-1 mRNA expression decreased in each group at radiation doses of 6 and 8 Gy. Finally, co-administration of radiotherapy and exogenous miR-132 inhibited the growth of HeLa cell transplant-induced tumors in nude mice more effectively than radiotherapy alone. These results suggest overexpression of miR-132 enhances the radiosensitivity of CC cells by down-regulating Bmi-1 and that miR-132 may be a useful new target for the treatment of CC.

  14. Down-regulation of the expression of CCAAT/enhancer binding protein α gene in cervical squamous cell carcinoma

    International Nuclear Information System (INIS)

    Pan, Zemin; Shao, Renfu; Zheng, Weinan; Zhang, Jinli; Gao, Rui; Li, Dongmei; Guo, Xiaoqing; Han, Hu; Li, Feng; Qu, Shen

    2014-01-01

    Cervical carcinoma is the second most common cancer and is an important cause of death in women worldwide. CCAAT/enhancer binding proteins (C/EBPs) are a family of transcription factors that regulate cellular differentiation and proliferation in a variety of tissues. However, the role of C/EBPα gene in cervical cancer is still not clear. We investigated the expression of C/EBPα gene in cervical squamous cell carcinoma. C/EBPα mRNA level was measured by real-time quantitative RT-PCR in cervical cancer tissues and their adjacent normal tissues. C/EBPα protein level was measured by immunohistochemistry. Methylation in the promoter of C/EBPα gene was detected by MALDI TOF MassARRAY. We transfected HeLa cells with C/EBPα expression vector. C/EBPα expression in HeLa cells was examined and HeLa cell proliferation was measured by MTT assay and HeLa cells migration was analyzed by matrigel-coated transwell migration assays. There were significant difference in C/EBPα protein expression between chronic cervicitis and cervical carcinoma (P < 0.001). CEBPα mRNA level was significantly lower in cervical cancer tissues than in normal cervical tissues (P < 0.01). Methylation of the promoter of CEBPα gene in CpG 5, CpG-14.15, CpG-19.20 were significantly higher in cervical cancer than in normal cervical tissues (P < 0.05, P < 0.01, P < 0.05, respectively). CEBPα pcDNA3.1 construct transfected into HeLa cells inhibited cell proliferation and decreased cell migration. Our results indicate that reduced C/EBPα gene expression may play a role in the development of cervical squamous cell carcinoma

  15. Exogenously applied plant growth regulators enhance the morpho-physiological growth and yield of rice under high temperature

    Directory of Open Access Journals (Sweden)

    Shah Fahad

    2016-08-01

    Full Text Available A two-year experiment was conducted to ascertain the effects of exogenously applied plant growth regulators (PGR on rice growth and yield attributes under high day (HDT and high night temperature (HNT. Two rice cultivars (IR-64 and Huanghuazhan were subjected to temperature treatments in controlled growth chambers and four different combinations of ascorbic acid (Vc, alpha-tocopherol (Ve, brassinosteroids (Br, methyl jasmonates (MeJA and triazoles (Tr were applied. High temperature severely affected rice morphology, and also reduced leaf area, above- and below-ground biomass, photosynthesis, and water use efficiency, while increased the leaf water potential of both rice cultivars. Grain yield and its related attributes except number of panicles, were reduced under high temperature. The HDT posed more negative effects on rice physiological attributes, while HNT was more detrimental for grain formation and yield. The Huanghuazhan performed better than IR-64 under high temperature stress with better growth and higher grain yield. Exogenous application of PGRs was helpful in alleviating the adverse effects of high temperature. Among PGR combinations, the Vc+Ve+MejA+Br was the most effective treatment for both cultivars under high temperature stress. The highest grain production by Vc+Ve+MejA+Br treated plants was due to enhanced photosynthesis, spikelet fertility and grain filling, which compensated the adversities of high temperature stress. Taken together, these results will be of worth for further understanding the adaptation and survival mechanisms of rice to high temperature and will assist in developing heat-resistant rice germplasm in future.

  16. Alleviation of reactive oxygen species enhances PUFA accumulation in Schizochytrium sp. through regulating genes involved in lipid metabolism

    Directory of Open Access Journals (Sweden)

    Sai Zhang

    2018-06-01

    Full Text Available The unicellular heterotrophic thraustochytrids are attractive candidates for commercial polyunsaturated fatty acids (PUFA production. However, the reactive oxygen species (ROS generated in their aerobic fermentation process often limits their PUFA titer. Yet, the specific mechanisms of ROS involvement in the crosstalk between oxidative stress and intracellular lipid synthesis remain poorly described. Metabolic engineering to improve the PUFA yield in thraustochytrids without compromising growth is an important aspect of economic feasibility. To fill this gap, we overexpressed the antioxidative gene superoxide dismutase (SOD1 by integrating it into the genome of thraustochytrid Schizochytrium sp. PKU#Mn4 using a novel genetic transformation system. This study reports the ROS alleviation, enhanced PUFA production and transcriptome changes resulting from the SOD1 overexpression. SOD1 activity in the recombinant improved by 5.2–71.6% along with 7.8–38.5% decline in ROS during the fermentation process. Interestingly, the total antioxidant capacity in the recombinant remained higher than wild-type and above zero in the entire process. Although lipid profile was similar to that of wild-type, the concentrations of major fatty acids in the recombinant were significantly (p ≤ 0.05 higher. The PUFA titer increased up to 1232 ± 41 mg/L, which was 32.9% higher (p ≤ 0.001 than the wild type. Transcriptome analysis revealed strong downregulation of genes potentially involved in β-oxidation of fatty acids in peroxisome and upregulation of genes catalyzing lipid biosynthesis. Our results enrich the knowledge on stress-induced PUFA biosynthesis and the putative role of ROS in the regulation of lipid metabolism in oleaginous thraustochytrids. This study provides a new and alternate strategy for cost-effective industrial fermentation of PUFA. Keywords: Polyunsaturated fatty acids, Schizochytrium sp., Superoxide dismutase, Transgene

  17. Enhanced photosynthetic capacity increases nitrogen metabolism through the coordinated regulation of carbon and nitrogen assimilation in Arabidopsis thaliana.

    Science.gov (United States)

    Otori, Kumi; Tanabe, Noriaki; Maruyama, Toshiki; Sato, Shigeru; Yanagisawa, Shuichi; Tamoi, Masahiro; Shigeoka, Shigeru

    2017-09-01

    Plant growth and productivity depend on interactions between the metabolism of carbon and nitrogen. The sensing ability of internal carbon and nitrogen metabolites (the C/N balance) enables plants to regulate metabolism and development. In order to investigate the effects of an enhanced photosynthetic capacity on the metabolism of carbon and nitrogen in photosynthetically active tissus (source leaves), we herein generated transgenic Arabidopsis thaliana plants (ApFS) that expressed cyanobacterial fructose-1,6-/sedoheptulose-1,7-bisphosphatase in their chloroplasts. The phenotype of ApFS plants was indistinguishable from that of wild-type plants at the immature stage. However, as plants matured, the growth of ApFS plants was superior to that of wild-type plants. Starch levels were higher in ApFS plants than in wild-type plants at 2 and 5 weeks. Sucrose levels were also higher in ApFS plants than in wild-type plants, but only at 5 weeks. On the other hand, the contents of various free amino acids were lower in ApFS plants than in wild-type plants at 2 weeks, but were similar at 5 weeks. The total C/N ratio was the same in ApFS plants and wild-type plants, whereas nitrite levels increased in parallel with elevations in nitrate reductase activity at 5 weeks in ApFS plants. These results suggest that increases in the contents of photosynthetic intermediates at the early growth stage caused a temporary imbalance in the free-C/free-N ratio and, thus, the feedback inhibition of the expression of genes involved in the Calvin cycle and induction of the expression of those involved in nitrogen metabolism due to supply deficient free amino acids for maintenance of the C/N balance in source leaves of ApFS plants.

  18. Resveratrol enhances airway surface liquid depth in sinonasal epithelium by increasing cystic fibrosis transmembrane conductance regulator open probability.

    Directory of Open Access Journals (Sweden)

    Shaoyan Zhang

    Full Text Available Chronic rhinosinusitis engenders enormous morbidity in the general population, and is often refractory to medical intervention. Compounds that augment mucociliary clearance in airway epithelia represent a novel treatment strategy for diseases of mucus stasis. A dominant fluid and electrolyte secretory pathway in the nasal airways is governed by the cystic fibrosis transmembrane conductance regulator (CFTR. The objectives of the present study were to test resveratrol, a strong potentiator of CFTR channel open probability, in preparation for a clinical trial of mucociliary activators in human sinus disease.Primary sinonasal epithelial cells, immortalized bronchoepithelial cells (wild type and F508del CFTR, and HEK293 cells expressing exogenous human CFTR were investigated by Ussing chamber as well as patch clamp technique under non-phosphorylating conditions. Effects on airway surface liquid depth were measured using confocal laser scanning microscopy. Impact on CFTR gene expression was measured by quantitative reverse transcriptase polymerase chain reaction.Resveratrol is a robust CFTR channel potentiator in numerous mammalian species. The compound also activated temperature corrected F508del CFTR and enhanced CFTR-dependent chloride secretion in human sinus epithelium ex vivo to an extent comparable to the recently approved CFTR potentiator, ivacaftor. Using inside out patches from apical membranes of murine cells, resveratrol stimulated an ~8 picosiemens chloride channel consistent with CFTR. This observation was confirmed in HEK293 cells expressing exogenous CFTR. Treatment of sinonasal epithelium resulted in a significant increase in airway surface liquid depth (in µm: 8.08+/-1.68 vs. 6.11+/-0.47,control,p<0.05. There was no increase CFTR mRNA.Resveratrol is a potent chloride secretagogue from the mucosal surface of sinonasal epithelium, and hydrates airway surface liquid by increasing CFTR channel open probability. The foundation for a

  19. Up-regulation of granzyme B and perforin by staphylococcal enterotoxin C2 mutant induces enhanced cytotoxicity in Hepa1–6 cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Guojun [Institute of Applied Ecology, Chinese Academy of Sciences, No.72 Wenhua Road Shenhe Dis., Shenyang, Liaoning (China); University of Chinese Academy of Sciences, Beijing (China); Xu, Mingkai, E-mail: mkxu@iae.ac.cn [Institute of Applied Ecology, Chinese Academy of Sciences, No.72 Wenhua Road Shenhe Dis., Shenyang, Liaoning (China); Zhang, Huiwen [Institute of Applied Ecology, Chinese Academy of Sciences, No.72 Wenhua Road Shenhe Dis., Shenyang, Liaoning (China); Song, Yubo [Institute of Applied Ecology, Chinese Academy of Sciences, No.72 Wenhua Road Shenhe Dis., Shenyang, Liaoning (China); University of Chinese Academy of Sciences, Beijing (China); Wang, Jian; Zhang, Chenggang [Institute of Applied Ecology, Chinese Academy of Sciences, No.72 Wenhua Road Shenhe Dis., Shenyang, Liaoning (China)

    2016-12-15

    Staphylococcal enterotoxin C2 (SEC2), a member of bacterial superantigen, is one of the most potent known activators of T lymphocytes. With this property, SEC2 has already been used in clinic as a tumor immunotherapy agent in China. To increase the antitumor activity, a SEC2 mutant named ST-4 (GKVTG102-106WWH) with amino acid substitutions in T cell receptor (TCR)-binding domain was generated by site-directed mutagenesis, and the molecular mechanism of the enhanced antitumor activity was investigated. Results showed that ST-4 could activate much more Vβ 8.2 and 8.3 T cells and NK cells compared with SEC2, and exhibited significantly enhanced immunocyte stimulation and antitumor activity in vitro. The synthetic peptide sequencing the residues of mutant TCR-binding domain could competitively inhibit the immunocyte stimulation activity of ST-4. Most importantly, ST-4 up-regulated granzyme B and perforin at both mRNA and protein levels. We also found that expression of proapoptotic proteins cytochrome c, BAX and activation of caspase-3, 9 was up-regulated, and antiapoptotic protein Bcl-xL was down-regulated in the treatment with either ST-4 or SEC2. When granzyme B inhibitor or perforin inhibitor is presented, tumor cell viability was significantly rescued. Taken together, we demonstrate that increased ST-4-TCR recognition contributed to massive T cells and NK cells activation. These activated cells released up-regulated granzyme B and perforin, which induced the enhanced tumor cells apoptosis by mitochondrial apoptotic pathway, and ultimately led to enhanced tumor cell growth inhibition. ST-4 may be a promising candidate for antitumor clinic usage in future. - Highlights: • We obtained a SEC2 mutant ST-4 with enhanced superantigen and antitumor activity. • Increased ST-4-TCR recognition contributed to massive T cells and NK cells activation. • Up-regulated GzmB and PRF1 in T cell by ST-4 induced enhanced tumor cells apoptosis. • Enhanced tumor cell apoptosis

  20. Down-regulation of Transducin-Like Enhancer of Split protein 4 in hepatocellular carcinoma promotes cell proliferation and epithelial-Mesenchymal-Transition

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Xiao-cai; Xiao, Cui-cui; Li, Hua [Department of Hepatic Surgery, 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou (China); Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou (China); Tai, Yan; Zhang, Qi [Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou (China); Yang, Yang, E-mail: yysysu2@163.com [Department of Hepatic Surgery, 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou (China)

    2016-08-19

    Background: Transducin-Like Enhancer of Split protein 4 (TLE4) has been reported to be involved in some subsets of acute myeloid leukemia and colorectal cancer. In the present study, we aimed to explore the role of TLE4 in tumorigenesis and cancer progression in hepatocellular carcinoma (HCC). Methods: The expression pattern of TLE4 in HCC was determined by Western-blot and qRT-PCR, gain-of-function and loss-of-function was used to explore the biological role of TLE4 in HCC cells. A xenograft model was established to confirm its effects on proliferation. Results: The protein expression levels of TLE4 were significantly down-regulated in HCC tissues compared to matched adjacent normal liver tissues. In vitro, down-regulation of TLE4 in Huh7 or SMMC-7721 promoted cell proliferation and ectopical expression of TLE4 in Hep3B or Bel-7404 suppressed cell proliferation. In addition, the cell colony formation ability was enhanced after down-regulation of TLE4 expression in Huh-7 but suppressed after over-expression in Hep3B. Furthermore, down-regulation of TLE4 increased the cell invasion ability, as well as increased the expression level of Vimentin and decreased that of E-cadherin, indicating a phenotype of epithelial-mesenchymal transition (EMT) in HCC cells. On the contrary, ectopical expression of TLE4 in HCC cells decreased the cell invasion ability and inhibited EMT. In vivo, compared to control group, xenograft tumor volumes were significantly decreased in TLE4 overexpression group. Conclusions: These results demonstrated that TLE4 might play important regulatory roles in cellular proliferation and EMT process in HCC. - Highlights: • TLE4 is significantly down-regulated in HCC samples. • Down regulated of TLE4 in HCC cells promotes cell proliferation. • Down regulated of TLE4 in HCC cells promotes epithelial-to-mesenchymal transition.

  1. Enhanced production of phenolic acids in cell suspension culture of Salvia leriifolia Benth. using growth regulators and sucrose.

    Science.gov (United States)

    Modarres, Masoomeh; Esmaeilzadeh Bahabadi, Sedigheh; Taghavizadeh Yazdi, Mohammad Ehsan

    2018-04-01

    Salvia leriifolia Benth. (Lamiaceae) is an endangered medicinal plant with hypoglycemic, anti-inflammatory and analgesic properties. Many of the beneficial effects of Salvia spp. are attributed to the phenolic compounds. In the present study, an efficient procedure has been developed for establishment of cell suspension culture of S. leriifolia as a strategy to obtain an in vitro phenolic acids producing cell line for the first time. The effect of growth regulators and various concentrations of sucrose have been analyzed, to optimize biomass growth and phenolic acids production. The callus used for this purpose was obtained from leaves of 15-day-old in vitro seedlings, on Murashige and Skoog (MS) basal medium supplemented with different hormone balances including benzylaminopurine (BAP) and indole butyric acid (IBA); 2,4-dichlorophenoxyacetic acid (2,4-D) and kinetin (KIN); naphthaleneacetic acid (NAA) and BAP. Modified MS medium supplemented with 5 mg/L BAP and 5 mg/L NAA was the optimal condition for callus formation with the highest induction rate (100%), the best callus growth and the highest phenolic acids content. No callus induction was observed in combinations of IBA and BAP. Cell suspension cultures were established by transferring 0.5 g of callus to 30 mL liquid MS medium supplemented with 5 mg/L BAP and 5 mg/L NAA. Dynamics of phenolic acids production has been investigated during the growth cycle of the suspension cultures. The maximum content of caffeic acid and salvianolic acid B were observed on the 15th day of the cultivation cycle while the highest amount of rosmarinic acid was observed on the first day. In response to various sucrose concentrations, cell cultures with 40 g/L sucrose not only produced the highest dry biomass but also the highest induction of caffeic acid and salvianolic acid B. The highest amount of rosmarinic acid was observed in media containing 50 g/L sucrose. These prepared cell suspension cultures provided a useful

  2. Regulator of G-protein signaling 5 (RGS5) inhibits cell proliferation and enhances radiosensitivity of human lung cancer cells

    International Nuclear Information System (INIS)

    Xu Zumin; Wang Jin; Zuo Yufang; Yu Zhonghua; Peng Fang; Hu Xiao; Zhou Qichao; Ma Honglian; Bao Yong; Chen Ming

    2014-01-01

    Objective: To investigate the effects of regulator and the underlying molecular mechanisms of G-protein signaling 5 (RGS5) on radiation response in human lung cancer cells. Methods: The effects of RGS5 on viability were determined by MTT assay, and apoptosis rate was detected by flow cytometry, in human lung cancer cells. The combined effect of ionizing radiation and RGS5 on tumor cells was detected by colony formation assay. The protein expression was detected by Western blot. Results: RGS5 overexpression remarkably inhibited the survival of human lung cancer cells, and the growth inhibition rate of RGS5 overexpression on A549 and Calu-3 cells were 44.4% (F = 29.18, P < 0.05) and 39.27% (F = 23.04, P < 0.05) at 48 h, and 54.3%(F = 103.45, P < 0.05), 44.7%(F = 108.02, P < 0.05) at 72 h post-irradiation, respectively. RGS5 might exert its inhibitory effects on human lung cancer cells by inducing tumor cell apoptosis, while the apoptotic cells rate in A549 and Calu-3 cells in control group, pTRiEX group and pTRiEX-RGS5 group were (1.3±0.2)%, (3.4±0.6)%, (19.6±2.3)% (F = 86.62, P < 0.05), and (3.2±0.8)%, (3.0±0.9)%, (12.8±1.8)% (F = 28.80, P < 0.05) at 36 h post-irradiation, respectively. Furthermore, RGS5 could sensitize the lung cancer cells to radiation. Conclusions: RGS5 might play an inhibitory role in human lung cancer cell proliferation, which may explain the pathoclinical observation thet high expression of RGSS is a favorable prognostic factor in NSCLC patients. In addition, RGS5 also enhance the anti-tumor effects of radiation in human lung cancer cells. (authors)

  3. Organization of physical interactomes as uncovered by network schemas.

    Science.gov (United States)

    Banks, Eric; Nabieva, Elena; Chazelle, Bernard; Singh, Mona

    2008-10-01

    Large-scale protein-protein interaction networks provide new opportunities for understanding cellular organization and functioning. We introduce network schemas to elucidate shared mechanisms within interactomes. Network schemas specify descriptions of proteins and the topology of interactions among them. We develop algorithms for systematically uncovering recurring, over-represented schemas in physical interaction networks. We apply our methods to the S. cerevisiae interactome, focusing on schemas consisting of proteins described via sequence motifs and molecular function annotations and interacting with one another in one of four basic network topologies. We identify hundreds of recurring and over-represented network schemas of various complexity, and demonstrate via graph-theoretic representations how more complex schemas are organized in terms of their lower-order constituents. The uncovered schemas span a wide range of cellular activities, with many signaling and transport related higher-order schemas. We establish the functional importance of the schemas by showing that they correspond to functionally cohesive sets of proteins, are enriched in the frequency with which they have instances in the H. sapiens interactome, and are useful for predicting protein function. Our findings suggest that network schemas are a powerful paradigm for organizing, interrogating, and annotating cellular networks.

  4. Activating Transcription Factor 3 regulates in part the enhanced tumour cell cytotoxicity of the histone deacetylase inhibitor M344 and cisplatin in combination

    Directory of Open Access Journals (Sweden)

    St Germain Carly

    2010-09-01

    Full Text Available Abstract Background Activating Transcription Factor (ATF 3 is a key regulator of the cellular integrated stress response whose expression has also been correlated with pro-apoptotic activities in tumour cell models. Combination treatments with chemotherapeutic drugs, such as cisplatin, and histone deacetylase (HDAC inhibitors have been demonstrated to enhance tumour cell cytotoxicity. We recently demonstrated a role for ATF3 in regulating cisplatin-induced apoptosis and others have shown that HDAC inhibition can also induce cellular stress. In this study, we evaluated the role of ATF3 in regulating the co-operative cytotoxicity of cisplatin in combination with an HDAC inhibitor. Results The HDAC inhibitor M344 induced ATF3 expression at the protein and mRNA level in a panel of human derived cancer cell lines as determined by Western blot and quantitative RT-PCR analyses. Combination treatment with M344 and cisplatin lead to increased induction of ATF3 compared with cisplatin alone. Utilizing the MTT cell viability assay, M344 treatments also enhanced the cytotoxic effects of cisplatin in these cancer cell lines. The mechanism of ATF3 induction by M344 was found to be independent of MAPKinase pathways and dependent on ATF4, a known regulator of ATF3 expression. ATF4 heterozygote (+/- and knock out (-/- mouse embryonic fibroblast (MEF as well as chromatin immunoprecipitation (ChIP assays were utilized in determining the mechanistic induction of ATF3 by M344. We also demonstrated that ATF3 regulates the enhanced cytotoxicity of M344 in combination with cisplatin as evidenced by attenuation of cytotoxicity in shRNAs targeting ATF3 expressing cells. Conclusion This study identifies the pro-apoptotic factor, ATF3 as a novel target of M344, as well as a mediator of the co-operative effects of cisplatin and M344 induced tumour cell cytotoxicity.

  5. Moving to the Beat: Using Music, Rhythm, and Movement to Enhance Self-Regulation in Early Childhood Classrooms

    Science.gov (United States)

    Williams, Kate E.

    2018-01-01

    Differences in early self-regulation skills contribute to disparities in success in early learning and school transition, as well as in childhood well-being. Self-regulation refers to managing emotional, cognitive, and behavioral processes that are conducive to positive adjustment and social relationships. Researchers have identified that various…

  6. Comparison of TALE designer transcription factors and the CRISPR/dCas9 in regulation of gene expression by targeting enhancers

    Science.gov (United States)

    Gao, Xuefei; Tsang, Jason C.H.; Gaba, Fortis; Wu, Donghai; Lu, Liming; Liu, Pentao

    2014-01-01

    The transcription activator–like effectors (TALEs) and the RNA-guided clustered regularly interspaced short palindromic repeat (CRISPR) associated protein (Cas9) utlilize distinct molecular mechanisms in targeting site recognition. The two proteins can be modified to carry additional functional domains to regulate expression of genomic loci in mammalian cells. In this study, we have compared the two systems in activation and suppression of the Oct4 and Nanog loci by targeting their enhancers. Although both are able to efficiently activate the luciferase reporters, the CRISPR/dCas9 system is much less potent in activating the endogenous loci and in the application of reprogramming somatic cells to iPS cells. Nevertheless, repression by CRISPR/dCas9 is comparable to or even better than TALE repressors. We demonstrated that dCas9 protein binding results in significant physical interference to binding of native transcription factors at enhancer, less efficient active histone markers induction or recruitment of activating complexes in gene activation. This study thus highlighted the merits and drawbacks of transcription regulation by each system. A combined approach of TALEs and CRISPR/dCas9 should provide an optimized solution to regulate genomic loci and to study genetic elements such as enhancers in biological processes including somatic cell reprogramming and guided differentiation. PMID:25223790

  7. Transcript profiles uncover temporal and stress-induced changes of metabolic pathways in germinating sugar beet seeds

    Directory of Open Access Journals (Sweden)

    Windhövel Andrea

    2008-12-01

    Full Text Available Abstract Background With a cultivation area of 1.75 Mio ha and sugar yield of 16.7 Mio tons in 2006, sugar beet is a crop of great economic importance in Europe. The productivity of sugar beet is determined significantly by seed vigour and field emergence potential; however, little is known about the molecular mechanisms underlying these traits. Both traits exhibit large variations within sugar beet germplasm that have been difficult to ascribe to either environmental or genetic causes. Among potential targets for trait improvement, an enhancement of stress tolerance is considered because of the high negative influence of environmental stresses on trait parameters. Extending our knowledge of genetic and molecular determinants of sugar beet germination, stress response and adaptation mechanisms would facilitate the detection of new targets for breeding crop with an enhanced field emergence potential. Results To gain insight into the sugar beet germination we initiated an analysis of gene expression in a well emerging sugar beet hybrid showing high germination potential under various environmental conditions. A total of 2,784 ESTs representing 2,251 'unigenes' was generated from dry mature and germinating seeds. Analysis of the temporal expression of these genes during germination under non-stress conditions uncovered drastic transcriptional changes accompanying a shift from quiescent to metabolically active stages of the plant life cycle. Assay of germination under stressful conditions revealed 157 genes showing significantly different expression patterns in response to stress. As deduced from transcriptome data, stress adaptation mechanisms included an alteration in reserve mobilization pathways, an accumulation of the osmoprotectant glycine betaine, late embryogenesis abundant proteins and detoxification enzymes. The observed transcriptional changes are supposed to be regulated by ABA-dependent signal transduction pathway. Conclusion This study

  8. SIRT1 Regulates Thyroid-Stimulating Hormone Release by Enhancing PIP5Kgamma Activity through Deacetylation of Specific Lysine Residues in Mammals.

    Directory of Open Access Journals (Sweden)

    Sayaka Akieda-Asai

    Full Text Available BACKGROUND: SIRT1, a NAD-dependent deacetylase, has diverse roles in a variety of organs such as regulation of endocrine function and metabolism. However, it remains to be addressed how it regulates hormone release there. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report that SIRT1 is abundantly expressed in pituitary thyrotropes and regulates thyroid hormone secretion. Manipulation of SIRT1 level revealed that SIRT1 positively regulated the exocytosis of TSH-containing granules. Using LC/MS-based interactomics, phosphatidylinositol-4-phosphate 5-kinase (PIP5Kgamma was identified as a SIRT1 binding partner and deacetylation substrate. SIRT1 deacetylated two specific lysine residues (K265/K268 in PIP5Kgamma and enhanced PIP5Kgamma enzyme activity. SIRT1-mediated TSH secretion was abolished by PIP5Kgamma knockdown. SIRT1 knockdown decreased the levels of deacetylated PIP5Kgamma, PI(4,5P(2, and reduced the secretion of TSH from pituitary cells. These results were also observed in SIRT1-knockout mice. CONCLUSIONS/SIGNIFICANCE: Our findings indicated that the control of TSH release by the SIRT1-PIP5Kgamma pathway is important for regulating the metabolism of the whole body.

  9. DOES UNCOVERED INTEREST RATE PARITY HOLD IN TURKEY?

    Directory of Open Access Journals (Sweden)

    Ozcan Karahan

    2012-01-01

    Full Text Available Most of the earlier empirical studies focusing on developed countries failed to give evidence in favor of the Uncovered Interest Rate Parity (UIP. After intensive financial liberalization processes and mostly preferred free exchange rate regimes, a new area of research starts to involve the investigation whether UIP holds for developing economies differently. Accordingly, we tested the UIP for Turkey’s monthly interest rate and exchange rate data between 2002 and 2011. We run conventional regressions in the form of Ordinary Least Squares (OLS and used a simple Generalized Autoregressive Conditional Heteroskedasticity (GARCH analysis. The empirical results of both methods do not support the validity of UIP for Turkey. Thus, together with most of the earlier empirical studies focusing on developed countries and detecting the invalidity of UIP, we can argue that the experience of Turkey and developed economies are not different.

  10. Uncovering growth-suppressive MicroRNAs in lung cancer

    DEFF Research Database (Denmark)

    Liu, Xi; Sempere, Lorenzo F; Galimberti, Fabrizio

    2009-01-01

    PURPOSE: MicroRNA (miRNA) expression profiles improve classification, diagnosis, and prognostic information of malignancies, including lung cancer. This study uncovered unique growth-suppressive miRNAs in lung cancer. EXPERIMENTAL DESIGN: miRNA arrays were done on normal lung tissues...... and adenocarcinomas from wild-type and proteasome degradation-resistant cyclin E transgenic mice to reveal repressed miRNAs in lung cancer. Real-time and semiquantitative reverse transcription-PCR as well as in situ hybridization assays validated these findings. Lung cancer cell lines were derived from each......-malignant human lung tissue bank. RESULTS: miR-34c, miR-145, and miR-142-5p were repressed in transgenic lung cancers. Findings were confirmed by real-time and semiquantitative reverse transcription-PCR as well as in situ hybridization assays. Similar miRNA profiles occurred in human normal versus malignant lung...

  11. Uncovering Listeria monocytogenes hypervirulence by harnessing its biodiversity

    Science.gov (United States)

    Charlier, Caroline; Touchon, Marie; Chenal-Francisque, Viviane; Leclercq, Alexandre; Criscuolo, Alexis; Gaultier, Charlotte; Roussel, Sophie; Brisabois, Anne; Disson, Olivier; Rocha, Eduardo P. C.; Brisse, Sylvain; Lecuit, Marc

    2016-01-01

    Microbial pathogenesis studies are typically performed with reference strains, thereby overlooking microbial intra-species virulence heterogeneity. Here we integrated human epidemiological and clinical data with bacterial population genomics to harness the biodiversity of the model foodborne pathogen Listeria monocytogenes and decipher the basis of its neural and placental tropisms. Taking advantage of the clonal structure of this bacterial species, we identify clones epidemiologically associated with either food or human central nervous system (CNS) and maternal-neonatal (MN) listeriosis. The latter are also most prevalent in patients without immunosuppressive comorbidities. Strikingly, CNS and MN clones are hypervirulent in a humanized mouse model of listeriosis. By integrating epidemiological data and comparative genomics, we uncovered multiple novel putative virulence factors and demonstrated experimentally the contribution of the first gene cluster mediating Listeria monocytogenes neural and placental tropisms. This study illustrates the exceptional power of harnessing microbial biodiversity to identify clinically relevant microbial virulence attributes. PMID:26829754

  12. TIME HORIZON AND UNCOVERED INTEREST PARITY IN EMERGING ECONOMIES

    Directory of Open Access Journals (Sweden)

    Norlida Hanim Mohd Salleh

    2011-07-01

    Full Text Available The aim of this study is to re-examine the well-known empirical puzzle of uncovered interest parity (UIP for emerging market economies with different prediction time horizons. The empirical results obtained using dynamic panel and time series techniques for monthly data from January 1995 to December 2009 eventually show that the panel data estimates are more powerful than those obtained by applying individual time series estimations and the significant contribution of the exchange rate prediction horizons in determining the status of UIP. This finding reveals that at the longer time horizon, the model has better econometric specification and thus more predictive power for exchange rate movements compared to the shorter time period. The findings can also be a signalling of well-integrated currency markets and a reliable guide to international investors as well as for the orderly conduct of monetary authorities.

  13. Uncovering the Geometry of Barrierless Reactions Using Lagrangian Descriptors.

    Science.gov (United States)

    Junginger, Andrej; Hernandez, Rigoberto

    2016-03-03

    Transition-state theories describing barrierless chemical reactions, or more general activated problems, are often hampered by the lack of a saddle around which the dividing surface can be constructed. For example, the time-dependent transition-state trajectory uncovering the nonrecrossing dividing surface in thermal reactions in the framework of the Langevin equation has relied on perturbative approaches in the vicinity of the saddle. We recently obtained an alternative approach using Lagrangian descriptors to construct time-dependent and recrossing-free dividing surfaces. This is a nonperturbative approach making no reference to a putative saddle. Here we show how the Lagrangian descriptor can be used to obtain the transition-state geometry of a dissipated and thermalized reaction across barrierless potentials. We illustrate the method in the case of a 1D Brownian motion for both barrierless and step potentials; however, the method is not restricted and can be directly applied to different kinds of potentials and higher dimensional systems.

  14. Down-regulation of ABCG2, a urate exporter, by parathyroid hormone enhances urate accumulation in secondary hyperparathyroidism.

    Science.gov (United States)

    Sugimoto, Ryusei; Watanabe, Hiroshi; Ikegami, Komei; Enoki, Yuki; Imafuku, Tadashi; Sakaguchi, Yoshiaki; Murata, Michiya; Nishida, Kento; Miyamura, Shigeyuki; Ishima, Yu; Tanaka, Motoko; Matsushita, Kazutaka; Komaba, Hirotaka; Fukagawa, Masafumi; Otagiri, Masaki; Maruyama, Toru

    2017-03-01

    Hyperuricemia occurs with increasing frequency among patients with hyperparathyroidism. However, the molecular mechanism by which the serum parathyroid hormone (PTH) affects serum urate levels remains unknown. This was studied in uremic rats with secondary hyperparathyroidism where serum urate levels were found to be increased and urate excretion in the intestine and kidney decreased, presumably due to down-regulation of the expression of the urate exporter ABCG2 in intestinal and renal epithelial membranes. These effects were prevented by administration of the calcimimetic cinacalcet, a PTH suppressor, suggesting that PTH may down-regulate ABCG2 expression. This was directly tested in intestinal Caco-2 cells where the expression of ABCG2 on the plasma membrane was down-regulated by PTH (1-34) while its mRNA level remained unchanged. Interestingly, an inactive PTH derivative (13-34) had no effect, suggesting that a posttranscriptional regulatory system acts through the PTH receptor to regulate ABCG2 plasma membrane expression. As found in an animal study, additional clinical investigations showed that treatment with cinacalcet resulted in significant reductions in serum urate levels together with decreases in PTH levels in patients with secondary hyperparathyroidism undergoing dialysis. Thus, PTH down-regulates ABCG2 expression on the plasma membrane to suppress intestinal and renal urate excretion, and the effects of PTH can be prevented by cinacalcet treatment. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  15. Dissecting engineered cell types and enhancing cell fate conversion via CellNet

    Science.gov (United States)

    Morris, Samantha A.; Cahan, Patrick; Li, Hu; Zhao, Anna M.; San Roman, Adrianna K.; Shivdasani, Ramesh A.; Collins, James J.; Daley, George Q.

    2014-01-01

    SUMMARY Engineering clinically relevant cells in vitro holds promise for regenerative medicine, but most protocols fail to faithfully recapitulate target cell properties. To address this, we developed CellNet, a network biology platform that determines whether engineered cells are equivalent to their target tissues, diagnoses aberrant gene regulatory networks, and prioritizes candidate transcriptional regulators to enhance engineered conversions. Using CellNet, we improved B cell to macrophage conversion, transcriptionally and functionally, by knocking down predicted B cell regulators. Analyzing conversion of fibroblasts to induced hepatocytes (iHeps), CellNet revealed an unexpected intestinal program regulated by the master regulator Cdx2. We observed long-term functional engraftment of mouse colon by iHeps, thereby establishing their broader potential as endoderm progenitors and demonstrating direct conversion of fibroblasts into intestinal epithelium. Our studies illustrate how CellNet can be employed to improve direct conversion and to uncover unappreciated properties of engineered cells. PMID:25126792

  16. The proteome and phosphoproteome of maize pollen uncovers fertility candidate proteins.

    Science.gov (United States)

    Chao, Qing; Gao, Zhi-Fang; Wang, Yue-Feng; Li, Zhe; Huang, Xia-He; Wang, Ying-Chun; Mei, Ying-Chang; Zhao, Biligen-Gaowa; Li, Liang; Jiang, Yu-Bo; Wang, Bai-Chen

    2016-06-01

    Maize is unique since it is both monoecious and diclinous (separate male and female flowers on the same plant). We investigated the proteome and phosphoproteome of maize pollen containing modified proteins and here we provide a comprehensive pollen proteome and phosphoproteome which contain 100,990 peptides from 6750 proteins and 5292 phosphorylated sites corresponding to 2257 maize phosphoproteins, respectively. Interestingly, among the total 27 overrepresented phosphosite motifs we identified here, 11 were novel motifs, which suggested different modification mechanisms in plants compared to those of animals. Enrichment analysis of pollen phosphoproteins showed that pathways including DNA synthesis/chromatin structure, regulation of RNA transcription, protein modification, cell organization, signal transduction, cell cycle, vesicle transport, transport of ions and metabolisms, which were involved in pollen development, the following germination and pollen tube growth, were regulated by phosphorylation. In this study, we also found 430 kinases and 105 phosphatases in the maize pollen phosphoproteome, among which calcium dependent protein kinases (CDPKs), leucine rich repeat kinase, SNF1 related protein kinases and MAPK family proteins were heavily enriched and further analyzed. From our research, we also uncovered hundreds of male sterility-associated proteins and phosphoproteins that might influence maize productivity and serve as targets for hybrid maize seed production. At last, a putative complex signaling pathway involving CDPKs, MAPKs, ubiquitin ligases and multiple fertility proteins was constructed. Overall, our data provides new insight for further investigation of protein phosphorylation status in mature maize pollen and construction of maize male sterile mutants in the future.

  17. Salinomycin enhances cisplatin-induced cytotoxicity in human lung cancer cells via down-regulation of AKT-dependent thymidylate synthase expression.

    Science.gov (United States)

    Ko, Jen-Chung; Zheng, Hao-Yu; Chen, Wen-Ching; Peng, Yi-Shuan; Wu, Chia-Hung; Wei, Chia-Li; Chen, Jyh-Cheng; Lin, Yun-Wei

    2016-12-15

    Salinomycin, a polyether antibiotic, acts as a highly selective potassium ionophore and has anticancer activity on various cancer cell lines. Cisplatin has been proved as chemotherapy drug for advanced human non-small cell lung cancer (NSCLC). Thymidylate synthase (TS) is a key enzyme in the pyrimidine salvage pathway, and increased expression of TS is thought to be associated with resistance to cisplatin. In this study, we showed that salinomycin (0.5-2μg/mL) treatment down-regulating of TS expression in an AKT inactivation manner in two NSCLC cell lines, human lung adenocarcinoma A549 and squamous cell carcinoma H1703 cells. Knockdown of TS using small interfering RNA (siRNA) or inhibiting AKT activity with PI3K inhibitor LY294002 enhanced the cytotoxicity and cell growth inhibition of salinomycin. A combination of cisplatin and salinomycin resulted in synergistic enhancement of cytotoxicity and cell growth inhibition in NSCLC cells, accompanied with reduced activation of phospho-AKT, and TS expression. Overexpression of a constitutive active AKT (AKT-CA) expression vector reversed the salinomycin and cisplatin-induced synergistic cytotoxicity. In contrast, pretreatment with LY294002 further decreased the cell viability in salinomycin and cisplatin cotreated cells. Our findings suggested that the down-regulation of AKT-mediated TS expression by salinomycin enhanced the cisplatin-induced cytotoxicity in NSCLC cells. These results may provide a rationale to combine salinomycin with cisplatin for lung cancer treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Uncovering the Recycling Potential of "New" WEEE in China.

    Science.gov (United States)

    Zeng, Xianlai; Gong, Ruying; Chen, Wei-Qiang; Li, Jinhui

    2016-02-02

    Newly defined categories of WEEE have increased the types of China's regulated WEEE from 5 to 14. Identification of the amounts and valuable-resource components of the "new" WEEE generated is critical to solving the e-waste problem, for both governmental policy decisions and recycling enterprise expansions. This study first estimates and predicts China's new WEEE generation for the period of 2010-2030 using material flow analysis and the lifespan model of the Weibull distribution, then determines the amounts of valuable resources (e.g., base materials, precious metals, and rare-earth minerals) encased annually in WEEE, and their dynamic transfer from in-use stock to waste. Main findings include the following: (i) China will generate 15.5 and 28.4 million tons WEEE in 2020 and 2030, respectively, and has already overtaken the U.S. to become the world's leading producer of e-waste; (ii) among all the types of WEEE, air conditioners, desktop personal computers, refrigerators, and washing machines contribute over 70% of total WEEE by weight. The two categories of EEE-electronic devices and electrical appliances-each contribute about half of total WEEE by weight; (iii) more and more valuable resources have been transferred from in-use products to WEEE, significantly enhancing the recycling potential of WEEE from an economic perspective; and (iv) WEEE recycling potential has been evolving from ∼16 (10-22) billion US$ in 2010, to an anticipated ∼42 (26-58) billion US$ in 2020 and ∼73.4 (44.5-103.4) billion US$ by 2030. All the obtained results can improve the knowledge base for closing the loop of WEEE recycling, and contribute to governmental policy making and the recycling industry's business development.

  19. MiR-155 induction by F. novicida but not the virulent F. tularensis results in SHIP down-regulation and enhanced pro-inflammatory cytokine response.

    Directory of Open Access Journals (Sweden)

    Thomas J Cremer

    2009-12-01

    Full Text Available The intracellular gram-negative bacterium Francisella tularensis causes the disease tularemia and is known for its ability to subvert host immune responses. Previous work from our laboratory identified the PI3K/Akt pathway and SHIP as critical modulators of host resistance to Francisella. Here, we show that SHIP expression is strongly down-regulated in monocytes and macrophages following infection with F. tularensis novicida (F.n.. To account for this negative regulation we explored the possibility that microRNAs (miRs that target SHIP may be induced during infection. There is one miR that is predicted to target SHIP, miR-155. We tested for induction and found that F.n. induced miR-155 both in primary monocytes/macrophages and in vivo. Using luciferase reporter assays we confirmed that miR-155 led to down-regulation of SHIP, showing that it specifically targets the SHIP 3'UTR. Further experiments showed that miR-155 and BIC, the gene that encodes miR-155, were induced as early as four hours post-infection in primary human monocytes. This expression was dependent on TLR2/MyD88 and did not require inflammasome activation. Importantly, miR-155 positively regulated pro-inflammatory cytokine release in human monocytes infected with Francisella. In sharp contrast, we found that the highly virulent type A SCHU S4 strain of Francisella tularensis (F.t. led to a significantly lower miR-155 response than the less virulent F.n. Hence, F.n. induces miR-155 expression and leads to down-regulation of SHIP, resulting in enhanced pro-inflammatory responses. However, impaired miR-155 induction by SCHU S4 may help explain the lack of both SHIP down-regulation and pro-inflammatory response and may account for the virulence of Type A Francisella.

  20. Social isolation mediated anxiety like behavior is associated with enhanced expression and regulation of BDNF in the female mouse brain.

    Science.gov (United States)

    Kumari, Anita; Singh, Padmanabh; Baghel, Meghraj Singh; Thakur, M K

    2016-05-01

    Adverse early life experience is prominent risk factors for numerous psychiatric illnesses, including mood and anxiety disorders. It imposes serious long-term costs on the individual as well as health and social systems. Hence, developing therapies that prevent the long-term consequences of early life stress is of utmost importance, and necessitates a better understanding of the mechanisms by which early life stress triggers long-lasting alterations in gene expression and behavior. Post-weaning isolation rearing of rodents models the behavioral consequences of adverse early life experiences in humans and it is reported to cause anxiety like behavior which is more common in case of females. Therefore, in the present study, we have studied the impact of social isolation of young female mice for 8weeks on the anxiety like behavior and the underlying molecular mechanism. Elevated plus maze and open field test revealed that social isolation caused anxiety like behavior. BDNF, a well-known molecule implicated in the anxiety like behavior, was up-regulated both at the message and protein level in cerebral cortex by social isolation. CREB-1 and CBP, which play a crucial role in BDNF transcription, were up-regulated at mRNA level in cerebral cortex by social isolation. HDAC-2, which negatively regulates BDNF expression, was down-regulated at mRNA and protein level in cerebral cortex by social isolation. Furthermore, BDNF acts in concert with Limk-1, miRNA-132 and miRNA-134 for the regulation of structural and morphological plasticity. Social isolation resulted in up-regulation of Limk-1 mRNA and miRNA-132 expression in the cerebral cortex. MiRNA-134, which inhibits the translation of Limk-1, was decreased in cerebral cortex by social isolation. Taken together, our study suggests that social isolation mediated anxiety like behavior is associated with up-regulation of BDNF expression and concomitant increase in the expression of CBP, CREB-1, Limk-1 and miRNA-132, and decrease

  1. Loss of Kdm5c Causes Spurious Transcription and Prevents the Fine-Tuning of Activity-Regulated Enhancers in Neurons

    Directory of Open Access Journals (Sweden)

    Marilyn Scandaglia

    2017-10-01

    Full Text Available During development, chromatin-modifying enzymes regulate both the timely establishment of cell-type-specific gene programs and the coordinated repression of alternative cell fates. To dissect the role of one such enzyme, the intellectual-disability-linked lysine demethylase 5C (Kdm5c, in the developing and adult brain, we conducted parallel behavioral, transcriptomic, and epigenomic studies in Kdm5c-null and forebrain-restricted inducible knockout mice. Together, genomic analyses and functional assays demonstrate that Kdm5c plays a critical role as a repressor responsible for the developmental silencing of germline genes during cellular differentiation and in fine-tuning activity-regulated enhancers during neuronal maturation. Although the importance of these functions declines after birth, Kdm5c retains an important genome surveillance role preventing the incorrect activation of non-neuronal and cryptic promoters in adult neurons.

  2. Abbreviated Resonant Frequency Training to Augment Heart Rate Variability and Enhance On-Demand Emotional Regulation in Elite Sport Support Staff.

    Science.gov (United States)

    Gross, Mike J; Shearer, David A; Bringer, Joy D; Hall, Ross; Cook, Christian J; Kilduff, Liam P

    2016-09-01

    Support and management staff in elite sport experience work-related stress and emotional disturbance to a similar extent as athletes (Fletcher and Wagstaff 2009). The resonant frequency breathing technique (Lehrer et al. 2000) can inhibit autonomic changes associated with stressful situations or events and as such provides a potential emotional regulation tool. The present study utilised five practitioner-led heart rate variability (HRV) biofeedback sessions and home practice via mobile applications to train support and management staff (n = 9) in resonant frequency breathing techniques. Although baseline HRV did not change from pre to post training, participants increased total HRV (i.e., SDNN; p = .006), parasympathetic HRV (i.e., RMSSD; p = .028) and HRV reflective of baroreflex function (i.e., low frequency power; p = .018) while accurately performing resonant frequency breathing without a breath pacer. Post-intervention questionnaire data revealed an increase (p = .032) in habitual use of somatic strategies for emotional regulation, and social validation data suggested that the technique enhanced emotional regulation at home, work and during international competition. HRV biofeedback and the resonant frequency technique provided an on-demand emotional regulation technique for elite sport support and management staff.

  3. Overexpression of Rice Auxilin-Like Protein, XB21, Induces Necrotic Lesions, up-Regulates Endocytosis-Related Genes, and Confers Enhanced Resistance to Xanthomonas oryzae pv. oryzae.

    Science.gov (United States)

    Park, Chang-Jin; Wei, Tong; Sharma, Rita; Ronald, Pamela C

    2017-12-01

    The rice immune receptor XA21 confers resistance to the bacterial pathogen, Xanthomonas oryzae pv. oryzae (Xoo). To elucidate the mechanism of XA21-mediated immunity, we previously performed a yeast two-hybrid screening for XA21 interactors and identified XA21 binding protein 21 (XB21). Here, we report that XB21 is an auxilin-like protein predicted to function in clathrin-mediated endocytosis. We demonstrate an XA21/XB21 in vivo interaction using co-immunoprecipitation in rice. Overexpression of XB21 in rice variety Kitaake and a Kitaake transgenic line expressing XA21 confers a necrotic lesion phenotype and enhances resistance to Xoo. RNA sequencing reveals that XB21 overexpression results in the differential expression of 8735 genes (4939 genes up- and 3846 genes down-regulated) (≥2-folds, FDR ≤0.01). The up-regulated genes include those predicted to be involved in 'cell death' and 'vesicle-mediated transport'. These results indicate that XB21 plays a role in the plant immune response and in regulation of cell death. The up-regulation of genes controlling 'vesicle-mediated transport' in XB21 overexpression lines is consistent with a functional role for XB21 as an auxilin.

  4. Effectiveness and student perceptions of an active learning activity using a headline news story to enhance in-class learning of cell cycle regulation.

    Science.gov (United States)

    Dirks-Naylor, Amie J

    2016-06-01

    An active learning activity was used to engage students and enhance in-class learning of cell cycle regulation in a PharmD level integrated biological sciences course. The aim of the present study was to determine the effectiveness and perception of the in-class activity. After completion of a lecture on the topic of cell cycle regulation, students completed a 10-question multiple-choice quiz before and after engaging in the activity. The activity involved reading of a headline news article published by ScienceDaily.com entitled "One Gene Lost Equals One limb Regained." The name of the gene was deleted from the article and, thus, the end goal of the activity was to determine the gene of interest by the description in the story. The activity included compiling a list of all potential gene candidates before sufficient information was given to identify the gene of interest (p21). A survey was completed to determine student perceptions of the activity. Quiz scores improved by an average of 20% after the activity (40.1 ± 1.95 vs. 59.9 ± 2.14,Pactivity, found the news article interesting, and believed that the activity improved their understanding of cell cycle regulation. The majority of students agreed that the in-class activity piqued their interest for learning the subject matter and also agreed that if they understand a concept during class, they are more likely to want to study that concept outside of class. In conclusion, the activity improved in-class understanding and enhanced interest in cell cycle regulation. Copyright © 2016 The American Physiological Society.

  5. Light-dependant intraretinal ion regulation by melanopsin in young awake and free moving mice evaluated with manganese-enhanced MRI

    OpenAIRE

    Berkowitz, Bruce A.; Roberts, Robin; Bissig, David

    2010-01-01

    Purpose To test the hypothesis that in young, functionally blind mice, light-dependent intraretinal ion regulation occurs via melanopsin. Methods Postnatal day (P) 7 wild type (WT, C57Bl/6) and melanopsin knockout (KO, opn4−/−, B6129) mice were light or dark adapted. Awake and freely moving animals were injected intraperitoneally (ip) with MnCl2. Four hours later, the mice in both groups were anesthetized and studied with manganese-enhanced MRI (MEMRI) to measure the extent of intraretinal up...

  6. Regular Exercise Enhances the Immune Response Against Microbial Antigens Through Up-Regulation of Toll-like Receptor Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Qishi Zheng

    2015-09-01

    Full Text Available Background/Aims: Regular physical exercise can enhance resistance to many microbial infections. However, little is known about the mechanism underlying the changes in the immune system induced by regular exercise. Methods: We recruited members of a university badminton club as the regular exercise (RE group and healthy sedentary students as the sedentary control (SC group. We investigated the distribution of peripheral blood mononuclear cell (PBMC subsets and functions in the two groups. Results: There were no significant differences in plasma cytokine levels between the RE and SC groups in the true resting state. However, enhanced levels of IFN-γ, TNF-α, IL-6, IFN-α and IL-12 were secreted by PBMCs in the RE group following microbial antigen stimulation, when compared to the SC group. In contrast, the levels of TNF-α and IL-6 secreted by PBMC in the RE group were suppressed compared with those in SC group following non-microbial antigen stimulation (concanavalin A or α-galactosylceramide. Furthermore, PBMC expression of TLR2, TLR7 and MyD88 was significantly increased in the RE group in response to microbial antigen stimulation. Conclusion: Regular exercise enhances immune cell activation in response to pathogenic stimulation leading to enhanced cytokine production mediated via the TLR signaling pathways.

  7. Uncovering transcriptional interactions via an adaptive fuzzy logic approach

    Directory of Open Access Journals (Sweden)

    Chen Chung-Ming

    2009-12-01

    Full Text Available Abstract Background To date, only a limited number of transcriptional regulatory interactions have been uncovered. In a pilot study integrating sequence data with microarray data, a position weight matrix (PWM performed poorly in inferring transcriptional interactions (TIs, which represent physical interactions between transcription factors (TF and upstream sequences of target genes. Inferring a TI means that the promoter sequence of a target is inferred to match the consensus sequence motifs of a potential TF, and their interaction type such as AT or RT is also predicted. Thus, a robust PWM (rPWM was developed to search for consensus sequence motifs. In addition to rPWM, one feature extracted from ChIP-chip data was incorporated to identify potential TIs under specific conditions. An interaction type classifier was assembled to predict activation/repression of potential TIs using microarray data. This approach, combining an adaptive (learning fuzzy inference system and an interaction type classifier to predict transcriptional regulatory networks, was named AdaFuzzy. Results AdaFuzzy was applied to predict TIs using real genomics data from Saccharomyces cerevisiae. Following one of the latest advances in predicting TIs, constrained probabilistic sparse matrix factorization (cPSMF, and using 19 transcription factors (TFs, we compared AdaFuzzy to four well-known approaches using over-representation analysis and gene set enrichment analysis. AdaFuzzy outperformed these four algorithms. Furthermore, AdaFuzzy was shown to perform comparably to 'ChIP-experimental method' in inferring TIs identified by two sets of large scale ChIP-chip data, respectively. AdaFuzzy was also able to classify all predicted TIs into one or more of the four promoter architectures. The results coincided with known promoter architectures in yeast and provided insights into transcriptional regulatory mechanisms. Conclusion AdaFuzzy successfully integrates multiple types of

  8. Regulation of Vapor Pressure Deficit by Greenhouse Micro-Fog Systems Improved Growth and Productivity of Tomato via Enhancing Photosynthesis during Summer Season.

    Directory of Open Access Journals (Sweden)

    Dalong Zhang

    Full Text Available The role of a proposed micro-fog system in regulating greenhouse environments and enhancing tomato (Solanum lycopersicum L. productivity during summer season was studied. Experiments were carried out in a multi-span glass greenhouse, which was divided into two identical compartments involving different environments: (1 without environment control and (2 with a micro-fog system operating when the air vapor pressure deficit (VPD of greenhouse was higher than 0.5 KPa. The micro-fog system effectively alleviated heat stress and evaporative demand in the greenhouse during summer season. The physiologically favourable environment maintained by micro-fog treatment significantly enhanced elongation of leaf and stem, which contributed to a substantial elevation of final leaf area and shoot biomass. These improvements in physiological and morphological traits resulted in around 12.3% increase of marketable tomato yield per plant. Relative growth rate (RGR of micro-fog treatment was also significantly higher than control plants, which was mainly determined by the substantial elevation in net assimilation rate (NAR, and to a lesser extent caused by leaf area ratio (LAR. Measurement of leaf gas exchange parameters also demonstrated that micro-fog treatment significantly enhanced leaf photosynthesis capacity. Taken together, manipulation of VPD in greenhouses by micro-fog systems effectively enhanced tomato growth and productivity via improving photosynthesis during summer season.

  9. Mutual enhancement of IL-2 and IL-7 on DNA vaccine immunogenicity mainly involves regulations on their receptor expression and receptor-expressing lymphocyte generation.

    Science.gov (United States)

    Zhang, Yonghong; Liang, Shuang; Li, Xiujin; Wang, Liyue; Zhang, Jianlou; Xu, Jian; Huo, Shanshan; Cao, Xuebin; Zhong, Zhenyu; Zhong, Fei

    2015-07-09

    Our previous study showed that IL-2 and IL-7 could mutually enhance the immunogenicity of canine parvovirus VP2 DNA vaccine, although the underlying mechanism remained unknown. Here, we used the OVA gene as a DNA vaccine in a mouse model to test their enhancement on DNA vaccine immunogenicity and to explore the molecular mechanism. Results showed that both IL-2 and IL-7 genes significantly increased the immunogenicity of OVA DNA vaccine in mice. Co-administration of IL-2 and IL-7 genes with OVA DNA significantly increased OVA-specific antibody titers, T cell proliferation and IFN-γ production compared with IL-2 or IL-7 alone, confirming that IL-2 and IL-7 mutually enhanced DNA vaccine immunogenicity. Mechanistically, we have shown that IL-2 significantly stimulated generation of IL-7 receptor-expressing lymphocytes, and that IL-7 significantly induced IL-2 receptor expression. These results contribute to an explanation of the mechanism of the mutual effects of IL-2 and IL-7 on enhancing DNA vaccine immunogenicity and provided a basis for further investigation on their mutual effects on adjuvant activity and immune regulation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Regulation of Vapor Pressure Deficit by Greenhouse Micro-Fog Systems Improved Growth and Productivity of Tomato via Enhancing Photosynthesis during Summer Season.

    Science.gov (United States)

    Zhang, Dalong; Zhang, Zhongdian; Li, Jianming; Chang, Yibo; Du, Qingjie; Pan, Tonghua

    2015-01-01

    The role of a proposed micro-fog system in regulating greenhouse environments and enhancing tomato (Solanum lycopersicum L.) productivity during summer season was studied. Experiments were carried out in a multi-span glass greenhouse, which was divided into two identical compartments involving different environments: (1) without environment control and (2) with a micro-fog system operating when the air vapor pressure deficit (VPD) of greenhouse was higher than 0.5 KPa. The micro-fog system effectively alleviated heat stress and evaporative demand in the greenhouse during summer season. The physiologically favourable environment maintained by micro-fog treatment significantly enhanced elongation of leaf and stem, which contributed to a substantial elevation of final leaf area and shoot biomass. These improvements in physiological and morphological traits resulted in around 12.3% increase of marketable tomato yield per plant. Relative growth rate (RGR) of micro-fog treatment was also significantly higher than control plants, which was mainly determined by the substantial elevation in net assimilation rate (NAR), and to a lesser extent caused by leaf area ratio (LAR). Measurement of leaf gas exchange parameters also demonstrated that micro-fog treatment significantly enhanced leaf photosynthesis capacity. Taken together, manipulation of VPD in greenhouses by micro-fog systems effectively enhanced tomato growth and productivity via improving photosynthesis during summer season.

  11. miR-133b down-regulates ABCC1 and enhances the sensitivity of CRC to anti-tumor drugs.

    Science.gov (United States)

    Chen, Miao; Li, Daojiang; Gong, Ni; Wu, Hao; Su, Chen; Xie, Canbin; Xiang, Hong; Lin, Changwei; Li, Xiaorong

    2017-08-08

    Multidrug resistance (MDR) is the main cause of failed chemotherapy treatments. Therefore, preventing MDR is pivotal in treating colorectal cancer (CRC). In a previous study miR-133b was shown to be a tumor suppressor. Additionally, in CRC cells transfected with miR-133b, ATP-binding cassette (ABC) subfamily C member 1(ABCC1) was shown to be significantly down regulated. Whether miR-133b also enhances the chemosensitivity of drugs used to treat CRC by targeting ABCC1 is still unclear. Here, we utilized flow cytometry and high-performance liquid chromatography (HPLC) analysis to identify the ability of miR-133b to reserve MDR in CRC. We then used a dual-luciferase reporter assay to validate that miR-133b targets ABCC1. Further in vivo experiments were designed to validate the method in which miR-133b reversed MDR in CRC cells. The results demonstrated that the level of miR-133b was down-regulated and the expression of ABCC1 was up-regulated in drug-resistant CRC cells compared to non-drug-resistant CRC cells. The restoration of miR-133b expression in CRC drug-resistant cells in vitro resulted in reduced IC50s to chemotherapeutic drugs, significantly induced G1 accumulation, inhibited growth and promoted necrosis in combination with either 5-fluorouracil (5-FU) or vincristine (VCR), and decreased the expression of ABCC1. The dual-luciferase assay demonstrated that miR-133b directly targets ABCC1. The combination of agomiRNA-133b with chemotherapeutic drugs in vivo inhibited tumor growth induced by CRC drug-resistant cells. A xenograft from the in vivo model resulted in up-regulated levels of miR-133b and down-regulated levels of ABCC1. Therefore, miR-133b enhances the chemosensitivity of CRC cells to anti-tumor drugs by directly down-regulating ABCC1. This discovery provides a therapeutic strategy in which miR-133b is used as a potential sensitizer for drug-resistant CRC.

  12. The CCAAT/enhancer binding protein (C/EBP δ is differently regulated by fibrillar and oligomeric forms of the Alzheimer amyloid-β peptide

    Directory of Open Access Journals (Sweden)

    Nilsson Lars NG

    2011-04-01

    Full Text Available Abstract Background The transcription factors CCAAT/enhancer binding proteins (C/EBP α, β and δ have been shown to be expressed in brain and to be involved in regulation of inflammatory genes in concert with nuclear factor κB (NF-κB. In general, C/EBPα is down-regulated, whereas both C/EBPβ and δ are up-regulated in response to inflammatory stimuli. In Alzheimer's disease (AD one of the hallmarks is chronic neuroinflammation mediated by astrocytes and microglial cells, most likely induced by the formation of amyloid-β (Aβ deposits. The inflammatory response in AD has been ascribed both beneficial and detrimental roles. It is therefore important to delineate the inflammatory mediators and signaling pathways affected by Aβ deposits with the aim of defining new therapeutic targets. Methods Here we have investigated the effects of Aβ on expression of C/EBP family members with a focus on C/EBPδ in rat primary astro-microglial cultures and in a transgenic mouse model with high levels of fibrillar Aβ deposits (tg-ArcSwe by western blot analysis. Effects on DNA binding activity were analyzed by electrophoretic mobility shift assay. Cross-talk between C/EBPδ and NF-κB was investigated by analyzing binding to a κB site using a biotin streptavidin-agarose pull-down assay. Results We show that exposure to fibril-enriched, but not oligomer-enriched, preparations of Aβ inhibit up-regulation of C/EBPδ expression in interleukin-1β-activated glial cultures. Furthermore, we observed that, in aged transgenic mice, C/EBPα was significantly down-regulated and C/EBPβ was significantly up-regulated. C/EBPδ, on the other hand, was selectively down-regulated in the forebrain, a part of the brain showing high levels of fibrillar Aβ deposits. In contrast, no difference in expression levels of C/EBPδ between wild type and transgenic mice was detected in the relatively spared hindbrain. Finally, we show that interleukin-1β-induced C/EBPδ DNA

  13. Uncovering patterns of technology use in consumer health informatics

    Science.gov (United States)

    Hung, Man; Conrad, Jillian; Hon, Shirley D.; Cheng, Christine; Franklin, Jeremy D.; Tang, Philip

    2014-01-01

    Internet usage and accessibility has grown at a staggering rate, influencing technology use for healthcare purposes. The amount of health information technology (Health IT) available through the Internet is immeasurable and growing daily. Health IT is now seen as a fundamental aspect of patient care as it stimulates patient engagement and encourages personal health management. It is increasingly important to understand consumer health IT patterns including who is using specific technologies, how technologies are accessed, factors associated with use, and perceived benefits. To fully uncover consumer patterns it is imperative to recognize common barriers and which groups they disproportionately affect. Finally, exploring future demand and predictions will expose significant opportunities for health IT. The most frequently used health information technologies by consumers are gathering information online, mobile health (mHealth) technologies, and personal health records (PHRs). Gathering health information online is the favored pathway for healthcare consumers as it is used by more consumers and more frequently than any other technology. In regard to mHealth technologies, minority Americans, compared with White Americans utilize social media, mobile Internet, and mobile applications more frequently. Consumers believe PHRs are the most beneficial health IT. PHR usage is increasing rapidly due to PHR integration with provider health systems and health insurance plans. Key issues that have to be explicitly addressed in health IT are privacy and security concerns, health literacy, unawareness, and usability. Privacy and security concerns are rated the number one reason for the slow rate of health IT adoption. PMID:24904713

  14. Testing and interpreting uncovered interest parity in Russia

    Directory of Open Access Journals (Sweden)

    Dmitry Vasilyev

    2017-06-01

    Full Text Available The failure of uncovered interest rate parity (UIP is a well-known phenomenon of the last thirty years. UIP failure is more prominent in advanced economies than in emerging market economies. Typically, UIP estimation for an advanced economy generates a negative coefficient, meaning that a higher interest rate in advanced economy A will result in the appreciation of economy A's exchange rate. For emerging market economies, higher interest rates usually correspond to future depreciation, although this depreciation is not sufficient for UIP to hold. This paper shows that UIP holds in Russia better than in other emerging market economies when the UIP equation accounts for a constant risk premium. Consequently, there is no forward premium puzzle for Russian data for 2001–2014. To determine the results for Russia and to compare them with the results for other countries, we estimate UIP first for Russia and then for advanced and emerging market economies using seemingly unrelated regressions and panel data analysis. By comparing the profitability of static and dynamic carry trade strategies, we also confirm that in emerging market economies, risk premiums are often constant, whereas in advanced economies, risk premiums are almost always volatile. This may explain why UIP holds better in emerging market economies. It also enables us to formulate a hypothesis that macroeconomic policies of emerging market economies (e.g., the accumulation of large foreign exchange reserves stabilize risk premiums.

  15. Uncovering the mechanism(s) of deep brain stimulation

    International Nuclear Information System (INIS)

    Li Gang; Yu Chao; Lin Ling; Lu, Stephen C-Y

    2005-01-01

    Deep brain stimulators, often called 'pacemakers for the brain', are implantable devices which continuously deliver impulse stimulation to specific targeted nuclei of deep brain structure, namely deep brain stimulation (DBS). To date, deep brain stimulation (DBS) is the most effective clinical technique for the treatment of several medically refractory movement disorders (e.g., Parkinson's disease, essential tremor, and dystonia). In addition, new clinical applications of DBS for other neurologic and psychiatric disorders (e.g., epilepsy and obsessive-compulsive disorder) have been put forward. Although DBS has been effective in the treatment of movement disorders and is rapidly being explored for the treatment of other neurologic disorders, the scientific understanding of its mechanisms of action remains unclear and continues to be debated in the scientific community. Optimization of DBS technology for present and future therapeutic applications will depend on identification of the therapeutic mechanism(s) of action. The goal of this review is to address our present knowledge of the effects of high-frequency stimulation within the central nervous system and comment on the functional implications of this knowledge for uncovering the mechanism(s) of DBS

  16. Uncovering Aberrant Mutant PKA Function with Flow Cytometric FRET

    Directory of Open Access Journals (Sweden)

    Shin-Rong Lee

    2016-03-01

    Full Text Available Biology has been revolutionized by tools that allow the detection and characterization of protein-protein interactions (PPIs. Förster resonance energy transfer (FRET-based methods have become particularly attractive as they allow quantitative studies of PPIs within the convenient and relevant context of living cells. We describe here an approach that allows the rapid construction of live-cell FRET-based binding curves using a commercially available flow cytometer. We illustrate a simple method for absolutely calibrating the cytometer, validating our binding assay against the gold standard isothermal calorimetry (ITC, and using flow cytometric FRET to uncover the structural and functional effects of the Cushing-syndrome-causing mutation (L206R on PKA’s catalytic subunit. We discover that this mutation not only differentially affects PKAcat’s binding to its multiple partners but also impacts its rate of catalysis. These findings improve our mechanistic understanding of this disease-causing mutation, while illustrating the simplicity, general applicability, and power of flow cytometric FRET.

  17. Gold nanoparticles regulate the blimp1/pax5 pathway and enhance antibody secretion in B-cells

    International Nuclear Information System (INIS)

    Lee, Chia-Hui; Syu, Shih-Han; Steven Huang, G; Chen, Yu-Shiun; Chen, Wen Liang; Hussain, Saber M; Aleksandrovich Onischuk, Andrei

    2014-01-01

    Nanoparticles are potential threats to human health and the environment; however, their medical applications as drug carriers targeting cancer cells bring hope to contemporary cancer therapy. As a model drug carrier, gold nanoparticles (GNPs) have been investigated extensively for in vivo toxicity. The effect of GNPs on the immune system, however, has rarely been examined. Antibody-secreting cells were treated with GNPs with diameters ranging from 2 to 50 nm. The GNPs enhanced IgG secretion in a size-dependent manner, with a peak of efficacy at 10 nm. The immune-stimulatory effect reached a maximum at 12 h after treatment but returned to control levels 24 h after treatment. This enhancing effect was validated ex vivo using B-cells isolated from mouse spleen. Evidence from RT-PCR and western blot experiments indicates that GNP-treatment upregulated B-lymphocyte-induced maturation protein 1 (blimp1) and downregulated paired box 5 (pax5). Immunostaining for blimp1 and pax5 in B-cells confirmed that the GNPs stimulated IgG secretion through the blimp1/pax5 pathway. The immunization of mice using peptide-conjugated GNPs indicated that the GNPs were capable of enhancing humoral immunity in a size-dependent manner. This effect was consistent with the bio-distribution of the GNPs in mouse spleen. In conclusion, in vitro, ex vivo, and in vivo evidence supports our hypothesis that GNPs enhance humoral immunity in mouse. The effect on the immune system should be taken into account if nanoparticles are used as carriers for drug delivery. In addition to their toxicity, the immune-stimulatory activity of nanoparticles could play an important role in human health and could have an environmental impact. (paper)

  18. Bixin regulates mRNA expression involved in adipogenesis and enhances insulin sensitivity in 3T3-L1 adipocytes through PPAR{gamma} activation

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Nobuyuki; Goto, Tsuyoshi; Taimatsu, Aki; Egawa, Kahori; Katoh, Sota; Kusudo, Tatsuya; Sakamoto, Tomoya; Ohyane, Chie; Lee, Joo-Young; Kim, Young-il; Uemura, Taku; Hirai, Shizuka [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji 611-0011 (Japan); Kawada, Teruo, E-mail: fat@kais.kyoto-u.ac.jp [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji 611-0011 (Japan)

    2009-12-25

    Insulin resistance is partly due to suppression of insulin-induced glucose uptake into adipocytes. The uptake is dependent on adipocyte differentiation, which is controlled at mRNA transcription level. The peroxisome proliferator-activated receptor (PPAR), a ligand-regulated nuclear receptor, is involved in the differentiation. Many food-derived compounds serve as ligands to activate or inactivate PPAR. In this study, we demonstrated that bixin and norbixin (annatto extracts) activate PPAR{gamma} by luciferase reporter assay using GAL4-PPAR chimera proteins. To examine the effects of bixin on adipocytes, 3T3-L1 adipocytes were treated with bixin or norbixin. The treatment induced mRNA expression of PPAR{gamma} target genes such as adipocyte-specific fatty acid-binding protein (aP2), lipoprotein lipase (LPL), and adiponectin in differentiated 3T3-L1 adipocytes and enhanced insulin-dependent glucose uptake. The observations indicate that bixin acts as an agonist of PPAR{gamma} and enhances insulin sensitivity in 3T3-L1 adipocytes, suggesting that bixin is a valuable food-derived compound as a PPAR ligand to regulate lipid metabolism and to ameliorate metabolic syndrome.

  19. Limitations on the concentration of radioactive elements substances (natural or enhanced by human activity) in building materials - a proposal for draft Israeli regulations

    International Nuclear Information System (INIS)

    Schlesinger, T.; Hareuveny, R.; Margaliot, M.

    1997-01-01

    Natural radioactive elements 40 K 228 U and 232 Th and their decay product such as 226 Ra and its short lived daughters occur in building materials in relatively high concentrations. 40 K and part of the above mentioned radionuclides cause external exposure while the inhalation of 222 Ra and its short lived progeny lead to internal exposure of the respiratory tract to alpha particles. In recent years there is a growing tendency to use new construction materials with naturally or technologically enhanced levels of radioactivity (e.g. phosphogypsum, fly ash, exotic minerals etc). This trend causes a growing health concern.The result of this concern is legislation activity and publication of guidance notes by national authorities and international professional organizations related to the radiological implications of these novel technologies. The Ministry of the Environment in Israel is authorized by Israeli legislation to control the exposure of the public to ionising radiation. The ministry asked in 1996 a professional group in the Radiation Protection Division in the Soreq NRC (the authors of this presentation) to study the radiological implications of the use of building materials with naturally or technologically enhanced concentrations of radioactive substances, and to submit draft regulations setting primary limits on excess exposure of the public to ionizing radiation from building materials, and derived limits related to concentrations of specific radionuclides in these materials.The draft regulations will be presented and the way of their derivation will be reviewed (authors)

  20. Prediction and characterisation of a highly conserved, remote and cAMP responsive enhancer that regulates Msx1 gene expression in cardiac neural crest and outflow tract.

    Science.gov (United States)

    Miller, Kerry Ann; Davidson, Scott; Liaros, Angela; Barrow, John; Lear, Marissa; Heine, Danielle; Hoppler, Stefan; MacKenzie, Alasdair

    2008-05-15

    Double knockouts of the Msx1 and Msx2 genes in the mouse result in severe cardiac outflow tract malformations similar to those frequently found in newborn infants. Despite the known role of the Msx genes in cardiac formation little is known of the regulatory systems (ligand receptor, signal transduction and protein-DNA interactions) that regulate the tissue-specific expression of the Msx genes in mammals during the formation of the outflow tract. In the present study we have used a combination of multi-species comparative genomics, mouse transgenic analysis and in-situ hybridisation to predict and validate the existence of a remote ultra-conserved enhancer that supports the expression of the Msx1 gene in migrating mouse cardiac neural crest and the outflow tract primordia. Furthermore, culturing of embryonic explants derived from transgenic lines with agonists of the PKC and PKA signal transduction systems demonstrates that this remote enhancer is influenced by PKA but not PKC dependent gene regulatory systems. These studies demonstrate the efficacy of combining comparative genomics and transgenic analyses and provide a platform for the study of the possible roles of Msx gene mis-regulation in the aetiology of congenital heart malformation.

  1. Overexpression of NtPR-Q Up-Regulates Multiple Defense-Related Genes in Nicotiana tabacum and Enhances Plant Resistance to Ralstonia solanacearum

    Directory of Open Access Journals (Sweden)

    Yuanman Tang

    2017-11-01

    Full Text Available Various classes of plant pathogenesis-related proteins have been identified in the past several decades. PR-Q, a member of the PR3 family encoding chitinases, has played an important role in regulating plant resistance and preventing pathogen infection. In this paper, we functionally characterized NtPR-Q in tobacco plants and found that the overexpression of NtPR-Q in tobacco Yunyan87 resulted in higher resistance to Ralstonia solanacearum inoculation. Surprisingly, overexpression of NtPR-Q led to the activation of many defense-related genes, such as salicylic acid (SA-responsive genes NtPR1a/c, NtPR2 and NtCHN50, JA-responsive gene NtPR1b and ET production-associated genes NtACC Oxidase and NtEFE26. Consistent with the role of NtPR-Q in multiple stress responses, NtPR-Q transcripts were induced by the exogenous hormones SA, ethylene and methyl jasmonate, which could enhance the resistance of tobacco to R. solanacearum. Collectively, our results suggested that NtPR-Q overexpression led to the up-regulation of defense-related genes and enhanced plant resistance to R. solanacearum infection.

  2. Hydrogen sulfide potentiates interleukin-1β-induced nitric oxide production via enhancement of extracellular signal-regulated kinase activation in rat vascular smooth muscle cells

    International Nuclear Information System (INIS)

    Jeong, Sun-Oh; Pae, Hyun-Ock; Oh, Gi-Su; Jeong, Gil-Saeng; Lee, Bok-Soo; Lee, Seoul; Kim, Du Yong; Rhew, Hyun Yul; Lee, Kang-Min; Chung, Hun-Taeg

    2006-01-01

    Hydrogen sulfide (H 2 S) and nitric oxide (NO) are endogenously synthesized from L-cysteine and L-arginine, respectively. They might constitute a cooperative network to regulate their effects. In this study, we investigated whether H 2 S could affect NO production in rat vascular smooth muscle cells (VSMCs) stimulated with interleukin-1β (IL-1β). Although H 2 S by itself showed no effect on NO production, it augmented IL-β-induced NO production and this effect was associated with increased expression of inducible NO synthase (iNOS) and activation of nuclear factor (NF)-κB. IL-1β activated the extracellular signal-regulated kinase 1/2 (ERK1/2), and this activation was also enhanced by H 2 S. Inhibition of ERK1/2 activation by the selective inhibitor U0126 inhibited IL-1β-induced NF-κB activation, iNOS expression, and NO production either in the absence or presence of H 2 S. Our findings suggest that H 2 S enhances NO production and iNOS expression by potentiating IL-1β-induced NF-κB activation through a mechanism involving ERK1/2 signaling cascade in rat VSMCs

  3. Salivary protein histatin 3 regulates cell proliferation by enhancing p27{sup Kip1} and heat shock cognate protein 70 ubiquitination

    Energy Technology Data Exchange (ETDEWEB)

    Imamura, Yasuhiro, E-mail: yimamura@po.mdu.ac.jp [Department of Pharmacology, Matsumoto Dental University, Shiojiri, Nagano 399-0781 (Japan); Wang, Pao-Li [Department of Bacteriology, Osaka Dental University, Hirakata, Osaka 573-1121 (Japan); Masuno, Kazuya [Department of Dental Education Innovation, Osaka Dental University, Hirakata, Osaka 573-1121 (Japan); Sogawa, Norio [Department of Pharmacology, Matsumoto Dental University, Shiojiri, Nagano 399-0781 (Japan)

    2016-02-05

    Histatins are salivary proteins with antimicrobial activities. We previously reported that histatin 3 binds to heat shock cognate protein 70 (HSC70), which is constitutively expressed, and induces DNA synthesis stimulation and promotes human gingival fibroblast (HGF) survival. However, the underlying mechanisms of histatin 3 remain largely unknown. Here, we found that the KRHH sequence of histatin 3 at the amino acid positions 5–8 was essential for enhancing p27{sup Kip1} (a cyclin-dependent kinase inhibitor) binding to HSC70 that occurred in a dose-dependent manner; histatin 3 enhanced the binding between p27{sup Kip1} and HSC70 during the G{sub 1}/S transition of HGFs as opposed to histatin 3-M(5–8) (substitution of KRHH for EEDD in histatin 3). Histatin 3, but not histatin 3-M(5–8), stimulated DNA synthesis and promoted HGF survival. Histatin 3 dose-dependently enhanced both p27{sup Kip1} and HSC70 ubiquitination, whereas histatin 3-M(5–8) did not. These findings provide further evidence that histatin 3 may be involved in the regulation of cell proliferation, particularly during G{sub 1}/S transition, via the ubiquitin–proteasome system of p27{sup Kip1} and HSC70. - Highlights: • KRHH amino acid sequence was required in histatin 3 to bind HSC70. • Histatin 3 enhanced HSC70 binding to p27{sup Kip1} during the G{sub 1}/S transition in HGFs. • KRHH sequence stimulated DNA synthesis and promoted cell survival. • Histatin 3 dose-dependently enhanced both p27{sup Kip1} and HSC70 ubiquitination. • Histatin 3 stimulates cell proliferation via the ubiquitin–proteasome system.

  4. Mice lacking the transcriptional regulator Bhlhe40 have enhanced neuronal excitability and impaired synaptic plasticity in the hippocampus.

    Directory of Open Access Journals (Sweden)

    Kelly A Hamilton

    Full Text Available Bhlhe40 is a transcription factor that is highly expressed in the hippocampus; however, its role in neuronal function is not well understood. Here, we used Bhlhe40 null mice on a congenic C57Bl6/J background (Bhlhe40 KO to investigate the impact of Bhlhe40 on neuronal excitability and synaptic plasticity in the hippocampus. Bhlhe40 KO CA1 neurons had increased miniature excitatory post-synaptic current amplitude and decreased inhibitory post-synaptic current amplitude, indicating CA1 neuronal hyperexcitability. Increased CA1 neuronal excitability was not associated with increased seizure severity as Bhlhe40 KO relative to +/+ (WT control mice injected with the convulsant kainic acid. However, significant reductions in long term potentiation and long term depression at CA1 synapses were observed in Bhlhe40 KO mice, indicating impaired hippocampal synaptic plasticity. Behavioral testing for spatial learning and memory on the Morris Water Maze (MWM revealed that while Bhlhe40 KO mice performed similarly to WT controls initially, when the hidden platform was moved to the opposite quadrant Bhlhe40 KO mice showed impairments in relearning, consistent with decreased hippocampal synaptic plasticity. To investigate possible mechanisms for increased neuronal excitability and decreased synaptic plasticity, a whole genome mRNA expression profile of Bhlhe40 KO hippocampus was performed followed by a chromatin immunoprecipitation sequencing (ChIP-Seq screen of the validated candidate genes for Bhlhe40 protein-DNA interactions consistent with transcriptional regulation. Of the validated genes identified from mRNA expression analysis, insulin degrading enzyme (Ide had the most significantly altered expression in hippocampus and was significantly downregulated on the RNA and protein levels; although Bhlhe40 did not occupy the Ide gene by ChIP-Seq. Together, these findings support a role for Bhlhe40 in regulating neuronal excitability and synaptic plasticity in

  5. Investigating AAK1-and GAK-Regulated Virus-Host Interactions Uncovers Broad-Spectrum Antivirals

    Science.gov (United States)

    2017-02-16

    AP1) and AP2M1 (AP2) were 527 selected from the Human ORFeome library of cDNA clones (65) (Open Biosystems) and 528 recombined into either pCherry...TSV01 Renilla reporter plasmid was a gift from Pei-Yong Shi (68). 534 Lentiviral constructs used for AP2 overexpression were cloned into the pRRLSIN...681 total of 10 days and observed daily for 28 days for lethality or clinical signs of disease. 682 683 Animal study approval/ Ethics Statement

  6. Transition metal ion FRET uncovers K(+) regulation of a neurotransmitter/sodium symporter

    DEFF Research Database (Denmark)

    Billesbølle, Christian B; Mortensen, Jonas S; Sohail, Azmat

    2016-01-01

    Neurotransmitter/sodium symporters (NSSs) are responsible for Na(+)-dependent reuptake of neurotransmitters and represent key targets for antidepressants and psychostimulants. LeuT, a prokaryotic NSS protein, constitutes a primary structural model for these transporters. Here we show that K...

  7. Uncovering co-expression gene network modules regulating fruit acidity in diverse apples.

    Science.gov (United States)

    Bai, Yang; Dougherty, Laura; Cheng, Lailiang; Zhong, Gan-Yuan; Xu, Kenong

    2015-08-16

    Acidity is a major contributor to fruit quality. Several organic acids are present in apple fruit, but malic acid is predominant and determines fruit acidity. The trait is largely controlled by the Malic acid (Ma) locus, underpinning which Ma1 that putatively encodes a vacuolar aluminum-activated malate transporter1 (ALMT1)-like protein is a strong candidate gene. We hypothesize that fruit acidity is governed by a gene network in which Ma1 is key member. The goal of this study is to identify the gene network and the potential mechanisms through which the network operates. Guided by Ma1, we analyzed the transcriptomes of mature fruit of contrasting acidity from six apple accessions of genotype Ma_ (MaMa or Mama) and four of mama using RNA-seq and identified 1301 fruit acidity associated genes, among which 18 were most significant acidity genes (MSAGs). Network inferring using weighted gene co-expression network analysis (WGCNA) revealed five co-expression gene network modules of significant (P acidity. Overall, this study provides important insight into the Ma1-mediated gene network controlling acidity in mature apple fruit of diverse genetic background.

  8. Down-regulation of LncRNA TUG1 enhances radiosensitivity in bladder cancer via suppressing HMGB1 expression

    OpenAIRE

    Jiang, Huijuan; Hu, Xigang; Zhang, Hongzhi; Li, Wenbo

    2017-01-01

    Background Long non-coding RNAs (lncRNAs) have been reported to regulate the sensitivity of different cancer cells to chemoradiotherapy. Aberrant expression of lncRNA Taurine-upregulated gene 1 (TUG1) has been found to be involved in the development of bladder cancer, however, its function and underlying mechanism in the radioresistance of bladder cancer remains unclear. Methods Quantitative real-time PCR (qRT-PCR) was conducted to measure the expression of TUG1 and HMGB1 mRNA in bladder canc...

  9. Regulation of galactolipid biosynthesis by overexpression of the rice MGD gene contributes to enhanced aluminum tolerance in tobacco

    Directory of Open Access Journals (Sweden)

    Meijuan eZhang

    2016-03-01

    Full Text Available Membrane lipid alterations affect Al tolerance in plants, but little is known about the regulation of membrane lipid metabolism in response to Al stress. Transgenic tobacco (Nicotiana tabacum overexpressing rice monogalactosyldiacylglycerol (MGDG synthase (OsMGD gene and wild-type tobacco plants were exposed to AlCl3, and the impact of Al toxicity on root growth, Al accumulation, plasma membrane integrity, lipid peroxidation and membrane lipid composition were investigated. Compared with the wild type, the transgenic plants exhibited rapid regrowth of roots after removal of Al and less damage to membrane integrity and lipid peroxidation under Al stress, meanwhile, the Al accumulation showed no difference between wild-type and transgenic plants. Lipid analysis showed that Al treatment dramatically decreased the content of MGDG and the ratio of MGDG to digalactosyldiacylglycerol (DGDG in wild-type plants, while it was unchanged in transgenic plants. The stable of MGDG level and the ratio of MGDG/DGDG contribute to maintain the membrane stability and permeability. Moreover, Al caused a significant increase in phospholipids in wild-type plants, resulting in a high proportion of phospholipids and low proportion of galactolipids, but these proportions were unaffected in transgenic plants. The high proportion of phospholipids could contribute to a higher rate of Al3+ binding in the membrane and thereby leads to more membrane perturbation and damage. These results show that the regulation of galactolipid biosynthesis could play an important role in maintaining membrane structure and function under Al stress.

  10. Systematically reviewing the potential of concept mapping technologies to promote self-regulated learning in primary and secondary science education

    DEFF Research Database (Denmark)

    Stevenson, Matt P.; Hartmeyer, Rikke; Bentsen, Peter

    2017-01-01

    We systematically searched five databases to assess the potential of concept mapping-based technologies to promote self-regulated learning in science education. Our search uncovered 17 relevant studies that investigated seven different types of learning technologies. We performed a narrative....... Computer software was particularly useful for developing cognitive strategies through ease of use. Teaching agents were particularly useful for developing metacognitive strategies by coupling visualisation of knowledge patterns with performance monitoring, aided by a teaching metaphor. Finally, mobile...... devices and teaching agents were most effective in enhancing motivation. Effects on knowledge gains remain unclear due to small sample sizes....

  11. New intelligent multifunctional SiO2/VO2 composite films with enhanced infrared light regulation performance, solar modulation capability, and superhydrophobicity.

    Science.gov (United States)

    Wang, Chao; Zhao, Li; Liang, Zihui; Dong, Binghai; Wan, Li; Wang, Shimin

    2017-01-01

    Highly transparent, energy-saving, and superhydrophobic nanostructured SiO 2 /VO 2 composite films have been fabricated using a sol-gel method. These composite films are composed of an underlying infrared (IR)-regulating VO 2 layer and a top protective layer that consists of SiO 2 nanoparticles. Experimental results showed that the composite structure could enhance the IR light regulation performance, solar modulation capability, and hydrophobicity of the pristine VO 2 layer. The transmittance of the composite films in visible region ( T lum ) was higher than 60%, which was sufficient to meet the requirements of glass lighting. Compared with pristine VO 2 films and tungsten-doped VO 2 film, the near IR control capability of the composite films was enhanced by 13.9% and 22.1%, respectively, whereas their solar modulation capability was enhanced by 10.9% and 22.9%, respectively. The water contact angles of the SiO 2 /VO 2 composite films were over 150°, indicating superhydrophobicity. The transparent superhydrophobic surface exhibited a high stability toward illumination as all the films retained their initial superhydrophobicity even after exposure to 365 nm light with an intensity of 160 mW . cm -2 for 10 h. In addition, the films possessed anti-oxidation and anti-acid properties. These characteristics are highly advantageous for intelligent windows or solar cell applications, given that they can provide surfaces with anti-fogging, rainproofing, and self-cleaning effects. Our technique offers a simple and low-cost solution to the development of stable and visible light transparent superhydrophobic surfaces for industrial applications.

  12. IL-27 regulates the adherence, proliferation, and migration of MSCs and enhances their regulatory effects on Th1 and Th2 subset generations.

    Science.gov (United States)

    Xu, Fenghuang; Yi, Junzhu; Wang, Zhuoya; Hu, Yejia; Han, Chunlei; Xue, Qun; Zhang, Xueguang; Luan, Xiying

    2017-08-01

    Interleukin 27 (IL-27) regulates T cell function and is involved in inflammation. It has been reported that human placenta-derived mesenchymal stromal cells (hPMSCs) can inhibit T cell responses and attenuate inflammation reactions. However, it is unclear whether IL-27 can regulate hPMSC function. Here, we examined the effects of IL-27 upon adherence, migration, and proliferation as well as the immunomodulatory effects of hPMSCs. The results show that IL-27 receptor α chain (IL-27Rα) is expressed in hPMSCs. IL-27 at 30 ng/ml inhibited hPMSC adherence and proliferation, while the migration of hPMSCs was promoted with IL-27 at doses of 20 or 30 ng/ml, as determined with use of real-time cell analysis (RTCA). Moreover, IL-27 promoted regulatory effects of hPMSCs through enhancing Th2 and suppressing Th1 subset generation from activated T cells in human peripheral blood. IL-27 also enhanced the ability of hPMSCs to secrete IL-10 from CD4 + T cells through increased expression levels of the programmed death ligand 1 (PDL1) in hPMSCs via the Janus kinase (JAK)/signal transducer and activator of transcription 1 (STAT1) signaling pathway. In conclusion, IL-27 has significant modulatory effects on adherence, proliferation, and migration of hPMSCs. IL-27 increased PDL1 expression levels in hPMSCs via the JAK/STAT1 pathway, which then enhanced the regulatory effects of hPMSCs upon Th1 and Th2 cell generations and IL-10 secretion from CD4 + T cells.

  13. Functional FRIGIDA allele enhances drought tolerance by regulating the P5CS1 pathway in Arabidopsis thaliana.

    Science.gov (United States)

    Chen, Qian; Zheng, Yan; Luo, Landi; Yang, Yongping; Hu, Xiangyang; Kong, Xiangxiang

    2018-01-01

    Flowering at the right time is important for the reproductive success of plants and their response to environmental stress. In Arabidopsis, a major determinant of natural variation in flowering time is FRIGIDA (FRI). In the present study, we show that overexpression of the functional FRIGIDA gene in wild-type Col background (ColFRI) positively enhances the drought tolerance by activating P5CS1 expression and promoting proline accumulation during water stress. Furthermore, no significant changes in FRI gene and protein expression levels were observed with drought treatment, whereas P5CS1 protein expression significantly increased. In contrast, vernalization treatment efficiently reduced P5CS1 expression levels and resulted in a decrease in drought tolerance in the ColFRI plants. The flc mutants with a functional FRI background also relieved FRI-mediated activation of P5CS1 during drought tolerance. Taken together, our findings reveal the novel function of FRI in enhancing drought resistance through its downstream P5CS1 pathway during water-deficit stress, which is dependent on its target, the FLC gene. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Challenges Faced by Regulators and Technical, Scientific and Support Organizations (TSOs) in Enhancing Nuclear Safety and Security

    International Nuclear Information System (INIS)

    Travers, W.D.

    2011-01-01

    Renewed interest in new reactor build programmes, not only in countries with already established nuclear programmes but also in many other countries with limited or no workforce experienced in the design, licensing, construction and operation of nuclear power plants, has resulted in a need for technical, scientific and support organizations (TSOs) to support regulatory bodies in carrying out their mandated responsibilities. The primary function of a regulatory body, such as the Federal Authority for Nuclear Regulation (FANR) in the United Arab Emirates (UAE), is to regulate the safe use of nuclear facilities and radioactive material for peaceful civilian purposes. In so doing, the regulatory body needs to provide a clear and focused approach to: safety, security and safeguards for licensing; inspection and enforcement of reactor design; construction; commissioning; operation; decommissioning; nuclear waste management activities; and the use, possession or transfer of special nuclear materials and activities within the country. Accomplishing this goal requires a highly educated, multidisciplinary, diverse workforce with significant work experience. Recognizing that it takes several decades and a lot of resources to achieve self-sufficiency, many countries, particularly emergent nuclear countries, would have to rely on TSOs to start their programmes and to carry out their oversight responsibilities. Towards that end, FANR is working closely with international counterparts, the International Atomic Energy Agency and TSOs to exchange information, expertise, industry experience and ongoing research to ensure that high levels of safety, security and safeguards are established and maintained in reactor design and operation throughout the life of the facility, and that special nuclear material within the UAE is properly documented and controlled, is not stolen, lost or diverted to any illicit or non-peaceful activities, and does not pose unreasonable radiological risk due

  15. Exogenous spermidine is enhancing tomato tolerance to salinity-alkalinity stress by regulating chloroplast antioxidant system and chlorophyll metabolism.

    Science.gov (United States)

    Li, Jianming; Hu, Lipan; Zhang, Li; Pan, Xiongbo; Hu, Xiaohui

    2015-12-29

    capacities for responding to salinity-alkalinity stress. Exogenous spermidine triggers effective protection against damage induced by salinity-alkalinity stress in tomato seedlings, probably by maintaining chloroplast structural integrity and alleviating salinity-alkalinity-induced oxidative damage, most likely through regulation of chlorophyll metabolism and the enzymatic and non-enzymatic antioxidant systems in chloroplast. Exogenous spermidine also exerts positive effects at the transcription level, such as down-regulation of the expression of the chlorophyllase gene and up-regulation of the expression of the porphobilinogen deaminase gene.

  16. Plant Signals Disrupt (regulate?) Arbuscular Mycorrhizal Fungal Growth Under Enhanced Ozone and CO2 Growing Conditions for Populus tremuloides

    Science.gov (United States)

    Miller, R. M.; Podila, G. K.

    2008-12-01

    evaluating microarray data of more than 2300 genes that are regulated (out of 25,000) in aspen mycorrhizal roots, the eCO2 responsive and eO3 tolerant aspen ecotype 271 demonstrated upregulation for antioxidant genes under eCO2+eO3 conditions. We found decreased expression of both neutral and acid invertase genes indicating that the availability of carbohydrate to the fungus is reduced. We also found an increase in plant amino acid transporters under eO3 and eCO2+eO3 that partitions more nitrogen to the plant from mycorrhizal roots and triggers the fungus into an N-starvation and lipid storage mode. This observation is supported by down-regulation of genes involved in nitrogen utilization in Glomus and the enrichment of hyphal 15N content, as well as an increase in the AMF marker storage lipid (neutral fatty acid 16:1w5c)in the root. The up-regulation of pathways involved in the formation of triglycerides that can be taken up by the fungus may be a critical step for changes in Glomus lipid metabolism. Also, in support of the above findings, is the rather high expression of genes involved in iron sequestration by aspen clone 271 when exposed to both eO3 and eCO2+eO3 fumigation. Iron is needed for both fatty acid (FA) desaturases and fatty acid synthase. Under eCO2+eO3, we found down-regulation of FA desaturases in Glomus, suggesting reduced levels of iron could be a potential signal for the fungus to go into storage mode and reduced growth of extraradical hyphae into the soil.

  17. A decentralized charging control strategy for plug-in electric vehicles to mitigate wind farm intermittency and enhance frequency regulation

    Science.gov (United States)

    Luo, Xiao; Xia, Shiwei; Chan, Ka Wing

    2014-02-01

    This paper proposes a decentralized charging control strategy for a large population of plug-in electric vehicles (PEVs) to neutralize wind power fluctuations so as to improve the regulation of system frequency. Without relying on a central control entity, each PEV autonomously adjusts its charging or discharging power in response to a communal virtual price signal and based on its own urgency level of charging. Simulation results show that under the proposed charging control, the aggregate PEV power can effectively neutralize wind power fluctuations in real-time while differential allocation of neutralization duties among the PEVs can be realized to meet the PEV users' charging requirements. Also, harmful wind-induced cyclic operations in thermal units can be mitigated. As shown in economic analysis, the proposed strategy can create cost saving opportunities for both PEV users and utility.

  18. Antisocial behaviour and psychopathy: Uncovering the externalizing link in the P3 modulation.

    Science.gov (United States)

    Pasion, Rita; Fernandes, Carina; Pereira, Mariana R; Barbosa, Fernando

    2017-03-22

    In 2009, Gao and Raine's meta-analysis analysed P3 modulation over the antisocial spectrum. However, some questions remained open regarding the P3 modulation patterns across impulsive and violent manifestations of antisocial behaviour, phenotypic components of psychopathy, and P3 components. A systematic review of 36 studies was conducted (N=3514) to extend previous results and to address these unresolved questions. A clear link between decreased P3 amplitude and antisocial behaviour was found. In psychopathy, dimensional approaches become more informative than taxonomic models. Distinct etiological pathways of psychopathy were evidenced in cognitive tasks: impulsive-antisocial psychopathic traits mainly predicted blunted P3 amplitude, while interpersonal-affective psychopathic traits explained enhanced P3 amplitude. Supporting the low fear hypothesis, the interpersonal-affective traits were associated with reduced P3 amplitude in emotional-affective learning tasks. From the accumulated knowledge we propose a framework of P3 amplitude modulation that uncovers the externalizing link between psychopathy and antisocial behaviour. However, the main hypotheses are exploratory and call for more data before stablishing robust conclusions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Comparison between uncovered and covered self-expandable metal stent placement in malignant duodenal obstruction.

    Science.gov (United States)

    Kim, Ji Won; Jeong, Ji Bong; Lee, Kook Lae; Kim, Byeong Gwan; Ahn, Dong Won; Lee, Jae Kyung; Kim, Su Hwan

    2015-02-07

    To compare the clinical outcomes of uncovered and covered self-expandable metal stent placements in patients with malignant duodenal obstruction. A total of 67 patients were retrospectively enrolled from January 2003 to June 2013. All patients had symptomatic obstruction characterized by nausea, vomiting, reduced oral intake, and weight loss. The exclusion criteria included asymptomatic duodenal obstruction, perforation or peritonitis, concomitant small bowel obstruction, or duodenal obstruction caused by benign strictures. The technical and clinical success rate, complication rate, and stent patency were compared according to the placement of uncovered (n = 38) or covered (n = 29) stents. The technical and clinical success rates did not differ between the uncovered and covered stent groups (100% vs 96.6% and 89.5% vs 82.8%). There were no differences in the overall complication rates between the uncovered and covered stent groups (31.6% vs 41.4%). However, stent migration occurred more frequently with covered than uncovered stents [20.7% (6/29) vs 0% (0/38), P stent patency was longer in uncovered than in covered stents [251 d (95%CI: 149.8 d-352.2 d) vs 139 d (95%CI: 45.5 d-232.5 d), P stent (70 d) and covered stent groups (60 d). Uncovered stents may be preferable in malignant duodenal obstruction because of their greater resistance to stent migration and longer stent patency than covered stents.

  20. Trichosanthes cucumerina extracts enhance glucose uptake and regulate adiponectin and leptin concentrations in 3T3-L1 adipocytes model

    Directory of Open Access Journals (Sweden)

    Sassi, A.,

    2017-10-01

    Full Text Available Trichosanthes cucumerina (Cucurbitaceae commonly known as Snake gourd or Labu Ular is considered the largest genre in the Cucurbitaceae family and is mainly found in the southeast areas of Asia. It has been used in Ayurvedic medicine as a treatment for certain diseases such as Diabetes mellitus, but these acclaims lack scientific-based evidence. In this study, water and ethanol extracts of three parts of Trichosanthes cucumerina namely; whole vegetable, peels, and seeds, were assessed for toxicity through a cell viability assay using 3T3-L1 pre-adipocytes model which revealed a maximum toleration concentration of 0.063 mg/mL. The extracts were further tested on adipocytes’ differentiation and positively showed a stimulation of lipid droplets formation during adipogenesis and significantly (p<0.001 increased glycerol release levels (75.34±3.69 μg/ml during adipolysis. The extracts also significantly (p<0.001 promoted the uptake of glucose into the cells (2636.22±91.33 Bq in an action similar to that of insulin. Similar results were observed during ELISA assay with a significant increase (p<0.001 in adiponectin concentrations (3593.1±225.25 ng/mL and a decrease in leptin concentrations (23870±5066.07 pg/mL. The present study results indicate a beneficial effect of Trichosanthes cucumerina extracts on adipogenesis, adipolysis and glucose uptake, in addition to a regulation of adiponectin and leptin concentrations in 3T3-L1 adipocytes which can be of clinical importance in energy regulation which is a key factor in treating diabetes, obesity, and metabolic syndrome.

  1. New Partners in Regulation of Gene Expression: The Enhancer of Trithorax and Polycomb Corto Interacts with Methylated Ribosomal Protein L12 Via Its Chromodomain

    Science.gov (United States)

    Coléno-Costes, Anne; Jang, Suk Min; de Vanssay, Augustin; Rougeot, Julien; Bouceba, Tahar; Randsholt, Neel B.; Gibert, Jean-Michel; Le Crom, Stéphane; Mouchel-Vielh, Emmanuèle

    2012-01-01

    Chromodomains are found in many regulators of chromatin structure, and most of them recognize methylated lysines on histones. Here, we investigate the role of the Drosophila melanogaster protein Corto's chromodomain. The Enhancer of Trithorax and Polycomb Corto is involved in both silencing and activation of gene expression. Over-expression of the Corto chromodomain (CortoCD) in transgenic flies shows that it is a chromatin-targeting module, critical for Corto function. Unexpectedly, mass spectrometry analysis reveals that polypeptides pulled down by CortoCD from nuclear extracts correspond to ribosomal proteins. Furthermore, real-time interaction analyses demonstrate that CortoCD binds with high affinity RPL12 tri-methylated on lysine 3. Corto and RPL12 co-localize with active epigenetic marks on polytene chromosomes, suggesting that both are involved in fine-tuning transcription of genes in open chromatin. RNA–seq based transcriptomes of wing imaginal discs over-expressing either CortoCD or RPL12 reveal that both factors deregulate large sets of common genes, which are enriched in heat-response and ribosomal protein genes, suggesting that they could be implicated in dynamic coordination of ribosome biogenesis. Chromatin immunoprecipitation experiments show that Corto and RPL12 bind hsp70 and are similarly recruited on gene body after heat shock. Hence, Corto and RPL12 could be involved together in regulation of gene transcription. We discuss whether pseudo-ribosomal complexes composed of various ribosomal proteins might participate in regulation of gene expression in connection with chromatin regulators. PMID:23071455

  2. Tumourigenic canine osteosarcoma cell lines associated with frizzled-6 up-regulation and enhanced side population cell frequency.

    Science.gov (United States)

    de Sá Rodrigues, L C; Holmes, K E; Thompson, V; Newton, M A; Stein, T J

    2017-03-01

    An increased serum alkaline phosphatase concentration is known to be associated with a negative prognosis in canine and human osteosarcoma. To expand upon previous studies regarding the biological relevance of increased serum alkaline phosphatase as a negative prognostic factor, xenogeneic heterotopic transplants were performed using six canine primary osteosarcoma cell lines generated from patients with differing serum alkaline phosphatase concentrations (three normal and three increased). Three of the six cell lines were capable of generating tumours and tumour formation was independent of the serum alkaline phosphatase status of the cell line. Microarray analysis identified 379 genes as being differentially expressed between the tumourigenic and non-tumourigenic cell lines. Frizzled-6 was upregulated to the greatest extent (7.78-fold) in tumourigenic cell lines compared with non-tumourigenic cell lines. Frizzled-6, a co-receptor for Wnt ligands has been associated with enhanced tumour-initiating cells and poor prognosis for other tumours. The increased expression of frizzled-6 was confirmed by quantitative reverse transcription polymerase chain reaction (QPCR) and Western blot analysis. Additionally, the tumourigenic cell lines also had an increase in the percentage of side population cells compared with non-tumourigenic cell lines (5.89% versus 1.58%, respectively). There were no differences in tumourigenicity, frizzled-6 or percentage of side population cells noted between osteosarcoma cell lines generated from patients of differing serum alkaline phosphatase concentration. However, to our knowledge this is the first study to identified frizzled-6 as a possible marker of osteosarcoma cell populations with enhanced tumourigenicity and side population cells. Future work will focus on defining the role of frizzled-6 in osteosarcoma tumourigenesis and tumour-initiating cells. © 2015 John Wiley & Sons Ltd.

  3. Hypoxia regulates the expression and localization of CCAAT/enhancer binding protein α by hypoxia inducible factor-1α in bladder transitional carcinoma cells.

    Science.gov (United States)

    Xue, Mei; Li, Xu; Chen, Wei

    2015-08-01

    Hypoxia inducible factor-1α (HIF-1α) is overexpressed in various types of solid tumor in humans, including bladder cancer. HIF-1α regulates the expression of a series of genes, which are involved in cell proliferation, differentiation, apoptosis, angiogenesis, migration and invasion and represents a potential therapeutic target for the treatment of human cancer. Despite extensive investigation of the effects of HIF-1α in the progression and metastasis of bladder cancer, the possible regulatory mechanisms underlying the effects of HIF-1α on bladder cancer cell proliferation and differentiation remain to be elucidated. It has been suggested that the transcription factor CCAAT/enhancer binding protein α (C/EBPα) acts as a tumor suppressor in several types of cancer cell, which are involved in regulating cell differentiation, proliferation and apoptosis. The present study confirmed that, in bladder cancer cells, the expression and localization of C/EBPα was regulated by hypoxia through an HIF-1α -dependent mechanism, which may be significant in bladder cancer cell proliferation and differentiation. The 5637 and T24 bladder cancer cell lines were incubated under normoxic and hypoxic conditions. The expression levels of HIF-1α and C/EBPα were detected by reverse transcription-quantitative polymerase chain reaction, western blotting and immunofluorescence analysis. The results revealed that, under hypoxic conditions, the protein expression levels of HIF-1α were markedly upregulated, but the mRNA levels were not altered. However, the mRNA and protein levels of C/EBPα were significantly reduced. The present study further analyzed the subcellular localization of C/EBPα, which was markedly decreased in the nuclei under hypoxic conditions. Following HIF-1α small interference RNA silencing of HIF-1α, downregulation of C/EBPα was prevented in the bladder cancer cells cultured under hypoxic conditions. In addition, groups of cells treated with 3-(5'-hydroxymethyl

  4. DNA-mediated dimerization on a compact sequence signature controls enhancer engagement and regulation by FOXA1.

    Science.gov (United States)

    Wang, Xuecong; Srivastava, Yogesh; Jankowski, Aleksander; Malik, Vikas; Wei, Yuanjie; Del Rosario, Ricardo C H; Cojocaru, Vlad; Prabhakar, Shyam; Jauch, Ralf

    2018-04-14

    FOXA1 is a transcription factor capable to bind silenced chromatin to direct context-dependent cell fate conversion. Here, we demonstrate that a compact palindromic DNA element (termed 'DIV' for its diverging half-sites) induces the homodimerization of FOXA1 with strongly positive cooperativity. Alternative structural models are consistent with either an indirect DNA-mediated cooperativity or a direct protein-protein interaction. The cooperative homodimer formation is strictly constrained by precise half-site spacing. Re-analysis of chromatin immunoprecipitation sequencing data indicates that the DIV is effectively targeted by FOXA1 in the context of chromatin. Reporter assays show that FOXA1-dependent transcriptional activity declines when homodimeric binding is disrupted. In response to phosphatidylinositol-3 kinase inhibition DIV sites pre-bound by FOXA1 such as at the PVT1/MYC locus exhibit a strong increase in accessibility suggesting a role of the DIV configuration in the chromatin closed-open dynamics. Moreover, several disease-associated single nucleotide polymorphisms map to DIV elements and show allelic differences in FOXA1 homodimerization, reporter gene expression and are annotated as quantitative trait loci. This includes the rs541455835 variant at the MAPT locus encoding the Tau protein associated with Parkinson's disease. Collectively, the DIV guides chromatin engagement and regulation by FOXA1 and its perturbation could be linked to disease etiologies.

  5. Influence of promoter/enhancer region haplotypes on MGMT transcriptional regulation: a potential biomarker for human sensitivity to alkylating agents.

    Science.gov (United States)

    Xu, Meixiang; Nekhayeva, Ilona; Cross, Courtney E; Rondelli, Catherine M; Wickliffe, Jeffrey K; Abdel-Rahman, Sherif Z

    2014-03-01

    The O6-methylguanine-DNA methyltransferase gene (MGMT) encodes the direct reversal DNA repair protein that removes alkyl adducts from the O6 position of guanine. Several single-nucleotide polymorphisms (SNPs) exist in the MGMT promoter/enhancer (P/E) region. However, the haplotype structure encompassing these SNPs and their functional/biological significance are currently unknown. We hypothesized that MGMT P/E haplotypes, rather than individual SNPs, alter MGMT transcription and can thus alter human sensitivity to alkylating agents. To identify the haplotype structure encompassing the MGMT P/E region SNPs, we sequenced 104 DNA samples from healthy individuals and inferred the haplotypes using the data generated. We identified eight SNPs in this region, namely T7C (rs180989103), T135G (rs1711646), G290A (rs61859810), C485A (rs1625649), C575A (rs113813075), G666A (rs34180180), C777A (rs34138162) and C1099T (rs16906252). Phylogenetics and Sequence Evolution analysis predicted 21 potential haplotypes that encompass these SNPs ranging in frequencies from 0.000048 to 0.39. Of these, 10 were identified in our study population as 20 paired haplotype combinations. To determine the functional significance of these haplotypes, luciferase reporter constructs representing these haplotypes were transfected into glioblastoma cells and their effect on MGMT promoter activity was determined. Compared with the most common (reference) haplotype 1, seven haplotypes significantly upregulated MGMT promoter activity (18-119% increase; P alkylating agents.

  6. Enhancer of rudimentary homologue interacts with scaffold attachment factor B at the nuclear matrix to regulate SR protein phosphorylation.

    Science.gov (United States)

    Drakouli, Sotiria; Lyberopoulou, Aggeliki; Papathanassiou, Maria; Mylonis, Ilias; Georgatsou, Eleni

    2017-08-01

    Scaffold attachment factor B1 (SAFB1) is an integral component of the nuclear matrix of vertebrate cells. It binds to DNA on scaffold/matrix attachment region elements, as well as to RNA and a multitude of different proteins, affecting basic cellular activities such as transcription, splicing and DNA damage repair. In the present study, we show that enhancer of rudimentary homologue (ERH) is a new molecular partner of SAFB1 and its 70% homologous paralogue, scaffold attachment factor B2 (SAFB2). ERH interacts directly in the nucleus with the C-terminal Arg-Gly-rich region of SAFB1/2 and co-localizes with it in the insoluble nuclear fraction. ERH, a small ubiquitous protein with striking homology among species and a unique structure, has also been implicated in fundamental cellular mechanisms. Our functional analyses suggest that the SAFB/ERH interaction does not affect SAFB1/2 function in transcription (e.g. as oestrogen receptor α co-repressors), although it reverses the inhibition exerted by SAFB1/2 on the splicing kinase SR protein kinase 1 (SRPK1), which also binds on the C-terminus of SAFB1/2. Accordingly, ERH silencing decreases lamin B receptor and SR protein phosphorylation, which are major SRPK1 substrates, further substantiating the role of SAFB1 and SAFB2 in the co-ordination of nuclear function. © 2017 Federation of European Biochemical Societies.

  7. A novel cold-regulated gene from Camellia sinensis, CsCOR1, enhances salt- and dehydration-tolerance in tobacco

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xian-Wen, E-mail: xianwenli01@sina.com [College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); College of Life Science, Xinyang Normal University, Xinyang 464000 (China); Key Laboratory of Horticultural Plant Biology of the Ministry of Education, Huazhong Agricultural University, Wuhan 430070 (China); Feng, Zhi-Guo; Yang, Hui-Min; Zhu, Xiao-Pei [College of Life Science, Xinyang Normal University, Xinyang 464000 (China); Liu, Jun, E-mail: liujun@mail.hzau.edu.cn [College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Key Laboratory of Horticultural Plant Biology of the Ministry of Education, Huazhong Agricultural University, Wuhan 430070 (China); Yuan, Hong-Yu, E-mail: yhongyu92@163.com [College of Life Science, Xinyang Normal University, Xinyang 464000 (China)

    2010-04-02

    In present research, the full-length cDNA and the genomic sequence of a novel cold-regulated gene, CsCOR1, were isolated from Camellia sinensis L. The deduced protein CsCOR1 contains a hydrophobic N-terminus as a signal peptide and a hydrophilic C-terminal domain that is rich in glycine, arginine and proline. Two internal repetitive tridecapeptide fragments (HSVTAGRGGYNRG) exist in the middle of the C-terminal domain and the two nucleotide sequences encoding them are identical. CsCOR1 was localized in the cell walls of transgenic-tobaccos via CsCOR1::GFP fusion approach. The expression of CsCOR1 in tea leaves was enhanced dramatically by both cold- and dehydration-stress. And overexpression of CsCOR1 in transgenic-tobaccos improved obviously the tolerance to salinity and dehydration.

  8. Dual-directional regulation of drug permeating amount by combining the technique of ion-pair complexation with chemical enhancers for the synchronous permeation of indapamide and bisoprolol in their compound patch through rabbit skin.

    Science.gov (United States)

    Song, Wenting; Cun, Dongmei; Quan, Peng; Liu, Nannan; Chen, Yang; Cui, Hongxia; Xiang, Rongwu; Fang, Liang

    2015-04-01

    To achieve the synchronous skin permeation of indapamide (IND) and bisoprolol (BSP) in their compound patch, the techniques of ion-pair complexation and chemical enhancers were combined to dual-directionally regulate drug permeating amounts. Ion-pair complexes of BSP and various organic acids were formed by the technique of ion-pair complexation. Among the complexes formed, bisoprolol tartrate (BSP.T) down-regulated the permeating amount of BSP to the same extent as that of IND. Then, to simultaneously up-regulate the amounts of the two drugs, an enhancer combination of 15.8% Span80 (SP), 6.0% Azone (AZ) and 2.2% N-methyl pyrrolidone (NMP) was obtained by central composite design and exhibited an outstanding and simultaneous enhancement on IND and BSP with enhancing ratio (ER) of 4.52 and 3.49, respectively. The effect of the dual-directional regulation was evaluated by in vitro permeation experiments and in vivo pharmacokinetic studies. For IND and BSP, their observed permeation profiles were comparable and their MAT (mean absorption time) showed no significant difference, which both demonstrated these two drugs achieved the synchronous skin permeation in their compound patch by the dual-directional regulation strategy of combining the technique of ion-pair complexation with chemical enhancers. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. 76 FR 4290 - Uncovered Innerspring Units From the People's Republic of China: Final Results of First...

    Science.gov (United States)

    2011-01-25

    ... Avenue, NW., Washington, DC 20230; telephone: (202) 482-1655. Case History With the issuance of the... material and then glued together in a linear fashion. Uncovered innersprings are classified under...

  10. 78 FR 17635 - Uncovered Innerspring Units From the People's Republic of China: Final Results of Antidumping...

    Science.gov (United States)

    2013-03-22

    ... DEPARTMENT OF COMMERCE International Trade Administration [A-570-928] Uncovered Innerspring Units... AGENCY: Import Administration, International Trade Administration, Department of Commerce. SUMMARY: On... Operations, Office 9, Import Administration, International Trade Administration, U.S. Department of Commerce...

  11. Uncovering cognitive processes: Different techniques that can contribute to cognitive load research and instruction

    NARCIS (Netherlands)

    Van Gog, Tamara; Kester, Liesbeth; Nievelstein, Fleurie; Giesbers, Bas; Fred, Paas

    2009-01-01

    Van Gog, T., Kester, L., Nievelstein, F., Giesbers, B., & Paas, F. (2009). Uncovering cognitive processes: Different techniques that can contribute to cognitive load research and instruction. Computers in Human Behavior, 25, 325-331.

  12. A late embryogenesis abundant protein HVA1 regulated by an inducible promoter enhances root growth and abiotic stress tolerance in rice without yield penalty.

    Science.gov (United States)

    Chen, Yi-Shih; Lo, Shuen-Fang; Sun, Peng-Kai; Lu, Chung-An; Ho, Tuan-Hua D; Yu, Su-May

    2015-01-01

    Regulation of root architecture is essential for maintaining plant growth under adverse environment. A synthetic abscisic acid (ABA)/stress-inducible promoter was designed to control the expression of a late embryogenesis abundant protein (HVA1) in transgenic rice. The background of HVA1 is low but highly inducible by ABA, salt, dehydration and cold. HVA1 was highly accumulated in root apical meristem (RAM) and lateral root primordia (LRP) after ABA/stress treatments, leading to enhanced root system expansion. Water-use efficiency (WUE) and biomass also increased in transgenic rice, likely due to the maintenance of normal cell functions and metabolic activities conferred by HVA1 which is capable of stabilizing proteins, under osmotic stress. HVA1 promotes lateral root (LR) initiation, elongation and emergence and primary root (PR) elongation via an auxin-dependent process, particularly by intensifying asymmetrical accumulation of auxin in LRP founder cells and RAM, even under ABA/stress-suppressive conditions. We demonstrate a successful application of an inducible promoter in regulating the spatial and temporal expression of HVA1 for improving root architecture and multiple stress tolerance without yield penalty. © 2014 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  13. Acquisition of negative complement regulators by the saprophyte Leptospira biflexa expressing LigA or LigB confers enhanced survival in human serum.

    Science.gov (United States)

    Castiblanco-Valencia, Mónica M; Fraga, Tatiana R; Breda, Leandro C D; Vasconcellos, Sílvio A; Figueira, Cláudio P; Picardeau, Mathieu; Wunder, Elsio; Ko, Albert I; Barbosa, Angela S; Isaac, Lourdes

    2016-05-01

    Leptospiral immunoglobulin-like (Lig) proteins are surface exposed molecules present in pathogenic but not in saprophytic Leptospira species. We have previously shown that Lig proteins interact with the soluble complement regulators Factor H (FH), FH like-1 (FHL-1), FH related-1 (FHR-1) and C4b Binding Protein (C4BP). In this study, we used the saprophyte L. biflexa serovar Patoc as a surrogate host to address the specific role of LigA and LigB proteins in leptospiral complement evasion. L. biflexa expressing LigA or LigB was able to acquire FH and C4BP. Bound complement regulators retained their cofactor activities of FI in the proteolytic cleavage of C3b and C4b. Moreover, heterologous expression of ligA and ligB genes in the saprophyte L. biflexa enhanced bacterial survival in human serum. Complement deposition on lig-transformed L. biflexa was assessed by flow cytometry analysis. With regard to MAC deposition, L. biflexa expressing LigA or LigB presented an intermediate profile: MAC deposition levels were greater than those found in the pathogenic L. interrogans, but lower than those observed for L. biflexa wildtype. In conclusion, Lig proteins contribute to in vitro control of complement activation on the leptospiral surface, promoting an increased bacterial survival in human serum. Copyright © 2016 European Federation of Immunological Societies. All rights reserved.

  14. Enhancement of 9α-Hydroxy-4-androstene-3,17-dione Production from Soybean Phytosterols by Deficiency of a Regulated Intramembrane Proteolysis Metalloprotease in Mycobacterium neoaurum.

    Science.gov (United States)

    Xiong, Liang-Bin; Sun, Wan-Ju; Liu, Yong-Jun; Wang, Feng-Qing; Wei, Dong-Zhi

    2017-12-06

    Modification of the sterol catabolism pathway in mycobacteria may result in the accumulation of some valuable steroid pharmaceutical intermediates, such as 9α-hydroxy-4-androstene-3,17-dione (9-OHAD). In previous work, sigma factor D (SigD) was identified as a negative factor of the 9-OHAD production in Mycobacterium neoaurum. Here, the deficiency of rip1 putatively coding for a regulated intramembrane proteolysis metalloprotease (Rip1), which could cleave the negative regulator of SigD (anti-SigD), enhanced the transcription of some key genes (choM1, kshA, and hsd4A) in the sterol catabolic pathway. Furthermore, the deletion of rip1 increased the consumption of phytosterols by 37.8% after 96 h of growth in M. neoaurum. The production of 9-OHAD in the engineered M. neoaurumΔkstD1ΔkstD2ΔkstD3Δrip1 (MnΔk123Δrip1) strain was ultimately increased by 27.3% compared to that in its parental strain M. neoaurumΔkstD1ΔkstD2ΔkstD3 (MnΔk123). This study further confirms the important role of SigD-related factors in the catabolism of sterols.

  15. Vorinostat enhances protein stability of p27 and p21 through negative regulation of Skp2 and Cks1 in human breast cancer cells.

    Science.gov (United States)

    Uehara, Norihisa; Yoshizawa, Katsuhiko; Tsubura, Airo

    2012-07-01

    Vorinostat is a histone deacetylase inhibitor that blocks cancer cell proliferation through the regulation of cyclin-dependent kinase inhibitors. We, herein, examined the involvement of S-phase kinase-associated protein 2 (Skp2) and cyclin-dependent kinase subunit 1 (Cks1), the components of the SCFSkp2-Cks1 (Skp1/Cul1/F-box protein) ubiquitin ligase complex, in the regulation of p27 and p21 during vorinostat-induced growth arrest of MDA-MB-231 and MCF-7 human breast cancer cells. Vorinostat significantly reduced BrdU incorporation in MDA-MB-231 and MCF-7 cells, which was associated with increased p27 and p21 protein levels without concomitant induction of p27 mRNA. Vorinostat-induced accumulation of p27 and p21 proteins was inversely correlated with the mRNA and protein levels of Skp2 and Cks1. Cycloheximide chase analysis revealed that vorinostat increased the half-life of p27 and p21 proteins. The accumulation of p27 and p21 proteins was attenuated by forced expression of Skp2 and Cks1, which conferred resistance to the vorinostat-induced S-phase reduction. These results suggest that vorinostat-induced growth arrest may be in part due to the enhanced protein stability of p27 and p21 through the downregulation of Skp2 and Cks1.

  16. Autism-Associated Chromatin Regulator Brg1/SmarcA4 Is Required for Synapse Development and Myocyte Enhancer Factor 2-Mediated Synapse Remodeling.

    Science.gov (United States)

    Zhang, Zilai; Cao, Mou; Chang, Chia-Wei; Wang, Cindy; Shi, Xuanming; Zhan, Xiaoming; Birnbaum, Shari G; Bezprozvanny, Ilya; Huber, Kimberly M; Wu, Jiang I

    2016-01-01

    Synapse development requires normal neuronal activities and the precise expression of synapse-related genes. Dysregulation of synaptic genes results in neurological diseases such as autism spectrum disorders (ASD). Mutations in genes encoding chromatin-remodeling factor Brg1/SmarcA4 and its associated proteins are the genetic causes of several developmental diseases with neurological defects and autistic symptoms. Recent large-scale genomic studies predicted Brg1/SmarcA4 as one of the key nodes of the ASD gene network. We report that Brg1 deletion in early postnatal hippocampal neurons led to reduced dendritic spine density and maturation and impaired synapse activities. In developing mice, neuronal Brg1 deletion caused severe neurological defects. Gene expression analyses indicated that Brg1 regulates a significant number of genes known to be involved in synapse function and implicated in ASD. We found that Brg1 is required for dendritic spine/synapse elimination mediated by the ASD-associated transcription factor myocyte enhancer factor 2 (MEF2) and that Brg1 regulates the activity-induced expression of a specific subset of genes that overlap significantly with the targets of MEF2. Our analyses showed that Brg1 interacts with MEF2 and that MEF2 is required for Brg1 recruitment to target genes in response to neuron activation. Thus, Brg1 plays important roles in both synapse development/maturation and MEF2-mediated synapse remodeling. Our study reveals specific functions of the epigenetic regulator Brg1 in synapse development and provides insights into its role in neurological diseases such as ASD. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  17. N-myc downstream-regulated gene 1 promotes oxaliplatin-triggered apoptosis in colorectal cancer cells via enhancing the ubiquitination of Bcl-2.

    Science.gov (United States)

    Yang, Xiao; Zhu, Fan; Yu, Chaoran; Lu, Jiaoyang; Zhang, Luyang; Lv, Yanfeng; Sun, Jing; Zheng, Minhua

    2017-07-18

    N-myc downstream-regulated gene1 (NDRG1) has been identified as a potent tumor suppressor gene. The molecular mechanisms of anti-tumor activity of NDRG1 involve its suppressive effects on a variety of tumorigenic signaling pathways. The purpose of this study was to investigate the role of NDRG1 in the apoptosis of colorectal cancer (CRC) cells. We first collected the clinical data of locally advanced rectal cancer (LARC) patients receiving oxaliplatin-based neoadjuvant chemotherapy in our medical center. Correlation analysis revealed that NDRG1 positively associated with the downstaging rates and prognosis of patients. Then, the effects of over-expression and depletion of NDRG1 gene on apoptosis of colorectal cancer were tested in vitro and in vivo. NDRG1 over-expression promoted apoptosis in colorectal cancer cells whereas depletion of NDRG1 resulted in resistance to oxaliplatin treatment. Furthermore, we observed that Bcl-2, a major anti-apoptotic protein, was regulated by NDRG1 at post-transcriptional level. By binding Protein kinase Cα (PKCα), a classical regulating factor of Bcl-2, NDRG1 enhanced the ubiquitination and degradation of Bcl-2, thus promoting apoptosis in CRC cells. In addition, NDRG1 inhibited tumor growth and promoted apoptosis in mouse xenograft model. In conclusion,NDRG1 promotes oxaliplatin-triggered apoptosis in colorectal cancer. Therefore, colorectal cancer patients can be stratified by the expression level of NDRG1. NDRG1-positive patients may benefit from oxaliplatin-containing chemotherapy regimens whereas those with negative NDRG1 expression should avoid the usage of this cytotoxic drug.

  18. Use of (Time-Domain) Vector Autoregressions to Test Uncovered Interest Parity

    OpenAIRE

    Takatoshi Ito

    1984-01-01

    In this paper, a vector autoregression model (VAR) is proposed in order to test uncovered interest parity (UIP) in the foreign exchange market. Consider a VAR system of the spot exchange rate (yen/dollar), the domestic (US) interest rate and the foreign (Japanese) interest rate, describing the interdependence of the domestic and international financia lmarkets. Uncovered interest parity is stated as a null hypothesis that the current difference between the two interest rates is equal to the d...

  19. Tumor Therapeutics Work as Stress Inducers to Enhance Tumor Sensitivity to Natural Killer (NK) Cell Cytolysis by Up-regulating NKp30 Ligand B7-H6.

    Science.gov (United States)

    Cao, Guoshuai; Wang, Jian; Zheng, Xiaodong; Wei, Haiming; Tian, Zhigang; Sun, Rui

    2015-12-11

    Immune cells are believed to participate in initiating anti-tumor effects during regular tumor therapy such as chemotherapy, radiation, hyperthermia, and cytokine injection. One of the mechanisms underlying this process is the expression of so-called stress-inducible immunostimulating ligands. Although the activating receptor NKG2D has been proven to play roles in tumor therapy through targeting its ligands, the role of NKp30, another key activating receptor, is seldom addressed. In this study, we found that the NKp30 ligand B7-H6 was widely expressed in tumor cells and closely correlated to their susceptibility to NK cell lysis. Further studies showed that treatment of tumor cells with almost all standard tumor therapeutics, including chemotherapy (cisplatin, 5-fluorouracil), radiation therapy, non-lethal heat shock, and cytokine therapy (TNF-α), could up-regulate the expression of B7-H6 in tumor cells and enhance tumor sensitivity to NK cell cytolysis. B7-H6 shRNA treatment effectively dampened sensitization of tumor cells to NK-mediated lysis. Our study not only reveals the possibility that tumor therapeutics work as stress inducers to enhance tumor sensitivity to NK cell cytolysis but also suggests that B7-H6 could be a potential target for tumor therapy in the future. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Regulation of H3K4me3 at Transcriptional Enhancers Characterizes Acquisition of Virus-Specific CD8+ T Cell-Lineage-Specific Function

    Directory of Open Access Journals (Sweden)

    Brendan E. Russ

    2017-12-01

    Full Text Available Infection triggers large-scale changes in the phenotype and function of T cells that are critical for immune clearance, yet the gene regulatory mechanisms that control these changes are largely unknown. Using ChIP-seq for specific histone post-translational modifications (PTMs, we mapped the dynamics of ∼25,000 putative CD8+ T cell transcriptional enhancers (TEs differentially utilized during virus-specific T cell differentiation. Interestingly, we identified a subset of dynamically regulated TEs that exhibited acquisition of a non-canonical (H3K4me3+ chromatin signature upon differentiation. This unique TE subset exhibited characteristics of poised enhancers in the naive CD8+ T cell subset and demonstrated enrichment for transcription factor binding motifs known to be important for virus-specific CD8+ T cell differentiation. These data provide insights into the establishment and maintenance of the gene transcription profiles that define each stage of virus-specific T cell differentiation.

  1. A better state-of-mind: deep breathing reduces state anxiety and enhances test performance through regulating test cognitions in children.

    Science.gov (United States)

    Khng, Kiat Hui

    2017-11-01

    A pre-test/post-test, intervention-versus-control experimental design was used to examine the effects, mechanisms and moderators of deep breathing on state anxiety and test performance in 122 Primary 5 students. Taking deep breaths before a timed math test significantly reduced self-reported feelings of anxiety and improved test performance. There was a statistical trend towards greater effectiveness in reducing state anxiety for boys compared to girls, and in enhancing test performance for students with higher autonomic reactivity in test-like situations. The latter moderation was significant when comparing high-versus-low autonomic reactivity groups. Mediation analyses suggest that deep breathing reduces state anxiety in test-like situations, creating a better state-of-mind by enhancing the regulation of adaptive-maladaptive thoughts during the test, allowing for better performance. The quick and simple technique can be easily learnt and effectively applied by most children to immediately alleviate some of the adverse effects of test anxiety on psychological well-being and academic performance.

  2. HMBA Enhances Prostratin-Induced Activation of Latent HIV-1 via Suppressing the Expression of Negative Feedback Regulator A20/TNFAIP3 in NF-κB Signaling

    Directory of Open Access Journals (Sweden)

    Duchu Chen

    2016-01-01

    Full Text Available In the past decade, much emphasis has been put on the transcriptional activation of HIV-1, which is proposed as a promised strategy for eradicating latent HIV-1 provirus. Two drugs, prostratin and hexamethylene bisacetamide (HMBA, have shown potent effects as inducers for releasing HIV-1 latency when used alone or in combination, although their cellular target(s are currently not well understood, especially under drug combination. Here, we have shown that HMBA and prostratin synergistically release HIV-1 latency via different mechanisms. While prostratin strongly stimulates HMBA-induced HIV-1 transcription via improved P-TEFb activation, HMBA is capable of boosting NF-κB-dependent transcription initiation by suppressing prostratin-induced expression of the deubiquitinase A20, a negative feedback regulator in the NF-κB signaling pathway. In addition, HMBA was able to increase prostratin-induced phosphorylation and degradation of NF-κB inhibitor IκBα, thereby enhancing and prolonging prostratin-induced nuclear translocation of NF-κB, a prerequisite for stimulation of transcription initiation. Thus, by blocking the negative feedback circuit, HMBA functions as a signaling enhancer of the NF-κB signaling pathway.

  3. Human endogenous retrovirus W env increases nitric oxide production and enhances the migration ability of microglia by regulating the expression of inducible nitric oxide synthase.

    Science.gov (United States)

    Xiao, Ran; Li, Shan; Cao, Qian; Wang, Xiuling; Yan, Qiujin; Tu, Xiaoning; Zhu, Ying; Zhu, Fan

    2017-06-01

    Human endogenous retrovirus W env (HERV-W env) plays a critical role in many neuropsychological diseases such as schizophrenia and multiple sclerosis (MS). These diseases are accompanied by immunological reactions in the central nervous system (CNS). Microglia are important immunocytes in brain inflammation that can produce a gasotransmitter-nitric oxide (NO). NO not only plays a role in the function of neuronal cells but also participates in the pathogenesis of various neuropsychological diseases. In this study, we reported increased NO production in CHME-5 microglia cells after they were transfected with HERV-W env. Moreover, HERV-W env increased the expression and function of human inducible nitric oxide synthase (hiNOS) and enhanced the promoter activity of hiNOS. Microglial migration was also enhanced. These data revealed that HERV-W env might contribute to increase NO production and microglial migration ability in neuropsychological disorders by regulating the expression of inducible NOS. Results from this study might lead to the identification of novel targets for the treatment of neuropsychological diseases, including neuroinflammatory diseases, stroke, and neurodegenerative diseases.

  4. Cavity-enhanced spectroscopies

    CERN Document Server

    van Zee, Roger

    2003-01-01

    ""Cavity-Enhanced Spectroscopy"" discusses the use of optical resonators and lasers to make sensitive spectroscopic measurements. This volume is written by the researcchers who pioneered these methods. The book reviews both the theory and practice behind these spectroscopic tools and discusses the scientific discoveries uncovered by these techniques. It begins with a chapter on the use of optical resonators for frequency stabilization of lasers, which is followed by in-depth chapters discussing cavity ring-down spectroscopy, frequency-modulated, cavity-enhanced spectroscopy, intracavity spectr

  5. Resveratrol strongly enhances the retinoic acid-induced superoxide generating activity via up-regulation of gp91-phox gene expression in U937 cells.

    Science.gov (United States)

    Kikuchi, Hidehiko; Mimuro, Hitomi; Kuribayashi, Futoshi

    2018-01-01

    The membrane bound cytochrome b 558 composed of gp91-phox and p22-phox proteins, and cytosolic proteins p40-, p47-and p67-phox are important components of superoxide (O 2 - )-generating system in phagocytes. Here, we describe that resveratrol, a pleiotropic phytochemical belonging to the stilbenoids, dramatically activates the O 2 - -generating system during retinoic acid (RA)-induced differentiation of human monoblastic leukemia U937 cells to macrophage-like cells. When U937 cells were cultured in the presence of RA and resveratrol, the O 2 - -generating activity increased more than 5-fold compared with that in the absence of the latter. Semiquantitative RT-PCR showed that co-treatment with RA and resveratrol strongly enhanced transcription of the gp91-phox compared with those of the RA-treatment only. On the other hand, immunoblot analysis revealed that co-treatment with RA and resveratrol caused remarkable accumulation of protein levels of gp91-phox (to 4-fold), p22-phox (to 5-fold) and p47-phox (to 4-fold) compared with those of the RA-treatment alone. In addition, ChIP assay suggested that resveratrol participates in enhancing the gene expression of gp91-phox via promoting acetylation of Lys-9 residues and Lys-14 residues of histone H3 within chromatin around the promoter regions of the gene. These results suggested that resveratrol strongly enhances the RA-induced O 2 - -generating activity via up-regulation of gp91-phox gene expression in U937 cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. TRAIL overexpression co-regulated by Egr1 and HRE enhances radiosensitivity of hypoxic A549 cells depending on its apoptosis inducing role.

    Science.gov (United States)

    Yang, Yan-Ming; Fang, Fang; Li, Xin; Yu, Lei; Wang, Zhi-Cheng

    2017-01-01

    Ionizing radiation can upregulate the expression levels of TRAIL and enhance tumor cell apoptosis. While Early growth response 1 (Egr1) gene promoter has radiation inducible characteristics, the expression for exogenous gene controlled by Egr1 promoter could be enhanced by ionizing radiation, but its efficiency is limited by tissue hypoxia. Hypoxia response elements (HREs) are important hypoxic response regulatory sequences and sensitivity enhancers. Therefore, we chose TRAIL as the gene radiotherapy to observe whether it is regulated by Egr1 and HER and its effects on A549 cells and its mechanism. The pcDNA3.1-Egr1-TRAIL (pc-E-hsT) and pcDNA3.1-HRE/Egr1-TRAIL (pc-H/E-hsT) plasmids containing Egr1-hsTRAIL and HRE/Egr1-hsTRAIL were transfected into A549 cells, the cells were treated by hypoxia and radiation. The TRAIL mRNA in the cells and protein concentration in the culture supernatants were measured by RT-PCR and ELISA, respectively. Mean lethal dose D0 value was evaluated with colony forming assay. The cell apoptotic rates were analyzed by FCM and TUNEL assay. Expression of DR4, DR5 and cleaved caspase-3 proteins were analyzed by western blotting. It showed that TRAIL mRNA expression and TRAIL concentration all significantly increased under hypoxia and/or radiation. D0 value of pc-H/E‑hsT transfected cells under hypoxia was lowest, indicating more high radiosensitivity. Hypoxia could not cause the pc-E-hsT transfected cell apoptotic rate increase, but there were promoting effects in pc-H/E-hsT transfected cells. DR4 had not obvious change in pc-E-hsT and pc-H/E-hsT transfected cells under normoxic and hypoxic condition, otherwise, DR5 and cleaved caspase-3 increased mostly in pc-H/E-hsT transfected cells under hypoxic condition. TRAIL overexpression was co-regulated by Egr1 and HRE. TRAIL might promote hypoxic A549 cell radiosensitivity and induce apoptosis depending on DR5 to caspase-3 pathways.

  7. The Chromatin Regulator Brpf1 Regulates Embryo Development and Cell Proliferation*

    Science.gov (United States)

    You, Linya; Yan, Kezhi; Zou, Jinfeng; Zhao, Hong; Bertos, Nicholas R.; Park, Morag; Wang, Edwin; Yang, Xiang-Jiao

    2015-01-01

    With hundreds of chromatin regulators identified in mammals, an emerging issue is how they modulate biological and pathological processes. BRPF1 (bromodomain- and PHD finger-containing protein 1) is a unique chromatin regulator possessing two PHD fingers, one bromodomain and a PWWP domain for recognizing multiple histone modifications. In addition, it binds to the acetyltransferases MOZ, MORF, and HBO1 (also known as KAT6A, KAT6B, and KAT7, respectively) to promote complex formation, restrict substrate specificity, and enhance enzymatic activity. We have recently showed that ablation of the mouse Brpf1 gene causes embryonic lethality at E9.5. Here we present systematic analyses of the mutant animals and demonstrate that the ablation leads to vascular defects in the placenta, yolk sac, and embryo proper, as well as abnormal neural tube closure. At the cellular level, Brpf1 loss inhibits proliferation of embryonic fibroblasts and hematopoietic progenitors. Molecularly, the loss reduces transcription of a ribosomal protein L10 (Rpl10)-like gene and the cell cycle inhibitor p27, and increases expression of the cell-cycle inhibitor p16 and a novel protein homologous to Scp3, a synaptonemal complex protein critical for chromosome association and embryo survival. These results uncover a crucial role of Brpf1 in controlling mouse embryo development and regulating cellular and gene expression programs. PMID:25773539

  8. Regulation of Adult CNS Axonal Regeneration by the Post-transcriptional Regulator Cpeb1

    Directory of Open Access Journals (Sweden)

    Wilson Pak-Kin Lou

    2018-01-01

    Full Text Available Adult mammalian central nervous system (CNS neurons are unable to regenerate following axonal injury, leading to permanent functional impairments. Yet, the reasons underlying this regeneration failure are not fully understood. Here, we studied the transcriptome and translatome shortly after spinal cord injury. Profiling of the total and ribosome-bound RNA in injured and naïve spinal cords identified a substantial post-transcriptional regulation of gene expression. In particular, transcripts associated with nervous system development were down-regulated in the total RNA fraction while remaining stably loaded onto ribosomes. Interestingly, motif association analysis of post-transcriptionally regulated transcripts identified the cytoplasmic polyadenylation element (CPE as enriched in a subset of these transcripts that was more resistant to injury-induced reduction at the transcriptome level. Modulation of these transcripts by overexpression of the CPE binding protein, Cpeb1, in mouse and Drosophila CNS neurons promoted axonal regeneration following injury. Our study uncovered a global evolutionarily conserved post-transcriptional mechanism enhancing regeneration of injured CNS axons.

  9. sRNA-Mediated Regulation of P-Fimbriae Phase Variation in Uropathogenic Escherichia coli

    DEFF Research Database (Denmark)

    Khandige, Surabhi; Kronborg, Tina; Uhlin, Bernt Eric

    2015-01-01

    Uropathogenic Escherichia coli (UPEC) are capable of occupying physiologically distinct intracellular and extracellular niches within the urinary tract. This feat requires the timely regulation of gene expression and small RNAs (sRNAs) are known to mediate such rapid adjustments in response to ch...... to changing environmental cues. This study aimed to uncover sRNA-mediated gene regulation in the UPEC strain UTI89, during infection of bladder epithelial cells. Hfq is an RNA chaperone known to facilitate and stabilize sRNA and target mRNA interactions with bacterial cells. The co...... to the discovery of a novel virulence-associated trans-acting sRNA-PapR. Deletion of papR was found to enhance adhesion of UTI89 to both bladder and kidney cell lines in a manner independent of type-1 fimbriae. We demonstrate PapR mediated posttranscriptional repression of the P-fimbriae phase regulator gene pap...

  10. When the Brain Takes 'BOLD' Steps: Real-Time fMRI Neurofeedback Can Further Enhance the Ability to Gradually Self-regulate Regional Brain Activation.

    Science.gov (United States)

    Sorger, Bettina; Kamp, Tabea; Weiskopf, Nikolaus; Peters, Judith Caroline; Goebel, Rainer

    2018-05-15

    participants further enhanced their gradual self-regulation ability. Our findings were observed across a wide variety of mental tasks and across clinical MR field strengths (i.e., at 1.5T and 3T), indicating that these findings are robust and can be generalized across mental tasks and scanner types. The suggested novel parametric activation paradigm enriches the spectrum of current rtfMRI-neurofeedback and BCI methodology and has considerable potential for fundamental and clinical neuroscience applications. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Nodal enhances the activity of FoxO3a and its synergistic interaction with Smads to regulate cyclin G2 transcription in ovarian cancer cells.

    Science.gov (United States)

    Fu, G; Peng, C

    2011-09-15

    Nodal, a member of the transforming growth factor-β superfamily, has been recently shown to suppress cell proliferation and to stimulate the expression of cyclin G2 (CCNG2) in human epithelial ovarian cancer cells. However, the precise mechanisms underlying these events are not fully understood. In this study, we investigated the transcriptional regulation of CCNG2 by the Nodal signaling pathway. In ovarian cancer cells, overexpression of Nodal or its receptors, activin receptor-like kinase 7 (ALK7) or ALK4, resulted in an increase in the CCNG2 promoter activity. Several putative Forkhead box class O (FoxO)3a-binding sites are present in the human CCNG2 promoter and overexpression of FoxO3a enhanced the CCNG2 promoter activity. The functional FoxO3a-binding element (FBE) was mapped to a proximal region located between -398 and -380 bp (FBE1) through deletion and mutation analyses, as well as chromatin immunoprecipitation (IP) assay. Interestingly, mutation of the FBE1 not only abolished the effect of FoxO3a, but also blocked Nodal-induced CCNG2 transcription. Nodal stimulated FoxO3a mRNA and protein expression through the canonical Smad pathway and suppressed FoxO3a inactivation by inhibiting AKT activity. Silencing of FoxO3a using small interfering RNA significantly reduced the effect of Nodal on the CCNG2 promoter activity. On the other hand, overexpression of Smad2 and Smad3 enhanced the FoxO3a-induced CCNG2 promoter activity whereas knockdown of Smad4 blocked the activity of FoxO3a. Furthermore, IP assays revealed that FoxO3a formed complexes with Smad proteins and that Nodal enhanced the binding of FoxO3a to the CCNG2 promoter. Finally, silencing of FoxO3a reversed the inhibitory effect of Nodal on cell proliferation. Taken together, these findings demonstrated that Nodal signaling promotes CCNG2 transcription by upregulating FoxO3a expression, inhibiting FoxO3a phosphorylation and enhancing its synergistic interaction with Smads. These results also suggest

  12. Dual‑sensitive HRE/Egr1 promoter regulates Smac overexpression and enhances radiation‑induced A549 human lung adenocarcinoma cell death under hypoxia.

    Science.gov (United States)

    Li, Chang-Feng; Chen, Li-Bo; Li, Dan-Dan; Yang, Lei; Zhang, Bao-Gang; Jin, Jing-Peng; Zhang, Ying; Zhang, Bin

    2014-08-01

    The aim of this study was to construct an expression vector carrying the hypoxia/radiation dual‑sensitive chimeric hypoxia response element (HRE)/early growth response 1 (Egr‑1) promoter in order to overexpress the therapeutic second mitochondria‑derived activator of caspases (Smac). Using this expression vector, the present study aimed to explore the molecular mechanism underlying radiotherapy‑induced A549 human lung adenocarcinoma cell death and apoptosis under hypoxia. The plasmids, pcDNA3.1‑Egr1‑Smac (pE‑Smac) and pcDNA3.1‑HRE/Egr-1‑Smac (pH/E‑Smac), were constructed and transfected into A549 human lung adenocarcinoma cells using the liposome method. CoCl2 was used to chemically simulate hypoxia, followed by the administration of 2 Gy X‑ray irradiation. An MTT assay was performed to detect cell proliferation and an Annexin V‑fluorescein isothiocyanate apoptosis detection kit was used to detect apoptosis. Quantitative polymerase chain reaction and western blot analyses were used for the detection of mRNA and protein expression, respectively. Infection with the pE‑Smac and pH/E‑Smac plasmids in combination with radiation and/or hypoxia was observed to enhance the expression of Smac. Furthermore, Smac overexpression was found to enhance the radiation‑induced inhibition of cell proliferation and promotion of cycle arrest and apoptosis. The cytochrome c/caspase‑9/caspase‑3 pathway was identified to be involved in this regulation of apoptosis. Plasmid infection in combination with X‑ray irradiation was found to markedly induce cell death under hypoxia. In conclusion, the hypoxia/radiation dual‑sensitive chimeric HRE/Egr‑1 promoter was observed to enhance the expression of the therapeutic Smac, as well as enhance the radiation‑induced inhibition of cell proliferation and promotion of cycle arrest and apoptosis under hypoxia. This apoptosis was found to involve the mitochondrial pathway.

  13. Destroyed documents: uncovering the science that Imperial Tobacco Canada sought to conceal.

    Science.gov (United States)

    Hammond, David; Chaiton, Michael; Lee, Alex; Collishaw, Neil

    2009-11-10

    In 1992, British American Tobacco had its Canadian affiliate, Imperial Tobacco Canada, destroy internal research documents that could expose the company to liability or embarrassment. Sixty of these destroyed documents were subsequently uncovered in British American Tobacco's files. Legal counsel for Imperial Tobacco Canada provided a list of 60 destroyed documents to British American Tobacco. Information in this list was used to search for copies of the documents in British American Tobacco files released through court disclosure. We reviewed and summarized this information. Imperial Tobacco destroyed documents that included evidence from scientific reviews prepared by British American Tobacco's researchers, as well as 47 original research studies, 35 of which examined the biological activity and carcinogenicity of tobacco smoke. The documents also describe British American Tobacco research on cigarette modifications and toxic emissions, including the ways in which consumers adapted their smoking behaviour in response to these modifications. The documents also depict a comprehensive research program on the pharmacology of nicotine and the central role of nicotine in smoking behaviour. British American Tobacco scientists noted that ".. the present scale of the tobacco industry is largely dependent on the intensity and nature of the pharmacological action of nicotine," and that "... should nicotine become less attractive to smokers, the future of the tobacco industry would become less secure." The scientific evidence contained in the documents destroyed by Imperial Tobacco demonstrates that British American Tobacco had collected evidence that cigarette smoke was carcinogenic and addictive. The evidence that Imperial Tobacco sought to destroy had important implications for government regulation of tobacco.

  14. Hepatitis B virus enhances cisplatin-induced hepatotoxicity via a mechanism involving suppression of glucose-regulated protein of 78 Kda.

    Science.gov (United States)

    Zhang, Xiaoxue; Zhang, Rui; Yang, HuiOu; Xiang, Qian; Jiang, Qing; He, Qi; Zhang, Ting; Chen, Chen; Zhu, Huifen; Wang, Qiang; Ning, Qin; Li, Yiwu; Lei, Ping; Shen, Guanxin

    2016-07-25

    Cisplatin is a classical platinum-based chemotherapeutic drug used in the treatment of many cancer types, including hepatocellular carcinoma (HCC). The application of cisplatin is significantly limited by its toxicity, which may be affected by various biological factors. Persistence of Hepatitis B virus (HBV) infection leads to HCC development and may be associated with higher incidence of severe hepatitis during chemotherapy. However, whether HBV alters the susceptibility of hepatocytes to cisplatin remains poorly understood. Here, we demonstrate that HBV transfection enhanced cisplatin-induced hepatotoxicity via a mechanism involving suppression of glucose-regulated protein of 78 KDa (Grp78), a major stress-induced chaperone that localizes to the endoplasmic reticulum. Silencing Grp78 gene increased the susceptibility of HepG2 to cisplatin by activating caspase-3. Grp78 expression was down-regulated by HBV infection both in vitro and in liver tissues of patients. We compared the cisplatin sensitivity of hepatoma cells either expressing (HepG2.2.15 cells) or not expressing the entire Hepatitis B Virus genome (HepG2). HepG2.2.15 cells showed increased sensitivity to cisplatin and a higher apoptosis rate. Overexpression of Grp78 counteracted the increase of sensitivity of HepG2.215 cells to cisplatin. Furthermore, we found that HBV disrupted Grp78 synthesis in response to cisplatin stimulation, which may trigger severe and prolonged endoplasmic reticulum (ER) stress that can induce cellular apoptosis. Our findings provide new information into the effect of HBV in the modulation of Grp78 expression, and, consequently on cisplatin-induced hepatotoxicity during viral infection. Copyright © 2016. Published by Elsevier Ireland Ltd.

  15. SPIN1, negatively regulated by miR-148/152, enhances Adriamycin resistance via upregulating drug metabolizing enzymes and transporter in breast cancer.

    Science.gov (United States)

    Chen, Xu; Wang, Ya-Wen; Gao, Peng

    2018-05-09

    Spindlin1 (SPIN1), a protein highly expressed in several human cancers, has been correlated with tumorigenesis and development. Alterations of drug metabolizing enzymes and drug transporters are major determinants of chemoresistance in tumor cells. However, whether the metabolizing enzymes and transporters are under the control of SPIN1 in breast cancer chemoresistance has not yet been defined. SPIN1 expression in breast cancer cells and tissues was detected by quantitative real-time PCR (qRT-PCR) and immunohistochemistry. Chemosensitivity assays in vitro and in vivo were performed to determine the effect of SPIN1 on Adriamycin resistance. Downstream effectors of SPIN1 were screened by microarray and confirmed by qRT-PCR and Western blot. Luciferase assay and Western blot were used to identify miRNAs regulating SPIN1. We showed that SPIN1 was significantly elevated in drug-resistant breast cancer cell lines and tissues, compared with the chemosensitive ones. SPIN1 enhanced Adriamycin resistance of breast cancer cells in vitro, and downregulation of SPIN1 by miRNA could decrease Adriamycin resistance in vivo. Mechanistically, drug metabolizing enzymes and transporter CYP2C8, UGT2B4, UGT2B17 and ABCB4 were proven to be downstream effectors of SPIN1. Notably, SPIN1 was identified as a direct target of the miR-148/152 family (miR-148a-3p, miR-148b-3p and miR-152-3p). As expected, miR-148a-3p, miR-148b-3p or miR-152-3p could increase Adriamycin sensitivity in breast cancer cells in vitro. Moreover, high expression of SPIN1 or low expression of the miR-148/152 family predicted poorer survival in breast cancer patients. Our results establish that SPIN1, negatively regulated by the miR-148/152 family, enhances Adriamycin resistance in breast cancer via upregulating the expression of drug metabolizing enzymes and drug transporter.

  16. Uncovering plant-pathogen crosstalk through apoplastic proteomic studies.

    Science.gov (United States)

    Delaunois, Bertrand; Jeandet, Philippe; Clément, Christophe; Baillieul, Fabienne; Dorey, Stéphan; Cordelier, Sylvain

    2014-01-01

    Plant pathogens have evolved by developing different strategies to infect their host, which in turn have elaborated immune responses to counter the pathogen invasion. The apoplast, including the cell wall and extracellular space outside the plasma membrane, is one of the first compartments where pathogen-host interaction occurs. The plant cell wall is composed of a complex network of polysaccharides polymers and glycoproteins and serves as a natural physical barrier against pathogen invasion. The apoplastic fluid, circulating through the cell wall and intercellular spaces, provides a means for delivering molecules and facilitating intercellular communications. Some plant-pathogen interactions lead to plant cell wall degradation allowing pathogens to penetrate into the cells. In turn, the plant immune system recognizes microbial- or damage-associated molecular patterns (MAMPs or DAMPs) and initiates a set of basal immune responses, including the strengthening of the plant cell wall. The establishment of defense requires the regulation of a wide variety of proteins that are involved at different levels, from receptor perception of the pathogen via signaling mechanisms to the strengthening of the cell wall or degradation of the pathogen itself. A fine regulation of apoplastic proteins is therefore essential for rapid and effective pathogen perception and for maintaining cell wall integrity. This review aims to provide insight into analyses using proteomic approaches of the apoplast to highlight the modulation of the apoplastic protein patterns during pathogen infection and to unravel the key players involved in plant-pathogen interaction.

  17. Enhanced dissolution and bioavailability of Nateglinide by microenvironmental pH-regulated ternary solid dispersion: in-vitro and in-vivo evaluation.

    Science.gov (United States)

    Wairkar, Sarika; Gaud, Ram; Jadhav, Namdeo

    2017-09-01

    Nateglinide, an Antidiabetic drug (BCS II), shows pH-dependent solubility and variable bioavailability. The purpose of study was to increase dissolution and bioavailability of Nateglinide by development of its microenvironmental pH-regulated ternary solid dispersion (MeSD). MeSD formulation of Nateglinide, poloxamer-188 and Na 2 CO 3 was prepared by melt dispersion in 1 : 2 : 0.2 w/w ratio and further characterised for solubility, In-vitro dissolution, microenvironmental pH, crystallinity/amorphism, physicochemical interactions, bioavailability in Wistar rats. Solubility of Nateglinide was increased notably in MeSD, and its in-vitro dissolution study showed fourfold increase in the dissolution, particularly in 1.2 pH buffer. Prominent reduction in the peak intensity of X-ray powder diffraction (XRPD) and absence of endotherm in DSC thermogram confirmed the amorphism of Nateglinide in MeSD. Attenuated total reflectance Fourier transform infrared spectra revealed the hydrogen bond interactions between Nateglinide and poloxamer-188. In-vivo study indicated that MeSD exhibited fourfold increase in area under curve over Nateglinide. Tmax of MeSD was observed at 0.25 h, which is beneficial for efficient management of postprandial sugar. Instead of mere transformation of the Nateglinide to its amorphous form as evidenced by DSC and XRPD, formation of a soluble carboxylate compound of Nateglinide in MeSD was predominantly responsible for dissolution and bioavailability enhancement. The study demonstrates the utility of MeSD in achieving pH-independent dissolution, reduced T max and enhanced bioavailability of Nateglinide. © 2017 Royal Pharmaceutical Society.

  18. C/EBPβ (CCAAT/enhancer-binding protein β) mediates progesterone production through transcriptional regulation in co-operation with SF-1 (steroidogenic factor-1).

    Science.gov (United States)

    Mizutani, Tetsuya; Ju, Yunfeng; Imamichi, Yoshitaka; Osaki, Tsukasa; Yazawa, Takashi; Kawabe, Shinya; Ishikane, Shin; Matsumura, Takehiro; Kanno, Masafumi; Kamiki, Yasue; Kimura, Kohei; Minamino, Naoto; Miyamoto, Kaoru

    2014-06-15

    The transcription factor SF-1 (steroidogenic factor-1) is a master regulator of steroidogenesis. Previously, we have found that SF-1 induces the differentiation of mesenchymal stem cells into steroidogenic cells. To elucidate the molecular mechanisms of SF-1-mediated functions, we attempted to identify protein components of the SF-1 nuclear protein complex in differentiated cells. SF-1 immunoaffinity chromatography followed by MS/MS analysis was performed, and 24 proteins were identified. Among these proteins, we focused on C/EBPβ (CCAAT/enhancer-binding protein β), which is an essential transcription factor for ovulation and luteinization, as the transcriptional mechanisms of C/EBPβ working together with SF-1 are poorly understood. C/EBPβ knockdown attenuated cAMP-induced progesterone production in granulosa tumour-derived KGN cells by altering STAR (steroidogenic acute regulatory protein), CYP11A1 (cytochrome P450, family 11, subfamily A, polypeptide 1) and HSD3B2 (hydroxy-δ-5-steroid dehydrogenase, 3β- and steroid δ-isomerase 2) expression. EMSA and ChIP assays revealed novel C/EBPβ-binding sites in the upstream regions of the HSD3B2 and CYP11A1 genes. These interactions were enhanced by cAMP stimulation. Luciferase assays showed that C/EBPβ-responsive regions were found in each promoter and C/EBPβ is involved in the cAMP-induced transcriptional activity of these genes together with SF-1. These results indicate that C/EBPβ is an important mediator of progesterone production by working together with SF-1, especially under tropic hormone-stimulated conditions.

  19. Vitamin K2-enhanced liver regeneration is associated with oval cell expansion and up-regulation of matrilin-2 expression in 2-AAF/PH rat model.

    Science.gov (United States)

    Lin, M; Sun, P; Zhang, G; Xu, X; Liu, G; Miao, H; Yang, Y; Xu, H; Zhang, L; Wu, P; Li, M

    2014-03-01

    Normal liver has a great potential of regenerative capacity after partial hepatectomy. In clinic, however, most patients receiving partial hepatectomy are usually suffering from chronic liver diseases with severely damaged hepatocyte population. Under these conditions, activation of hepatic progenitor cell (oval cell in rodents) population might be considered as an alternative mean to enhance liver functional recovery. Vitamin K2 has been shown to promote liver functional recovery in patients with liver cirrhosis. In this study, we explored the possibility of vitamin K2 treatment in activating hepatic oval cell for liver regeneration with the classic 2-acetamido-fluorene/partial hepatectomy (2-AAF/PH) model in Sprague-Dawley rats. In 2-AAF/PH animals, vitamin K2 treatment induced a dose-dependent increase of liver regeneration as assessed by the weight ratio of remnant liver versus whole body and by measuring serum albumin level. In parallel, a drastic expansion of oval cell population as assessed by anti-OV6 and anti-CK19 immunostaining was noticed in the periportal zone of the remnant liver. Since matrilin-2 was linked to oval cell proliferation and liver regeneration after partial hepatectomy, we assessed its expression at both the mRNA and protein levels. The results revealed a significant increase after vitamin K2 treatment in parallel with the expansion of oval cell population. Consistently, knocking down matrilin-2 expression in vivo largely reduced vitamin K2-induced liver regeneration and oval cell proliferation in 2-AAF/PH animals. In conclusion, these data suggest that vitamin K2 treatment enhances liver regeneration after partial hepatectomy, which is associated with oval cell expansion and matrilin-2 up-regulation.

  20. NMDA receptors regulate nicotine-enhanced brain reward function and intravenous nicotine self-administration: role of the ventral tegmental area and central nucleus of the amygdala.

    Science.gov (United States)

    Kenny, Paul J; Chartoff, Elena; Roberto, Marisa; Carlezon, William A; Markou, Athina

    2009-01-01

    Nicotine is considered an important component of tobacco responsible for the smoking habit in humans. Nicotine increases glutamate-mediated transmission throughout brain reward circuitries. This action of nicotine could potentially contribute to its intrinsic rewarding and reward-enhancing properties, which motivate consumption of the drug. Here we show that the competitive N-methyl-D-aspartate (NMDA) receptor antagonist LY235959 (0.5-2.5 mg per kg) abolished nicotine-enhanced brain reward function, reflected in blockade of the lowering of intracranial self-stimulation (ICSS) thresholds usually observed after experimenter-administered (0.25 mg per kg) or intravenously self-administered (0.03 mg per kg per infusion) nicotine injections. The highest LY235959 dose (5 mg per kg) tested reversed the hedonic valence of nicotine from positive to negative, reflected in nicotine-induced elevations of ICSS thresholds. LY235959 doses that reversed nicotine-induced lowering of ICSS thresholds also markedly decreased nicotine self-administration without altering responding for food reinforcement, whereas the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor antagonist NBQX had no effects on nicotine intake. In addition, nicotine self-administration upregulated NMDA receptor subunit expression in the central nucleus of the amygdala (CeA) and ventral tegmental area (VTA), suggesting important interactions between nicotine and the NMDA receptor. Furthermore, nicotine (1 microM) increased NMDA receptor-mediated excitatory postsynaptic currents in rat CeA slices, similar to its previously described effects in the VTA. Finally, infusion of LY235959 (0.1-10 ng per side) into the CeA or VTA decreased nicotine self-administration. Taken together, these data suggest that NMDA receptors, including those in the CeA and VTA, gate the magnitude and valence of the effects of nicotine on brain reward systems, thereby regulating motivation to consume the drug.

  1. LncRNA MEG3 enhances cisplatin sensitivity in non-small cell lung cancer by regulating miR-21-5p/SOX7 axis

    Directory of Open Access Journals (Sweden)

    Wang P

    2017-10-01

    Full Text Available Pei Wang,* Dong Chen,* Hongbing Ma, Yong LiDepartment of Cardiothoracic Surgery, Huaihe Hospital of Henan University, Kaifeng, People’s Republic of China *These authors contributed equally to this work Background: Long noncoding RNAs (lncRNAs have been revealed to play essential role in drug resistance of multiple cancers. LncRNA MEG3 was previously reported to be associated with cisplatin (DDP resistance in non-small cell lung cancer (NSCLC cells. However, the molecular mechanism of MEG3 affecting DDP resistance in NSCLC remains to be further illustrated. In this study, we attempted to discuss whether MEG3 also could function as a competing endogenous RNA to regulate DDP resistance in NSCLC.Materials and methods: The expression of MEG3, miR-21-5p, and sex-determining region Y-box 7 (SOX7 in NSCLC tissues or cells was examined by quantitative real-time polymerase chain reaction (qRT-PCR. 3-(4,5-Dimethylthazol-2-yl-2,5-diphenyltetrazolium bromide (MTT, flow cytometry, and caspase-3 activity analysis were applied to assess the DDP sensitivity of NSCLC cells. The interaction between MEG3, miR-21-5p, and SOX7 was explored by luciferase reporter assay, RNA immunoprecipitation (RIP assay, qRT-PCR, and Western blot. Mouse NSCLC transplanted tumor was established to verify the functional role of MEG3 in DDP resistance in vivo.Results: MEG3 was downregulated in DDP-resistant NSCLC cells. Overexpression of MEG3 enhanced DDP sensitivity of NSCLC cells in vitro. MEG3 directly interacted with miR-21-5p and suppressed its expression. miR-21-5p significantly abolished the effects of MEG3 on DDP resistance via modulating cell proliferation and apoptosis. SOX7 was identified as a direct target of miR-21-5p and MEG3 positively regulated SOX7 expression by suppressing miR-21-5p. Moreover, MEG3 knockdown-induced pro-proliferative and anti-apoptotic effects were reversed in DDP-resistant NSCLC cells by upregulating SOX7. Furthermore, upregulation of MEG3 induced

  2. Unique small RNA signatures uncovered in the tammar wallaby genome

    Directory of Open Access Journals (Sweden)

    Lindsay James

    2012-10-01

    Full Text Available Abstract Background Small RNAs have proven to be essential regulatory molecules encoded within eukaryotic genomes. These short RNAs participate in a diverse array of cellular processes including gene regulation, chromatin dynamics and genome defense. The tammar wallaby, a marsupial mammal, is a powerful comparative model for studying the evolution of regulatory networks. As part of the genome sequencing initiative for the tammar, we have explored the evolution of each of the major classes of mammalian small RNAs in an Australian marsupial for the first time, including the first genome-scale analysis of the newest class of small RNAs, centromere repeat associated short interacting RNAs (crasiRNAs. Results Using next generation sequencing, we have characterized the major classes of small RNAs, micro (mi RNAs, piwi interacting (pi RNAs, and the centromere repeat associated short interacting (crasi RNAs in the tammar. We examined each of these small RNA classes with respect to the newly assembled tammar wallaby genome for gene and repeat features, salient features that define their canonical sequences, and the constitution of both highly conserved and species-specific members. Using a combination of miRNA hairpin predictions and co-mapping with miRBase entries, we identified a highly conserved cluster of miRNA genes on the X chromosome in the tammar and a total of 94 other predicted miRNA producing genes. Mapping all miRNAs to the tammar genome and comparing target genes among tammar, mouse and human, we identified 163 conserved target genes. An additional nine genes were identified in tammar that do not have an orthologous miRNA target in human and likely represent novel miRNA-regulated genes in the tammar. A survey of the tammar gonadal piRNAs shows that these small RNAs are enriched in retroelements and carry members from both marsupial and tammar-specific repeat classes. Lastly, this study includes the first in-depth analyses of the newly

  3. A novel cold-regulated gene from Phlox subulata, PsCor413im1, enhances low temperature tolerance in Arabidopsis.

    Science.gov (United States)

    Zhou, Aimin; Sun, Hongwei; Feng, Shuang; Zhou, Mi; Gong, Shufang; Wang, Jingang; Zhang, Shuzhen

    2018-01-08

    Low temperature stress adversely affects plant growth, development, and crop productivity. Analysis of the function of genes in the response of plants to low temperature stress is essential for understanding the mechanism of chilling and freezing tolerance. In this study, PsCor413im1, a novel cold-regulated gene isolated from Phlox subulata, was transferred to Arabidopsis to investigate its function under low temperature stress. Real-time quantitative PCR analysis revealed that PsCor413im1 expression was induced by cold and abscisic acid. Subcellular localization revealed that PsCor413im1-GFP fusion protein was localized to the periphery of the chloroplast, consistent with the localization of chloroplast inner membrane protein AtCor413im1, indicating that PsCor413im1 is a chloroplast membrane protein. Furthermore, the N-terminal of PsCor413im1 was determined to be necessary for its localization. Compared to the wild-type plants, transgenic plants showed higher germination and survival rates under cold and freezing stress. Moreover, the expression of AtCor15 in transgenic plants was higher than that in the wild-type plants under cold stress. Taken together, our results suggest that the overexpression of PsCor413im1 enhances low temperature tolerance in Arabidopsis. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Apoptosis Signal-Regulating Kinase 1 Is Involved in Brain-Derived Neurotrophic Factor (BDNF)-Enhanced Cell Motility and Matrix Metalloproteinase 1 Expression in Human Chondrosarcoma Cells

    Science.gov (United States)

    Lin, Chih-Yang; Chang, Sunny Li-Yun; Fong, Yi-Chin; Hsu, Chin-Jung; Tang, Chih-Hsin

    2013-01-01

    Chondrosarcoma is the primary malignancy of bone that is characterized by a potent capacity to invade locally and cause distant metastasis, and is therefore associated with poor prognoses. Chondrosarcoma further shows a predilection for metastasis to the lungs. The brain-derived neurotrophic factor (BDNF) is a small molecule in the neurotrophin family of growth factors that is associated with the disease status and outcome of cancers. However, the effect of BDNF on cell motility in human chondrosarcoma cells is mostly unknown. Here, we found that human chondrosarcoma cell lines had significantly higher cell motility and BDNF expression compared to normal chondrocytes. We also found that BDNF increased cell motility and expression of matrix metalloproteinase-1 (MMP-1) in human chondrosarcoma cells. BDNF-mediated cell motility and MMP-1 up-regulation were attenuated by Trk inhibitor (K252a), ASK1 inhibitor (thioredoxin), JNK inhibitor (SP600125), and p38 inhibitor (SB203580). Furthermore, BDNF also promoted Sp1 activation. Our results indicate that BDNF enhances the migration and invasion activity of chondrosarcoma cells by increasing MMP-1 expression through a signal transduction pathway that involves the TrkB receptor, ASK1, JNK/p38, and Sp1. BDNF thus represents a promising new target for treating chondrosarcoma metastasis. PMID:23892595

  5. PPARα induced NOS1 phosphorylation via PI3K/Akt in guinea pig antral mucous cells: NO-enhancement in Ca(2+)-regulated exocytosis.

    Science.gov (United States)

    Tanaka, Saori; Hosogi, Shigekuni; Sawabe, Yukinori; Shimamoto, Chikao; Matsumura, Hitoshi; Inui, Toshio; Marunaka, Yoshinori; Nakahari, Takashi

    2016-01-01

    A PPARα (peroxisome proliferation activation receptor α) agonist (GW7647) activates nitric oxide synthase 1 (NOS1) to produce NO leading to cGMP accumulation in antral mucous cells. In this study, we examined how PPARα activates NOS1. The NO production stimulated by GW7647 was suppressed by inhibitors of PI3K (wortmannin) and Akt (AKT 1/2 Kinase Inhibitor, AKT-inh), although it was also suppressed by the inhibitors of PPARα (GW6471) and NOS1 (N-PLA). GW7647 enhanced the ACh (acetylcholine)-stimulated exocytosis (Ca(2+)-regulated exocytosis) mediated via NO, which was abolished by GW6471, N-PLA, wortmannin, and AKT-inh. The Western blotting revealed that GW7647 phosphorylates NOS1 via phosphorylation of PI3K/Akt in antral mucous cells. The immunofluorescence examinations demonstrated that PPARα existing with NOS1 co-localizes with PI3K and Akt in the cytoplasm of antral mucous cells. ACh alone and AACOCF3, an analogue of arachidonic acid (AA), induced the NOS1 phosphorylation via PI3K/Akt to produce NO, which was inhibited by GW6471. Since AA is a natural ligand for PPARα, ACh stimulates PPARα probably via AA. In conclusion, PPARα activates NOS1 via PI3K/Akt phosphorylation to produce NO in antral mucous cells during ACh stimulation.

  6. The Lin28/let-7 Axis Regulates Glucose Metabolism

    NARCIS (Netherlands)

    Zhu, Hao; Shyh-Chang, Ng; Segre, Ayellet V.; Shinoda, Gen; Shah, Samar P.; Einhorn, William S.; Takeuchi, Ayumu; Engreitz, Jesse M.; Hagan, John P.; Kharas, Michael G.; Urbach, Achia; Thornton, James E.; Triboulet, Robinson; Gregory, Richard I.; Altshuler, David; Daley, George Q.

    2011-01-01

    The let-7 tumor suppressor microRNAs are known for their regulation of oncogenes, while the RNA-binding proteins Lin28a/b promote malignancy by inhibiting let-7 biogenesis. We have uncovered unexpected roles for the Lin28/let-7 pathway in regulating-metabolism. When overexpressed in mice, both

  7. Comparison of Covered Versus Uncovered Stents for Benign Superior Vena Cava (SVC) Obstruction.

    Science.gov (United States)

    Haddad, Mustafa M; Simmons, Benjamin; McPhail, Ian R; Kalra, Manju; Neisen, Melissa J; Johnson, Matthew P; Stockland, Andrew H; Andrews, James C; Misra, Sanjay; Bjarnason, Haraldur

    2018-05-01

    To identify whether long-term symptom relief and stent patency vary with the use of covered versus uncovered stents for the treatment of benign SVC obstruction. We retrospectively identified all patients with benign SVC syndrome treated to stent placement between January 2003 and December 2015 (n = 59). Only cases with both clinical and imaging follow-up were included (n = 47). In 33 (70%) of the patients, the obstruction was due to a central line or pacemaker wires, and in 14 (30%), the cause was fibrosing mediastinitis. Covered stents were placed in 17 (36%) of the patients, and 30 (64%) patients had an uncovered stent. Clinical and treatment outcomes, complications, and the percent stenosis of each stent were evaluated. Technical success was achieved in all cases at first attempt. Average clinical and imaging follow-up in years was 2.7 (range 0.1-11.1) (covered) and 1.7 (range 0.2-10.5) (uncovered), respectively. There was a significant difference (p = 0.044) in the number of patients who reported a return of symptoms between the covered (5/17 or 29.4%) and uncovered (18/30 or 60%) groups. There was also a significant difference (p = stenosis after stent placement between the covered [17.9% (range 0-100) ± 26.2] and uncovered [48.3% (range 6.8-100) ± 33.5] groups. No significant difference (p = 0.227) was found in the time (days) between the date of the procedure and the date of clinical follow-up where a return of symptoms was reported [covered: 426.6 (range 28-1554) ± 633.9 and uncovered 778.1 (range 23-3851) ± 1066.8]. One patient in the uncovered group had non-endovascular surgical intervention (innominate to right atrial bypass), while none in the covered group required surgical intervention. One major complication (SIR grade C) occurred that consisted of a pericardial hemorrhagic effusion after angioplasty that required covered stent placement. There were no procedure-related deaths. Both covered and uncovered stents can be used for

  8. Uncovering Urban Temporal Patterns from Geo-Tagged Photography.

    Directory of Open Access Journals (Sweden)

    Silvia Paldino

    Full Text Available We live in a world where digital trails of different forms of human activities compose big urban data, allowing us to detect many aspects of how people experience the city in which they live or come to visit. In this study we propose to enhance urban planning by taking into a consideration individual preferences using information from an unconventional big data source: dataset of geo-tagged photographs that people take in cities which we then use as a measure of urban attractiveness. We discover and compare a temporal behavior of residents and visitors in ten most photographed cities in the world. Looking at the periodicity in urban attractiveness, the results show that the strongest periodic patterns for visitors are usually weekly or monthly. Moreover, by dividing cities into two groups based on which continent they belong to (i.e., North America or Europe, it can be concluded that unlike European cities, behavior of visitors in the US cities in general is similar to the behavior of their residents. Finally, we apply two indices, called "dilatation attractiveness index" and "dilatation index", to our dataset which tell us the spatial and temporal attractiveness pulsations in the city. The proposed methodology is not only important for urban planning, but also does support various business and public stakeholder decision processes, concentrated for example around the question how to attract more visitors to the city or estimate the impact of special events organized there.

  9. Uncovering the essential links in online commercial networks

    Science.gov (United States)

    Zeng, Wei; Fang, Meiling; Shao, Junming; Shang, Mingsheng

    2016-09-01

    Recommender systems are designed to effectively support individuals' decision-making process on various web sites. It can be naturally represented by a user-object bipartite network, where a link indicates that a user has collected an object. Recently, research on the information backbone has attracted researchers' interests, which is a sub-network with fewer nodes and links but carrying most of the relevant information. With the backbone, a system can generate satisfactory recommenda- tions while saving much computing resource. In this paper, we propose an enhanced topology-aware method to extract the information backbone in the bipartite network mainly based on the information of neighboring users and objects. Our backbone extraction method enables the recommender systems achieve more than 90% of the accuracy of the top-L recommendation, however, consuming only 20% links. The experimental results show that our method outperforms the alternative backbone extraction methods. Moreover, the structure of the information backbone is studied in detail. Finally, we highlight that the information backbone is one of the most important properties of the bipartite network, with which one can significantly improve the efficiency of the recommender system.

  10. Uncovering Urban Temporal Patterns from Geo-Tagged Photography.

    Science.gov (United States)

    Paldino, Silvia; Kondor, Dániel; Bojic, Iva; Sobolevsky, Stanislav; González, Marta C; Ratti, Carlo

    2016-01-01

    We live in a world where digital trails of different forms of human activities compose big urban data, allowing us to detect many aspects of how people experience the city in which they live or come to visit. In this study we propose to enhance urban planning by taking into a consideration individual preferences using information from an unconventional big data source: dataset of geo-tagged photographs that people take in cities which we then use as a measure of urban attractiveness. We discover and compare a temporal behavior of residents and visitors in ten most photographed cities in the world. Looking at the periodicity in urban attractiveness, the results show that the strongest periodic patterns for visitors are usually weekly or monthly. Moreover, by dividing cities into two groups based on which continent they belong to (i.e., North America or Europe), it can be concluded that unlike European cities, behavior of visitors in the US cities in general is similar to the behavior of their residents. Finally, we apply two indices, called "dilatation attractiveness index" and "dilatation index", to our dataset which tell us the spatial and temporal attractiveness pulsations in the city. The proposed methodology is not only important for urban planning, but also does support various business and public stakeholder decision processes, concentrated for example around the question how to attract more visitors to the city or estimate the impact of special events organized there.

  11. Uncovering of melanin fluorescence in human skin tissue

    Science.gov (United States)

    Scholz, Matthias; Stankovic, Goran; Seewald, Gunter; Leupold, Dieter

    2007-07-01

    Due to its extremely low fluorescence quantum yield, in the conventionally (one-photon) excited autofluorescence of skin tissue, melanin fluorescence is masked by several other endogenous and possibly also exogenous fluorophores (e.g. NADH, FAD, Porphyrins). A first step to enhance the melanin contribution had been realized by two-photon fs-pulse excitation in the red/near IR, based on the fact that melanin can be excited by stepwise two-photon absorption, whereas all other fluorophores in this spectral region allow only simultaneous two-photon excitation. Now, the next and decisive step has been realized: Using an extremely sensitive detection system, for the first time twophoton fluorescence of skin tissue excited with pulses in the ns-range could be measured. The motivation for this step was based on the fact that the population density of the fluorescent level resulting from a stepwise excitation has a different dependence of the pulse duration than that from a simultaneous excitation (Δt2 vs. Δt). Due to this strong discrimination between the fluorophores, practically pure melanin fluorescence can be obtained. Examples for in-vivo, ex-vivo as well as paraffin embedded skin tissue will be shown. The content of information with respect to early diagnosis of skin deseases will be discussed.

  12. Uncovering Urban Temporal Patterns from Geo-Tagged Photography

    Science.gov (United States)

    Paldino, Silvia; Kondor, Dániel; Sobolevsky, Stanislav; González, Marta C.; Ratti, Carlo

    2016-01-01

    We live in a world where digital trails of different forms of human activities compose big urban data, allowing us to detect many aspects of how people experience the city in which they live or come to visit. In this study we propose to enhance urban planning by taking into a consideration individual preferences using information from an unconventional big data source: dataset of geo-tagged photographs that people take in cities which we then use as a measure of urban attractiveness. We discover and compare a temporal behavior of residents and visitors in ten most photographed cities in the world. Looking at the periodicity in urban attractiveness, the results show that the strongest periodic patterns for visitors are usually weekly or monthly. Moreover, by dividing cities into two groups based on which continent they belong to (i.e., North America or Europe), it can be concluded that unlike European cities, behavior of visitors in the US cities in general is similar to the behavior of their residents. Finally, we apply two indices, called “dilatation attractiveness index” and “dilatation index”, to our dataset which tell us the spatial and temporal attractiveness pulsations in the city. The proposed methodology is not only important for urban planning, but also does support various business and public stakeholder decision processes, concentrated for example around the question how to attract more visitors to the city or estimate the impact of special events organized there. PMID:27935979

  13. Covered versus uncovered self-expandable metal stents for malignant biliary strictures: A meta-analysis and systematic review.

    Science.gov (United States)

    Moole, Harsha; Bechtold, Matthew L; Cashman, Micheal; Volmar, Fritz H; Dhillon, Sonu; Forcione, David; Taneja, Deepak; Puli, Srinivas R

    2016-09-01

    Self-expandable metal stents (SEMS) are used for palliating inoperable malignant biliary strictures. It is unclear if covered metal stents are superior to uncovered metal stents in these patients. We compared clinical outcomes in patients with covered and uncovered stents. Studies using covered and uncovered metallic stents for palliation in patients with malignant biliary stricture were reviewed. Articles were searched in MEDLINE, PubMed, and Ovid journals. Fixed and random effects models were used to calculate the pooled proportions. Initial search identified 1436 reference articles, of which 132 were selected and reviewed. Thirteen studies (n = 2239) for covered and uncovered metallic stents which met the inclusion criteria were included in this analysis. Odds ratio for stent occlusion rates in covered vs. uncovered stents was 0.79 (95 % CI = 0.65 to 0.96). Survival benefit in patients with covered vs. uncovered stents showed the odds ratio to be 1.29 (95 % CI = 0.95 to 1.74). Pooled odds ratio for migration of covered vs. uncovered stents was 9.9 (95 % CI = 4.5 to 22.3). Covered stents seemed to have significantly lesser occlusion rates, increased odds of migration, and increased odds of pancreatitis compared to uncovered stents. There was no statistically significant difference in the survival benefit, overall adverse event rate, and patency period of covered vs. uncovered metal stents in patients with malignant biliary strictures.

  14. Vaporous Marketing: Uncovering Pervasive Electronic Cigarette Advertisements on Twitter.

    Science.gov (United States)

    Clark, Eric M; Jones, Chris A; Williams, Jake Ryland; Kurti, Allison N; Norotsky, Mitchell Craig; Danforth, Christopher M; Dodds, Peter Sheridan

    2016-01-01

    Twitter has become the "wild-west" of marketing and promotional strategies for advertisement agencies. Electronic cigarettes have been heavily marketed across Twitter feeds, offering discounts, "kid-friendly" flavors, algorithmically generated false testimonials, and free samples. All electronic cigarette keyword related tweets from a 10% sample of Twitter spanning January 2012 through December 2014 (approximately 850,000 total tweets) were identified and categorized as Automated or Organic by combining a keyword classification and a machine trained Human Detection algorithm. A sentiment analysis using Hedonometrics was performed on Organic tweets to quantify the change in consumer sentiments over time. Commercialized tweets were topically categorized with key phrasal pattern matching. The overwhelming majority (80%) of tweets were classified as automated or promotional in nature. The majority of these tweets were coded as commercialized (83.65% in 2013), up to 33% of which offered discounts or free samples and appeared on over a billion twitter feeds as impressions. The positivity of Organic (human) classified tweets has decreased over time (5.84 in 2013 to 5.77 in 2014) due to a relative increase in the negative words 'ban', 'tobacco', 'doesn't', 'drug', 'against', 'poison', 'tax' and a relative decrease in the positive words like 'haha', 'good', 'cool'. Automated tweets are more positive than organic (6.17 versus 5.84) due to a relative increase in the marketing words like 'best', 'win', 'buy', 'sale', 'health', 'discount' and a relative decrease in negative words like 'bad', 'hate', 'stupid', 'don't'. Due to the youth presence on Twitter and the clinical uncertainty of the long term health complications of electronic cigarette consumption, the protection of public health warrants scrutiny and potential regulation of social media marketing.

  15. Vaporous Marketing: Uncovering Pervasive Electronic Cigarette Advertisements on Twitter.

    Directory of Open Access Journals (Sweden)

    Eric M Clark

    Full Text Available Twitter has become the "wild-west" of marketing and promotional strategies for advertisement agencies. Electronic cigarettes have been heavily marketed across Twitter feeds, offering discounts, "kid-friendly" flavors, algorithmically generated false testimonials, and free samples.All electronic cigarette keyword related tweets from a 10% sample of Twitter spanning January 2012 through December 2014 (approximately 850,000 total tweets were identified and categorized as Automated or Organic by combining a keyword classification and a machine trained Human Detection algorithm. A sentiment analysis using Hedonometrics was performed on Organic tweets to quantify the change in consumer sentiments over time. Commercialized tweets were topically categorized with key phrasal pattern matching.The overwhelming majority (80% of tweets were classified as automated or promotional in nature. The majority of these tweets were coded as commercialized (83.65% in 2013, up to 33% of which offered discounts or free samples and appeared on over a billion twitter feeds as impressions. The positivity of Organic (human classified tweets has decreased over time (5.84 in 2013 to 5.77 in 2014 due to a relative increase in the negative words 'ban', 'tobacco', 'doesn't', 'drug', 'against', 'poison', 'tax' and a relative decrease in the positive words like 'haha', 'good', 'cool'. Automated tweets are more positive than organic (6.17 versus 5.84 due to a relative increase in the marketing words like 'best', 'win', 'buy', 'sale', 'health', 'discount' and a relative decrease in negative words like 'bad', 'hate', 'stupid', 'don't'.Due to the youth presence on Twitter and the clinical uncertainty of the long term health complications of electronic cigarette consumption, the protection of public health warrants scrutiny and potential regulation of social media marketing.

  16. Cyproterone acetate enhances TRAIL-induced androgen-independent prostate cancer cell apoptosis via up-regulation of death receptor 5.

    Science.gov (United States)

    Chen, Linjie; Wolff, Dennis W; Xie, Yan; Lin, Ming-Fong; Tu, Yaping

    2017-03-07

    Virtually all prostate cancer deaths occur due to obtaining the castration-resistant phenotype after prostate cancer cells escaped from apoptosis and/or growth suppression initially induced by androgen receptor blockade. TNF-related apoptosis-inducing ligand (TRAIL) was an attractive cancer therapeutic agent due to its minimal toxicity to normal cells and remarkable apoptotic activity in tumor cells. However, most localized cancers including prostate cancer are resistant to TRAIL-induced apoptosis, thereby creating a therapeutic challenge of inducing TRAIL sensitivity in cancer cells. Herein the effects of cyproterone acetate, an antiandrogen steroid, on the TRAIL-induced apoptosis of androgen receptor-negative prostate cancer cells are reported. Cell apoptosis was assessed by both annexin V/propidium iodide labeling and poly (ADP-ribose) polymerase cleavage assays. Gene and protein expression changes were determined by quantitative real-time PCR and western blot assays. The effect of cyproterone acetate on gene promoter activity was determined by luciferase reporter assay. Cyproterone acetate but not AR antagonist bicalutamide dramatically increased the susceptibility of androgen receptor-negative human prostate cancer PC-3 and DU145 cells to TRAIL-induced apoptosis but no effects on immortalized human prostate stromal PS30 cells and human embryonic kidney HEK293 cells. Further investigation of the TRAIL-induced apoptosis pathway revealed that cyproterone acetate exerted its effect by selectively increasing death receptor 5 (DR5) mRNA and protein expression. Cyproterone acetate treatment also increased DR5 gene promoter activity, which could be abolished by mutation of a consensus binding domain of transcription factor CCAAT-enhancer-binding protein homologous protein (CHOP) in the DR5 gene promoter. Cyproterone acetate increases CHOP expression in a concentration and time-dependent manner and endoplasmic reticulum stress reducer 4-phenylbutyrate could block

  17. Uncovering Web search strategies in South African higher education

    Directory of Open Access Journals (Sweden)

    Surika Civilcharran

    2016-11-01

    Full Text Available Background: In spite of the enormous amount of information available on the Web and the fact that search engines are continuously evolving to enhance the search experience, students are nevertheless faced with the difficulty of effectively retrieving information. It is, therefore, imperative for the interaction between students and search tools to be understood and search strategies to be identified, in order to promote successful information retrieval. Objectives: This study identifies the Web search strategies used by postgraduate students and forms part of a wider study into information retrieval strategies used by postgraduate students at the University of KwaZulu-Natal (UKZN, Pietermaritzburg campus, South Africa. Method: Largely underpinned by Thatcher’s cognitive search strategies, the mixed-methods approach was utilised for this study, in which questionnaires were employed in Phase 1 and structured interviews in Phase 2. This article reports and reflects on the findings of Phase 2, which focus on identifying the Web search strategies employed by postgraduate students. The Phase 1 results were reported in Civilcharran, Hughes and Maharaj (2015. Results: Findings reveal the Web search strategies used for academic information retrieval. In spite of easy access to the invisible Web and the advent of meta-search engines, the use of Web search engines still remains the preferred search tool. The UKZN online library databases and especially the UKZN online library, Online Public Access Catalogue system, are being underutilised. Conclusion: Being ranked in the top three percent of the world’s universities, UKZN is investing in search tools that are not being used to their full potential. This evidence suggests an urgent need for students to be trained in Web searching and to have a greater exposure to a variety of search tools. This article is intended to further contribute to the design of undergraduate training programmes in order to deal

  18. Human T-lymphotropic virus type-1 p30 alters cell cycle G2 regulation of T lymphocytes to enhance cell survival

    Directory of Open Access Journals (Sweden)

    Silverman Lee

    2007-07-01

    Full Text Available Abstract Background Human T-lymphotropic virus type-1 (HTLV-1 causes adult T-cell leukemia/lymphoma and is linked to a number of lymphocyte-mediated disorders. HTLV-1 contains both regulatory and accessory genes in four pX open reading frames. pX ORF-II encodes two proteins, p13 and p30, whose roles are still being defined in the virus life cycle and in HTLV-1 virus-host cell interactions. Proviral clones of HTLV-1 with pX ORF-II mutations diminish the ability of the virus to maintain viral loads in vivo. p30 expressed exogenously differentially modulates CREB and Tax-responsive element-mediated transcription through its interaction with CREB-binding protein/p300 and while acting as a repressor of many genes including Tax, in part by blocking tax/rex RNA nuclear export, selectively enhances key gene pathways involved in T-cell signaling/activation. Results Herein, we analyzed the role of p30 in cell cycle regulation. Jurkat T-cells transduced with a p30 expressing lentivirus vector accumulated in the G2-M phase of cell cycle. We then analyzed key proteins involved in G2-M checkpoint activation. p30 expression in Jurkat T-cells resulted in an increase in phosphorylation at serine 216 of nuclear cell division cycle 25C (Cdc25C, had enhanced checkpoint kinase 1 (Chk1 serine 345 phosphorylation, reduced expression of polo-like kinase 1 (PLK1, diminished phosphorylation of PLK1 at tyrosine 210 and reduced phosphorylation of Cdc25C at serine 198. Finally, primary human lymphocyte derived cell lines immortalized by a HTLV-1 proviral clone defective in p30 expression were more susceptible to camptothecin induced apoptosis. Collectively these data are consistent with a cell survival role of p30 against genotoxic insults to HTLV-1 infected lymphocytes. Conclusion Collectively, our data are the first to indicate that HTLV-1 p30 expression results in activation of the G2-M cell cycle checkpoint, events that would promote early viral spread and T

  19. Recombinant bovine growth hormone (rBGH) enhances somatic growth by regulating the GH-IGF axis in fingerlings of gilthead sea bream (Sparus aurata).

    Science.gov (United States)

    Vélez, Emilio J; Perelló, Miquel; Azizi, Sheida; Moya, Alberto; Lutfi, Esmail; Pérez-Sánchez, Jaume; Calduch-Giner, Josep A; Navarro, Isabel; Blasco, Josefina; Fernández-Borràs, Jaume; Capilla, Encarnación; Gutiérrez, Joaquim

    2018-02-01

    The growth hormone (GH)/insulin-like growth factors (IGFs) endocrine axis is the main growth-regulator system in vertebrates. Some authors have demonstrated the positive effects on growth of a sustained-release formulation of a recombinant bovine GH (rBGH) in different fish species. The aim of this work was to characterize the effects of a single injection of rBGH in fingerlings of gilthead sea bream on growth, GH-IGF axis, and both myogenic and osteogenic processes. Thus, body weight and specific growth rate were significantly increased in rBGH-treated fish respect to control fish at 6weeks post-injection, whereas the hepatosomatic index was decreased and the condition factor and mesenteric fat index were unchanged, altogether indicating enhanced somatic growth. Moreover, rBGH injection increased the plasma IGF-I levels in parallel with a rise of hepatic mRNA from total IGF-I, IGF-Ic and IGF-II, the binding proteins IGFBP-1a and IGFBP-2b, and also the receptors IGF-IRb, GHR-I and GHR-II. In skeletal muscle, the expression of IGF-Ib and GHR-I was significantly increased but that of IGF-IRb was reduced; the mRNA levels of myogenic regulatory factors, proliferation and differentiation markers (PCNA and MHC, respectively), or that of different molecules of the signaling pathway (TOR/AKT) were unaltered. Besides, the growth inhibitor myostatin (MSTN1 and MSTN2) and the hypertrophic marker (MLC2B) expression resulted significantly enhanced, suggesting altogether that the muscle is in a non-proliferative stage of development. Contrarily in bone, although the expression of most molecules of the GH/IGF axis was decreased, the mRNA levels of several osteogenic genes were increased. The histology analysis showed a GH induced lipolytic effect with a clear decrease in the subcutaneous fat layer. Overall, these results reveal that a better growth potential can be achieved on this species and supports the possibility to improve growth and quality through the optimization of its

  20. Ultraconservation identifies a small subset of extremely constrained developmental enhancers

    Energy Technology Data Exchange (ETDEWEB)

    Pennacchio, Len A.; Visel, Axel; Prabhakar, Shyam; Akiyama, Jennifer A.; Shoukry, Malak; Lewis, Keith D.; Holt, Amy; Plajzer-Frick, Ingrid; Afzal, Veena; Rubin, Edward M.; Pennacchio, Len A.

    2007-10-01

    While experimental studies have suggested that non-coding ultraconserved DNA elements are central nodes in the regulatory circuitry that specifies mammalian embryonic development, the possible functional relevance of their>200bp of perfect sequence conservation between human-mouse-rat remains obscure 1,2. Here we have compared the in vivo enhancer activity of a genome-wide set of 231 non-exonic sequences with ultraconserved cores to that of 206 sequences that are under equivalently severe human-rodent constraint (ultra-like), but lack perfect sequence conservation. In transgenic mouse assays, 50percent of the ultraconserved and 50percent of the ultra-like conserved elements reproducibly functioned as tissue-specific enhancers at embryonic day 11.5. In this in vivo assay, we observed that ultraconserved enhancers and constrained non-ultraconserved enhancers targeted expression to a similar spectrum of tissues with a particular enrichment in the developing central nervous system. A human genome-wide comparative screen uncovered ~;;2,600 non-coding elements that evolved under ultra-like human-rodent constraint and are similarly enriched near transcriptional regulators and developmental genes as the much smaller number of ultraconserved elements. These data indicate that ultraconserved elements possessing absolute human-rodent sequence conservation are not distinct from other non-coding elements that are under comparable purifying selection in mammals and suggest they are principal constituents of the cis-regulatory framework of mammalian development.

  1. Uncovering the genetic landscape for multiple sleep-wake traits.

    Directory of Open Access Journals (Sweden)

    Christopher J Winrow

    Full Text Available Despite decades of research in defining sleep-wake properties in mammals, little is known about the nature or identity of genes that regulate sleep, a fundamental behaviour that in humans occupies about one-third of the entire lifespan. While genome-wide association studies in humans and quantitative trait loci (QTL analyses in mice have identified candidate genes for an increasing number of complex traits and genetic diseases, the resources and time-consuming process necessary for obtaining detailed quantitative data have made sleep seemingly intractable to similar large-scale genomic approaches. Here we describe analysis of 20 sleep-wake traits from 269 mice from a genetically segregating population that reveals 52 significant QTL representing a minimum of 20 genomic loci. While many (28 QTL affected a particular sleep-wake trait (e.g., amount of wake across the full 24-hr day, other loci only affected a trait in the light or dark period while some loci had opposite effects on the trait during the light vs. dark. Analysis of a dataset for multiple sleep-wake traits led to previously undetected interactions (including the differential genetic control of number and duration of REM bouts, as well as possible shared genetic regulatory mechanisms for seemingly different unrelated sleep-wake traits (e.g., number of arousals and REM latency. Construction of a Bayesian network for sleep-wake traits and loci led to the identification of sub-networks of linkage not detectable in smaller data sets or limited single-trait analyses. For example, the network analyses revealed a novel chain of causal relationships between the chromosome 17@29cM QTL, total amount of wake, and duration of wake bouts in both light and dark periods that implies a mechanism whereby overall sleep need, mediated by this locus, in turn determines the length of each wake bout. Taken together, the present results reveal a complex genetic landscape underlying multiple sleep-wake traits

  2. Vaporous Marketing: Uncovering Pervasive Electronic Cigarette Advertisements on Twitter

    Science.gov (United States)

    Jones, Chris A.; Williams, Jake Ryland; Kurti, Allison N.; Norotsky, Mitchell Craig; Danforth, Christopher M.; Dodds, Peter Sheridan

    2016-01-01

    Background Twitter has become the “wild-west” of marketing and promotional strategies for advertisement agencies. Electronic cigarettes have been heavily marketed across Twitter feeds, offering discounts, “kid-friendly” flavors, algorithmically generated false testimonials, and free samples. Methods All electronic cigarette keyword related tweets from a 10% sample of Twitter spanning January 2012 through December 2014 (approximately 850,000 total tweets) were identified and categorized as Automated or Organic by combining a keyword classification and a machine trained Human Detection algorithm. A sentiment analysis using Hedonometrics was performed on Organic tweets to quantify the change in consumer sentiments over time. Commercialized tweets were topically categorized with key phrasal pattern matching. Results The overwhelming majority (80%) of tweets were classified as automated or promotional in nature. The majority of these tweets were coded as commercialized (83.65% in 2013), up to 33% of which offered discounts or free samples and appeared on over a billion twitter feeds as impressions. The positivity of Organic (human) classified tweets has decreased over time (5.84 in 2013 to 5.77 in 2014) due to a relative increase in the negative words ‘ban’, ‘tobacco’, ‘doesn’t’, ‘drug’, ‘against’, ‘poison’, ‘tax’ and a relative decrease in the positive words like ‘haha’, ‘good’, ‘cool’. Automated tweets are more positive than organic (6.17 versus 5.84) due to a relative increase in the marketing words like ‘best’, ‘win’, ‘buy’, ‘sale’, ‘health’, ‘discount’ and a relative decrease in negative words like ‘bad’, ‘hate’, ‘stupid’, ‘don’t’. Conclusions Due to the youth presence on Twitter and the clinical uncertainty of the long term health complications of electronic cigarette consumption, the protection of public health warrants scrutiny and potential regulation of social media

  3. TaMYB13-1, a R2R3 MYB transcription factor, regulates the fructan synthetic pathway and contributes to enhanced fructan accumulation in bread wheat

    Science.gov (United States)

    Kooiker, Maarten; Drenth, Janneke; Glassop, Donna; McIntyre, C. Lynne; Xue, Gang-Ping

    2013-01-01

    Fructans are the major component of temporary carbon reserve in the stem of temperate cereals, which is used for grain filling. Three families of fructosyltransferases are directly involved in fructan synthesis in the vacuole of Triticum aestivum. The regulatory network of the fructan synthetic pathway is largely unknown. Recently, a sucrose-upregulated wheat MYB transcription factor (TaMYB13-1) was shown to be capable of activating the promoter activities of sucrose:sucrose 1-fructosyltransferase (1-SST) and sucrose:fructan 6-fructosyltransferase (6-SFT) in transient transactivation assays. This work investigated TaMYB13-1 target genes and their influence on fructan synthesis in transgenic wheat. TaMYB13-1 overexpression resulted in upregulation of all three families of fructosyltransferases including fructan:fructan 1-fructosyltransferase (1-FFT). A γ-vacuolar processing enzyme (γ-VPE1), potentially involved in processing the maturation of fructosyltransferases in the vacuole, was also upregulated by TaMYB13-1 overexpression. Multiple TaMYB13 DNA-binding motifs were identified in the Ta1-FFT1 and Taγ-VPE1 promoters and were bound strongly by TaMYB13-1. The expression profiles of these target genes and TaMYB13-1 were highly correlated in recombinant inbred lines and during stem development as well as the transgenic and non-transgenic wheat dataset, further supporting a direct regulation of these genes by TaMYB13-1. TaMYB13-1 overexpression in wheat led to enhanced fructan accumulation in the leaves and stems and also increased spike weight and grain weight per spike in transgenic plants under water-limited conditions. These data suggest that TaMYB13-1 plays an important role in coordinated upregulation of genes necessary for fructan synthesis and can be used as a molecular tool to improve the high fructan trait. PMID:23873993

  4. Integrating stormwater and greywater treatment for thermal regulation and the enhancement of biological diversity using mass balance of water as a design criteria

    Energy Technology Data Exchange (ETDEWEB)

    Mankiewicz, P.S.; Simon, D.B. [Gaia Inst., Bronx, NY (United States)

    2007-07-01

    This paper presented green roof projects scheduled for construction in New York City in 2007 which will test the hypothesis that green roof water budgets can favorably impact energy consumption in buildings and in their immediate surroundings. It presented specific methods and applications to move water and partition heat through vegetation to reach complementary goals in both ecology and economics of increasing plant coverage, decreasing urban summer temperature, and eliminating the expense of treating stormwater and greywater through evaporative cooling. A commercial facility will be retrofitted with a green roof and photovoltaic (PV) array as well as a below grade stormwater capture and recycle system. The overall energy efficiency, as well as PV performance, will be enhanced by coupling a green roof with water treatment with photovoltaic energy capture. Condensers for this building will be situated beneath a green roof and next to a vegetated landscape, resulting in cool air that is expected to increase air conditioning efficiencies. The objective is zero stormwater discharge into the combined sewer. The density of plant coverage, the quantity of available water, and the output of crops were studied in detail. The interdependent criteria of thermal partitioning, water loss, leaf area index, and green roof energetics have begun to receive attention because green roof evaluation has begun to focus on the ability of plants to discharge quantities of water into the atmosphere, and because this water movement pathway has large physical chemical impacts on the thermal environment. This paper revealed that green roofs contribute to thermal regulation and energy savings, with a kilowatt usage difference of 20 per cent or greater for black versus green roofs. 26 refs., 2 figs.

  5. Thiourea, a ROS scavenger, regulates source-to-sink relationship to enhance crop yield and oil content in Brassica juncea (L..

    Directory of Open Access Journals (Sweden)

    Manish Pandey

    Full Text Available In the present agricultural scenario, the major thrust is to increase crop productivity so as to ensure sustainability. In an earlier study, foliar application of thiourea (TU; a non physiological thiol based ROS scavenger has been demonstrated to enhance the stress tolerance and yield of different crops under field condition. Towards this endeavor, present work deals with the effect of TU on photosynthetic efficiency and source-to-sink relationship of Indian mustard (Brassica juncea for understanding its mode of action. The application of TU increased the efficiency of both PSI and PSII photosystems and vegetative growth of plant. The comparative analysis of sucrose to starch ratio and expression level of sugar transporters confirmed the higher source and sink strength in response to TU treatment. The biochemical evidence in support of this was derived from higher activities of sucrose phosphate synthase and fructose-1,6-bis-phosphatase at source; and sucrose synthase and different classes of invertases at both source and sink. This indicated an overall increase in photoassimilate level at sink. An additional contribution through pod photosynthesis was confirmed through the analysis of phosphoenol pyruvate carboxylase enzyme activity and level of organic acids. The increased photoassimilate level was also co-ordinated with acetyl coA carboxylase mediated oil biosynthesis. All these changes were ultimately reflected in the form of 10 and 20% increase in total yield and oil content, respectively under TU treatment as compared to control. Additionally, no change was observed in oil composition of seeds derived from TU treated plants. The study thus signifies the co-ordinated regulation of key steps of photosynthesis and source-to-sink relationship through the external application of TU resulting in increased crop yield and oil content.

  6. l-Methionine anti-biofilm activity against Pseudomonas aeruginosa is enhanced by the cystic fibrosis transmembrane conductance regulator potentiator, ivacaftor.

    Science.gov (United States)

    Cho, Do-Yeon; Lim, Dong-Jin; Mackey, Calvin; Weeks, Christopher G; Peña Garcia, Jaime A; Skinner, Daniel; Grayson, Jessica W; Hill, Harrison S; Alexander, David K; Zhang, Shaoyan; Woodworth, Bradford A

    2018-05-01

    Biofilms may contribute to refractory chronic rhinosinusitis (CRS), as they lead to antibiotic resistance and failure of effective clinical treatment. l-Methionine is an amino acid with reported biofilm-inhibiting properties. Ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator with mild antimicrobial activity via inhibition of bacterial DNA gyrase and topoisomerase IV. The objective of this study was to evaluate whether co-treatment with ivacaftor and l-methionine can reduce the formation of Pseudomonas aeruginosa biofilms. P aeruginosa (PAO-1 strain) biofilms were studied in the presence of l-methionine and/or ivacaftor. For static biofilm assays, PAO-1 was cultured in a 48-well plate for 72 hours with stepwise combinations of these agents. Relative biofilm inhibitions were measured according to optical density of crystal violet stain at 590 nm. Live/dead assays (BacTiter-Glo™ assay, Promega) were imaged with laser scanning confocal microscopy. An agar diffusion test was used to confirm antibacterial effects of the drugs. l-Methionine (0.5 μM) significantly reduced PAO-1 biofilm mass (32.4 ± 18.0%; n = 4; p l-methionine (two-way analysis of variane, p = 0.0415) compared with corresponding concentrations of l-methionine alone. Ivacaftor enhanced the anti-biofilm activity of l-methionine against the PAO-1 strain of P aeruginosa. Further studies evaluating the efficacy of ivacaftor/l-methionine combinations for P aeruginosa sinusitis are planned. © 2018 ARS-AAOA, LLC.

  7. Uncovering Potential Applications of Cyanobacteria and Algal Metabolites in Biology, Agriculture and Medicine: Current Status and Future Prospects

    Science.gov (United States)

    Singh, Rachana; Parihar, Parul; Singh, Madhulika; Bajguz, Andrzej; Kumar, Jitendra; Singh, Samiksha; Singh, Vijay P.; Prasad, Sheo M.

    2017-01-01

    Cyanobacteria and algae having complex photosynthetic systems can channelize absorbed solar energy into other forms of energy for production of food and metabolites. In addition, they are promising biocatalysts and can be used in the field of “white biotechnology” for enhancing the sustainable production of food, metabolites, and green energy sources such as biodiesel. In this review, an endeavor has been made to uncover the significance of various metabolites like phenolics, phytoene/terpenoids, phytols, sterols, free fatty acids, photoprotective compounds (MAAs, scytonemin, carotenoids, polysaccharides, halogenated compounds, etc.), phytohormones, cyanotoxins, biocides (algaecides, herbicides, and insecticides) etc. Apart from this, the importance of these metabolites as antibiotics, immunosuppressant, anticancer, antiviral, anti-inflammatory agent has also been discussed. Metabolites obtained from cyanobacteria and algae have several biotechnological, industrial, pharmaceutical, and cosmetic uses which have also been discussed in this review along with the emerging technology of their harvesting for enhancing the production of compounds like bioethanol, biofuel etc. at commercial level. In later sections, we have discussed genetically modified organisms and metabolite production from them. We have also briefly discussed the concept of bioprocessing highlighting the functioning of companies engaged in metabolites production as well as their cost effectiveness and challenges that are being addressed by these companies. PMID:28487674

  8. Uncovering Potential Applications of Cyanobacteria and Algal Metabolites in Biology, Agriculture and Medicine: Current Status and Future Prospects

    Directory of Open Access Journals (Sweden)

    Vijay P. Singh

    2017-04-01

    Full Text Available Cyanobacteria and algae having complex photosynthetic systems can channelize absorbed solar energy into other forms of energy for production of food and metabolites. In addition, they are promising biocatalysts and can be used in the field of “white biotechnology” for enhancing the sustainable production of food, metabolites, and green energy sources such as biodiesel. In this review, an endeavor has been made to uncover the significance of various metabolites like phenolics, phytoene/terpenoids, phytols, sterols, free fatty acids, photoprotective compounds (MAAs, scytonemin, carotenoids, polysaccharides, halogenated compounds, etc., phytohormones, cyanotoxins, biocides (algaecides, herbicides, and insecticides etc. Apart from this, the importance of these metabolites as antibiotics, immunosuppressant, anticancer, antiviral, anti-inflammatory agent has also been discussed. Metabolites obtained from cyanobacteria and algae have several biotechnological, industrial, pharmaceutical, and cosmetic uses which have also been discussed in this review along with the emerging technology of their harvesting for enhancing the production of compounds like bioethanol, biofuel etc. at commercial level. In later sections, we have discussed genetically modified organisms and metabolite production from them. We have also briefly discussed the concept of bioprocessing highlighting the functioning of companies engaged in metabolites production as well as their cost effectiveness and challenges that are being addressed by these companies.

  9. Epistemically Virtuous Risk Management : Financial Due Diligence and Uncovering the Madoff Fraud

    NARCIS (Netherlands)

    de Bruin, Boudewijn; Luetge, Christoph; Jauernig, Johanna

    2014-01-01

    The chapter analyses how Bernard Madoff’s Ponzi scheme was uncovered by Harry Markopolos, an employee of Rampart Investment Management, LLC, and the contribution of so-called epistemic virtues to Markopolos’ success. After Rampart had informed the firm about an allegedly highly successful hedge fund

  10. Uncovering the Best Skill Multimap by Constraining the Error Probabilities of the Gain-Loss Model

    Science.gov (United States)

    Anselmi, Pasquale; Robusto, Egidio; Stefanutti, Luca

    2012-01-01

    The Gain-Loss model is a probabilistic skill multimap model for assessing learning processes. In practical applications, more than one skill multimap could be plausible, while none corresponds to the true one. The article investigates whether constraining the error probabilities is a way of uncovering the best skill assignment among a number of…

  11. Using Text Mining to Uncover Students' Technology-Related Problems in Live Video Streaming

    Science.gov (United States)

    Abdous, M'hammed; He, Wu

    2011-01-01

    Because of their capacity to sift through large amounts of data, text mining and data mining are enabling higher education institutions to reveal valuable patterns in students' learning behaviours without having to resort to traditional survey methods. In an effort to uncover live video streaming (LVS) students' technology related-problems and to…

  12. Feminist Approaches to Triangulation: Uncovering Subjugated Knowledge and Fostering Social Change in Mixed Methods Research

    Science.gov (United States)

    Hesse-Biber, Sharlene

    2012-01-01

    This article explores the deployment of triangulation in the service of uncovering subjugated knowledge and promoting social change for women and other oppressed groups. Feminist approaches to mixed methods praxis create a tight link between the research problem and the research design. An analysis of selected case studies of feminist praxis…

  13. 77 FR 21961 - Uncovered Innerspring Units From the People's Republic of China: Final Results and Final...

    Science.gov (United States)

    2012-04-12

    ... material and then glued together in a linear fashion. Uncovered innersprings are classified under... responsibility concerning the return or destruction of proprietary information disclosed under the APO, which... notification of the return/destruction of APO materials or conversion to judicial protective order is hereby...

  14. 76 FR 80337 - Uncovered Innerspring Units From the People's Republic of China: Rescission of Antidumping Duty...

    Science.gov (United States)

    2011-12-23

    ... fashion. Uncovered innersprings are classified under subheading 9404.29.9010, 9404.29.9005 and 9404.29... (``APO'') of their responsibility concerning the return or destruction of proprietary information... written notification of the return or destruction of APO materials or conversion to judicial protective...

  15. Evaluating the thermal and electrical performance of several uncovered PVT collectors with a field test

    NARCIS (Netherlands)

    de Keizer, C.; de Jong, M.; Mendes, T.; Katiyar, M.; Folkerts, W.; Rindt, C.C.M.; Zondag, H.A.

    Recently, there has been a lot of interest in PV thermal systems, which generate both heat and power. Within the WenSDak project, several companies and research institutes work together to (further) develop several uncovered PVT collectors. The outdoor performance of prototypes of these collectors

  16. Uncovering the Motivating Factors behind Writing in English in en EFL Context

    Science.gov (United States)

    Büyükyavuz, Oya; Çakir, Ismail

    2014-01-01

    Writing in a language, whether the target or native, is regarded as a complex activity operating on multiple cognitive levels. This study aimed to uncover the factors which motivate teacher trainees of English to write in English in an EFL context. The study also investigated the differences in the ways teacher trainees are motivated in terms of…

  17. Comparison of covered and uncovered self-expandable stents in the treatment of malignant biliary obstruction.

    Science.gov (United States)

    Flores Carmona, Diana Yamel; Alonso Lárraga, Juan Octavio; Hernández Guerrero, Angélica; Ramírez Solís, Mauro Eduardo

    2016-05-01

    Drainage with metallic stents is the treatment of choice in malignant obstructive jaundice. Technical and clinical success with metallic stents is obtained in over 90% and 80% of cases, respectively. There are self-expandable metallic stents designed to increase permeability. The aim of this study was to describe the results obtained with totally covered self-expandable and uncovered self-expandable metallic stents in the palliative treatment of malignant biliary obstruction. Sixty eight patients with malignant obstructive jaundice secondary to pancreatobiliary or metastatic disease not amenable to surgery were retrospectively included. Two groups were created: group A (covered self-expandable metallic stents) (n = 22) and group B (uncovered self-expandable metallic stents) (n = 46). Serum total bilirubin, direct bilirubin, alkaline phosphatase and gamma glutamyl transferase levels decreased in both groups and no statistically significant difference was detected (p = 0.800, p = 0.190, p = 0.743, p = 0.521). Migration was greater with covered stents but it was not statistically significant either (p = 0.101). Obstruction was greater in the group with uncovered stents but it was not statistically significant either (p = 0.476). There are no differences when using covered self-expandable stents or uncovered self-expandable stents in terms of technical and clinical success or complications in the palliative treatment of malignant obstructive jaundice.

  18. Community Mapping in Action: Uncovering Resources and Assets for Young Children and Their Families

    Science.gov (United States)

    Ordonez-Jasis, Rosario; Myck-Wayne, Janice

    2012-01-01

    Community mapping is a promising practice that can assist early intervention/early childhood special education (EI/ECSE) professionals uncover the depth and diversity of community needs, resources, and learning opportunities, in the neighborhoods surrounding their schools. Community mapping is an inquiry-based method that situates learning in the…

  19. Revisiting Uncovered Interest Rate Parity: Switching Between UIP and the Random Walk

    NARCIS (Netherlands)

    R. Huisman (Ronald); R.J. Mahieu (Ronald)

    2007-01-01

    textabstractIn this paper, we examine in which periods uncovered interest rate parity was likely to hold. Empirical research has shown mixed evidence on UIP. The main finding is that it doesn’t hold, although some researchers were not able to reject UIP in periods with large interest differentials

  20. Long Term Follow-up of a Transjugular Intrahepatic Portosystemic Shunt: A Comparison of Covered and Uncovered Stents

    Energy Technology Data Exchange (ETDEWEB)

    Joo, Seung Moon; Park, Jae Hyung; Kim, Hyo Cheol; Jae, Hwan Jun; Chung, Jin Wook [Seoul National University Hospital, Seoul (Korea, Republic of)

    2009-01-15

    To evaluate the long term patency of transjugular intrahepatic portosystemic shunts (TIPS) and to compare the patency rate of covered and uncovered stents in TIPS. The study population included 78 patients with portal hypertension that underwent TIPS between January 1999 and July 2007 at our institution using uncovered stents in 53 patients and covered stents in 25 patients. The primary and secondary patency rates of TIPS were estimated to compare the uncovered and covered stent groups. The primary and secondary patency rates of the TIPS patients were found to be 83.9% and 93.9% at the 6 month follow-up and 73.5% and 88.5% at the12 month follow-up for uncovered and covered stents, respectively. A breakdown patency rates for the 12 month follow-up revealed that the primary patency rates were 76.6% and 66.3% for uncovered and covered stents, respectively; whereas, the secondary patency rates were 94.3% and 73.8% for the uncovered and covered stents, respectively. A comparative analysis did not provide evidence to suggest that a difference exists between the patency rates of the uncovered and covered stent groups (p>0.05). No significant difference was found between the patency rates of the uncovered and covered stent groups. A follow-up to this study would be a more thorough randomized evaluation of the different types of covered stents to compare long-term patency rates.

  1. MicroRNA-9 enhances sensitivity to cetuximab in epithelial phenotype hepatocellular carcinoma cells through regulation of the eukaryotic translation initiation factor 5A-2.

    Science.gov (United States)

    Xue, Fei; Liang, Yuntian; Li, Zhenrong; Liu, Yanhui; Zhang, Hongwei; Wen, Yu; Yan, Lei; Tang, Qiang; Xiao, Erhui; Zhang, Dongyi

    2018-01-01

    Hepatocellular carcinoma (HCC) is one of the most widespread malignant human tumors worldwide. Treatment options include radiotherapy, surgical intervention and chemotherapy; however, drug resistance is an ongoing treatment concern. In the present study, the effects of a microRNA (miR/miRNA), miR-9, on the sensitivity of HCC cell lines to the epidermal growth factor receptor inhibitor, cetuximab, were examined. miR-9 has been proposed to serve a role in tumorigenesis and tumor progression. In the present study, bioinformatics analyses identified the eukaryotic translation initiation factor 5A2 (eIF-5A-2) as a target of miR-9. The expression levels of miR-9 and eIF-5A-2 were examined by reverse transcription-quantitative polymerase chain reaction and HCC cell lines were transfected with miR-9 mimics and inhibitors to determine the effects of the miRNA on cell proliferation and viability. The miR-9 mimic was revealed to significantly increase the sensitivity of epithelial phenotype HCC cells (Hep3B and Huh7) to cetuximab, while the miR-9 inhibitor triggered the opposite effect. There were no significant differences in sensitivity to cetuximab observed in mesenchymal phenotype HCC cells (SNU387 and SNU449). Cells lines displaying high expression levels of eIF-5A-2 were more resistant to cetuximab. Transfection of cells with a miR-9 mimic resulted in downregulation of the expression of eIF-5A-2 mRNA, while an miR-9 inhibitor increased expression. When expression of eIF-5A-2 was knocked down with siRNA, the effects of miR-9 on cetuximab sensitivity were no longer observed. Taken together, these data support a role for miR-9 in enhancing the sensitivity of epithelial phenotype HCC cells to cetuximab through regulation of eIF-5A-2.

  2. Eliminating a global regulator of carbon catabolite repression enhances the conversion of aromatic lignin monomers to muconate in Pseudomonas putida KT2440

    Directory of Open Access Journals (Sweden)

    Christopher W. Johnson

    2017-12-01

    Full Text Available Carbon catabolite repression refers to the preference of microbes to metabolize certain growth substrates over others in response to a variety of regulatory mechanisms. Such preferences are important for the fitness of organisms in their natural environments, but may hinder their performance as domesticated microbial cell factories. In a Pseudomonas putida KT2440 strain engineered to convert lignin-derived aromatic monomers such as p-coumarate and ferulate to muconate, a precursor to bio-based nylon and other chemicals, metabolic intermediates including 4-hydroxybenzoate and vanillate accumulate and subsequently reduce productivity. We hypothesized that these metabolic bottlenecks may be, at least in part, the effect of carbon catabolite repression caused by glucose or acetate, more preferred substrates that must be provided to the strain for supplementary energy and cell growth. Using mass spectrometry-based proteomics, we have identified the 4-hydroxybenzoate hydroxylase, PobA, and the vanillate demethylase, VanAB, as targets of the Catabolite Repression Control (Crc protein, a global regulator of carbon catabolite repression. By deleting the gene encoding Crc from this strain, the accumulation of 4-hydroxybenzoate and vanillate are reduced and, as a result, muconate production is enhanced. In cultures grown on glucose, the yield of muconate produced from p-coumarate after 36 h was increased nearly 70% with deletion of the gene encoding Crc (94.6 ± 0.6% vs. 56.0 ± 3.0% (mol/mol while the yield from ferulate after 72 h was more than doubled (28.3 ± 3.3% vs. 12.0 ± 2.3% (mol/mol. The effect of eliminating Crc was similar in cultures grown on acetate, with the yield from p-coumarate just slightly higher in the Crc deletion strain after 24 h (47.7 ± 0.6% vs. 40.7 ± 3.6% (mol/mol and the yield from ferulate increased more than 60% after 72 h (16.9 ± 1.4% vs. 10.3 ± 0.1% (mol/mol. These results are an example of the benefit that reducing

  3. Cholesterol enhances amyloid {beta} deposition in mouse retina by modulating the activities of A{beta}-regulating enzymes in retinal pigment epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jiying [Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519 (Japan); Ohno-Matsui, Kyoko, E-mail: k.ohno.oph@tmd.ac.jp [Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519 (Japan); Morita, Ikuo [Section of Cellular Physiological Chemistry, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519 (Japan)

    2012-08-10

    Highlights: Black-Right-Pointing-Pointer Cholesterol-treated RPE produces more A{beta} than non-treated RPE. Black-Right-Pointing-Pointer Neprilysin expression and activity decreased in cholesterol-treated RPE. Black-Right-Pointing-Pointer {alpha}-Secretase expression and activity decreased in cholesterol-treated RPE. Black-Right-Pointing-Pointer Cholesterol-enriched diet induced subRPE deposits in aged mice. Black-Right-Pointing-Pointer A{beta} were present in cholesterol-enriched-diet-induced subRPE deposits in aged mice. -- Abstract: Subretinally-deposited amyloid {beta} (A{beta}) is a main contributor of developing age-related macular degeneration (AMD). However, the mechanism causing A{beta} deposition in AMD eyes is unknown. Hypercholesterolemia is a significant risk for developing AMD. Thus, we investigated the effects of cholesterol on A{beta} production in retinal pigment epithelial (RPE) cells in vitro and in the mouse retina in vivo. RPE cells isolated from senescent (12-month-old) C57BL/6 mice were treated with 10 {mu}g/ml cholesterol for 48 h. A{beta} amounts in culture supernatants were measured by ELISA. Activity and expression of enzymes and proteins that regulate A{beta} production were examined by activity assay and real time PCR. The retina of mice fed cholesterol-enriched diet was examined by transmission electron microscopy. Cholesterol significantly increased A{beta} production in cultured RPE cells. Activities of A{beta} degradation enzyme; neprilysin (NEP) and anti-amyloidogenic secretase; {alpha}-secretase were significantly decreased in cell lysates of cholesterol-treated RPE cells compared to non-treated cells, but there was no change in the activities of {beta}- or {gamma}-secretase. mRNA levels of NEP and {alpha}-secretase (ADAM10 and ADAM17) were significantly lower in cholesterol-treated RPE cells than non-treated cells. Senescent (12-month-old) mice fed cholesterol-enriched chow developed subRPE deposits containing A{beta}, whereas

  4. Partially Covered Metal Stents May Not Prolong Stent Patency Compared to Uncovered Stents in Unresectable Malignant Distal Biliary Obstruction

    Science.gov (United States)

    Kim, Jae Yun; Ko, Gyu Bong; Lee, Tae Hoon; Park, Sang-Heum; Lee, Yun Nah; Cho, Young Sin; Jung, Yunho; Chung, Il-Kwun; Choi, Hyun Jong; Cha, Sang-Woo; Moon, Jong Ho; Cho, Young Deok; Kim, Sun-Joo

    2017-01-01

    Background/Aims Controversy still exists regarding the benefits of covered self-expandable metal stents (SEMSs) compared to uncovered SEMSs. We aimed to compare the patency and stent-related adverse events of partially covered SEMSs (PC-SEMSs) and uncovered SEMSs in unresectable malignant distal biliary obstruction. Methods A total of 134 patients who received a PC-SEMS or uncovered SEMS for palliation of unresectable malignant distal biliary obstruction were reviewed retrospectively. The main outcome measures were stent patency, stent-related adverse events, and overall survival. Results The median stent patency was 118 days (range, 3 to 802 days) with PC-SEMSs and 105 days (range, 2 to 485 days) with uncovered SEMSs (p=0.718). The overall endoscopic revision rate due to stent dysfunction was 36.6% (26/71) with PC-SEMSs and 36.5% (23/63) with uncovered SEMSs (p=0.589). Tumor ingrowth was more frequent with uncovered SEMSs (4.2% vs 19.1%, p=0.013), but migration was more frequent with PC-SEMSs (11.2% vs 1.5%, p=0.04). The incidence of stent-related adverse events was 2.8% (2/71) with PC-SEMSs and 9.5% (6/63) with uncovered SEMSs (p=0.224). The median overall survival was 166 days with PC-SEMSs and 168 days with uncovered SEMSs (p=0.189). Conclusions Compared to uncovered SEMSs, PC-SEMSs did not prolong stent patency in unresectable malignant distal biliary obstruction. Stent migration was more frequent with PC-SEMSs. However, tumor ingrowth was less frequent with PC-SEMSs compared to uncovered SEMSs. PMID:28208003

  5. Analysis of the synaptotagmin family during reconstituted membrane fusion. Uncovering a class of inhibitory isoforms.

    Science.gov (United States)

    Bhalla, Akhil; Chicka, Michael C; Chapman, Edwin R

    2008-08-01

    Ca(2+)-triggered exocytosis in neurons and neuroendocrine cells is regulated by the Ca(2+)-binding protein synaptotagmin (syt) I. Sixteen additional isoforms of syt have been identified, but little is known concerning their biochemical or functional properties. Here, we assessed the abilities of fourteen syt isoforms to directly regulate SNARE (soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein receptor)-catalyzed membrane fusion. One group of isoforms stimulated neuronal SNARE-mediated fusion in response to Ca(2+), while another set inhibited SNARE catalyzed fusion in both the absence and presence of Ca(2+). Biochemical analysis revealed a strong correlation between the ability of syt isoforms to bind 1,2-dioleoyl phosphatidylserine (PS) and t-SNAREs in a Ca(2+)-promoted manner with their abilities to enhance fusion, further establishing PS and SNAREs as critical effectors for syt action. The ability of syt I to efficiently stimulate fusion was specific for certain SNARE pairs, suggesting that syts might contribute to the specificity of intracellular membrane fusion reactions. Finally, a subset of inhibitory syts down-regulated the ability of syt I to activate fusion, demonstrating that syt isoforms can modulate the function of each other.

  6. Tissue-Specific Gain of RTK Signalling Uncovers Selective Cell Vulnerability during Embryogenesis.

    Directory of Open Access Journals (Sweden)

    Yannan Fan

    Full Text Available The successive events that cells experience throughout development shape their intrinsic capacity to respond and integrate RTK inputs. Cellular responses to RTKs rely on different mechanisms of regulation that establish proper levels of RTK activation, define duration of RTK action, and exert quantitative/qualitative signalling outcomes. The extent to which cells are competent to deal with fluctuations in RTK signalling is incompletely understood. Here, we employ a genetic system to enhance RTK signalling in a tissue-specific manner. The chosen RTK is the hepatocyte growth factor (HGF receptor Met, an appropriate model due to its pleiotropic requirement in distinct developmental events. Ubiquitously enhanced Met in Cre/loxP-based Rosa26(stopMet knock-in context (Del-R26(Met reveals that most tissues are capable of buffering enhanced Met-RTK signalling thus avoiding perturbation of developmental programs. Nevertheless, this ubiquitous increase of Met does compromise selected programs such as myoblast migration. Using cell-type specific Cre drivers, we genetically showed that altered myoblast migration results from ectopic Met expression in limb mesenchyme rather than in migrating myoblasts themselves. qRT-PCR analyses show that ectopic Met in limbs causes molecular changes such as downregulation in the expression levels of Notum and Syndecan4, two known regulators of morphogen gradients. Molecular and functional studies revealed that ectopic Met expression in limb mesenchyme does not alter HGF expression patterns and levels, but impairs HGF bioavailability. Together, our findings show that myoblasts, in which Met is endogenously expressed, are capable of buffering increased RTK levels, and identify mesenchymal cells as a cell type vulnerable to ectopic Met-RTK signalling. These results illustrate that embryonic cells are sensitive to alterations in the spatial distribution of RTK action, yet resilient to fluctuations in signalling levels of an

  7. Uncovering Wildlife

    Science.gov (United States)

    Travis, Holly

    2016-01-01

    Many ground-dwelling amphibians, reptiles, small mammals, insects, and other arthropods seek cover during their resting hours. Their natural hideaways include underground burrows, rotting logs, and leaf litter, which are widely distributed and difficult to discover and observe. To make observation easier, scientists, educators, and students can…

  8. Meta-analysis of cancer transcriptomes: A new approach to uncover molecular pathological events in different cancer tissues

    Directory of Open Access Journals (Sweden)

    Sundus Iqbal

    2014-03-01

    Full Text Available To explore secrets of metastatic cancers, individual expression of true sets of respective genes must spread across the tissue. In this study, meta-analysis for transcriptional profiles of oncogenes was carried out to hunt critical genes or networks helping in metastasizing cancers. For this, transcriptomic analysis of different cancerous tissues causing leukemia, lung, liver, spleen, colorectal, colon, breast, bladder, and kidney cancers was performed by extracting microarray expression data from online resource; Gene Expression Omnibus. A newly developed bioinformatics technique; Dynamic Impact Approach (DIA was applied for enrichment analysis of transcriptional profiles using Database for Annotation Visualization and Integrated Discovery (DAVID. Furthermore, oPOSSUM (v. 2.0 and Cytoscape (v. 2.8.2 were used for in-depth analysis of transcription factors and regulatory gene networks respectively. DAVID analysis uncovered the most significantly enriched pathways in molecular functions that were 'Ubiquitin thiolesterase activity' up regulated in blood, breast, bladder, colorectal, lung, spleen, prostrate cancer. 'Transforming growth factor beta receptor activity' was inhibited in all cancers except leukemia, colon and liver cancer. oPOSSUM further revealed highly over-represented Transcription Factors (TFs; Broad-complex_3, Broad-complex_4, and Foxd3 except for leukemia and bladder cancer. From these findings, it is possible to target genes and networks, play a crucial role in the development of cancer. In the future, these transcription factors can serve as potential candidates for the therapeutic drug targets which can impede the deadly spread.

  9. Identification and allelic dissection uncover roles of lncRNAs in secondary growth of Populus tomentosa.

    Science.gov (United States)

    Zhou, Daling; Du, Qingzhang; Chen, Jinhui; Wang, Qingshi; Zhang, Deqiang

    2017-10-01

    Long non-coding RNAs (lncRNAs) function in various biological processes. However, their roles in secondary growth of plants remain poorly understood. Here, 15,691 lncRNAs were identified from vascular cambium, developing xylem, and mature xylem of Populus tomentosa with high and low biomass using RNA-seq, including 1,994 lncRNAs that were differentially expressed (DE) among the six libraries. 3,569 cis-regulated and 3,297 trans-regulated protein-coding genes were predicted as potential target genes (PTGs) of the DE lncRNAs to participate in biological regulation. Then, 476 and 28 lncRNAs were identified as putative targets and endogenous target mimics (eTMs) of Populus known microRNAs (miRNAs), respectively. Genome re-sequencing of 435 individuals from a natural population of P. tomentosa found 34,015 single nucleotide polymorphisms (SNPs) within 178 lncRNA loci and 522 PTGs. Single-SNP associations analysis detected 2,993 associations with 10 growth and wood-property traits under additive and dominance model. Epistasis analysis identified 17,656 epistatic SNP pairs, providing evidence for potential regulatory interactions between lncRNAs and their PTGs. Furthermore, a reconstructed epistatic network, representing interactions of 8 lncRNAs and 15 PTGs, might enrich regulation roles of genes in the phenylpropanoid pathway. These findings may enhance our understanding of non-coding genes in plants. © The Author 2017. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

  10. Epistemically Virtuous Risk Management: Financial Due Diligence and Uncovering the Madoff Fraud

    OpenAIRE

    de Bruin, Boudewijn; Luetge, Christoph; Jauernig, Johanna

    2014-01-01

    The chapter analyses how Bernard Madoff’s Ponzi scheme was uncovered by Harry Markopolos, an employee of Rampart Investment Management, LLC, and the contribution of so-called epistemic virtues to Markopolos’ success. After Rampart had informed the firm about an allegedly highly successful hedge fund run by Madoff, Markopolos used qualitative and quantitative methods from financial due diligence to examine Madoff’s risks, returns and strategy, ultimately to conclude that Madoff was running a l...

  11. Uncovering the role of the East Asian jet stream and heterogeneities in atmospheric rivers affecting the western United States.

    Science.gov (United States)

    Zhang, Wei; Villarini, Gabriele

    2018-01-30

    Atmospheric rivers (ARs) exert major socioeconomic repercussions along the US West Coast by inducing heavy rainfall, flooding, strong winds, and storm surge. Despite the significant societal and economic repercussions of these storms, our understanding of the physical drivers responsible for their interannual variability is limited, with different climate modes identified as possible mechanisms. Here we show that the Pacific-Japan (PJ) teleconnections/patterns and the East Asian subtropical jet (EASJ) exhibit a strong linkage with the total frequency of ARs making landfall over the western United States, much stronger than the other potential climate modes previously considered. While our findings indicate that the PJ pattern and EASJ are the most relevant climate modes driving the overall AR activity, we also uncover heterogeneities in AR tracks. Specifically, we show that not all ARs making landfall along the West Coast come from a single population, but rather that it is possible to stratify these storms into three clusters. While the PJ pattern and EASJ are major drivers of AR activity for two clusters, the cluster that primarily affects the US Southwest is largely driven by other climate modes [El Niño Southern Oscillation (ENSO), the Atlantic meridional mode (AMM), the Pacific-North America (PNA) teleconnection pattern, and the North Pacific Gyre Oscillation (NPGO)]. Therefore, important regional differences exist and this information can substantially enhance our ability to predict and prepare for these storms and their impacts.

  12. Conformable covered versus uncovered self-expandable metallic stents for palliation of malignant gastroduodenal obstruction: a randomized prospective study.

    Science.gov (United States)

    Lim, Sun Gyo; Kim, Jin Hong; Lee, Kee Myung; Shin, Sung Jae; Kim, Chan Gyoo; Kim, Kyung Ho; Kim, Ho Gak; Yang, Chang Heon

    2014-07-01

    A conformable self-expandable metallic stent was developed to overcome the limitation of previous self-expandable metallic stents. The aim of this study was to evaluate outcomes after placement of conformable covered and uncovered self-expandable metallic stents for palliation of malignant gastroduodenal obstruction. A single-blind, randomized, parallel-group, prospective study were conducted in 4 medical centres between March 2009 and July 2012. 134 patients with unresectable malignant gastroduodenal obstruction were assigned to a covered double-layered (n=66) or uncovered unfixed-cell braided (n=68) stent placement group. Primary analysis was performed to compare re-intervention rates between two groups. 120 patients were analysed (59 in the covered group and 61 in the uncovered group). Overall rates of re-intervention were not significantly different between the two groups: 13/59 (22.0%) in the covered group vs. 13/61 (21.3%) in the uncovered group, p=0.999. Stent migration was more frequent in the covered group than in the uncovered group (p=0.003). The tumour ingrowth rate was higher in the uncovered group than in the covered group (p=0.016). The rates of re-intervention did not significantly differ between the two stents. Conformable covered double-layered and uncovered unfixed-cell braided stents were associated with different patterns of stent malfunction. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  13. Comprehensive benchmarking reveals H2BK20 acetylation as a distinctive signature of cell-state-specific enhancers and promoters.

    Science.gov (United States)

    Kumar, Vibhor; Rayan, Nirmala Arul; Muratani, Masafumi; Lim, Stefan; Elanggovan, Bavani; Xin, Lixia; Lu, Tess; Makhija, Harshyaa; Poschmann, Jeremie; Lufkin, Thomas; Ng, Huck Hui; Prabhakar, Shyam

    2016-05-01

    Although over 35 different histone acetylation marks have been described, the overwhelming majority of regulatory genomics studies focus exclusively on H3K27ac and H3K9ac. In order to identify novel epigenomic traits of regulatory elements, we constructed a benchmark set of validated enhancers by performing 140 enhancer assays in human T cells. We tested 40 chromatin signatures on this unbiased enhancer set and identified H2BK20ac, a little-studied histone modification, as the most predictive mark of active enhancers. Notably, we detected a novel class of functionally distinct enhancers enriched in H2BK20ac but lacking H3K27ac, which was present in all examined cell lines and also in embryonic forebrain tissue. H2BK20ac was also unique in highlighting cell-type-specific promoters. In contrast, other acetylation marks were present in all active promoters, regardless of cell-type specificity. In stimulated microglial cells, H2BK20ac was more correlated with cell-state-specific expression changes than H3K27ac, with TGF-beta signaling decoupling the two acetylation marks at a subset of regulatory elements. In summary, our study reveals a previously unknown connection between histone acetylation and cell-type-specific gene regulation and indicates that H2BK20ac profiling can be used to uncover new dimensions of gene regulation. © 2016 Kumar et al.; Published by Cold Spring Harbor Laboratory Press.

  14. Multi-frequency complex network from time series for uncovering oil-water flow structure.

    Science.gov (United States)

    Gao, Zhong-Ke; Yang, Yu-Xuan; Fang, Peng-Cheng; Jin, Ning-De; Xia, Cheng-Yi; Hu, Li-Dan

    2015-02-04

    Uncovering complex oil-water flow structure represents a challenge in diverse scientific disciplines. This challenge stimulates us to develop a new distributed conductance sensor for measuring local flow signals at different positions and then propose a novel approach based on multi-frequency complex network to uncover the flow structures from experimental multivariate measurements. In particular, based on the Fast Fourier transform, we demonstrate how to derive multi-frequency complex network from multivariate time series. We construct complex networks at different frequencies and then detect community structures. Our results indicate that the community structures faithfully represent the structural features of oil-water flow patterns. Furthermore, we investigate the network statistic at different frequencies for each derived network and find that the frequency clustering coefficient enables to uncover the evolution of flow patterns and yield deep insights into the formation of flow structures. Current results present a first step towards a network visualization of complex flow patterns from a community structure perspective.

  15. Transcriptomic Analysis of Long Non-Coding RNAs and Coding Genes Uncovers a Complex Regulatory Network That Is Involved in Maize Seed Development

    Directory of Open Access Journals (Sweden)

    Ming Zhu

    2017-10-01

    Full Text Available Long non-coding RNAs (lncRNAs have been reported to be involved in the development of maize plant. However, few focused on seed development of maize. Here, we identified 753 lncRNA candidates in maize genome from six seed samples. Similar to the mRNAs, lncRNAs showed tissue developmental stage specific and differential expression, indicating their putative role in seed development. Increasing evidence shows that crosstalk among RNAs mediated by shared microRNAs (miRNAs represents a novel layer of gene regulation, which plays important roles in plant development. Functional roles and regulatory mechanisms of lncRNAs as competing endogenous RNAs (ceRNA in plants, particularly in maize seed development, are unclear. We combined analyses of consistently altered 17 lncRNAs, 840 mRNAs and known miRNA to genome-wide investigate potential lncRNA-mediated ceRNA based on “ceRNA hypothesis”. The results uncovered seven novel lncRNAs as potential functional ceRNAs. Functional analyses based on their competitive coding-gene partners by Gene Ontology (GO and KEGG biological pathway demonstrated that combined effects of multiple ceRNAs can have major impacts on general developmental and metabolic processes in maize seed. These findings provided a useful platform for uncovering novel mechanisms of maize seed development and may provide opportunities for the functional characterization of individual lncRNA in future studies.

  16. Chromatin Regulation of Estrogen-Mediated Transcription in Breast Cancer: Rules for Binding Sites in Nucleosomes and Modified Histones that Enhance ER Binding

    National Research Council Canada - National Science Library

    Chrivia, John C

    2005-01-01

    .... Using gel shift assays, we tested whether ER can bind these nucleosomes. We have also found that the non-histone chromatin protein HMOB2 enhances binding of ER to an ERE located at the center of the nucleosome...

  17. Direct interactions of OCA-B and TFII-I regulate immunoglobulin heavy-chain gene transcription by facilitating enhancer-promoter communication.

    Science.gov (United States)

    Ren, Xiaodi; Siegel, Rachael; Kim, Unkyu; Roeder, Robert G

    2011-05-06

    B cell-specific coactivator OCA-B, together with Oct-1/2, binds to octamer sites in promoters and enhancers to activate transcription of immunoglobulin (Ig) genes, although the mechanisms underlying their roles in enhancer-promoter communication are unknown. Here, we demonstrate a direct interaction of OCA-B with transcription factor TFII-I, which binds to DICE elements in Igh promoters, that affects transcription at two levels. First, OCA-B relieves HDAC3-mediated Igh promoter repression by competing with HDAC3 for binding to promoter-bound TFII-I. Second, and most importantly, Igh 3' enhancer-bound OCA-B and promoter-bound TFII-I mediate promoter-enhancer interactions, in both cis and trans, that are important for Igh transcription. These and other results reveal an important function for OCA-B in Igh 3' enhancer function in vivo and strongly favor an enhancer mechanism involving looping and facilitated factor recruitment rather than a tracking mechanism. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. OECD/NEA International Conference on Global Nuclear Safety Enhancement Organised in co-operation with the Nuclear Regulation Authority (NRA) of Japan On the Occasion of the 50. Anniversary of Japan Joining the OECD

    International Nuclear Information System (INIS)

    Tanaka, Shunichi; Oshima, Kenzo; Fuketa, Toyoshi; Echavarri, Luis E.; ); Ostendorff, William C.; Viktorovich Ferapontov, Alexey; Lachaume, Jean-Luc; Yoo, Guk Hee; Lyons, James E.; ); Weightman, Mike; ); Gurria, Angel; ); Ishihara, Hirotaka

    2014-04-01

    On 8 April 2014 in Tokyo, Japan, an international conference on enhancing global nuclear safety was held by the Nuclear Energy Agency (NEA) of the Organisation for Economic Co-operation and Development(OECD), in co-operation with the Nuclear Regulation Authority (NRA) of Japan. This document brings together the 12 presentations (slides) given at this conference organized in 3 sessions: 1 - Opening Session: Opening Remarks (S. Tanaka); Statement by L.E. Echavarri; Session 1 - Global Safety Enhancements: USNRC Actions in Response to the Fukushima Nuclear Accident (W.C. Ostendorff); Synergy of National and International Regulatory Efforts to Enhance Global Nuclear Safety (A. Viktorovich Ferapontov); Global Safety Enhancements, The French Nuclear Safety Authority (ASN)'s position (J.L. Lachaume); Nuclear Safety and Security Commission builds up safety and security (G.H. Yoo); Session 2 - Learning from Experience to Improve Safety: Lessons Learned from the Fukushima Dai-ichi Accident and Responses in New Regulatory Requirements (T. Fuketa); NEA Activities to Enhance the Nuclear Regulatory Framework (L.E. Echavarri); Learning from Experience to Improve Safety - its importance, its mechanisms and its challenges (J.E. Lyons); Learning from Experience to Improve Nuclear Safety - A Perspective from the UK (M. Weightman); Conclusions and Closing Remarks (A. Gurria, H. Ishihara)

  19. The progesterone-induced enhancement of object recognition memory consolidation involves activation of the extracellular signal-regulated kinase (ERK) and mammalian target of rapamycin (mTOR) pathways in the dorsal hippocampus

    Science.gov (United States)

    Orr, Patrick T.; Rubin, Amanda J.; Fan, Lu; Kent, Brianne A.; Frick, Karyn M.

    2012-01-01

    Although much recent work has elucidated the biochemical mechanisms underlying the modulation of memory by 17β-estradiol, little is known about the signaling events through which progesterone (P) regulates memory. We recently demonstrated that immediate post-training infusion of P into the dorsal hippocampus enhances object recognition memory consolidation in young ovariectomized female mice (Orr et al., 2009). The goal of the present study was to identify the biochemical alterations that might underlie this mnemonic enhancement. We hypothesized that the P-induced enhancement of object recognition would be dependent on activation of the ERK and mTOR pathways. In young ovariectomized mice, we found that bilateral dorsal hippocampal infusion of P significantly increased levels of phospho-p42 ERK and the mTOR substrate S6K in the dorsal hippocampus 5 minutes after infusion. Phospho-p42 ERK levels were downregulated 15 minutes after infusion and returned to baseline 30 minutes after infusion, suggesting a biphasic effect of P on ERK activation. Dorsal hippocampal ERK and mTOR activation were necessary for P to facilitate memory consolidation, as suggested by the fact that inhibitors of both pathways infused into the dorsal hippocampus immediately after training blocked the P-induced enhancement of object recognition. Collectively, these data provide the first demonstration that the ability of P to enhance memory consolidation depends on the rapid activation of cell signaling and protein synthesis pathways in the dorsal hippocampus. PMID:22265866

  20. Virus-induced down-regulation of GmERA1A and GmERA1B genes enhances the stomatal response to abscisic acid and drought resistance in soybean.

    Directory of Open Access Journals (Sweden)

    Takuya Ogata

    Full Text Available Drought is a major threat to global soybean production. The limited transformation potential and polyploid nature of soybean have hindered functional analysis of soybean genes. Previous research has implicated farnesylation in the plant's response to abscisic acid (ABA and drought tolerance. We therefore used virus-induced gene silencing (VIGS to evaluate farnesyltransferase genes, GmERA1A and GmERA1B (Glycine max Enhanced Response to ABA1-A and -B, as potential targets for increasing drought resistance in soybean. Apple latent spherical virus (ALSV-mediated GmERA1-down-regulated soybean leaves displayed an enhanced stomatal response to ABA and reduced water loss and wilting under dehydration conditions, suggesting that GmERA1A and GmERA1B negatively regulate ABA signaling in soybean guard cells. The findings provide evidence that the ALSV-VIGS system, which bypasses the need to generate transgenic plants, is a useful tool for analyzing gene function using only a single down-regulated leaf. Thus, the ALSV-VIGS system could constitute part of a next-generation molecular breeding pipeline to accelerate drought resistance breeding in soybean.

  1. Evolution of microRNA diversity and regulation in animals

    NARCIS (Netherlands)

    Berezikov, E.

    2011-01-01

    In the past decade, microRNAs (miRNAs) have been uncovered as key regulators of gene expression at the post-transcriptional level. The ancient origin of miRNAs, their dramatic expansion in bilaterian animals and their function in providing robustness to transcriptional programmes suggest that miRNAs

  2. Functional Variants at the 11q13 Risk Locus for Breast Cancer Regulate Cyclin D1 Expression through Long-Range Enhancers

    Science.gov (United States)

    French, Juliet D.; Ghoussaini, Maya; Edwards, Stacey L.; Meyer, Kerstin B.; Michailidou, Kyriaki; Ahmed, Shahana; Khan, Sofia; Maranian, Mel J.; O’Reilly, Martin; Hillman, Kristine M.; Betts, Joshua A.; Carroll, Thomas; Bailey, Peter J.; Dicks, Ed; Beesley, Jonathan; Tyrer, Jonathan; Maia, Ana-Teresa; Beck, Andrew; Knoblauch, Nicholas W.; Chen, Constance; Kraft, Peter; Barnes, Daniel; González-Neira, Anna; Alonso, M. Rosario; Herrero, Daniel; Tessier, Daniel C.; Vincent, Daniel; Bacot, Francois; Luccarini, Craig; Baynes, Caroline; Conroy, Don; Dennis, Joe; Bolla, Manjeet K.; Wang, Qin; Hopper, John L.; Southey, Melissa C.; Schmidt, Marjanka K.; Broeks, Annegien; Verhoef, Senno; Cornelissen, Sten; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Fasching, Peter A.; Loehberg, Christian R.; Ekici, Arif B.; Beckmann, Matthias W.; Peto, Julian; dos Santos Silva, Isabel; Johnson, Nichola; Aitken, Zoe; Sawyer, Elinor J.; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Marme, Frederik; Schneeweiss, Andreas; Sohn, Christof; Burwinkel, Barbara; Guénel, Pascal; Truong, Thérèse; Laurent-Puig, Pierre; Menegaux, Florence; Bojesen, Stig E.; Nordestgaard, Børge G.; Nielsen, Sune F.; Flyger, Henrik; Milne, Roger L.; Zamora, M. Pilar; Arias Perez, Jose Ignacio; Benitez, Javier; Anton-Culver, Hoda; Brenner, Hermann; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Meindl, Alfons; Lichtner, Peter; Schmutzler, Rita K.; Engel, Christoph; Brauch, Hiltrud; Hamann, Ute; Justenhoven, Christina; Aaltonen, Kirsimari; Heikkilä, Päivi; Aittomäki, Kristiina; Blomqvist, Carl; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Sueta, Aiko; Bogdanova, Natalia V.; Antonenkova, Natalia N.; Dörk, Thilo; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Wu, Anna H.; Tseng, Chiu-chen; Van Den Berg, David; Stram, Daniel O.; Lambrechts, Diether; Peeters, Stephanie; Smeets, Ann; Floris, Giuseppe; Chang-Claude, Jenny; Rudolph, Anja; Nickels, Stefan; Flesch-Janys, Dieter; Radice, Paolo; Peterlongo, Paolo; Bonanni, Bernardo; Sardella, Domenico; Couch, Fergus J.; Wang, Xianshu; Pankratz, Vernon S.; Lee, Adam; Giles, Graham G.; Severi, Gianluca; Baglietto, Laura; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Le Marchand, Loic; Simard, Jacques; Goldberg, Mark S.; Labrèche, France; Dumont, Martine; Teo, Soo Hwang; Yip, Cheng Har; Ng, Char-Hong; Vithana, Eranga Nishanthie; Kristensen, Vessela; Zheng, Wei; Deming-Halverson, Sandra; Shrubsole, Martha; Long, Jirong; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Mulligan, Anna Marie; Devilee, Peter; Seynaeve, Caroline; García-Closas, Montserrat; Figueroa, Jonine; Chanock, Stephen J.; Lissowska, Jolanta; Czene, Kamila; Klevebring, Daniel; Schoof, Nils; Hooning, Maartje J.; Martens, John W.M.; Collée, J. Margriet; Tilanus-Linthorst, Madeleine; Hall, Per; Li, Jingmei; Liu, Jianjun; Humphreys, Keith; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Cox, Angela; Balasubramanian, Sabapathy P.; Blot, William; Signorello, Lisa B.; Cai, Qiuyin; Pharoah, Paul D.P.; Healey, Catherine S.; Shah, Mitul; Pooley, Karen A.; Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young; Hartman, Mikael; Miao, Hui; Sng, Jen-Hwei; Sim, Xueling; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Sangrajrang, Suleeporn; Gaborieau, Valerie; McKay, James; Toland, Amanda E.; Ambrosone, Christine B.; Yannoukakos, Drakoulis; Godwin, Andrew K.; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Chen, Shou-Tung; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Schoemaker, Minouk J.; Ponder, Bruce A.J.; Nevanlinna, Heli; Brown, Melissa A.; Chenevix-Trench, Georgia; Easton, Douglas F.; Dunning, Alison M.

    2013-01-01

    Analysis of 4,405 variants in 89,050 European subjects from 41 case-control studies identified three independent association signals for estrogen-receptor-positive tumors at 11q13. The strongest signal maps to a transcriptional enhancer element in which the G allele of the best candidate causative variant rs554219 increases risk of breast cancer, reduces both binding of ELK4 transcription factor and luciferase activity in reporter assays, and may be associated with low cyclin D1 protein levels in tumors. Another candidate variant, rs78540526, lies in the same enhancer element. Risk association signal 2, rs75915166, creates a GATA3 binding site within a silencer element. Chromatin conformation studies demonstrate that these enhancer and silencer elements interact with each other and with their likely target gene, CCND1. PMID:23540573

  3. MAP Kinase Cascades Regulate the Cold Response by Modulating ICE1 Protein Stability.

    Science.gov (United States)

    Zhao, Chunzhao; Wang, Pengcheng; Si, Tong; Hsu, Chuan-Chih; Wang, Lu; Zayed, Omar; Yu, Zheping; Zhu, Yingfang; Dong, Juan; Tao, W Andy; Zhu, Jian-Kang

    2017-12-04

    Mitogen-activated protein kinase cascades are important signaling modules that convert environmental stimuli into cellular responses. We show that MPK3, MPK4, and MPK6 are rapidly activated after cold treatment. The mpk3 and mpk6 mutants display increased expression of CBF genes and enhanced freezing tolerance, whereas constitutive activation of the MKK4/5-MPK3/6 cascade in plants causes reduced expression of CBF genes and hypersensitivity to freezing, suggesting that the MKK4/5-MPK3/6 cascade negatively regulates the cold response. MPK3 and MPK6 can phosphorylate ICE1, a basic-helix-loop-helix transcription factor that regulates the expression of CBF genes, and the phosphorylation promotes the degradation of ICE1. Interestingly, the MEKK1-MKK2-MPK4 pathway constitutively suppresses MPK3 and MPK6 activities and has a positive role in the cold response. Furthermore, the MAPKKK YDA and two calcium/calmodulin-regulated receptor-like kinases, CRLK1 and CRLK2, negatively modulate the cold activation of MPK3/6. Our results uncover important roles of MAPK cascades in the regulation of plant cold response. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. AtPDS over-expression in tomato: exposing unique patterns of carotenoid self-regulation and an alternative strategy for the enhancement of fruit carotenoid content

    Science.gov (United States)

    The regulation of plant carotenogenesis is an active research area for both biological discovery and practical implementation. In tomato, we demonstrate additional bottlenecks exist in the poly-cis-transformation of phytoene to lycopene in the context of ripening-induced PSY1 expression and activity...

  5. The Effect of Flipped Classroom Strategy Using Blackboard Mash-Up Tools in Enhancing Achievement and Self-Regulated Learning Skills of University Students

    Science.gov (United States)

    El-Senousy, Hala; Alquda, Jumana

    2017-01-01

    The flipped classroom strategy (FCRS) is an innovative instructional approach that flips the traditional teacher-centered classroom into student-centered learning, by switching the classroom and home activities using the available educational technology. This paper examined the effect of (FCRS) on students' achievement and self-regulated learning…

  6. Eucalyptus globulus extract protects against UVB-induced photoaging by enhancing collagen synthesis via regulation of TGF-β/Smad signals and attenuation of AP-1.

    Science.gov (United States)

    Park, Bom; Hwang, Eunson; Seo, Seul A; Cho, Jin-Gyeong; Yang, Jung-Eun; Yi, Tae-Hoo

    2018-01-01

    UV irradiation triggers the overproduction of matrix metalloproteinases and collagen degradation, which in turn causes increased pigmentation, dryness, and deep wrinkling of the skin. These chronic symptoms are collectively referred to as photoaging. Eucalyptus globulus is an evergreen tree that is widely used in cosmetics because of its antimicrobial activity. In this study, we investigated the protective effect of 50% ethanol extracts of Eucalyptus globulus on UV-induced photoaging in vitro and in vivo. Normal human dermal fibroblasts were treated with Eucalyptus globulus at concentrations ranging from 1 to 100 μg/mL after UVB or non-UVB irradiation. We found that Eucalyptus globulus suppressed the expression of MMPs and IL-6, but increased the expression of TGF-β1 and procollagen type 1. In addition, Eucalyptus globulus inhibited activation of the AP-1 transcription factor, an inducer of MMPs. Eucalyptus globulus was also found to regulate TGF-β/Smad signaling by reversing the activity of negative Smad regulators. Lastly, in vivo studies showed that topical application of Eucalyptus globulus on UVB-irradiated hairless mice reduced wrinkle formation and dryness by down-regulating MMP-1 and up-regulating expression of elastin, TGF-β1, and procollagen type 1. Taken together, these data suggest that Eucalyptus globulus may be a useful agent in cosmetic products. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. The Use of Gestural Modes to Enhance Expressive Conducting at All Levels of Entering Behavior through the Use of Illustrators, Affect Displays and Regulators

    Science.gov (United States)

    Mathers, Andrew

    2009-01-01

    In this article, I discuss the use of illustrators, affect displays and regulators, which I consider to be non-verbal communication categories through which conductors can employ a more varied approach to body use, gesture and non-verbal communication. These categories employ the use of a conductor's hands and arms, face, eyes and body in a way…

  8. Functional variants at the 11q13 risk locus for breast cancer regulate cyclin D1 expression through long-range enhancers

    DEFF Research Database (Denmark)

    French, Juliet D; Ghoussaini, Maya; Edwards, Stacey L

    2013-01-01

    Analysis of 4,405 variants in 89,050 European subjects from 41 case-control studies identified three independent association signals for estrogen-receptor-positive tumors at 11q13. The strongest signal maps to a transcriptional enhancer element in which the G allele of the best candidate causativ...

  9. Exploring the relationship between online buyers and sellers of image and performance enhancing drugs (IPEDs): Quality issues, trust and self-regulation

    NARCIS (Netherlands)

    van de Ven, K.; Koenraadt, R.M.

    2017-01-01

    Background Online drug markets are expanding the boundaries of drug supply including the sale and purchase of image and performance enhancing drugs (IPEDs). However, the role of the internet in IPED markets, and in particular the ways in which these substances are supplied via the surface web, has

  10. Regulation of tumour related genes by dynamic epigenetic alteration at enhancer regions in gastric epithelial cells infected by Epstein-Barr virus.

    Science.gov (United States)

    Okabe, Atsushi; Funata, Sayaka; Matsusaka, Keisuke; Namba, Hiroe; Fukuyo, Masaki; Rahmutulla, Bahityar; Oshima, Motohiko; Iwama, Atsushi; Fukayama, Masashi; Kaneda, Atsushi

    2017-08-11

    Epstein-Barr virus (EBV) infection is associated with tumours such as Burkitt lymphoma, nasopharyngeal carcinoma, and gastric cancer. We previously showed that EBV(+) gastric cancer presents an extremely high-methylation epigenotype and this aberrant DNA methylation causes silencing of multiple tumour suppressor genes. However, the mechanisms that drive EBV infection-mediated tumorigenesis, including other epigenomic alteration, remain unclear. We analysed epigenetic alterations induced by EBV infection especially at enhancer regions, to elucidate their contribution to tumorigenesis. We performed ChIP sequencing on H3K4me3, H3K4me1, H3K27ac, H3K27me3, and H3K9me3 in gastric epithelial cells infected or not with EBV. We showed that repressive marks were redistributed after EBV infection, resulting in aberrant enhancer activation and repression. Enhancer dysfunction led to the activation of pathways related to cancer hallmarks (e.g., resisting cell death, disrupting cellular energetics, inducing invasion, evading growth suppressors, sustaining proliferative signalling, angiogenesis, and tumour-promoting inflammation) and inactivation of tumour suppressive pathways. Deregulation of cancer-related genes in EBV-infected gastric epithelial cells was also observed in clinical EBV(+) gastric cancer specimens. Our analysis showed that epigenetic alteration associated with EBV-infection may contribute to tumorigenesis through enhancer activation and repression.

  11. Nicotine shifts the temporal activation of hippocampal protein kinase A and extracellular signal-regulated kinase 1/2 to enhance long-term, but not short-term, hippocampus-dependent memory.

    Science.gov (United States)

    Gould, Thomas J; Wilkinson, Derek S; Yildirim, Emre; Poole, Rachel L F; Leach, Prescott T; Simmons, Steven J

    2014-03-01

    Acute nicotine enhances hippocampus-dependent learning through nicotine binding to β2-containing nicotinic acetylcholine receptors (nAChRs), but it is unclear if nicotine is targeting processes involved in short-term memory (STM) leading to a strong long-term memory (LTM) or directly targeting LTM. In addition, the molecular mechanisms involved in the effects of nicotine on learning are unknown. Previous research indicates that protein kinase A (PKA), extracellular signal-regulated kinase 1/2 (ERK1/2), and protein synthesis are crucial for LTM. Therefore, the present study examined the effects of nicotine on STM and LTM and the involvement of PKA, ERK1/2, and protein synthesis in the nicotine-induced enhancement of hippocampus-dependent contextual learning in C57BL/6J mice. The protein synthesis inhibitor anisomycin impaired contextual conditioning assessed at 4 h but not 2 h post-training, delineating time points for STM (2 h) and LTM (4 h and beyond). Nicotine enhanced contextual conditioning at 4, 8, and 24 h but not 2 h post-training, indicating nicotine specifically enhances LTM but not STM. Furthermore, nicotine did not rescue deficits in contextual conditioning produced by anisomycin, suggesting that the nicotine enhancement of contextual conditioning occurs through a protein synthesis-dependent mechanism. In addition, inhibition of dorsal hippocampal PKA activity blocked the effect of acute nicotine on learning, and nicotine shifted the timing of learning-related PKA and ERK1/2 activity in the dorsal and ventral hippocampus. Thus, the present results suggest that nicotine specifically enhances LTM through altering the timing of PKA and ERK1/2 signaling in the hippocampus, and suggests that the timing of PKA and ERK1/2 activity could contribute to the strength of memories. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. The invisible Web uncovering information sources search engines can't see

    CERN Document Server

    Sherman, Chris

    2001-01-01

    Enormous expanses of the Internet are unreachable with standard web search engines. This book provides the key to finding these hidden resources by identifying how to uncover and use invisible web resources. Mapping the invisible Web, when and how to use it, assessing the validity of the information, and the future of Web searching are topics covered in detail. Only 16 percent of Net-based information can be located using a general search engine. The other 84 percent is what is referred to as the invisible Web-made up of information stored in databases. Unlike pages on the visible Web, informa

  13. Networking for proteins : A yeast two-hybrid and RNAi profiling approach to uncover C. elegans cell polarity regulators

    NARCIS (Netherlands)

    Koorman, T.|info:eu-repo/dai/nl/337456038

    2016-01-01

    Cell polarity is a near universal trait of life and guides many aspects of animal development. Although a number of key polarity proteins have been identified, many interactions with proteins acting downstream likely remain to be elucidated. Mutations in polarity proteins or deregulation of polarity

  14. Biochemical quantitation of the eIF5A hypusination in Arabidopsis thaliana uncovers ABA-dependent regulation

    Science.gov (United States)

    Belda-Palazón, Borja; Nohales, María A.; Rambla, José L.; Aceña, José L.; Delgado, Oscar; Fustero, Santos; Martínez, M. Carmen; Granell, Antonio; Carbonell, Juan; Ferrando, Alejandro

    2014-01-01

    The eukaryotic translation elongation factor eIF5A is the only protein known to contain the unusual amino acid hypusine which is essential for its biological activity. This post-translational modification is achieved by the sequential action of the enzymes deoxyhypusine synthase (DHS) and deoxyhypusine hydroxylase (DOHH). The crucial molecular function of eIF5A during translation has been recently elucidated in yeast and it is expected to be fully conserved in every eukaryotic cell, however the functional description of this pathway in plants is still sparse. The genetic approaches with transgenic plants for either eIF5A overexpression or antisense have revealed some activities related to the control of cell death processes but the molecular details remain to be characterized. One important aspect of fully understanding this pathway is the biochemical description of the hypusine modification system. Here we have used recombinant eIF5A proteins either modified by hypusination or non-modified to establish a bi-dimensional electrophoresis (2D-E) profile for the three eIF5A protein isoforms and their hypusinated or unmodified proteoforms present in Arabidopsis thaliana. The combined use of the recombinant 2D-E profile together with 2D-E/western blot analysis from whole plant extracts has provided a quantitative approach to measure the hypusination status of eIF5A. We have used this information to demonstrate that treatment with the hormone abscisic acid produces an alteration of the hypusine modification system in Arabidopsis thaliana. Overall this study presents the first biochemical description of the post-translational modification of eIF5A by hypusination which will be functionally relevant for future studies related to the characterization of this pathway in Arabidopsis thaliana. PMID:24904603

  15. Additional file 5: Figure S1. of Uncovering co-expression gene network modules regulating fruit acidity in diverse apples

    OpenAIRE

    Bai, Yang; Dougherty, Laura; Cheng, Lailiang; Zhong, Gan-Yuan; Xu, Kenong

    2015-01-01

    Analysis of modules Black, Brown, Blue and Yellow. (A) Module eigengene values across the 29 samples, including 17 in Ma_ on left and 12 in mama on right. Samples are represented by the combination of a letter (abbreviated cultivar name) and a number (replicate) (see legends in Fig. 1, 4 for keys). (B) Correlation between module membership (MM) and gene significance (GS) for malate. (PPTX 75 kb)

  16. CCAAT/enhancer binding protein beta (C/EBPβ) isoform balance as a regulator of epithelial-mesenchymal transition in mouse mammary epithelial cells

    International Nuclear Information System (INIS)

    Miura, Yuka; Hagiwara, Natsumi; Radisky, Derek C.; Hirai, Yohei

    2014-01-01

    Activation of the epithelial-mesenchymal transition (EMT) program promotes cell invasion and metastasis, and is reversed through mesenchymal-epithelial transition (MET) after formation of distant metastases. Here, we show that an imbalance of gene products encoded by the transcriptional factor C/EBPβ, LAP (liver-enriched activating protein) and LIP (liver-enriched inhibitory protein), can regulate both EMT- and MET-like phenotypic changes in mouse mammary epithelial cells. By using tetracycline repressive LIP expression constructs, we found that SCp2 cells, a clonal epithelial line of COMMA1-D cells, expressed EMT markers, lost the ability to undergo alveolar-like morphogenesis in 3D Matrigel, and acquired properties of benign adenoma cells. Conversely, we found that inducible expression of LAP in SCg6 cells, a clonal fibroblastic line of COMMA1-D cells, began to express epithelial keratins with suppression of proliferation. The overexpression of the C/EBPβ gene products in these COMMA1-D derivatives was suppressed by long-term cultivation on tissue culture plastic, but gene expression was maintained in cells grown on Matrigel or exposed to proteasome inhibitors. Thus, imbalances of C/EBPβ gene products in mouse mammary epithelial cells, which are affected by contact with basement membrane, are defined as a potential regulator of metastatic potential. - Highlights: • We created a temporal imbalance of C/EBPβ gene products in the mammary model cells. • The temporal up-regulation of LIP protein induced EMT-like cell behaviors. • The temporal up-regulation of LAP protein induced MET-like cell behaviors. • Excess amount of C/EBPβ gene products were eliminated by proteasomal-degradation. • Basement membrane components attenuated proteasome-triggered protein elimination

  17. Metformin Causes G1-Phase Arrest via Down-Regulation of MiR-221 and Enhances TRAIL Sensitivity through DR5 Up-Regulation in Pancreatic Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Ryoichi Tanaka

    Full Text Available Although many chemotherapeutic strategies against cancer have been developed, pancreatic cancer is one of the most aggressive and intractable types of malignancies. Therefore, new strategies and anti-cancer agents are necessary to treat this disease. Metformin is a widely used drug for type-2 diabetes, and is also known as a promising candidate anti-cancer agent from recent studies in vitro and in vivo. However, the mechanisms of metformin's anti-cancer effects have not been elucidated. We demonstrated that metformin suppressed the expression of miR-221, one of the most well-known oncogenic microRNAs, in human pancreatic cancer PANC-1 cells. Moreover, we showed that the down-regulation of miR-221 by metformin caused G1-phase arrest via the up-regulation of p27, one of the direct targets of miR-221. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL is also a promising agent for cancer treatment. While recent studies showed that treatment with only TRAIL was not effective against pancreatic cancer cells, the present data showed that metformin sensitized p53-mutated pancreatic cancer cells to TRAIL. Metformin induced the expressions of death receptor 5 (DR5, a receptor for TRAIL, and Bim with a pro-apoptotic function in the downstream of TRAIL-DR5 pathway. We suggest that the up-regulation of these proteins may contribute to sensitization of TRAIL-induced apoptosis. The combination therapy of metformin and TRAIL could therefore be effective in the treatment of pancreatic cancer.

  18. Investing in the Early Childhood Mental Health Workforce Development: Enhancing Professionals' Competencies to Support Emotion and Behavior Regulation in Young Children.

    Science.gov (United States)

    Ritblatt, Shulamit N; Hokoda, Audrey; Van Liew, Charles

    2017-09-19

    This paper delineates a preventive approach to early childhood mental health by preparing the workforce to provide relational, sensitive care to young children ages 0-5. One of the most prevalent issues in early childhood is behavioral challenges and the inability of young children to regulate themselves. This leads to an expulsion rate in early childhood (3-4 times higher than K-12 expulsion rate) and future mental health issues. The Early Childhood Social-Emotional and Behavior Regulation Intervention Specialist (EC-SEBRIS) graduate level certificate program was created to strengthen early care and education providers with the knowledge and practice of how to support emotion and behavior regulation in young children in their groups. Evaluation data provide evidence that early care and education professionals increased in their perception of self-efficacy and in their sensitivity of care and skills to support behavioral health in young children. Results indicated that the children in their care showed less challenging behaviors and increased social competencies. This manuscript highlights the importance of prevention and the dire need to provide young children with high-quality, appropriate care to support their mental health.

  19. CCAAT/Enhancer-Binding Protein α Is a Crucial Regulator of Human Fat Mass and Obesity Associated Gene Transcription and Expression

    Directory of Open Access Journals (Sweden)

    Wei Ren

    2014-01-01

    Full Text Available Several susceptibility loci have been reported associated with obesity and T2DM in GWAS. Fat mass and obesity associated gene (FTO is the first gene associated with body mass index (BMI and risk for diabetes in diverse patient populations. FTO is highly expressed in the brain and pancreas, and is involved in regulating dietary intake and energy expenditure. While much is known about the epigenetic mutations contributing to obesity and T2DM, less is certain with the expression regulation of FTO gene. In this study, a highly conserved canonical C/EBPα binding site was located around position −45~−54 bp relative to the human FTO gene transcriptional start site. Site-directed mutagenesis of the putative C/EBPα binding sites decreased FTO promoter activity. Overexpression and RNAi studies also indicated that C/EBPα was required for the expression of FTO. Chromatin immunoprecipitation (ChIP experiment was carried out and the result shows direct binding of C/EBPα to the putative binding regions in the FTO promoter. Collectively, our data suggest that C/EBPα may act as a positive regulator binding to FTO promoter and consequently, activates the gene transcription.

  20. Uncovering New Thermal and Elastic Properties of Nanostructured Materials Using Coherent EUV Light

    Science.gov (United States)

    Hernandez Charpak, Jorge Nicolas

    directly probe the dynamics of phonons in complex materials, which is critical to both technological applications and fundamental condensed matter physics. I developed a proof of concept model and used it to extract the first experimental differential conductivity phonon mean free path (MFP) spectra for silicon and sapphire, which compare well with first-principles calculations. However, a complete picture of the physics is still elusive. Thus, I developed a computational solver for the phonon Boltzmann transport equation in realistic experimental geometries. Using this approach, I successfully found confirmation of the influence of the period in thermal transport from periodic heat sources: a smaller periodicity can enhance the heat dissipation efficiency. This result is qualitatively consistent with the results of the "collectively-diffusive regime", but more work is needed for a full theoretical quantitative picture of the experimental results. In other work, I used coherent EUV nanometrology to simultaneously measure, in a non-contact and non-destructive way, Young's modulus and, for the first time, Poisson's ratio of ultra-thin films. I successfully extracted the full elastic tensor of the thinnest films to date (10.9nm). Moreover, by using our technique on a series of low-k dielectric sub-100 nm SiC:H films, I uncovered an unexpected transition from compressible to non-compressible behavior. This new behavior is observed for materials whose network connectivity had been modified through hydrogenation (that breaks bonds in order to decrease the dielectric constant of these materials). This finding demonstrates that coherent EUV nanometrology provides a valuable, quantitative new tool for measuring nanomaterial properties with dimensions an order of magnitude smaller than what was possible with traditional techniques. I also present here some of my written work on science and technology policy studies. I present my thoughts on the Kuhnian model of scientific

  1. Epidermal growth factor regulation of glutathione S-transferase gene expression in the rat is mediated by class Pi glutathione S-transferase enhancer I.

    OpenAIRE

    Matsumoto, M; Imagawa, M; Aoki, Y

    2000-01-01

    Using chloramphenicol acetyltransferase assays we showed that epidermal growth factor (EGF), transforming growth factor alpha (TGF alpha), and 3,3',4,4',5-pentachlorobiphenyl (PenCB) induce class Pi glutathione S-transferase (GSTP1) in primary cultured rat liver parenchymal cells. GSTP1 enhancer I (GPEI), which is required for the stimulation of GSTP1 expression by PenCB, also mediates EGF and TGF alpha stimulation of GSTP1 gene expression. However, hepatocyte growth factor and insulin did no...

  2. A pilot investigation of the potential for incorporating lifelog technology into executive function rehabilitation for enhanced transfer of self-regulation skills to everyday life

    OpenAIRE

    Cuberos-Urbano, Gustavo; Caracuel, Alfonso; Valls-Serrano, Carlos; Garcia-Mochon, Letitia; Gracey, Fergus; Verdejo-Garcia, Antonio

    2018-01-01

    The objective of the study was to identify the potential target and effect size of goal management training (GMT) enhanced with life-logging technology compared with standard GMT on a range of possible primary outcomes reflecting cognitive and ecological aspects of executive functioning and quality of life. Sixteen patients with acquired brain injury involving executive dysfunction were randomly allocated to one of the two interventions: seven weeks of GMT (n = 8), or seven weeks of GMT+Lifel...

  3. Abscisic Acid Regulation of Root Hydraulic Conductivity and Aquaporin Gene Expression Is Crucial to the Plant Shoot Growth Enhancement Caused by Rhizosphere Humic Acids.

    Science.gov (United States)

    Olaetxea, Maite; Mora, Verónica; Bacaicoa, Eva; Garnica, María; Fuentes, Marta; Casanova, Esther; Zamarreño, Angel M; Iriarte, Juan C; Etayo, David; Ederra, Iñigo; Gonzalo, Ramón; Baigorri, Roberto; García-Mina, Jose M

    2015-12-01

    The physiological and metabolic mechanisms behind the humic acid-mediated plant growth enhancement are discussed in detail. Experiments using cucumber (Cucumis sativus) plants show that the shoot growth enhancement caused by a structurally well-characterized humic acid with sedimentary origin is functionally associated with significant increases in abscisic acid (ABA) root concentration and root hydraulic conductivity. Complementary experiments involving a blocking agent of cell wall pores and water root transport (polyethylenglycol) show that increases in root hydraulic conductivity are essential in the shoot growth-promoting action of the model humic acid. Further experiments involving an inhibitor of ABA biosynthesis in root and shoot (fluridone) show that the humic acid-mediated enhancement of both root hydraulic conductivity and shoot growth depended on ABA signaling pathways. These experiments also show that a significant increase in the gene expression of the main root plasma membrane aquaporins is associated with the increase of root hydraulic conductivity caused by the model humic acid. Finally, experimental data suggest that all of these actions of model humic acid on root functionality, which are linked to its beneficial action on plant shoot growth, are likely related to the conformational structure of humic acid in solution and its interaction with the cell wall at the root surface. © 2015 American Society of Plant Biologists. All Rights Reserved.

  4. Integrative Genetic and Epigenetic Analysis Uncovers Regulatory Mechanisms of Autoimmune Disease.

    Science.gov (United States)

    Shooshtari, Parisa; Huang, Hailiang; Cotsapas, Chris

    2017-07-06

    Genome-wide association studies in autoimmune and inflammatory diseases (AID) have uncovered hundreds of loci mediating risk. These associations are preferentially located in non-coding DNA regions and in particular in tissue-specific DNase I hypersensitivity sites (DHSs). While these analyses clearly demonstrate the overall enrichment of disease risk alleles on gene regulatory regions, they are not designed to identify individual regulatory regions mediating risk or the genes under their control, and thus uncover the specific molecular events driving disease risk. To do so we have departed from standard practice by identifying regulatory regions which replicate across samples and connect them to the genes they control through robust re-analysis of public data. We find significant evidence of regulatory potential in 78/301 (26%) risk loci across nine autoimmune and inflammatory diseases, and we find that individual genes are targeted by these effects in 53/78 (68%) of these. Thus, we are able to generate testable mechanistic hypotheses of the molecular changes that drive disease risk. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  5. Uncovering Sundanese Values by Analyzing Symbolic Meaning of Ménak Priangan Clothing (1800-1942)

    Science.gov (United States)

    Karmila, M.; Suciati; Widiaty, I.

    2016-04-01

    This study investigates symbolic meanings found in the Sunda ethnic clothing, particularly the Menak Priangan clothing. This study aims to uncover and document those symbolic meanings found in the Menak Priangan clothing as an effort to develop Sunda cultural artefacts of West Java. This study on Menak Priangan clothing applies ethnography (visual) and aesthetic methods. The visual method is utilized in order to uncover local cultural (Sunda) values found in Menak Priangan clothing visualization, including: design, model, name, and representing colours, which then directed towards local Sundanese aesthetic concepts living within the Priangan community. Furthermore, aesthetic method is used to explore role of aesthetic values in empowering visual cultural values within certain community, particularly Sunda aesthetic values. The study results show that since the 19th century, Sunda ethnic clothing was limited to Priangan Sunda only, while traditional clothing wearing by Priangan people reflects their social strata, consisting of: a. Menak Gede (Menak pangluhurna: mayor), bearing raden title, b. Menak Leutik/Santana (mayor assistant), titles: asep, mas, agus, ujang, (Nyimas for woman), c. Somah/Cacah: ordinary people/lower class. Clothing is a cultural phenomenon within certain culture reflecting such society experiences. For Menak people, clothing and its accessories have important meanings. They wear such traditional clothing and accessories as a symbol of power they have within bureaucratic structure and as a symbol of social status they bear within traditional community structure.

  6. Dual-specificity phosphatase 6 (Dusp6), a negative regulator of FGF2/ERK1/2 signaling, enhances 17β-estradiol-induced cell growth in endometrial adenocarcinoma cell.

    Science.gov (United States)

    Zhang, Hui; Guo, Qiufen; Wang, Chong; Yan, Lei; Fu, Yibing; Fan, Mingjun; Zhao, Xingbo; Li, Mingjiang

    2013-08-25

    Dual-specificity phosphatase 6 (Dusp6) is a negative feedback mechanism of fibroblast growth factors (FGFs)/mitogen-activated protein kinase (MAPK)/ERK1/2 signaling. The aim of this study was to explore the expression of Dusp6 in human endometrial adenocarcinomas and the role of Dusp6 expression in the growth regulation of endometrial adenocarcinoma cell. We found that Dusp6 was over-expressed in human endometrial adenocarcinomas. In Ishikawa cells, plasmid-driven Dusp6 expression efficiently blocked the activity of FGF2-induced MAPK/ERK1/2 signaling. Unexpectedly, Dusp6 expression significantly enhanced the growth of Ishikawa cells. In Dusp6 forced-expression cells, 17β-estradiol stimulation increased the cell growth by all most threefolds. In addition, progesterone treatment reduced the cell growth to about half both in Ishikawa cells with and without forced-Dusp6-expression. Dusp6 over-expression is involved in the pathogenesis and development of human endometrial adenocarcinomas. Dusp6 functions as a negative regulator of FGF2/ERK1/2 signaling but enhances the growth and 17β-estradiol-induced cell growth in endometrial adenocarcinoma cell. Copyright © 2013. Published by Elsevier Ireland Ltd.

  7. Deep developmental transcriptome sequencing uncovers numerous new genes and enhances gene annotation in the sponge Amphimedon queenslandica.

    Science.gov (United States)

    Fernandez-Valverde, Selene L; Calcino, Andrew D; Degnan, Bernard M

    2015-05-15

    The demosponge Amphimedon queenslandica is amongst the few early-branching metazoans with an assembled and annotated draft genome, making it an important species in the study of the origin and early evolution of animals. Current gene models in this species are largely based on in silico predictions and low coverage expressed sequence tag (EST) evidence. Amphimedon queenslandica protein-coding gene models are improved using deep RNA-Seq data from four developmental stages and CEL-Seq data from 82 developmental samples. Over 86% of previously predicted genes are retained in the new gene models, although 24% have additional exons; there is also a marked increase in the total number of annotated 3' and 5' untranslated regions (UTRs). Importantly, these new developmental transcriptome data reveal numerous previously unannotated protein-coding genes in the Amphimedon genome, increasing the total gene number by 25%, from 30,060 to 40,122. In general, Amphimedon genes have introns that are markedly smaller than those in other animals and most of the alternatively spliced genes in Amphimedon undergo intron-retention; exon-skipping is the least common mode of alternative splicing. Finally, in addition to canonical polyadenylation signal sequences, Amphimedon genes are enriched in a number of unique AT-rich motifs in their 3' UTRs. The inclusion of developmental transcriptome data has substantially improved the structure and composition of protein-coding gene models in Amphimedon queenslandica, providing a more accurate and comprehensive set of genes for functional and comparative studies. These improvements reveal the Amphimedon genome is comprised of a remarkably high number of tightly packed genes. These genes have small introns and there is pervasive intron retention amongst alternatively spliced transcripts. These aspects of the sponge genome are more similar unicellular opisthokont genomes than to other animal genomes.

  8. Pulsed Electromagnetic Field Regulates MicroRNA 21 Expression to Activate TGF-β Signaling in Human Bone Marrow Stromal Cells to Enhance Osteoblast Differentiation

    Directory of Open Access Journals (Sweden)

    Nagarajan Selvamurugan

    2017-01-01

    Full Text Available Pulsed electromagnetic fields (PEMFs have been documented to promote bone fracture healing in nonunions and increase lumbar spinal fusion rates. However, the molecular mechanisms by which PEMF stimulates differentiation of human bone marrow stromal cells (hBMSCs into osteoblasts are not well understood. In this study the PEMF effects on hBMSCs were studied by microarray analysis. PEMF stimulation of hBMSCs’ cell numbers mainly affected genes of cell cycle regulation, cell structure, and growth receptors or kinase pathways. In the differentiation and mineralization stages, PEMF regulated preosteoblast gene expression and notably, the transforming growth factor-beta (TGF-β signaling pathway and microRNA 21 (miR21 were most highly regulated. PEMF stimulated activation of Smad2 and miR21-5p expression in differentiated osteoblasts, and TGF-β signaling was essential for PEMF stimulation of alkaline phosphatase mRNA expression. Smad7, an antagonist of the TGF-β signaling pathway, was found to be miR21-5p’s putative target gene and PEMF caused a decrease in Smad7 expression. Expression of Runx2 was increased by PEMF treatment and the miR21-5p inhibitor prevented the PEMF stimulation of Runx2 expression in differentiating cells. Thus, PEMF could mediate its effects on bone metabolism by activation of the TGF-β signaling pathway and stimulation of expression of miR21-5p in hBMSCs.

  9. Energy and Cost Saving of a Photovoltaic-Phase Change Materials (PV-PCM System through Temperature Regulation and Performance Enhancement of Photovoltaics

    Directory of Open Access Journals (Sweden)

    Ahmad Hasan

    2014-03-01

    Full Text Available The current research seeks to maintain high photovoltaic (PV efficiency and increased operating PV life by maintaining them at a lower temperature. Solid-liquid phase change materials (PCM are integrated into PV panels to absorb excess heat by latent heat absorption mechanism and regulate PV temperature. Electrical and thermal energy efficiency analysis of PV-PCM systems is conducted to evaluate their effectiveness in two different climates. Finally costs incurred due to inclusion of PCM into PV system and the resulting benefits are discussed in this paper. The results show that such systems are financially viable in higher temperature and higher solar radiation environment.

  10. USP22 knockdown enhanced chemosensitivity of hepatocellular carcinoma cells to 5-Fu by up-regulation of Smad4 and suppression of Akt

    OpenAIRE

    Zhang, Jing; Luo, Nan; Tian, Yu; Li, Jiazhi; Yang, Xiaozhou; Yin, Huimin; Xiao, Congshu; Sheng, Jie; Li, Yang; Tang, Bo; Li, Rongkuan

    2017-01-01

    USP22, a member of the deubiquitinases (DUBs) family, is known to be a key subunit of the human Spt-Ada-Gcn5 acetyltransferase (hSAGA) transcriptional cofactor complex. Within hSAGA, USP22 removes ubiquitin from histone proteins, thus regulating the transcription and expression of downstream genes. USP22 plays important roles in many cancers; however, its effect and the mechanism underlying HCC chemoresistance remain unclear. In the present study, we found that USP22 was highly expressed in c...

  11. Suppression of microRNA-629 enhances sensitivity of cervical cancer cells to 1'S-1'-acetoxychavicol acetate via regulating RSU1.

    Science.gov (United States)

    Phuah, Neoh Hun; Azmi, Mohamad Nurul; Awang, Khalijah; Nagoor, Noor Hasima

    2017-01-01

    Cervical cancer is the fourth most frequent malignancy affecting women worldwide, but drug resistance and toxicities remain a major challenge in chemotherapy. The use of natural compounds is promising because they are less toxic and able to target multiple signaling pathways. The 1'S-1'-acetoxychavicol acetate (ACA), a natural compound isolated from wild ginger Alpinia conchigera , induced cytotoxicity on various cancer cells including cervical cancer. MicroRNAs (miRNAs) are short noncoding RNAs that regulate numerous biological processes, such as apoptosis and chemosensitivity. Past studies reported that miR-629 is upregulated in many cancers, and its expression was altered in ACA-treated cervical cancer cells. However, the role of miR-629 in regulating sensitivity toward ACA or other anticancer agents has not been reported. Hence, this study aims to investigate the role of miR-629 in regulating response toward ACA on cervical cancer cells. The miR-629 expression following transfection with miR-629 hairpin inhibitor and hairpin inhibitor negative control was measured using quantitative real-time polymerase chain reaction (RT-qPCR). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to investigate sensitivity toward ACA. Apoptosis was detected using Annexin V/propidium iodide and Caspase 3/7 assays. The gene target for miR-629 was identified using miRNA target prediction programs, luciferase reporter assay and Western blots. Gene overexpression studies were performed to evaluate its role in regulating response toward ACA. Transfection with miR-629 hairpin inhibitor downregulated its expression in both cervical cancer cell lines. Suppression of miR-629 increased sensitivity toward ACA by reducing cell proliferation and inducing apoptosis. Luciferase reporter assay confirmed RSU1 as a direct target of miR-629. Overexpression of miR-629 decreased RSU1 protein expression, while inhibition of miR-629 increased RSU1 protein expression

  12. Phosphorylation of the adaptor protein SH2B1β regulates its ability to enhance growth hormone-dependent macrophage motility

    OpenAIRE

    Su, Hsiao-Wen; Lanning, Nathan J.; Morris, David L.; Argetsinger, Lawrence S.; Lumeng, Carey N.; Carter-Su, Christin

    2013-01-01

    Previous studies have shown that growth hormone (GH) recruits the adapter protein SH2B1β to the GH-activated, GH receptor-associated tyrosine kinase JAK2, implicating SH2B1β in GH-dependent actin cytoskeleton remodeling, and suggesting that phosphorylation at serines 161 and 165 in SH2B1β releases SH2B1β from the plasma membrane. Here, we examined the role of SH2B1β in GH regulation of macrophage migration. We show that GH stimulates migration of cultured RAW264.7 macrophages, and primary cul...

  13. The KNOXI Transcription Factor SHOOT MERISTEMLESS Regulates Floral Fate in Arabidopsis.

    Science.gov (United States)

    Roth, Ohad; Alvarez, John; Levy, Matan; Bowman, John L; Ori, Naomi; Shani, Eilon

    2018-05-09

    Plants have evolved a unique and conserved developmental program that enables the conversion of leaves into floral organs. Elegant genetic and molecular work has identified key regulators of flower meristem identity. However, further understanding of flower meristem specification has been hampered by redundancy and by pleiotropic effects. The KNOXI transcription factor SHOOT MERISTEMLESS (STM) is a well-characterized regulator of shoot apical meristem maintenance. Arabidopsis thaliana stm loss-of-function mutants arrest shortly after germination, and therefore the knowledge on later roles of STM in later processes, including flower development, is limited. Here, we uncover a role for STM in the specification of flower meristem identity. Silencing STM in the APETALA1 (AP1) expression domain in the ap1-4 mutant background resulted in a leafy-flower phenotype, and an intermediate stm-2 allele enhanced the flower meristem identity phenotype of ap1-4. Transcriptional profiling of STM perturbation suggested that STM activity affects multiple floral fate genes, among them the F-Box protein-encoding gene UNUSUAL FLORAL ORGANS (UFO). In agreement with this notion, stm-2 enhanced the ufo-2 floral fate phenotype, and ectopic UFO expression rescued the leafy flowers in genetic backgrounds with compromised AP1 and STM activities. This work suggests a genetic mechanism that underlies the activity of STM in the specification of flower meristem identity. © 2018 American Society of Plant Biologists. All rights reserved.

  14. Regulation of adipocyte 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1 by CCAAT/enhancer-binding protein (C/EBP β isoforms, LIP and LAP.

    Directory of Open Access Journals (Sweden)

    Cristina L Esteves

    Full Text Available 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1 catalyses intracellular regeneration of active glucocorticoids, notably in liver and adipose tissue. 11β-HSD1 is increased selectively in adipose tissue in human obesity, a change implicated in the pathogenesis of metabolic syndrome. With high fat (HF-feeding, adipose tissue 11β-HSD1 is down-regulated in mice, plausibly to counteract metabolic disease. Transcription of 11β-HSD1 is directly regulated by members of the CCAAT/enhancer binding protein (C/EBP family. Here we show that while total C/EBPβ in adipose tissue is unaltered by HF diet, the ratio of the C/EBPβ isoforms liver-enriched inhibitor protein (LIP and liver-enriched activator protein (LAP (C/EBPβ-LIP:LAP is increased in subcutaneous adipose. This may cause changes in 11β-HSD1 expression since genetically modified C/EBPβ((+/L mice, with increased C/EBPβ-LIP:LAP ratio, have decreased subcutaneous adipose 11β-HSD1 mRNA levels, whereas C/EBPβ(ΔuORF mice, with decreased C/EBPβ-LIP:LAP ratio, show increased subcutaneous adipose 11β-HSD1. C/EBPβ-LIP:LAP ratio is regulated by endoplasmic reticulum (ER stress and mTOR signalling, both of which are altered in obesity. In 3T3-L1 adipocytes, 11β-HSD1 mRNA levels were down-regulated following induction of ER stress by tunicamycin but were up-regulated following inhibition of mTOR by rapamycin. These data point to a central role for C/EBPβ and its processing to LIP and LAP in transcriptional regulation of 11β-HSD1 in adipose tissue. Down-regulation of 11β-HSD1 by increased C/EBPβ-LIP:LAP in adipocytes may be part of a nutrient-sensing mechanism counteracting nutritional stress generated by HF diet.

  15. Regulation of Pancreatic β Cell Mass by Cross-Interaction between CCAAT Enhancer Binding Protein β Induced by Endoplasmic Reticulum Stress and AMP-Activated Protein Kinase Activity.

    Directory of Open Access Journals (Sweden)

    Tomokazu Matsuda

    Full Text Available During the development of type 2 diabetes, endoplasmic reticulum (ER stress leads to not only insulin resistance but also to pancreatic beta cell failure. Conversely, cell function under various stressed conditions can be restored by reducing ER stress by activating AMP-activated protein kinase (AMPK. However, the details of this mechanism are still obscure. Therefore, the current study aims to elucidate the role of AMPK activity during ER stress-associated pancreatic beta cell failure. MIN6 cells were loaded with 5-amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide (AICAR and metformin to assess the relationship between AMPK activity and CCAAT enhancer binding protein β (C/EBPβ expression levels. The effect of C/EBPβ phosphorylation on expression levels was also investigated. Vildagliptin and metformin were administered to pancreatic beta cell-specific C/EBPβ transgenic mice to investigate the relationship between C/EBPβ expression levels and AMPK activity in the pancreatic islets. When pancreatic beta cells are exposed to ER stress, the accumulation of the transcription factor C/EBPβ lowers the AMP/ATP ratio, thereby decreasing AMPK activity. In an opposite manner, incubation of MIN6 cells with AICAR or metformin activated AMPK, which suppressed C/EBPβ expression. In addition, administration of the dipeptidyl peptidase-4 inhibitor vildagliptin and metformin to pancreatic beta cell-specific C/EBPβ transgenic mice decreased C/EBPβ expression levels and enhanced pancreatic beta cell mass in proportion to the recovery of AMPK activity. Enhanced C/EBPβ expression and decreased AMPK activity act synergistically to induce ER stress-associated pancreatic beta cell failure.

  16. USP22 knockdown enhanced chemosensitivity of hepatocellular carcinoma cells to 5-Fu by up-regulation of Smad4 and suppression of Akt.

    Science.gov (United States)

    Zhang, Jing; Luo, Nan; Tian, Yu; Li, Jiazhi; Yang, Xiaozhou; Yin, Huimin; Xiao, Congshu; Sheng, Jie; Li, Yang; Tang, Bo; Li, Rongkuan

    2017-04-11

    USP22, a member of the deubiquitinases (DUBs) family, is known to be a key subunit of the human Spt-Ada-Gcn5 acetyltransferase (hSAGA) transcriptional cofactor complex. Within hSAGA, USP22 removes ubiquitin from histone proteins, thus regulating the transcription and expression of downstream genes. USP22 plays important roles in many cancers; however, its effect and the mechanism underlying HCC chemoresistance remain unclear. In the present study, we found that USP22 was highly expressed in chemoresistant HCC tissues and cells and was correlated with the prognosis of HCC patients who received chemotherapy. Silencing USP22 in chemoresistant HCC Bel/Fu cells dramatically inhibited proliferation, migration, invasion and epithelial-mesenchymal transition in vitro; suppressed tumorigenic and metastatic capacities in vivo; and inhibited drug resistance-related proteins (MDR1, LRP, MRP1). Mechanistically, we found that USP22 knockdown exerts its function through down-regulating PI3K and activating Smad4, which inhibited phosphorylation of Akt. Silencing Smad4 blocked USP22 knockdown-induced Akt inhibition in Bel/Fu cells. Our results, for the first time, provide evidence that USP22 plays a critical role in the development of chemoresistant HCC cells and that high USP22 expression serves as a molecular marker for the prognosis of HCC patients who undergo chemotherapy.

  17. Fisetin Enhances the Cytotoxicity of Gemcitabine by Down-regulating ERK-MYC in MiaPaca-2 Human Pancreatic Cancer Cells.

    Science.gov (United States)

    Kim, Nayoung; Kang, Min-Jung; Lee, Sang Hyub; Son, Jun Hyuk; Lee, Ji Eun; Paik, Woo Hyun; Ryu, Ji Kon; Kim, Yong-Tae

    2018-06-01

    Pancreatic cancer is a highly lethal malignancy with a poor prognosis. This study was set up to investigate the combined effect of gemcitabine and fisetin, a natural flavonoid from plants, on human pancreatic cancer cells. Meterials and Methods: Cytotoxic effect of fisetin in combination with gemcitabine on MiaPaca-2 cells was evaluated by the MTT assay, caspase 3/7 assay and propidium iodide/Annexin V. Extracellular signal-regulated kinase (ERK)-v-myc avian myelocytomatosis viral oncogene homolog (MYC) pathway was investigated by western blotting and quantitative real-time polymerase chain reaction. Combination treatment with fisetin and gemcitabine inhibited the proliferation of pancreatic cancer cells within 72 h and induced apoptosis, as indicated by activation of caspase 3/7. Fisetin down-regulated ERK at the protein and mRNA levels, and reduced ERK-induced MYC instability at the protein level. Fisetin sensitized human pancreatic cancer cells to gemcitabine-induced cytotoxicity through inhibition of ERK-MYC signaling. These results suggest that the combination of fisetin and gemcitabine could be developed as a novel potent therapeutic. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  18. Dopamine D1 receptors and phosphorylation of dopamine- and cyclic AMP-regulated phosphoprotein-32 in the medial preoptic area are involved in experience-induced enhancement of male sexual behavior in rats.

    Science.gov (United States)

    McHenry, Jenna A; Bell, Genevieve A; Parrish, Bradley P; Hull, Elaine M

    2012-08-01

    The medial preoptic area (MPOA) is an integral site for male sexual behavior. Dopamine is released in the MPOA before and during copulation and facilitates male rat sexual behavior. Repeated sexual experience and noncopulatory exposures to an estrous female facilitate subsequent copulation. However, the neurobiological mechanisms that mediate such enhancement remain unclear. Here, we examined the role of dopamine D₁ receptors in the MPOA in experience-induced enhancement of male sexual behavior in rats. In experiment 1, microinjections of the D₁ antagonist SCH-23390 into the MPOA before each of seven daily 30-min noncopulatory exposures to a receptive female impaired copulation on a drug-free test on Day 8, compared to vehicle-treated female-exposed animals. Copulatory performance in drug-treated animals was similar to that of vehicle-treated males that had not been preexposed to females. This effect was site specific. There were no group differences in locomotor activity in an open field on the copulation test day. In experiment 2, a separate cohort of animals was used to examine phosphorylation of dopamine- and cAMP-regulated phosphoprotein (DARPP-32) in the MPOA of animals with acute and/or chronic sexual experience. DARPP-32 is a downstream marker of D₁ receptor signaling and substrate of cAMP-dependent protein kinase (PKA). Western immunoblot analysis revealed that p-DARPP-32 expression was greatest in the MPOA of males that received both acute and chronic sexual experience, compared to all other mated conditions and naïve controls. These data suggest that D₁ receptors in the MPOA contribute to experience-induced enhancement of male sexual behavior, perhaps through a PKA regulated mechanism.

  19. Wedelolactone enhances osteoblastogenesis by regulating Wnt/β-catenin signaling pathway but suppresses osteoclastogenesis by NF-κB/c-fos/NFATc1 pathway.

    Science.gov (United States)

    Liu, Yan-Qiu; Hong, Zhi-Lai; Zhan, Li-Bin; Chu, Hui-Ying; Zhang, Xiao-Zhe; Li, Guo-Hui

    2016-08-25

    Bone homeostasis is maintained by formation and destruction of bone, which are two processes tightly coupled and controlled. Targeting both stimulation on bone formation and suppression on bone resorption becomes a promising strategy for treating osteoporosis. In this study, we examined the effect of wedelolactone, a natural product from Ecliptae herba, on osteoblastogenesis as well as osteoclastogenesis. In mouse bone marrow mesenchymal stem cells (BMSC), wedelolactone stimulated osteoblast differentiation and bone mineralization. At the molecular level, wedelolactone directly inhibited GSK3β activity and enhanced the phosphorylation of GSK3β, thereafter stimulated the nuclear translocation of β-catenin and runx2. The expression of osteoblastogenesis-related marker gene including osteorix, osteocalcin and runx2 increased. At the same concentration range, wedelolactone inhibited RANKL-induced preosteoclastic RAW264.7 actin-ring formation and bone resorption pits. Further, wedelolactone blocked NF-kB/p65 phosphorylation and abrogated the NFATc1 nuclear translocation. As a result, osteoclastogenesis-related marker gene expression decreased, including c-src, c-fos, and cathepsin K. In ovariectomized mice, administration of wedelolactone prevented ovariectomy-induced bone loss by enhancing osteoblast activity and inhibiting osteoclast activity. Together, these data demonstrated that wedelolactone facilitated osteoblastogenesis through Wnt/GSK3β/β-catenin signaling pathway and suppressed RANKL-induced osteoclastogenesis through NF-κB/c-fos/NFATc1 pathway. These results suggested that wedelolacone could be a novel dual functional therapeutic agent for osteoporosis.

  20. CbRCI35, a cold responsive peroxidase from Capsella bursa-pastoris regulates reactive oxygen species homeostasis and enhances cold tolerance in tobacco

    Directory of Open Access Journals (Sweden)

    Juan Lin

    2016-10-01

    Full Text Available Low temperature affects gene regulatory networks and alters cellular metabolism to inhibit plant growth. Peroxidases are widely distributed in plants and play a large role in adjusting and controlling reactive oxygen species (ROS homeostasis in response to abiotic stresses such as low temperature. The Rare Cold-Inducible 35 gene from Capsella bursa-pastoris (CbRCI35 belongs to the type III peroxidase family and has been reported to be a cold responsive gene in plants. Here we performed an expressional characterization of CbRCI35 under cold and ionic liquid treatments. The promoter of CbRCI35 was also cloned and its activity was examined using the GUS reporter system. CbRCI35 protein was localized in the cytoplasm according to sequence prediction and GFP fusion assay. Heterologous expression tests revealed that CbRCI35 conferred enhanced resistance to low temperature and activated endogenous cold responsive signaling in tobacco. Furthermore, in the normal condition the ROS accumulation was moderately enhanced while after chilling exposure superoxide dismutase (SOD activity was increased in CbRCI53 transgenic plants. The ROS metabolism related genes expression was altered accordingly. We conclude that CbRCI35 modulates ROS homeostasis and contributes to cold tolerance in plants.

  1. The effect of excess expression of GFP in a novel heart-specific green fluorescence zebrafish regulated by nppa enhancer at early embryonic development.

    Science.gov (United States)

    Huang, Wen; Deng, Yun; Dong, Wei; Yuan, Wuzhou; Wan, Yongqi; Mo, Xiaoyan; Li, Yongqing; Wang, Zequn; Wang, Yuequn; Ocorr, Karen; Zhang, Bo; Lin, Shuo; Wu, Xiushan

    2011-02-01

    In order to study the impalpable effect of GFP in homozygous heart-specific GFP-positive zebrafish during the early stage, the researchers analyzed the heart function of morphology and physiology at the first 3 days after fertilization. This zebrafish line was produced by a large-scale Tol2 transposon mediated enhancer trap screen that generated a transgenic zebrafish with a heart-specific expression of green fluorescent protein (GFP)-tagged under control of the nppa enhancer. In situ hybridization experiments showed that the nppa:GFP line faithfully recapitulated both the spatial and temporal expressions of the endogenous nppa. Green fluorescence was intensively and specifically expressed in the myocardial cells located both in the heart chambers and in the atrioventricular canal. The embryonic heart of nppa:GFP line developed normally compared with those in the wild type. There was no difference between the nappa:GFP and wild type lines with respect to heart rate, overall size, ejection volume, and fractional shortening. Thus the excess expression of GFP in this transgenic line seemed to exert no detrimental effects on zebrafish hearts during the early stages.

  2. Lysine Deacetylases and Regulated Glycolysis in Macrophages.

    Science.gov (United States)

    Shakespear, Melanie R; Iyer, Abishek; Cheng, Catherine Youting; Das Gupta, Kaustav; Singhal, Amit; Fairlie, David P; Sweet, Matthew J

    2018-06-01

    Regulated cellular metabolism has emerged as a fundamental process controlling macrophage functions, but there is still much to uncover about the precise signaling mechanisms involved. Lysine acetylation regulates the activity, stability, and/or localization of metabolic enzymes, as well as inflammatory responses, in macrophages. Two protein families, the classical zinc-dependent histone deacetylases (HDACs) and the NAD-dependent HDACs (sirtuins, SIRTs), mediate lysine deacetylation. We describe here mechanisms by which classical HDACs and SIRTs directly regulate specific glycolytic enzymes, as well as evidence that links these protein deacetylases to the regulation of glycolysis-related genes. In these contexts, we discuss HDACs and SIRTs as key control points for regulating immunometabolism and inflammatory outputs from macrophages. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. Suppression of microRNA-629 enhances sensitivity of cervical cancer cells to 1′S-1′-acetoxychavicol acetate via regulating RSU1

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    Phuah NH

    2017-03-01

    Full Text Available Neoh Hun Phuah,1 Mohamad Nurul Azmi,2 Khalijah Awang,2 Noor Hasima Nagoor1,3 1Faculty of Science, Institute of Biological Science (Genetics and Molecular Biology, 2Faculty of Science, Department of Chemistry, Centre for Natural Product Research and Drug Discovery (CENAR, 3Centre for Research in Biotechnology for Agriculture (CEBAR, University of Malaya, Kuala Lumpur, Malaysia Background: Cervical cancer is the fourth most frequent malignancy affecting women worldwide, but drug resistance and toxicities remain a major challenge in chemotherapy. The use of natural compounds is promising because they are less toxic and able to target multiple signaling pathways. The 1'S-1'-acetoxychavicol acetate (ACA, a natural compound isolated from wild ginger Alpinia conchigera, induced cytotoxicity on various cancer cells including cervical cancer. MicroRNAs (miRNAs are short noncoding RNAs that regulate numerous biological processes, such as apoptosis and chemosensitivity. Past studies reported that miR-629 is upregulated in many cancers, and its expression was altered in ACA-treated cervical cancer cells. However, the role of miR-629 in regulating sensitivity toward ACA or other anticancer agents has not been reported. Hence, this study aims to investigate the role of miR-629 in regulating response toward ACA on cervical cancer cells.  Methods: The miR-629 expression following transfection with miR-629 hairpin inhibitor and hairpin inhibitor negative control was measured using quantitative real-time polymerase chain reaction (RT-qPCR. The 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay was used to investigate sensitivity toward ACA. Apoptosis was detected using Annexin V/propidium iodide and Caspase 3/7 assays. The gene target for miR-629 was identified using miRNA target prediction programs, luciferase reporter assay and Western blots. Gene overexpression studies were performed to evaluate its role in regulating response toward ACA

  4. Expression of Stipa purpurea SpCIPK26 in Arabidopsis thaliana Enhances Salt and Drought Tolerance and Regulates Abscisic Acid Signaling

    Science.gov (United States)

    Zhou, Yanli; Sun, Xudong; Yang, Yunqiang; Li, Xiong; Cheng, Ying; Yang, Yongping

    2016-01-01

    Stipa purpurea (S. purpurea) is the dominant plant species in the alpine steppe of the Qinghai-Tibet Plateau, China. It is highly resistant to cold and drought conditions. However, the underlying mechanisms regulating the stress tolerance are unknown. In this study, a CIPK gene from S. purpurea (SpCIPK26) was isolated. The SpCIPK26 coding region consisted of 1392 bp that encoded 464 amino acids. The protein has a highly conserved catalytic structure and regulatory domain. The expression of SpCIPK26 was induced by drought and salt stress. SpCIPK26 overexpression in Arabidopsis thaliana (A. thaliana) plants provided increased tolerance to drought and salt stress in an abscisic acid (ABA)-dependent manner. Compared with wild-type A. thaliana plants, SpCIPK26-overexpressing plants had higher survival rates, water potentials, and photosynthetic efficiency (Fv/Fm), as well as lower levels of reactive oxygen species (ROS) following exposure to drought and salt stress. Gene expression analyses indicated stress-inducible genes (RD29A, RD29B, and ABF2) and a ROS-scavenger gene (CAT1) were upregulated in SpCIPK26-overexpressing plants after stress treatments. All of these marker genes are associated with ABA-responsive cis-acting elements. Additionally, the similarities in the gene expression patterns following ABA, mannitol, and NaCl treatments suggest SpCIPK26 has an important role during plant responses to drought and salt stress and in regulating ABA signaling. PMID:27338368

  5. Specific down-regulation of XIAP with RNA interference enhances the sensitivity of canine tumor cell-lines to TRAIL and doxorubicin

    Directory of Open Access Journals (Sweden)

    Rothuizen Jan

    2006-09-01

    Full Text Available Abstract Background Apoptosis resistance occurs in various tumors. The anti-apoptotic XIAP protein is responsible for inhibiting apoptosis by reducing caspase-3 activation. Our aim is to evaluate whether RNA inhibition against XIAP increases the sensitivity of canine cell-lines for chemotherapeutics such as TRAIL and doxorubicin. We used small interfering RNA's (siRNA directed against XIAP in three cell-lines derived from bile-duct epithelia (BDE, mammary carcinoma (P114, and osteosarcoma (D17. These cell-lines represent frequently occurring canine cancers and are highly comparable to their human counterparts. XIAP down-regulation was measured by means of quantitative PCR (Q-PCR and Western blotting. The XIAP depleted cells were treated with a serial dilution of TRAIL or doxorubicin and compared to mock- and nonsense-treated controls. Viability was measured with a MTT assay. Results All XIAP siRNA treated cell-lines showed a mRNA down-regulation over 80 percent. Western blot analysis confirmed mRNA measurements. No compensatory effect of IAP family members was seen in XIAP depleted cells. The sensitivity of XIAP depleted cells for TRAIL was highest in BDE cells with an increase in the ED50 of 14-fold, compared to mock- and nonsense-treated controls. The sensitivity of P114 and D17 cell-lines increased six- and five-fold, respectively. Doxorubicin treatment in XIAP depleted cells increased sensitivity in BDE cells more than eight-fold, whereas P114 and D17 cell-lines showed an increase in sensitivity of three- and five-fold, respectively. Conclusion XIAP directed siRNA's have a strong sensitizing effect on TRAIL-reduced cell-viability and a smaller but significant effect with the DNA damaging drug doxorubicin. The increase in efficacy of chemotherapeutics with XIAP depletion provides the rationale for the use of XIAP siRNA's in insensitive canine tumors.

  6. Overexpression of cell cycle regulator CDCA3 promotes oral cancer progression by enhancing cell proliferation with prevention of G1 phase arrest

    International Nuclear Information System (INIS)

    Uchida, Fumihiko; Uzawa, Katsuhiro; Kasamatsu, Atsushi; Takatori, Hiroaki; Sakamoto, Yosuke; Ogawara, Katsunori; Shiiba, Masashi; Tanzawa, Hideki; Bukawa, Hiroki

    2012-01-01

    Cell division cycle associated 3 (CDCA3), part of the Skp1-cullin-F-box (SCF) ubiquitin ligase, refers to a trigger of mitotic entry and mediates destruction of the mitosis inhibitory kinase. Little is known about the relevance of CDCA3 to human malignancy including oral squamous cell carcinoma (OSCC). We aimed to characterize the expression state and function of CDCA3 in OSCC. We evaluated CDCA3 mRNA and protein expression in both OSCC-derived cell lines and primary OSCCs and performed functional analyses of CDCA3 in OSCC-derived cells using the shRNA system. The CDCA3 expression at both the mRNA and protein levels was frequently up-regulated in all cell lines examined and primary tumors (mRNA, 51/69, 74 %; protein, 79/95, 83 %) compared to normal controls (p < 0.001). In contrast, no significant level of CDCA3 protein expression was seen in oral premalignant lesions (OPLs) (n = 20) compared with the expression in OSCCs. Among the clinical variables analyzed, the CDCA3 expression status was closely related to tumor size (p < 0.05). In addition, suppression of CDCA3 expression with shRNA significantly (p < 0.05) inhibited cellular proliferation compared with the control cells by arresting cell-cycle progression at the G1 phase. Further, there was up-regulation of the cyclin-dependent kinase inhibitors (p21 Cip1 , p27 Kip1 , p15 INK4B , and p16 INK4A ) in the knockdown cells. The current results showed that overexpression of CDCA3 occurs frequently during oral carcinogenesis and this overexpression might be associated closely with progression of OSCCs by preventing the arrest of cell-cycle progression at the G1 phase via decreased expression of the cyclin-dependent kinase inhibitors

  7. TET2 Regulates Mast Cell Differentiation and Proliferation through Catalytic and Non-catalytic Activities

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    Sara Montagner

    2016-05-01

    Full Text Available Summary: Dioxygenases of the TET family impact genome functions by converting 5-methylcytosine (5mC in DNA to 5-hydroxymethylcytosine (5hmC. Here, we identified TET2 as a crucial regulator of mast cell differentiation and proliferation. In the absence of TET2, mast cells showed disrupted gene expression and altered genome-wide 5hmC deposition, especially at enhancers and in the proximity of downregulated genes. Impaired differentiation of Tet2-ablated cells could be relieved or further exacerbated by modulating the activity of other TET family members, and mechanistically it could be linked to the dysregulated expression of C/EBP family transcription factors. Conversely, the marked increase in proliferation induced by the loss of TET2 could be rescued exclusively by re-expression of wild-type or catalytically inactive TET2. Our data indicate that, in the absence of TET2, mast cell differentiation is under the control of compensatory mechanisms mediated by other TET family members, while proliferation is strictly dependent on TET2 expression. : The impact of TET enzymes on gene expression and cell function is incompletely understood. Montagner et al. investigate the TET-mediated regulation of mast cell differentiation and function, uncover transcriptional pathways regulated by TET2, and identify both enzymatic activity-dependent and -independent functions of TET2. Keywords: differentiation, DNA hydroxymethylation, epigenetics, mast cells, proliferation, TET

  8. Regulating the Regulator

    Energy Technology Data Exchange (ETDEWEB)

    1992-08-26

    The article reports on a challenge to the UK electricity regulator to defend his record by the Coalition for Fair Electricity Regulation (COFFER). The challenge centres on whether the obligation for the regional electric companies (REC) to purchase power from the cheapest source is being enforced. This is related to the wider issue of whether the REC's support of combined-cycle gas turbine (CCGT) is economic. COFFER considers that uneconomic gas-fired power plants are being allowed to displace economic coal-fired stations. Aspects discussed include the background to the dispute and the costs of CCGT and coal fired power generation. 1 fig., 1 tab.

  9. Influence of DNA-methylation on zinc homeostasis in myeloid cells: Regulation of zinc transporters and zinc binding proteins.

    Science.gov (United States)

    Kessels, Jana Elena; Wessels, Inga; Haase, Hajo; Rink, Lothar; Uciechowski, Peter

    2016-09-01

    The distribution of intracellular zinc, predominantly regulated through zinc transporters and zinc binding proteins, is required to support an efficient immune response. Epigenetic mechanisms such as DNA methylation are involved in the expression of these genes. In demethylation experiments using 5-Aza-2'-deoxycytidine (AZA) increased intracellular (after 24 and 48h) and total cellular zinc levels (after 48h) were observed in the myeloid cell line HL-60. To uncover the mechanisms that cause the disturbed zinc homeostasis after DNA demethylation, the expression of human zinc transporters and zinc binding proteins were investigated. Real time PCR analyses of 14 ZIP (solute-linked carrier (SLC) SLC39A; Zrt/IRT-like protein), and 9 ZnT (SLC30A) zinc transporters revealed significantly enhanced mRNA expression of the zinc importer ZIP1 after AZA treatment. Because ZIP1 protein was also enhanced after AZA treatment, ZIP1 up-regulation might be the mediator of enhanced intracellular zinc levels. The mRNA expression of ZIP14 was decreased, whereas zinc exporter ZnT3 mRNA was also significantly increased; which might be a cellular reaction to compensate elevated zinc levels. An enhanced but not significant chromatin accessibility of ZIP1 promoter region I was detected by chromatin accessibility by real-time PCR (CHART) assays after demethylation. Additionally, DNA demethylation resulted in increased mRNA accumulation of zinc binding proteins metallothionein (MT) and S100A8/S100A9 after 48h. MT mRNA was significantly enhanced after 24h of AZA treatment also suggesting a reaction of the cell to restore zinc homeostasis. These data indicate that DNA methylation is an important epigenetic mechanism affecting zinc binding proteins and transporters, and, therefore, regulating zinc homeostasis in myeloid cells. Copyright © 2016 Elsevier GmbH. All rights reserved.

  10. Electric-regulated enhanced in-plane uniaxial anisotropy in FeGa/PMN-PT composite using oblique pulsed laser deposition

    Science.gov (United States)

    Zhang, Yi; Huang, Chaojuan; Turghun, Mutellip; Duan, Zhihua; Wang, Feifei; Shi, Wangzhou

    2018-04-01

    The FeGa film with in-plane uniaxial magnetic anisotropy was fabricated onto different oriented single-crystal lead magnesium niobate-lead titanate using oblique pulsed laser deposition. An enhanced in-plane uniaxial magnetic anisotropy field of FeGa film can be adjusted from 18 Oe to 275 Oe by tuning the oblique angle and polarizing voltage. The competitive relationship of shape anisotropy and strain anisotropy has been discussed, which was induced by oblique angle and polarizing voltage, respectively. The (100)-oriented and (110)-oriented PMN-PT show completely different characters on voltage-dependent magnetic properties, which could be attributed to various anisotropy directions depended on different strain directions.

  11. Astaxanthin down-regulates Rad51 expression via inactivation of AKT kinase to enhance mitomycin C-induced cytotoxicity in human non-small cell lung cancer cells.

    Science.gov (United States)

    Ko, Jen-Chung; Chen, Jyh-Cheng; Wang, Tai-Jing; Zheng, Hao-Yu; Chen, Wen-Ching; Chang, Po-Yuan; Lin, Yun-Wei

    2016-04-01

    Astaxanthin has been demonstrated to exhibit a wide range of beneficial effects, including anti-inflammatory and anti-cancer properties. However, the molecular mechanism of astaxanthin-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells has not been identified. Rad51 plays a central role in homologous recombination, and studies show that chemo-resistant carcinomas exhibit high levels of Rad51 expression. In this study, astaxanthin treatment inhibited cell viability and proliferation of two NSCLC cells, A549 and H1703. Astaxanthin treatment (2.5-20 μM) decreased Rad51 expression and phospho-AKT(Ser473) protein level in a time and dose-dependent manner. Furthermore, expression of constitutively active AKT (AKT-CA) vector rescued the decreased Rad51 mRNA and protein levels in astaxanthin-treated NSCLC cells. Combined treatment with phosphatidylinositol 3-kinase (PI3K) inhibitors (LY294002 or wortmannin) further decreased the Rad51 expression in astaxanthin-exposed A549 and H1703 cells. Knockdown of Rad51 expression by transfection with si-Rad51 RNA or cotreatment with LY294002 further enhanced the cytotoxicity and cell growth inhibition of astaxanthin. Additionally, mitomycin C (MMC) as an anti-tumor antibiotic is widely used in clinical NSCLC chemotherapy. Combination of MMC and astaxanthin synergistically resulted in cytotoxicity and cell growth inhibition in NSCLC cells, accompanied with reduced phospho-AKT(Ser473) level and Rad51 expression. Overexpression of AKT-CA or Flag-tagged Rad51 reversed the astaxanthin and MMC-induced synergistic cytotoxicity. In contrast, pretreatment with LY294002 further decreased the cell viability in astaxanthin and MMC co-treated cells. In conclusion, astaxanthin enhances MMC-induced cytotoxicity by decreasing Rad51 expression and AKT activation. These findings may provide rationale to combine astaxanthin with MMC for the treatment of NSCLC. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Exploring the relationship between online buyers and sellers of image and performance enhancing drugs (IPEDs): Quality issues, trust and self-regulation.

    Science.gov (United States)

    van de Ven, Katinka; Koenraadt, Rosa

    2017-12-01

    Online drug markets are expanding the boundaries of drug supply including the sale and purchase of image and performance enhancing drugs (IPEDs). However, the role of the internet in IPED markets, and in particular the ways in which these substances are supplied via the surface web, has rarely been considered. This article examines the online IPED market in order to inform drug policy and to provide a nuanced understanding of retailers involved, particularly exploring the relationship between buyers and sellers. This paper is based on two extensive research projects conducted in the Netherlands and Belgium. The first project focuses on muscle drugs and is based on 64 IPED dealing cases, semi-structured interviews with authorities (N=32), and dealers (N=15), along with an analysis of 10 steroid-selling websites. The second research project primarily focuses on weight loss drugs and sexual enhancers in the Netherlands, and relies on interviews with authorities (N=38), suppliers (N=30), and consumers (N=10), analysis of 69 criminal case files, and an online analysis. In the literature, the illicit online sale of IPEDs is generally associated with illegal online pharmacies that try to mislead buyers. While confirmed in our research, we also illustrate that there are online suppliers who invest in customer relationships and services, and that users are aware of the illegal nature of their business. These e-vendors incorporate a 'social supply business model' by providing the best possible service to their customers and attempting to minimise risks in order to attract, satisfy and maintain customers. As it is likely that users will continue to make use of the internet to order IPEDs, regardless of closing down selling websites, it is first of all important to counteract these online sources by educating all types of consumers and providing harm reduction services. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Down-regulation of Wild-type p53-induced Phosphatase 1 (Wip1) Plays a Critical Role in Regulating Several p53-dependent Functions in Premature Senescent Tumor Cells*

    Science.gov (United States)

    Crescenzi, Elvira; Raia, Zelinda; Pacifico, Francesco; Mellone, Stefano; Moscato, Fortunato; Palumbo, Giuseppe; Leonardi, Antonio

    2013-01-01

    Premature or drug-induced senescence is a major cellular response to chemotherapy in solid tumors. The senescent phenotype develops slowly and is associated with chronic DNA damage response. We found that expression of wild-type p53-induced phosphatase 1 (Wip1) is markedly down-regulated during persistent DNA damage and after drug release during the acquisition of the senescent phenotype in carcinoma cells. We demonstrate that down-regulation of Wip1 is required for maintenance of permanent G2 arrest. In fact, we show that forced expression of Wip1 in premature senescent tumor cells induces inappropriate re-initiation of mitosis, uncontrolled polyploid progression, and cell death by mitotic failure. Most of the effects of Wip1 may be attributed to its ability to dephosphorylate p53 at Ser15 and to inhibit DNA damage response. However, we also uncover a regulatory pathway whereby suppression of p53 Ser15 phosphorylation is associated with enhanced phosphorylation at Ser46, increased p53 protein levels, and induction of Noxa expression. On the whole, our data indicate that down-regulation of Wip1 expression during premature senescence plays a pivotal role in regulating several p53-dependent aspects of the senescent phenotype. PMID:23612976

  14. Cryptic diversity in Australian stick insects (Insecta; Phasmida) uncovered by the DNA barcoding approach.

    Science.gov (United States)

    Velonà, A; Brock, P D; Hasenpusch, J; Mantovani, B

    2015-05-18

    The barcoding approach was applied to analyze 16 Australian morphospecies of the order Phasmida, with the aim to test if it could be suitable as a tool for phasmid species identification and if its discrimination power would allow uncovering of cryptic diversity. Both goals were reached. Eighty-two specimens representing twelve morphospecies (Sipyloidea sp. A, Candovia annulata, Candovia sp. A, Candovia sp. B, Candovia sp. C, Denhama austrocarinata, Xeroderus kirbii, Parapodacanthus hasenpuschorum, Tropidoderus childrenii, Cigarrophasma tessellatum, Acrophylla wuelfingi, Eurycantha calcarata) were correctly recovered as clades through the molecular approach, their sequences forming monophyletic and well-supported clusters. In four instances, Neighbor-Joining tree and barcoding gap analyses supported either a specific (Austrocarausius mercurius, Anchiale briareus) or a subspecific (Anchiale austrotessulata, Extatosoma tiaratum) level of divergence within the analyzed morphospecies. The lack of an appropriate database of homologous coxI sequences prevented more detailed identification of undescribed taxa.

  15. Uncovered Interest Parity in Central and Eastern Europe: Convergence and the Global Financial Crisis

    Directory of Open Access Journals (Sweden)

    Fabio Filipozzi

    2012-12-01

    Full Text Available This paper presents tests of uncovered interest parity in Croatia, the Czech Republic, Hungary, Poland and Romania; all countries in Central and Eastern Europe with floating exchange rates. Data are monthly and the trading horizon is three months. The estimations show that the UIP hypothesis is rejected for the full sample from 1999 to 2011 for all five countries. A number of reasons for the rejection were investigated. Rolling regressions show that standard versions of the UIP essentially lose all explanatory power in 2008-10, which was a period in which the global financial crisis led to instability in currency and interest markets in Central and Eastern Europe. Two indicators of global risk aversion were also found to enter significantly in the many UIP estimations. Finally, the size of the interest rates spread also seems to be of importance, at least for Poland and Romania

  16. Parasitic resistive switching uncovered from complementary resistive switching in single active-layer oxide memory device

    Science.gov (United States)

    Zhu, Lisha; Hu, Wei; Gao, Chao; Guo, Yongcai

    2017-12-01

    This paper reports the reversible transition processes between the bipolar and complementary resistive switching (CRS) characteristics on the binary metal-oxide resistive memory devices of Pt/HfO x /TiN and Pt/TaO x /TiN by applying the appropriate bias voltages. More interestingly, by controlling the amplitude of the negative bias, the parasitic resistive switching effect exhibiting repeatable switching behavior is uncovered from the CRS behavior. The electrical observation of the parasitic resistive switching effect can be explained by the controlled size of the conductive filament. This work confirms the transformation and interrelationship among the bipolar, parasitic, and CRS effects, and thus provides new insight into the understanding of the physical mechanism of the binary metal-oxide resistive switching memory devices.

  17. Intermittent fasting uncovers and rescues cognitive phenotypes in PTEN neuronal haploinsufficient mice.

    Science.gov (United States)

    Cabral-Costa, J V; Andreotti, D Z; Mello, N P; Scavone, C; Camandola, S; Kawamoto, E M

    2018-06-05

    Phosphatase and tensin homolog (PTEN) is an important protein with key modulatory functions in cell growth and survival. PTEN is crucial during embryogenesis and plays a key role in the central nervous system (CNS), where it directly modulates neuronal development and synaptic plasticity. Loss of PTEN signaling function is associated with cognitive deficits and synaptic plasticity impairment. Accordingly, Pten mutations have a strong link with autism spectrum disorder. In this study, neuronal Pten haploinsufficient male mice were subjected to a long-term environmental intervention - intermittent fasting (IF) - and then evaluated for alterations in exploratory, anxiety and learning and memory behaviors. Although no significant effects on spatial memory were observed, mutant mice showed impaired contextual fear memory in the passive avoidance test - an outcome that was effectively rescued by IF. In this study, we demonstrated that IF modulation, in addition to its rescue of the memory deficit, was also required to uncover behavioral phenotypes otherwise hidden in this neuronal Pten haploinsufficiency model.

  18. Health Detectives: Uncovering the Mysteries of Disease (LBNL Science at the Theater)

    Energy Technology Data Exchange (ETDEWEB)

    Bissell, Mina; Canaria, Christie; Celnicker, Susan; Karpen, Gary

    2012-04-23

    In this April 23, 2012 Science at the Theater event, Berkeley Lab scientists discuss how they uncover the mysteries of disease in unlikely places. Speakers and topics include: World-renowned cancer researcher Mina Bissell's pioneering research on the role of the cellular microenvironment in breast cancer has changed the conversation about the disease. How does DNA instability cause disease? To find out, Christie Canaria images neural networks to study disorders such as Huntington's disease. Fruit flies can tell us a lot about ourselves. Susan Celniker explores the fruit fly genome to learn how our genome works. DNA is not destiny. Gary Karpen explores how environmental factors shape genome function and disease through epigenetics.

  19. Strategies and approaches in plasmidome studies—uncovering plasmid diversity disregarding of linear elements?

    Science.gov (United States)

    Dib, Julián R.; Wagenknecht, Martin; Farías, María E.; Meinhardt, Friedhelm

    2015-01-01

    The term plasmid was originally coined for circular, extrachromosomal genetic elements. Today, plasmids are widely recognized not only as important factors facilitating genome restructuring but also as vehicles for the dissemination of beneficial characters within bacterial communities. Plasmid diversity has been uncovered by means of culture-dependent or -independent approaches, such as endogenous or exogenous plasmid isolation as well as PCR-based detection or transposon-aided capture, respectively. High-throughput-sequencing made possible to cover total plasmid populations in a given environment, i.e., the plasmidome, and allowed to address the quality and significance of self-replicating genetic elements. Since such efforts were and still are rather restricted to circular molecules, here we put equal emphasis on the linear plasmids which—despite their frequent occurrence in a large number of bacteria—are largely neglected in prevalent plasmidome conceptions. PMID:26074886

  20. Heuristic Artificial Bee Colony Algorithm for Uncovering Community in Complex Networks

    Directory of Open Access Journals (Sweden)

    Yuquan Guo

    2017-01-01

    Full Text Available Community structure is important for us to understand the functions and structure of the complex networks. In this paper, Heuristic Artificial Bee Colony (HABC algorithm based on swarm intelligence is proposed for uncovering community. The proposed HABC includes initialization, employed bee searching, onlooker searching, and scout bee searching. In initialization stage, the nectar sources with simple community structure are generated through network dynamic algorithm associated with complete subgraph. In employed bee searching and onlooker searching stages, the searching function is redefined to address the community problem. The efficiency of searching progress can be improved by a heuristic function which is an average agglomerate probability of two neighbor communities. Experiments are carried out on artificial and real world networks, and the results demonstrate that HABC will have better performance in terms of comparing with the state-of-the-art algorithms.

  1. The hidden Heuchera: How science Twitter uncovered a globally imperiled species in Pennsylvania, USA

    Directory of Open Access Journals (Sweden)

    Scott Schuette

    2018-04-01

    Full Text Available The genus Heuchera is recognized as one of the most diverse endemic radiations of Saxifragaceae in North America, yet species delimitation and geographic distribution within the group remain controversial. Many species remain difficult to identify, including Heuchera alba, a narrow Appalachian endemic and globally imperiled (G2 taxon recorded only from West Virginia and Virginia that occurs in sympatry with H. pubescens and H. americana. A recent survey of the cliffside flora of the Shikellamy Bluffs, PA recorded dozens of Heuchera individuals that, through the use of social media, were positively identified as H. alba. Aided by examination of historical herbarium records, subsequent searches of similar habitats in Pennsylvania led to the discovery of seven more populations and established a significant range expansion for this rare species. The uncovering of H. alba in Pennsylvania is an exciting conservation outcome and an example of what can happen when botanists embrace a combination of modern and classical approaches to discovery and collaboration.

  2. Uncovering values-based practice: VBP's implicit commitments to subjectivism and relativism.

    Science.gov (United States)

    Cassidy, Ben

    2013-06-01

    Despite assertions to the contrary, KWM Fulford's values-based practice is implicitly committed to subjectivism when it comes to reasoning about values. This renders the approach unworkable. The act of merely uncovering underlying values is not enough to effect change and, therefore, resolve problems if we have no way, even in principle, of determining which values are right and which are wrong. Fulford's only departure from subjectivism about value is his commitment to 'framework values', which seems grounded in a version of ethical relativism. I argue that we need to reject both subjectivism and relativism if progress within ethical discussions about practice is to be meaningful and a real possibility. © 2013 John Wiley & Sons Ltd.

  3. Uncovering beat deafness: detecting rhythm disorders with synchronized finger tapping and perceptual timing tasks.

    Science.gov (United States)

    Dalla Bella, Simone; Sowiński, Jakub

    2015-03-16

    A set of behavioral tasks for assessing perceptual and sensorimotor timing abilities in the general population (i.e., non-musicians) is presented here with the goal of uncovering rhythm disorders, such as beat deafness. Beat deafness is characterized by poor performance in perceiving durations in auditory rhythmic patterns or poor synchronization of movement with auditory rhythms (e.g., with musical beats). These tasks include the synchronization of finger tapping to the beat of simple and complex auditory stimuli and the detection of rhythmic irregularities (anisochrony detection task) embedded in the same stimuli. These tests, which are easy to administer, include an assessment of both perceptual and sensorimotor timing abilities under different conditions (e.g., beat rates and types of auditory material) and are based on the same auditory stimuli, ranging from a simple metronome to a complex musical excerpt. The analysis of synchronized tapping data is performed with circular statistics, which provide reliable measures of synchronization accuracy (e.g., the difference between the timing of the taps and the timing of the pacing stimuli) and consistency. Circular statistics on tapping data are particularly well-suited for detecting individual differences in the general population. Synchronized tapping and anisochrony detection are sensitive measures for identifying profiles of rhythm disorders and have been used with success to uncover cases of poor synchronization with spared perceptual timing. This systematic assessment of perceptual and sensorimotor timing can be extended to populations of patients with brain damage, neurodegenerative diseases (e.g., Parkinson's disease), and developmental disorders (e.g., Attention Deficit Hyperactivity Disorder).

  4. Impact of Environmental Regulation and Technical Progress on Industrial Carbon Productivity: An Approach Based on Proxy Measure

    Directory of Open Access Journals (Sweden)

    Huan Zhang

    2016-08-01

    Full Text Available This research aims to study the main influencing factors of China’s industrial carbon productivity by incorporating environmental regulation and technical progress into an econometric model. The paper focuses on data from 35 of China’s industrial sectors and covers the period from 2006 to 2014, in order to examine the impact of environmental regulation and technical progress on carbon productivity. Methods applied include panel fixed effect model, panel random effect model and two stage least squares with instrumental variables (IV-2SLS. The effect of environmental regulation and technical progress has industrial heterogeneity. The paper subdivides industrial sectors into capital and technology intensive, resource intensive and labor intensive sectors according to factor intensiveness. The estimation results of the subgroups have uncovered that for capital and technology intensive and resource intensive sectors, environmental regulation has a more significant impact than technical progress; while for labor intensive sectors, innovation more significantly influences carbon productivity. In addition, foreign direct investment (FDI and industrialization level facilitate improving carbon productivity for the full sample. By contrast, industrial structure inhibits the overall industrial carbon productivity. The industry-specific results indicate that for capital and technology intensive sectors, optimizing of the industrial structure can improve carbon productivity; for resource intensive sectors, FDI and energy consumption structure should be emphasized more; for labor intensive sectors, industrialization levels help enhance carbon productivity. Finally the industrial sector-specific policy suggestions are proposed.

  5. Biallelic mutations in the 3' exonuclease TOE1 cause pontocerebellar hypoplasia and uncover a role in snRNA processing

    DEFF Research Database (Denmark)

    Lardelli, Rea M.; Schaffer, Ashleigh E.; Eggens, Veerle R C

    2017-01-01

    ) is a unique recessive syndrome characterized by neurodegeneration and ambiguous genitalia. We studied 12 human families with PCH7, uncovering biallelic, loss-of-function mutations in TOE1, which encodes an unconventional deadenylase. toe1-morphant zebrafish displayed midbrain and hindbrain degeneration...... of TOE1 accumulated 3'-end-extended pre-snRNAs, and the immunoisolated TOE1 complex was sufficient for 3'-end maturation of snRNAs. Our findings identify the cause of a neurodegenerative syndrome linked to snRNA maturation and uncover a key factor involved in the processing of snRNA 3' ends....

  6. Visualized and precise design of artificial small RNAs for regulating T7 RNA polymerase and enhancing recombinant protein folding in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Yujia Zhao

    2016-12-01

    Full Text Available Small non-coding RNAs (sRNAs have received much attention in recent years due to their unique biological properties, which can efficiently and specifically tune target gene expressions in bacteria. Inspired by natural sRNAs, recent works have proposed the use of artificial sRNAs (asRNAs as genetic tools to regulate desired gene that has been applied in several fields, such as metabolic engineering and bacterial physiology studies. However, the rational design of asRNAs is still a challenge. In this study, we proposed structure and length as two criteria to implement rational visualized and precise design of asRNAs. T7 expression system was one of the most useful recombinant protein expression systems. However, it was deeply limited by the formation of inclusion body. To settle this problem, we designed a series of asRNAs to inhibit the T7 RNA polymerase (Gene1 expression to balance the rate between transcription and folding of recombinant protein. Based on the heterologous expression of Aspergillus oryzae Li-3 glucuronidase in E. coli, the asRNA-antigene1-17bp can effectively decrease the inclusion body and increase the enzyme activity by 169.9%.

  7. Combination Treatments with Luteolin and Fisetin Enhance Anti-Inflammatory Effects in High Glucose-Treated THP-1 Cells Through Histone Acetyltransferase/Histone Deacetylase Regulation.

    Science.gov (United States)

    Kim, Arang; Yun, Jung-Mi

    2017-08-01

    Hyperglycemia leads to diabetes and its diabetic complications. In this study, we investigated the synergistic effects of luteolin and fisetin on proinflammatory cytokine secretion and its underlying epigenetic regulation in human monocytes exposed to hyperglycemic (HG) concentrations. Human monocytic cells (THP-1) were cultured under controlled (14.5 mM mannitol), normoglycemic (5.5 mM glucose), or HG (20 mM glucose) conditions in the absence or presence of the two phytochemicals for 48 h. Whereas HG conditions significantly induced histone acetylation, nuclear factor-kappa B (NF-κB) activation, interleukin 6, and tumor necrosis factor-α release from THP-1 cells; combination treatments with the two phytochemicals (500 nM fisetin, and l μM and 500 nM luteolin) suppressed NF-κB activity and inflammatory cytokine release. Fisetin, luteolin, and their combination treatments also significantly decreased the activity of histone acetyltransferase, a known NF-κB coactivator; inhibited reactive oxygen species production; and activated sirtuin (SIRT)1 and forkhead box O3a (FOXO3a) expressions (P < .05). Thus, combination treatments with the two phytochemicals inhibited HG condition-induced cytokine production in monocytes, through epigenetic changes involving NF-κB activation. We, therefore, suggest that combination treatments with luteolin and fisetin may be a potential candidate for the treatment and prevention of diabetes and its complications.

  8. O-linked N-acetylglucosamine transferase enhances secretory clusterin expression via liver X receptors and sterol response element binding protein regulation in cervical cancer.

    Science.gov (United States)

    Kim, Min Jun; Choi, Mee Young; Lee, Dong Hoon; Roh, Gu Seob; Kim, Hyun Joon; Kang, Sang Soo; Cho, Gyeong Jae; Kim, Yoon Sook; Choi, Wan Sung

    2018-01-12

    O-linked N-acetylglucosamine transferase (OGT) expression is increased in various cancer types, indicating the potential importance of O-GlcNAcylation in tumorigenesis. Secretory clusterin (sCLU) is involved in cancer cell proliferation and drug resistance, and recently, liver X receptors (LXRs) and sterol response element binding protein-1 (SREBP-1) were reported to regulate sCLU transcription. Here, we found that sCLU is significantly increased in cervical cancer cell lines, which have higher expression levels of O-GlcNAc and OGT than keratinocytes. OGT knockdown decreased expression of LXRs, SREBP-1 and sCLU through hypo-O-GlcNAcylation of LXRs. Additionally, treatment with Thiamet G, O-GlcNAcase OGA inhibitor, increased expression of O-GlcNAcylation and sCLU, and high glucose increased levels of LXRs, SREBP-1 and sCLU in HeLa cells. Moreover, OGT knockdown induced G 0 /G 1 phase cell cycle arrest and late apoptosis in cisplatin-treated HeLa cells, and decreased viability compared to OGT intact HeLa cells. Taken together, these findings suggest that OGT, O-GlcNAcylated LXRs, and SREBP-1 increase sCLU expression in cervical cancer cells, which contributes to drug resistance.

  9. Ectopic Expression of Hrf1 Enhances Bacterial Resistance via Regulation of Diterpene Phytoalexins, Silicon and Reactive Oxygen Species Burst in Rice

    Science.gov (United States)

    Zhong, Weigong; Yang, Jie; Okada, Kazunori; Yamane, Hisakazu; Zhang, Lei; Wang, Guang; Wang, Dong; Xiao, Shanshan; Chang, Shanshan; Qian, Guoliang; Liu, Fengquan

    2012-01-01

    Harpin proteins as elicitor derived from plant gram negative bacteria such as Xanthomonas oryzae pv. oryzae (Xoo), Erwinia amylovora induce disease resistance in plants by activating multiple defense responses. However, it is unclear whether phytoalexin production and ROS burst are involved in the disease resistance conferred by the expression of the harpinXoo protein in rice. In this article, ectopic expression of hrf1 in rice enhanced resistance to bacterial blight. Accompanying with the activation of genes related to the phytoalexin biosynthesis pathway in hrf1-transformed rice, phytoalexins quickly and consistently accumulated concurrent with the limitation of bacterial growth rate. Moreover, the hrf1-transformed rice showed an increased ability for ROS scavenging and decreased hydrogen peroxide (H2O2) concentration. Furthermore, the localization and relative quantification of silicon deposition in rice leaves was detected by scanning electron microscopy (SEM) and energy-dispersive X-ray spectrometer (EDS). Finally, the transcript levels of defense response genes increased in transformed rice. These results show a correlation between Xoo resistance and phytoalexin production, H2O2, silicon deposition and defense gene expression in hrf1-transformed rice. These data are significant because they provide evidence for a better understanding the role of defense responses in the incompatible interaction between bacterial disease and hrf1-transformed plants. These data also supply an opportunity for generating nonspecific resistance to pathogens. PMID:22970151

  10. Epidermal growth factor regulation of glutathione S-transferase gene expression in the rat is mediated by class Pi glutathione S-transferase enhancer I.

    Science.gov (United States)

    Matsumoto, M; Imagawa, M; Aoki, Y

    2000-07-01

    Using chloramphenicol acetyltransferase assays we showed that epidermal growth factor (EGF), transforming growth factor alpha (TGF alpha), and 3,3',4,4',5-pentachlorobiphenyl (PenCB) induce class Pi glutathione S-transferase (GSTP1) in primary cultured rat liver parenchymal cells. GSTP1 enhancer I (GPEI), which is required for the stimulation of GSTP1 expression by PenCB, also mediates EGF and TGF alpha stimulation of GSTP1 gene expression. However, hepatocyte growth factor and insulin did not stimulate GPEI-mediated gene expression. On the other hand, the antioxidant reagents butylhydroxyanisole and t-butylhydroquinone, stimulated GPEI-mediated gene expression, but the level of GSTP1 mRNA was not elevated. Our observations suggest that EGF and TGF alpha induce GSTP1 by the same signal transduction pathway as PenCB. Since the sequence of GPEI is similar to that of the antioxidant responsive element (ARE), some factors which bind to ARE might play a role in GPEI-mediated gene expression.

  11. Ectopic expression of Hrf1 enhances bacterial resistance via regulation of diterpene phytoalexins, silicon and reactive oxygen species burst in rice.

    Directory of Open Access Journals (Sweden)

    Wenqi Li

    Full Text Available Harpin proteins as elicitor derived from plant gram negative bacteria such as Xanthomonas oryzae pv. oryzae (Xoo, Erwinia amylovora induce disease resistance in plants by activating multiple defense responses. However, it is unclear whether phytoalexin production and ROS burst are involved in the disease resistance conferred by the expression of the harpin(Xoo protein in rice. In this article, ectopic expression of hrf1 in rice enhanced resistance to bacterial blight. Accompanying with the activation of genes related to the phytoalexin biosynthesis pathway in hrf1-transformed rice, phytoalexins quickly and consistently accumulated concurrent with the limitation of bacterial growth rate. Moreover, the hrf1-transformed rice showed an increased ability for ROS scavenging and decreased hydrogen peroxide (H(2O(2 concentration. Furthermore, the localization and relative quantification of silicon deposition in rice leaves was detected by scanning electron microscopy (SEM and energy-dispersive X-ray spectrometer (EDS. Finally, the transcript levels of defense response genes increased in transformed rice. These results show a correlation between Xoo resistance and phytoalexin production, H(2O(2, silicon deposition and defense gene expression in hrf1-transformed rice. These data are significant because they provide evidence for a better understanding the role of defense responses in the incompatible interaction between bacterial disease and hrf1-transformed plants. These data also supply an opportunity for generating nonspecific resistance to pathogens.

  12. HPLC-ESI-MS(n) Analysis, Fed-Batch Cultivation Enhances Bioactive Compound Biosynthesis and Immune-Regulative Effect of Adventitious Roots in Pseudostellaria heterophylla.

    Science.gov (United States)

    Wang, Juan; Li, Jing; Li, Hongfa; Wu, Xiaolei; Gao, Wenyuan

    2015-09-01

    A electrospray ionization tandem mass spectrometry (ESI-MS(n)) analysis was performed in order to identify the active composition in Pseudostellaria heterophylla adventitious roots. Pseudostellarin A, C, D, and G were identified from P. heterophylla adventitious roots on the basis of LC-MS(n) analysis. The culture conditions of adventitious roots were optimized, and datasets were subjected to a partial least squares discriminant analysis (PLS-DA), in which the growth ratio and some compounds showed a positive correlation with an aeration volume of 0.3 vvm and inoculum density of 0.15 %. Fed-batch cultivation enhanced the contents of total saponin, polysaccharides, and specific oxygen uptaker rate (SOUR). The maximum dry root weight (4.728 g l(-1)) was achieved in the 3/4 Murashige and Skoog (MS) medium group. PLS-DA showed that polysaccharides contributed significantly to the clustering of different groups and showed a positive correlation in the MS medium group. The delayed-type hypersensitivity (DTH) reaction on the mice induced by 2,4-dinitrofluorobenzene (DNFB) was applied to compare the immunocompetence effects of adventitious roots (AR) with field native roots (NR) of P. heterophylla. As a result, AR possessed a similar immunoregulation function as NR.

  13. ‘OMICS’-approach to regulate ripening and enhance fruit shelf-life in banana: an important fruit crop for food security

    Directory of Open Access Journals (Sweden)

    Subhankar Mohanty

    2017-12-01

    In this study, proteins were phenol extracted from different fruit tissues (peel and pulp during different developmental (40, 60, 80 and 90-days after flowering and ripening stages (2, 4, 6, 8, 10 and 12-days after ripening of banana (cv.Grand naine, and resolved using global proteome approach. 2-D gel images were further submitted to powerful image analysis software (Image Master Platinum, Version.7.1 for qualitative and quantitative analysis. Several protein spots showed fold-change (increase and decrease in abundance, and some protein spots are unique to certain developmental and ripening stages, after image analysis.  Further, spots of interest were subjected to both MALDI-TOF/TOF-MS and LC-MS/MS (Q-TOF mass spectrophotometry for protein mass fingerprinting and peptide sequencing, after tryptic digestion of the excised protein spots. In parallel, experiments are in progress to subject the samples for transcriptome (RNAseq. analysis. Based on protein/gene sequence information corresponding genes will be isolated and cloned, and knowledge will be utilized for RNAi constructs preparation to define individual role of identified key proteins/genes in ripening and enhancing fruit shelf-life in banana.

  14. Development and application of a cost-benefit framework for energy reliability. Using probabilistic methods in network planning and regulation to enhance social welfare. The N-1 rule

    International Nuclear Information System (INIS)

    Nooij, Michiel de; Baarsma, Barbara; Bloemhof, Gabriel; Dijk, Harold; Slootweg, Han

    2010-01-01

    Although electricity is crucial to many activities in developed societies, guaranteeing a maximum reliability of supply to end-users is extremely costly. This situation gives rise to a trade-off between the costs and benefits of reliability. The Dutch government has responded to this trade-off by changing the rule stipulating that electricity networks must be able to maintain supply even if one component fails (known as the N-1 rule), even in maintenance situations. This rule was changed by adding the phrase 'unless the costs exceed the benefits.' We have developed a cost-benefit framework for the implementation and application of this new rule. The framework requires input on failure probability, the cost of supply interruptions to end-users and the cost of investments. A case study of the Dutch grid shows that the method is indeed practicable and that it is highly unlikely that N-1 during maintenance will enhance welfare in the Netherlands. Therefore, including the limitation 'unless the costs exceed the benefits' in the rule has been a sensible policy for the Netherlands, and would also be a sensible policy for other countries. (author)

  15. Up-regulation of an N-terminal truncated 3-hydroxy-3-methylglutaryl CoA reductase enhances production of essential oils and sterols in transgenic Lavandula latifolia.

    Science.gov (United States)

    Muñoz-Bertomeu, Jesús; Sales, Ester; Ros, Roc; Arrillaga, Isabel; Segura, Juan

    2007-11-01

    Spike lavender (Lavandula latifolia) essential oil is widely used in the perfume, cosmetic, flavouring and pharmaceutical industries. Thus, modifications of yield and composition of this essential oil by genetic engineering should have important scientific and commercial applications. We generated transgenic spike lavender plants expressing the Arabidopsis thaliana HMG1 cDNA, encoding the catalytic domain of 3-hydroxy-3-methylglutaryl CoA reductase (HMGR1S), a key enzyme of the mevalonic acid (MVA) pathway. Transgenic T0 plants accumulated significantly more essential oil constituents as compared to controls (up to 2.1- and 1.8-fold in leaves and flowers, respectively). Enhanced expression of HMGR1S also increased the amount of the end-product sterols, beta-sitosterol and stigmasterol (average differences of 1.8- and 1.9-fold, respectively), but did not affect the accumulation of carotenoids or chlorophylls. We also analysed T1 plants derived from self-pollinated seeds of T0 lines that flowered after growing for 2 years in the greenhouse. The increased levels of essential oil and sterols observed in the transgenic T0 plants were maintained in the progeny that inherited the HMG1 transgene. Our results demonstrate that genetic manipulation of the MVA pathway increases essential oil yield in spike lavender, suggesting a contribution for this cytosolic pathway to monoterpene and sesquiterpene biosynthesis in leaves and flowers of the species.

  16. Opposite effects of alcohol in regulating stress-induced changes in body weight between the two mouse lines with enhanced or low opioid system activity.

    Science.gov (United States)

    Sacharczuk, Mariusz; Sadowski, Bogdan; Jaszczak, Kazimierz; Lipkowski, Andrzej W; Swiergiel, Artur H

    2010-04-19

    Considering the involvement of the opioid system in alcoholism, depression and metabolism - known risk factors in human obesity, we studied the effects of chronic mild stress (CMS) and alcohol intake on body weight in two mouse lines selected for high (HA-high analgesia) or low (LA-low analgesia) swim stress-induced analgesia. In comparison to LA mice, HA mice exhibit an upregulation of opioid receptor system function, different depression-like behavior and reduced energy expenditure in stress. LA animals showed enhanced basal and CMS-induced alcohol drinking versus HA. Now we report different effects of alcohol under no stress (control) and CMS conditions on food intake and body weight between the lines. CMS in animals with no access to alcohol increased body weight in both HA and LA mice, with no effect of CMS on food intake in either line and without differences between the lines. In LA mice alcohol reduced body weight under both conditions although significantly more under the control than CMS conditions. In contrast, in HA mice alcohol increased body weight more under the CMS than under control conditions. The results suggest that opioid system may modulate effects of alcohol on stress -induced changes in body weight. (c) 2010 Elsevier Inc. All rights reserved.

  17. Molybdenum Sulfide Induce Growth Enhancement Effect of Rice ( Oryza sativa L.) through Regulating the Synthesis of Chlorophyll and the Expression of Aquaporin Gene.

    Science.gov (United States)

    Li, Yadong; Jin, Qian; Yang, Desong; Cui, Jianghu

    2018-04-25

    Molybdenum sulfide (MoS 2 ) has been applied widely in industrial and environmental application, leading to increasing release into environment. So far, no studies have been investigated with regard to the potential effect of MoS 2 on plants. Herein, we studied the impact of MoS 2 on the growth, chlorophyll content, lipid peroxidation, antioxidase system, and aquaporins of rice for the first time. Results showed that MoS 2 did not significantly affect the germination of rice seeds, malonaldehyde (MDA) content, and the antioxidant enzyme activity. While the length and biomass of rice root and shoot, chlorophyll content index (CCI), and expression of aquaporin genes were significantly increased. Based on these results, we concluded that MoS 2 promoted rice growth through (i) the promotion of nitrogen source assimilation, (ii) the enhancement of photosynthesis, enzymatic-related biochemical reactions, and metabolic processes, subsequently, (iii) the acceleration of cell division and expansion, furthermore (iv) no abiotic stress and favorable condition of antioxidant enzyme system. These results provided an important insight into the further application of MoS 2 on agriculture and environment.

  18. A pilot investigation of the potential for incorporating lifelog technology into executive function rehabilitation for enhanced transfer of self-regulation skills to everyday life.

    Science.gov (United States)

    Cuberos-Urbano, Gustavo; Caracuel, Alfonso; Valls-Serrano, Carlos; García-Mochón, Leticia; Gracey, Fergus; Verdejo-García, Antonio

    2018-06-01

    The objective of the study was to identify the potential target and effect size of goal management training (GMT) enhanced with life-logging technology compared with standard GMT on a range of possible primary outcomes reflecting cognitive and ecological aspects of executive functioning and quality of life. Sixteen patients with acquired brain injury involving executive dysfunction were randomly allocated to one of the two interventions: seven weeks of GMT (n = 8), or seven weeks of GMT+Lifelog (n = 8). Outcome measures included a battery of executive function tests, the Dysexecutive Questionnaire (DEX) and the Quality of Life after Brain Injury scale (QOLIBRI), measured pre- and post-interventions. Within-group changes were assessed with related-samples t-tests and estimation of effect sizes. GMT+Lifelog was associated with significant changes, of medium to large effect size, in response inhibition (Stroop), multitasking (Strategy Application and Multiple Errand tests), DEX Intentionality and Positive Affect subscales and QOLIBRI Daily Life and Autonomy, subscales. GMT alone was associated with significant changes of overall quality of life. It was concluded that GMT+Lifelog holds promise to optimise the impact of GMT on executive dysfunction and quality of life.

  19. TaNAC1 acts as a negative regulator of stripe rust resistance in wheat, enhances susceptibility to Pseudomonas syringae, and promotes lateral root development in transgenic Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Fengtao eWang

    2015-02-01

    Full Text Available Plant-specific NAC transcription factors constitute a large family and play important roles in regulating plant developmental processes and responses to environmental stresses, but only some of them have been investigated for effects on disease reaction in cereal crops. Virus-induced gene silencing (VIGS is an effective strategy for rapid functional analysis of genes in plant tissues. In this study, TaNAC1, encoding a new member of the NAC1 subgroup, was cloned from bread wheat and characterized. It is a transcription factor localized in the cell nucleus, and contains an activation domain in its C-terminal. TaNAC1 was strongly expressed in wheat roots and was involved in responses to infection by the obligate pathogen Puccinia striiformis f. sp. tritici and defense-related hormone treatments such as salicylic acid, methyl jasmonate and ethylene. Knockdown of TaNAC1 with barley stripe mosaic virus-induced gene silencing (BSMV-VIGS enhanced stripe rust resistance. TaNAC1-overexpression in Arabidopsis plants gave enhanced susceptibility, attenuated systemic-acquired resistance to Pseudomonas syringae DC3000, and promoted lateral root development. Jasmonic acid-signaling pathway genes PDF1.2 and ORA59 were constitutively expressed in transgenic plants. TaNAC1 overexpression suppressed the expression levels of resistance-related genes PR1 and PR2 involved in SA signaling and AtWRKY70, which functions as a connection node between the JA- and SA-signaling pathways. Collectively, TaNAC1 is a novel NAC member of the NAC1 subgroup, negatively regulates plant disease resistance, and may modulate plant JA- and SA-signaling defense cascades.

  20. DNA methylcytosine dioxygenase ten-eleven translocation 2 enhances lipopolysaccharide-induced cytokine expression in human dental pulp cells by regulating MyD88 hydroxymethylation.

    Science.gov (United States)

    Wang, Xinxuan; Feng, Zhihui; Li, Qimeng; Yi, Baicheng; Xu, Qiong

    2018-04-13

    Dental pulp inflammation is a bacterially driven inflammation process characterized by the local accumulation of cytokines/chemokines that participate in destructive processes in the pulp. Multiple mechanisms are involved in dental pulp inflammation, including epigenetic events, such as DNA methylation/demethylation. Ten-eleven translocation 2 (TET2) is a recently discovered DNA methylcytosine dioxygenase that plays important roles in inflammatory disease. However, its role in the inflammatory response of dental pulp is unknown. We observed elevated mRNA and protein levels of TET2 after lipopolysaccharide (LPS) stimulation in human dental pulp cells (hDPCs). To identify the effects of TET2 on cytokine expression, TET2 was knocked down and cytokines were detected using a cytokine antibody array after LPS stimulation. The protein expression of GM-CSF, IL-6, IL-8 and RANTES decreased in the LPS-induced hDPCs following TET2 knockdown. The downregulated expression levels of IL-6 and IL-8 were further confirmed by real-time quantitative polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). Additionally, the phosphorylation levels of IKK-α/β, p65 and IκBα of the NF-κB signaling pathway were decreased in the TET2-silenced group. Furthermore, the global 5-hydroxymethylcytosine (5hmC) level was significantly decreased and the genomic 5-methylcytosine (5mC) level was increased in the TET2-deficient hDPCs; TET2 depletion resulted in a decrease in the 5hmC level of the MyD88 promoter following LPS stimulation. These findings indicate that TET2 knockdown inhibits LPS-induced inflammatory response in hDPCs by downregulating MyD88 hydroxymethylation. Thus, TET2-dependent DNA demethylation might play an important role in dental pulp inflammation as an epigenetic regulator.

  1. Role of plant growth regulators and a saprobic fungus in enhancement of metal phytoextraction potential and stress alleviation in pearl millet.

    Science.gov (United States)

    Firdaus-e-Bareen; Shafiq, Muhammad; Jamil, Sidra

    2012-10-30

    "Assisted phytoextraction" involving application of chemical additives such as plant growth regulators (PGRs) has become a trend in phytoremediation technology. This study identifies a cost-effective, naturally available crude PGR (PGR1) that produces the same effects as the commercial PGR (PGR2), increasing metal uptake by plants and the reduction of metal stress. Assisted phytoextraction by pearl millet (Pennisetum glaucum) from a multi-metal (Cd, Cr, Cu, Fe, Na and Zn) contaminated soil medium with tannery solid waste (TSW) soil amendments of 5 and 10%, was evaluated in a full-factorial pot trial with PGR1, PGR2 and Trichoderma pseudokoningii as factors. The effects of these phytoextraction assistants were measured through dry biomass production, heavy metal uptake, stress tolerance enzymes catalase (CAT) and superoxide dismutase (SOD), soluble protein content of plant, and phytoextraction efficiency. Dry biomass and multi-metal accumulation were the highest in the soil treatments with a combined application of PGR1, PGR2 and T. pseudokoningii and the lowest in the control. The soluble protein contents and the SOD and CAT values were the highest in the 10% TSW treatment provided with PGR2+T. pseudokoningii, while the lowest were in the control. Thus, application of crude PGR in combination with other phytoextraction assistants can increase biomass production as well as multi-metal accumulation in plants. However, the biochemical properties of the plant depend on the level of TSW stress in the soil treatment as well as the type of phytoextraction assistants. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Inhibition of Mef2a Enhances Neovascularization via Post-transcriptional Regulation of 14q32 MicroRNAs miR-329 and miR-494

    Directory of Open Access Journals (Sweden)

    Sabine M.J. Welten

    2017-06-01

    Full Text Available Improving the efficacy of neovascularization is a promising strategy to restore perfusion of ischemic tissues in patients with peripheral arterial disease. The 14q32 microRNA cluster is highly involved in neovascularization. The Mef2a transcription factor has been shown to induce transcription of the microRNAs within this cluster. We inhibited expression of Mef2a using gene-silencing oligonucleotides (GSOs in an in vivo hind limb ischemia model. Treatment with GSO-Mef2a clearly improved blood flow recovery within 3 days (44% recovery versus 25% recovery in control and persisted until 14 days after ischemia induction (80% recovery versus 60% recovery in control. Animals treated with GSO-Mef2a showed increased arteriogenesis and angiogenesis in the relevant muscle tissues. Inhibition of Mef2a decreased expression of 14q32 microRNAs miR-329 (p = 0.026 and miR-494 (trend, p = 0.06, but not of other 14q32 microRNAs, nor of 14q32 microRNA precursors. Because Mef2a did not influence 14q32 microRNA transcription, we hypothesized it functions as an RNA-binding protein that influences processing of 14q32 microRNA miR-329 and miR-494. Mef2A immunoprecipitation followed by RNA isolation and rt/qPCR confirmed direct binding of MEF2A to pri-miR-494, supporting this hypothesis. Our study demonstrates a novel function for Mef2a in post-ischemic neovascularization via post-transcriptional regulation of 14q32 microRNAs miR-329 and miR-494.

  3. Market, Regulation, Market, Regulation

    DEFF Research Database (Denmark)

    Frankel, Christian; Galland, Jean-Pierre

    2015-01-01

    barriers to trade in Europe, realized the free movement of products by organizing progressively several orders of markets and regulation. Based on historical and institutional documents, on technical publications, and on interviews, this article relates how the European Commission and the Member States had......This paper focuses on the European Regulatory system which was settled both for opening the Single Market for products and ensuring the consumers' safety. It claims that the New Approach and Standardization, and the Global Approach to conformity assessment, which suppressed the last technical...... alternatively recourse to markets and to regulations, at the three main levels of the New Approach Directives implementation. The article focuses also more specifically on the Medical Devices sector, not only because this New Approach sector has long been controversial in Europe, and has recently been concerned...

  4. Tamoxifen enhances erlotinib-induced cytotoxicity through down-regulating AKT-mediated thymidine phosphorylase expression in human non-small-cell lung cancer cells.

    Science.gov (United States)

    Ko, Jen-Chung; Chiu, Hsien-Chun; Syu, Jhan-Jhang; Jian, Yi-Jun; Chen, Chien-Yu; Jian, Yun-Ting; Huang, Yi-Jhen; Wo, Ting-Yu; Lin, Yun-Wei

    2014-03-01

    Tamoxifen is a triphenylethylene nonsteroidal estrogen receptor (ER) antagonist used worldwide as an adjuvant hormone therapeutic agent in the treatment of breast cancer. However, the molecular mechanism of tamoxifen-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells has not been identified. Thymidine phosphorylase (TP) is an enzyme of the pyrimidine salvage pathway which is upregulated in cancers. In this study, tamoxifen treatment inhibited cell survival in two NSCLC cells, H520 and H1975. Treatment with tamoxifen decreased TP mRNA and protein levels through AKT inactivation. Furthermore, expression of constitutively active AKT (AKT-CA) vectors significantly rescued the decreased TP protein and mRNA levels in tamoxifen-treated NSCLC cells. In contrast, combination treatment with PI3K inhibitors (LY294002 or wortmannin) and tamoxifen further decreased the TP expression and cell viability of NSCLC cells. Knocking down TP expression by transfection with small interfering RNA of TP enhanced the cytotoxicity and cell growth inhibition of tamoxifen. Erlotinib (Tarceva, OSI-774), an orally available small molecular inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, is approved for clinical treatment of NSCLC. Compared to a single agent alone, tamoxifen combined with erlotinib resulted in cytotoxicity and cell growth inhibition synergistically in NSCLC cells, accompanied with reduced activation of phospho-AKT and phospho-ERK1/2, and reduced TP protein levels. These findings may have implications for the rational design of future drug regimens incorporating tamoxifen and erlotinib for the treatment of NSCLC. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Minocycline enhances mitomycin C-induced cytotoxicity through down-regulating ERK1/2-mediated Rad51 expression in human non-small cell lung cancer cells.

    Science.gov (United States)

    Ko, Jen-Chung; Wang, Tai-Jing; Chang, Po-Yuan; Syu, Jhan-Jhang; Chen, Jyh-Cheng; Chen, Chien-Yu; Jian, Yun-Ting; Jian, Yi-Jun; Zheng, Hao-Yu; Chen, Wen-Ching; Lin, Yun-Wei

    2015-10-01

    Minocycline is a semisynthetic tetracycline derivative; it has anti-inflammatory and anti-cancer effects distinct from its antimicrobial function. However, the molecular mechanism of minocycline-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells has not been identified. Rad51 plays a central role in homologous recombination and high levels of Rad51 expression are observed in chemo- or radioresistant carcinomas. Our previous studies have shown that the MKK1/2-ERK1/2 signal pathway maintains the expression of Rad51 in NSCLC cells. In this study, minocycline treatment inhibited cell viability and proliferation of two NSCLC cells, A549 and H1975. Treatment with minocycline decreased Rad51 mRNA and protein levels through MKK1/2-ERK1/2 inactivation. Furthermore, expression of constitutively active MKK1 (MKK1-CA) vectors significantly rescued the decreased Rad51 protein and mRNA levels in minocycline-treated NSCLC cells. However, combined treatment with MKK1/2 inhibitor U0126 and minocycline further decreased the Rad51 expression and cell viability of NSCLC cells. Knocking down Rad51 expression by transfection with small interfering RNA of Rad51 enhanced the cytotoxicity and cell growth inhibition of minocycline. Mitomycin C (MMC) is typically used as a first or second line regimen to treat NSCLC. Compared to a single agent alone, MMC combined with minocycline resulted in cytotoxicity and cell growth inhibition synergistically in NSCLC cells, accompanied with reduced activation of phospho-ERK1/2, and reduced Rad51 protein levels. Overexpression of MKK1-CA or Flag-tagged Rad51 could reverse the minocycline and MMC-induced synergistic cytotoxicity. These findings may have implications for the rational design of future drug regimens incorporating minocycline and MMC for the treatment of NSCLC. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Surface-enhanced Raman spectroscopy introduced into the International Standard Organization (ISO) regulations as an alternative method for detection and identification of pathogens in the food industry.

    Science.gov (United States)

    Witkowska, Evelin; Korsak, Dorota; Kowalska, Aneta; Księżopolska-Gocalska, Monika; Niedziółka-Jönsson, Joanna; Roźniecka, Ewa; Michałowicz, Weronika; Albrycht, Paweł; Podrażka, Marta; Hołyst, Robert; Waluk, Jacek; Kamińska, Agnieszka

    2017-02-01

    We show that surface-enhanced Raman spectroscopy (SERS) coupled with principal component analysis (PCA) can serve as a fast, reliable, and easy method for detection and identification of food-borne bacteria, namely Salmonella spp., Listeria monocytogenes, and Cronobacter spp., in different types of food matrices (salmon, eggs, powdered infant formula milk, mixed herbs, respectively). The main aim of this work was to introduce the SERS technique into three ISO (6579:2002; 11290-1:1996/A1:2004; 22964:2006) standard procedures required for detection of these bacteria in food. Our study demonstrates that the SERS technique is effective in distinguishing very closely related bacteria within a genus grown on solid and liquid media. The advantages of the proposed ISO-SERS method for bacteria identification include simplicity and reduced time of analysis, from almost 144 h required by standard methods to 48 h for the SERS-based approach. Additionally, PCA allows one to perform statistical classification of studied bacteria and to identify the spectrum of an unknown sample. Calculated first and second principal components (PC-1, PC-2) account for 96, 98, and 90% of total variance in the spectra and enable one to identify the Salmonella spp., L. monocytogenes, and Cronobacter spp., respectively. Moreover, the presented study demonstrates the excellent possibility for simultaneous detection of analyzed food-borne bacteria in one sample test (98% of PC-1 and PC-2) with a goal of splitting the data set into three separated clusters corresponding to the three studied bacteria species. The studies described in this paper suggest that SERS represents an alternative to standard microorganism diagnostic procedures. Graphical Abstract New approach of the SERS strategy for detection and identification of food-borne bacteria, namely S. enterica, L. monocytogenes, and C. sakazakii in selected food matrices.

  7. Phytoextraction of contaminated urban soils by Panicum virgatum L. enhanced with application of a plant growth regulator (BAP) and citric acid.

    Science.gov (United States)

    Aderholt, Matthew; Vogelien, Dale L; Koether, Marina; Greipsson, Sigurdur

    2017-05-01

    Lead (Pb) contamination in soil represents a threat to human health. Phytoextraction has gained attention as a potential alternative to traditional remediation methods because of lower cost and minimal soil disruption. The North American native switchgrass (Panicum virgatum L.) was targeted due to its ability to produce high biomass and grow across a variety of ecozones. In this study switchgrass was chemically enhanced with applications of the soil-fungicide benomyl, chelates (EDTA and citric acid), and PGR to optimize phytoextraction of Pb and zinc (Zn) from contaminated urban soils in Atlanta, GA. Exogenous application of two plant hormones was compared in multiple concentrations to determine effects on switchgrass growth: indole-3-acetic acid (IAA), and Gibberellic Acid (GA 3 ), and one PGR benzylaminopurine (BAP), The PGR BAP (1.0 μM) was found to generate a 48% increase in biomass compared to Control plants. Chemical application of citric acid, EDTA, benomyl, and BAP were tested separately and in combination in a pot experiment in an environmentally controlled greenhouse to determine the efficacy of phtyoextraction by switchgrass. Soil acidification by citric acid application resulted in highest level of aluminum (Al) and iron (Fe) in plants foliage resulting in severe phytotoxic effects. Total Pb phytoextraction was significantly highest in plants treated with combined chemical application of B + C and B + C + H. Suppression of AMF activities by benomyl application significantly increased concentrations of Al and Fe in roots. Application of benomyl reduced AMF colonization but was also shown to dramatically increase levels of septa fungi infection as compared to Control plants. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. SlMAPK3 enhances tolerance to tomato yellow leaf curl virus (TYLCV) by regulating salicylic acid and jasmonic acid signaling in tomato (Solanum lycopersicum).

    Science.gov (United States)

    Li, Yunzhou; Qin, Lei; Zhao, Jingjing; Muhammad, Tayeb; Cao, Hehe; Li, Hailiang; Zhang, Yan; Liang, Yan

    2017-01-01

    Several recent studies have reported on the role of mitogen-activated protein kinase (MAPK3) in plant immune responses. However, little is known about how MAPK3 functions in tomato (Solanum lycopersicum L.) infected with tomato yellow leaf curl virus (TYLCV). There is also uncertainty about the connection between plant MAPK3 and the salicylic acid (SA) and jasmonic acid (JA) defense-signaling pathways. The results of this study indicated that SlMAPK3 participates in the antiviral response against TYLCV. Tomato seedlings were inoculated with TYLCV to investigate the possible roles of SlMAPK1, SlMAPK2, and SlMAPK3 against this virus. Inoculation with TYLCV strongly induced the expression and the activity of all three genes. Silencing of SlMAPK1, SlMAPK2, and SlMAPK3 reduced tolerance to TYLCV, increased leaf H2O2 concentrations, and attenuated expression of defense-related genes after TYLCV infection, especially in SlMAPK3-silenced plants. Exogenous SA and methyl jasmonic acid (MeJA) both significantly induced SlMAPK3 expression in tomato leaves. Over-expression of SlMAPK3 increased the transcript levels of SA/JA-mediated defense-related genes (PR1, PR1b/SlLapA, SlPI-I, and SlPI-II) and enhanced tolerance to TYLCV. After TYLCV inoculation, the leaves of SlMAPK3 over-expressed plants compared with wild type plants showed less H2O2 accumulation and greater superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) activity. Overall, the results suggested that SlMAPK3 participates in the antiviral response of tomato to TYLCV, and that this process may be through either the SA or JA defense-signaling pathways.

  9. SlMAPK3 enhances tolerance to tomato yellow leaf curl virus (TYLCV by regulating salicylic acid and jasmonic acid signaling in tomato (Solanum lycopersicum.

    Directory of Open Access Journals (Sweden)

    Yunzhou Li

    Full Text Available Several recent studies have reported on the role of mitogen-activated protein kinase (MAPK3 in plant immune responses. However, little is known about how MAPK3 functions in tomato (Solanum lycopersicum L. infected with tomato yellow leaf curl virus (TYLCV. There is also uncertainty about the connection between plant MAPK3 and the salicylic acid (SA and jasmonic acid (JA defense-signaling pathways. The results of this study indicated that SlMAPK3 participates in the antiviral response against TYLCV. Tomato seedlings were inoculated with TYLCV to investigate the possible roles of SlMAPK1, SlMAPK2, and SlMAPK3 against this virus. Inoculation with TYLCV strongly induced the expression and the activity of all three genes. Silencing of SlMAPK1, SlMAPK2, and SlMAPK3 reduced tolerance to TYLCV, increased leaf H2O2 concentrations, and attenuated expression of defense-related genes after TYLCV infection, especially in SlMAPK3-silenced plants. Exogenous SA and methyl jasmonic acid (MeJA both significantly induced SlMAPK3 expression in tomato leaves. Over-expression of SlMAPK3 increased the transcript levels of SA/JA-mediated defense-related genes (PR1, PR1b/SlLapA, SlPI-I, and SlPI-II and enhanced tolerance to TYLCV. After TYLCV inoculation, the leaves of SlMAPK3 over-expressed plants compared with wild type plants showed less H2O2 accumulation and greater superoxide dismutase (SOD, peroxidase (POD, catalase (CAT, and ascorbate peroxidase (APX activity. Overall, the results suggested that SlMAPK3 participates in the antiviral response of tomato to TYLCV, and that this process may be through either the SA or JA defense-signaling pathways.

  10. Uncovering the unknown: A grounded theory study exploring the impact of self-awareness on the culture of feedback in residency education.

    Science.gov (United States)

    Ramani, Subha; Könings, Karen; Mann, Karen V; van der Vleuten, Cees

    2017-10-01

    Self-assessment and reflection are essential for meaningful feedback. We aimed to explore whether the well-known Johari window model of self-awareness could guide feedback conversations between faculty and residents and enhance the institutional feedback culture. We had previously explored perceptions of residents and faculty regarding sociocultural factors impacting feedback. We re-analyzed data targeting themes related to self-assessment, reflection, feedback seeking and acceptance, aiming to generate individual and institutional feedback strategies applicable to each quadrant of the window. We identified the following themes for each quadrant: (1) Behaviors known to self and others - Validating the known; (2) Behaviors unknown to self but known to others - Accepting the blind; (3) Behaviors known to self and unknown to others - Disclosure of hidden; and (4) Behaviors unknown to self and others - Uncovering the unknown. Normalizing self-disclosure of limitations, encouraging feedback seeking, training in nonjudgmental feedback and providing opportunities for longitudinal relationships could promote self-awareness, ultimately expanding the "open" quadrant of the Johari window. The Johari window, a model of self-awareness in interpersonal communications, could provide a robust framework for individuals to improve their feedback conversations and institutions to design feedback initiatives that enhance its quality and impact.

  11. Comparative analysis of the Photorhabdus luminescens and the Yersinia enterocolitica genomes: uncovering candidate genes involved in insect pathogenicity

    Directory of Open Access Journals (Sweden)

    Fuchs Thilo M

    2008-01-01

    Full Text Available Abstract Background Photorhabdus luminescens and Yersinia enterocolitica are both enteric bacteria which are associated with insects. P. luminescens lives in symbiosis with soil nematodes and is highly pathogenic towards insects but not to humans. In contrast, Y. enterocolitica is widely found in the environment and mainly known to cause gastroenteritis in men, but has only recently been shown to be also toxic for insects. It is expected that both pathogens share an overlap of genetic determinants that play a role within the insect host. Results A selective genome comparison was applied. Proteins belonging to the class of two-component regulatory systems, quorum sensing, universal stress proteins, and c-di-GMP signalling have been analysed. The interorganismic synopsis of selected regulatory systems uncovered common and distinct signalling mechanisms of both pathogens used for perception of signals within the insect host. Particularly, a new class of LuxR-like regulators was identified, which might be involved in detecting insect-specific molecules. In addition, the genetic overlap unravelled a two-component system that is unique for the genera Photorhabdus and Yersinia and is therefore suggested to play a major role in the pathogen-insect relationship. Our analysis also highlights factors of both pathogens that are expressed at low temperatures as encountered in insects in contrast to higher (body temperature, providing evidence that temperature is a yet under-investigated environmental signal for bacterial adaptation to various hosts. Common degradative metabolic pathways are described that might be used to explore nutrients within the insect gut or hemolymph, thus enabling the proliferation of P. luminescens and Y. enterocolitica in their invertebrate hosts. A strikingly higher number of genes encoding insecticidal toxins and other virulence factors in P. luminescens compared to Y. enterocolitica correlates with the higher virulence of P

  12. High glucose enhances cAMP level and extracellular signal-regulated kinase phosphorylation in Chinese hamster ovary cell: Usage of Br-cAMP in foreign protein β-galactosidase expression.

    Science.gov (United States)

    Lin, Hsiao-Hsien; Lee, Tsung-Yih; Liu, Ting-Wei; Tseng, Ching-Ping

    2017-07-01

    Glucose is a carbon source for Chinese hamster ovary (CHO) cell growth, while low growth rate is considered to enhance the production of recombinant proteins. The present study reveals that glucose concentrations higher than 1 g/L reduce the growth rate and substantially increase in cAMP (∼300%) at a high glucose concentration (10 g/L). High glucose also enhances the phosphorylation of extracellular signal-regulated kinase (ERK) and p27 kip by Western blot analysis. To determine whether the phosphorylation of ERK is involved in the mechanism, a cyclic-AMP dependent protein kinase A (PKA) inhibitor (H-8) or MEK (MAPKK) inhibitor (PD98059) was added to block ERK phosphorylation. We show that both the high glucose-induced ERK phosphorylation and growth rate return to baseline levels. These results suggest that the cAMP/PKA and MAP signaling pathways are involved in the abovementioned mechanism. Interestingly, the direct addition of 8-bromo-cAMP (Br-cAMP), a membrane-permeable cAMP analog, can mimic the similar effects produced by high glucose. Subsequently Br-cAMP could induce β-galactosidase (β-Gal) recombinant protein expression by 1.6-fold. Furthermore, Br-cAMP can additionally enhance the β-Gal production (from 2.8- to 4.5-fold) when CHO cells were stimulated with glycerol, thymidine, dimethyl sulfoxide, pentanoic acid, or sodium butyrate. Thus, Br-cAMP may be used as an alternative agent in promoting foreign protein expression for CHO cells. Copyright © 2017. Published by Elsevier B.V.

  13. Uncovering the Links between Prospective Teachers' Personal Responsibility, Academic Optimism, Hope, and Emotions about Teaching: A Mediation Analysis

    Science.gov (United States)

    Eren, Altay

    2014-01-01

    Prospective teachers' sense of personal responsibility has not been examined together with their academic optimism, hope, and emotions about teaching in a single study to date. However, to consider hope, academic optimism, and emotions about teaching together with personal responsibility is important to uncover the factors affecting…

  14. Characterization of Smoc-1 uncovers two transcript variants showing differential tissue and age specific expression in Bubalus bubalis

    Science.gov (United States)

    Srivastava, Jyoti; Premi, Sanjay; Kumar, Sudhir; Parwez, Iqbal; Ali, Sher

    2007-01-01

    Background Secreted modular calcium binding protein-1 (Smoc-1) belongs to the BM-40 family which has been implicated with tissue remodeling, angiogenesis and bone mineralization. Besides its anticipated role in embryogenesis, Smoc-1 has been characterized only in a few mammalian species. We made use of the consensus sequence (5' CACCTCTCCACCTGCC 3') of 33.15 repeat loci to explore the buffalo transcriptome and uncovered the Smoc-1 transcript tagged with this repeat. The main objective of this study was to gain an insight into its structural and functional organization, and expressional status of Smoc-1 in water buffalo, Bubalus bubalis. Results We cloned and characterized the buffalo Smoc-1, including its copy number status, in-vitro protein expression, tissue & age specific transcription/translation, chromosomal mapping and localization to the basement membrane zone. Buffalo Smoc-1 was found to encode a secreted matricellular glycoprotein containing two EF-hand calcium binding motifs homologous to that of BM-40/SPARC family. In buffalo, this single copy gene consisted of 12 exons and was mapped onto the acrocentric chromosome 11. Though this gene was found to be evolutionarily conserved, the buffalo Smoc-1 showed conspicuous nucleotide/amino acid changes altering its secondary structure compared to that in other mammals. In silico analysis of the Smoc-1 proposed its glycoprotein nature with a calcium dependent conformation. Further, we unveiled two transcript variants of this gene, varying in their 3'UTR lengths but both coding for identical protein(s). Smoc-1 evinced highest expression of both the variants in liver and modest to negligible in other tissues. The relative expression of variant-02 was markedly higher compared to that of variant-01 in all the tissues examined. Moreover, expression of Smoc-1, though modest during the early ages, was conspicuously enhanced after 1 year and remained consistently higher during the entire life span of buffalo with gradual

  15. Combining Novel Simulation Methods and Nucleation Theory to Uncover the Secrets of Gas Hydrates

    Energy Technology Data Exchange (ETDEWEB)

    Keyes, Thomas [Boston Univ., MA (United States). Dept. of Chemistry

    2016-04-14

    Conventional computer simulation methods fail for some of the most important problems. With the design and application of innovative algorithms, this project achieved a breakthrough for the case of systems undergoing first-order phase transitions. We gave a complete simulation protocol based upon a well optimized version of our "generalized replica exchange method". The transition of primary interest was gas hydrate formation, a process of significance for climate science and natural gas retrieval. Since hydrates consist of guest molecules in the cages of a water matrix, β ice, the freezing and melting of water was also studied. New information was uncovered about the transition pathways and thermodynamics. Some highlights are 1. the finding that in a very dilute solution without deep supercooling, representative of real-world conditions and very challenging to conventional algorithms, methane can act as a catalyst to drive the formation of large amounts of β ice with empty cages as metastable intermediates, which might be filled by additional methane in a mechanism for hydrate formation, and 2. illumination of the role of metastable cubic ice in water freezing, with determination of the surface tensions of the cubic, hexagonal, and β ices, and the free energy difference of cubic vs hexagonal ice. Work was begun on lipid systems, bilayers and nanoreactors promising for energy-related photoreductions, and targets for future research. Our methods yielded what is arguably the most complete description of the composite lipid/water phases and the transition pathways among them.

  16. Uncovering neurodevelopmental windows of susceptibility to manganese exposure using dentine microspatial analyses.

    Science.gov (United States)

    Claus Henn, Birgit; Austin, Christine; Coull, Brent A; Schnaas, Lourdes; Gennings, Chris; Horton, Megan K; Hernández-Ávila, Mauricio; Hu, Howard; Téllez-Rojo, Martha Maria; Wright, Robert O; Arora, Manish

    2018-02-01

    Associations between manganese (Mn) and neurodevelopment may depend on dose and exposure timing, but most studies cannot measure exposure variability over time well. We apply temporally informative tooth-matrix biomarkers to uncover windows of susceptibility in early life when Mn is associated with visual motor ability in childhood. We also explore effect modification by lead (Pb) and child sex. Participants were drawn from the ELEMENT (Early Life Exposures in MExico and NeuroToxicology) longitudinal birth cohort studies. We reconstructed dose and timing of prenatal and early postnatal Mn and Pb exposures for 138 children by analyzing deciduous teeth using laser ablation-inductively coupled plasma-mass spectrometry. Neurodevelopment was assessed between 6 and 16 years of age using the Wide Range Assessment of Visual Motor Abilities (WRAVMA). Mn associations with total WRAVMA scores and subscales were estimated with multivariable generalized additive mixed models. We examined Mn interactions with Pb and child sex in stratified models. Levels of dentine Mn were highest in the second trimester and declined steeply over the prenatal period, with a slower rate of decline after birth. Mn was positively associated with visual spatial and total WRAVMA scores in the second trimester, among children with lower (windows in which Mn was associated with visual-spatial abilities. Our results suggest that Mn associations are driven in large part by exposure timing, with beneficial effects found for prenatal levels and toxic effects found for postnatal levels. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Ethnomathematics study: uncovering units of length, area, and volume in Kampung Naga Society

    Science.gov (United States)

    Septianawati, T.; Turmudi; Puspita, E.

    2017-02-01

    During this time, mathematics is considered as something neutral and not associated with culture. It can be seen from mathematics learning in the school which adopt many of foreign mathematics learning are considered more advanced (western). In fact, Indonesia is a rich country in cultural diversity. In the cultural activities, there are mathematical ideas that were considered a important thing in the mathematics learning. A study that examines the idea or mathematical practices in a variety of cultural activities are known as ethnomathematics. In Indonesia, there are some ethnic maintain their ancestral traditions, one of them is Kampung Naga. Therefore, this study was conducted in Kampung Naga. This study aims to uncover units of length, area, and volume used by Kampung Naga society. This study used a qualitative approach and ethnography methods. In this research, data collection is done through the principles of ethnography such as observation, interviews, documentation, and field notes. The results of this study are units of length, area, and volume used by Kampung Naga society and its conversion into standard units. This research is expected to give information to the public that mathematics has a relationship with culture and become recommendation to mathematics curriculum in Indonesia.

  18. The work is never ending: uncovering teamwork sustainability using realistic evaluation.

    Science.gov (United States)

    Frykman, Mandus; von Thiele Schwarz, Ulrica; Muntlin Athlin, Åsa; Hasson, Henna; Mazzocato, Pamela

    2017-03-20

    Purpose The purpose of this paper is to uncover the mechanisms influencing the sustainability of behavior changes following the implementation of teamwork. Design/methodology/approach Realistic evaluation was combined with a framework (DCOM®) based on applied behavior analysis to study the sustainability of behavior changes two and a half years after the initial implementation of teamwork at an emergency department. The DCOM® framework was used to categorize the mechanisms of behavior change interventions (BCIs) into the four categories of direction, competence, opportunity, and motivation. Non-participant observation and interview data were used. Findings The teamwork behaviors were not sustained. A substantial fallback in managerial activities in combination with a complex context contributed to reduced direction, opportunity, and motivation. Reduced direction made staff members unclear about how and why they should work in teams. Deterioration of opportunity was evident from the lack of problem-solving resources resulting in accumulated barriers to teamwork. Motivation in terms of management support and feedback was reduced. Practical implications The implementation of complex organizational changes in complex healthcare contexts requires continuous adaption and managerial activities well beyond the initial implementation period. Originality/value By integrating the DCOM® framework with realistic evaluation, this study responds to the call for theoretically based research on behavioral mechanisms that can explain how BCIs interact with context and how this interaction influences sustainability.

  19. Gene Expression Deconvolution for Uncovering Molecular Signatures in Response to Therapy in Juvenile Idiopathic Arthritis.

    Directory of Open Access Journals (Sweden)

    Ang Cui

    Full Text Available Gene expression-based signatures help identify pathways relevant to diseases and treatments, but are challenging to construct when there is a diversity of disease mechanisms and treatments in patients with complex diseases. To overcome this challenge, we present a new application of an in silico gene expression deconvolution method, ISOpure-S1, and apply it to identify a common gene expression signature corresponding to response to treatment in 33 juvenile idiopathic arthritis (JIA patients. Using pre- and post-treatment gene expression profiles only, we found a gene expression signature that significantly correlated with a reduction in the number of joints with active arthritis, a measure of clinical outcome (Spearman rho = 0.44, p = 0.040, Bonferroni correction. This signature may be associated with a decrease in T-cells, monocytes, neutrophils and platelets. The products of most differentially expressed genes include known biomarkers for JIA such as major histocompatibility complexes and interleukins, as well as novel biomarkers including α-defensins. This method is readily applicable to expression datasets of other complex diseases to uncover shared mechanistic patterns in heterogeneous samples.

  20. Uncovering a New Moral Dilemma of Economic Optimization in Biotechnological Processing.

    Science.gov (United States)

    Vochozka, Marek; Stehel, Vojtěch; Maroušková, Anna

    2017-06-08

    The trend of emerging biorefineries is to process the harvest as efficiently as possible and without any waste. From the most valuable phytomass, refined medicines, enzymes, dyes and other special reactants are created. Functional foods, food ingredients, oils, alcohol, solvents, plastics, fillers and a wide variety of other chemical products follow. After being treated with nutrient recovery techniques (for fertilizer production), biofuels or soil improvers are produced from the leftovers. Economic optimization algorithms have confirmed that such complex biorefineries can be financially viable only when a high degree of feedstock concentration is included. Because the plant material is extremely voluminous before processing, the farming intensity of special plants increases in the nearest vicinity of agglomerations where the biorefineries are built for logistical reasons. Interdisciplinary analyses revealed that these optimization measures lead to significantly increased pollen levels in neighbouring urban areas and subsequently an increased risk of allergies, respectively costs to the national health system. A new moral dilemma between the shareholder's profit and public interest was uncovered and subjected to disputation.

  1. Uncovering Special Nuclear Materials by Low-energy Nuclear Reaction Imaging.

    Science.gov (United States)

    Rose, P B; Erickson, A S; Mayer, M; Nattress, J; Jovanovic, I

    2016-04-18

    Weapons-grade uranium and plutonium could be used as nuclear explosives with extreme destructive potential. The problem of their detection, especially in standard cargo containers during transit, has been described as "searching for a needle in a haystack" because of the inherently low rate of spontaneous emission of characteristic penetrating radiation and the ease of its shielding. Currently, the only practical approach for uncovering well-shielded special nuclear materials is by use of active interrogation using an external radiation source. However, the similarity of these materials to shielding and the required radiation doses that may exceed regulatory limits prevent this method from being widely used in practice. We introduce a low-dose active detection technique, referred to as low-energy nuclear reaction imaging, which exploits the physics of interactions of multi-MeV monoenergetic photons and neutrons to simultaneously measure the material's areal density and effective atomic number, while confirming the presence of fissionable materials by observing the beta-delayed neutron emission. For the first time, we demonstrate identification and imaging of uranium with this novel technique using a simple yet robust source, setting the stage for its wide adoption in security applications.

  2. Uncovering the Connection Between Low-Frequency Dynamics and Phase Transformation Phenomena in Molecular Solids

    Science.gov (United States)

    Ruggiero, Michael T.; Zhang, Wei; Bond, Andrew D.; Mittleman, Daniel M.; Zeitler, J. Axel

    2018-05-01

    The low-frequency motions of molecules in the condensed phase have been shown to be vital to a large number of physical properties and processes. However, in the case of disordered systems, it is often difficult to elucidate the atomic-level details surrounding these phenomena. In this work, we have performed an extensive experimental and computational study on the molecular solid camphor, which exhibits a rich and complex structure-dynamics relationship, and undergoes an order-disorder transition near ambient conditions. The combination of x-ray diffraction, variable temperature and pressure terahertz time-domain spectroscopy, ab initio molecular dynamics, and periodic density functional theory calculations enables a complete picture of the phase transition to be obtained, inclusive of mechanistic, structural, and thermodynamic phenomena. Additionally, the low-frequency vibrations of a disordered solid are characterized for the first time with atomic-level precision, uncovering a clear link between such motions and the phase transformation. Overall, this combination of methods allows for significant details to be obtained for disordered solids and the associated transformations, providing a framework that can be directly applied for a wide range of similar systems.

  3. Affinity purification mass spectrometry analysis of PD-1 uncovers SAP as a new checkpoint inhibitor.

    Science.gov (United States)

    Peled, Michael; Tocheva, Anna S; Sandigursky, Sabina; Nayak, Shruti; Philips, Elliot A; Nichols, Kim E; Strazza, Marianne; Azoulay-Alfaguter, Inbar; Askenazi, Manor; Neel, Benjamin G; Pelzek, Adam J; Ueberheide, Beatrix; Mor, Adam

    2018-01-16

    Programmed cell death-1 (PD-1) is an essential inhibitory receptor in T cells. Antibodies targeting PD-1 elicit durable clinical responses in patients with multiple tumor indications. Nevertheless, a significant proportion of patients do not respond to anti-PD-1 treatment, and a better understanding of the signaling pathways downstream of PD-1 could provide biomarkers for those whose tumors respond and new therapeutic approaches for those whose tumors do not. We used affinity purification mass spectrometry to uncover multiple proteins associated with PD-1. Among these proteins, signaling lymphocytic activation molecule-associated protein (SAP) was functionally and mechanistically analyzed for its contribution to PD-1 inhibitory responses. Silencing of SAP augmented and overexpression blocked PD-1 function. T cells from patients with X-linked lymphoproliferative disease (XLP), who lack functional SAP, were hyperresponsive to PD-1 signaling, confirming its inhibitory role downstream of PD-1. Strikingly, signaling downstream of PD-1 in purified T cell subsets did not correlate with PD-1 surface expression but was inversely correlated with intracellular SAP levels. Mechanistically, SAP opposed PD-1 function by acting as a molecular shield of key tyrosine residues that are targets for the tyrosine phosphatase SHP2, which mediates PD-1 inhibitory properties. Our results identify SAP as an inhibitor of PD-1 function and SHP2 as a potential therapeutic target in patients with XLP.

  4. Novel resistance functions uncovered using functional metagenomic investigations of resistance reservoirs

    Directory of Open Access Journals (Sweden)

    Erica C. Pehrsson

    2013-06-01

    Full Text Available Rates of infection with antibiotic-resistant bacteria have increased precipitously over the past several decades, with far-reaching healthcare and societal costs. Recent evidence has established a link between antibiotic resistance genes in human pathogens and those found in non-pathogenic, commensal, and environmental organisms, prompting deeper investigation of natural and human-associated reservoirs of antibiotic resistance. Functional metagenomic selections, in which shotgun-cloned DNA fragments are selected for their ability to confer survival to an indicator host, have been increasingly applied to the characterization of many antibiotic resistance reservoirs. These experiments have demonstrated that antibiotic resistance genes are highly diverse and widely distributed, many times bearing little to no similarity to known sequences. Through unbiased selections for survival to antibiotic exposure, functional metagenomics can improve annotations by reducing the discovery of false-positive resistance and by allowing for the identification of previously unrecognizable resistance genes. In this review, we summarize the novel resistance functions uncovered using functional metagenomic investigations of natural and human-impacted resistance reservoirs. Examples of novel antibiotic resistance genes include those highly divergent from known sequences, those for which sequence is entirely unable to predict resistance function, bifunctional resistance genes, and those with unconventional, atypical resistance mechanisms. Overcoming antibiotic resistance in the clinic will require a better understanding of existing resistance reservoirs and the dissemination networks that govern horizontal gene exchange, informing best practices to limit the spread of resistance-conferring genes to human pathogens.

  5. Plastome Sequencing of Ten Nonmodel Crop Species Uncovers a Large Insertion of Mitochondrial DNA in Cashew.

    Science.gov (United States)

    Rabah, Samar O; Lee, Chaehee; Hajrah, Nahid H; Makki, Rania M; Alharby, Hesham F; Alhebshi, Alawiah M; Sabir, Jamal S M; Jansen, Robert K; Ruhlman, Tracey A

    2017-11-01

    In plant evolution, intracellular gene transfer (IGT) is a prevalent, ongoing process. While nuclear and mitochondrial genomes are known to integrate foreign DNA via IGT and horizontal gene transfer (HGT), plastid genomes (plastomes) have resisted foreign DNA incorporation and only recently has IGT been uncovered in the plastomes of a few land plants. In this study, we completed plastome sequences for l0 crop species and describe a number of structural features including variation in gene and intron content, inversions, and expansion and contraction of the inverted repeat (IR). We identified a putative in cinnamon ( J. Presl) and other sequenced Lauraceae and an apparent functional transfer of to the nucleus of quinoa ( Willd.). In the orchard tree cashew ( L.), we report the insertion of an ∼6.7-kb fragment of mitochondrial DNA into the plastome IR. BLASTn analyses returned high identity hits to mitogenome sequences including an intact open reading frame. Using three plastome markers for five species of , we generated a phylogeny to investigate the distribution and timing of the insertion. Four species share the insertion, suggesting that this event occurred <20 million yr ago in a single clade in the genus. Our study extends the observation of mitochondrial to plastome IGT to include long-lived tree species. While previous studies have suggested possible mechanisms facilitating IGT to the plastome, more examples of this phenomenon, along with more complete mitogenome sequences, will be required before a common, or variable, mechanism can be elucidated. Copyright © 2017 Crop Science Society of America.

  6. Degenerate primer MOB typing of multiresistant clinical isolates of E. coli uncovers new plasmid backbones.

    Science.gov (United States)

    Garcillán-Barcia, M Pilar; Ruiz del Castillo, Belén; Alvarado, Andrés; de la Cruz, Fernando; Martínez-Martínez, Luis

    2015-01-01

    Degenerate Primer MOB Typing is a PCR-based protocol for the classification of γ-proteobacterial transmissible plasmids in five phylogenetic relaxase MOB families. It was applied to a multiresistant E. coli collection, previously characterized by PCR-based replicon-typing, in order to compare both methods. Plasmids from 32 clinical isolates of multiresistant E. coli (19 extended spectrum beta-lactamase producers and 13 non producers) and their transconjugants were analyzed. A total of 95 relaxases were detected, at least one per isolate, underscoring the high potential of these strains for antibiotic-resistance transmission. MOBP12 and MOBF12 plasmids were the most abundant. Most MOB subfamilies detected were present in both subsets of the collection, indicating a shared mobilome among multiresistant E. coli. The plasmid profile obtained by both methods was compared, which provided useful data upon which decisions related to the implementation of detection methods in the clinic could be based. The phylogenetic depth at which replicon and MOB-typing classify plasmids is different. While replicon-typing aims at plasmid replication regions with non-degenerate primers, MOB-typing classifies plasmids into relaxase subfamilies using degenerate primers. As a result, MOB-typing provides a deeper phylogenetic depth than replicon-typing and new plasmid groups are uncovered. Significantly, MOB typing identified 17 plasmids and an integrative and conjugative element, which were not detected by replicon-typing. Four of these backbones were different from previously reported elements. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Uncovering buffered pleiotropy: a genome-scale screen for mel-28 genetic interactors in Caenorhabditis elegans.

    Science.gov (United States)

    Fernandez, Anita G; Mis, Emily K; Lai, Allison; Mauro, Michael; Quental, Angela; Bock, Carly; Piano, Fabio

    2014-01-10

    mel-28 (maternal-effect-lethal-28) encodes a conserved protein required for nuclear envelope function and chromosome segregation in Caenorhabditis elegans. Because mel-28 is a strict maternal-effect lethal gene, its function is required in the early embryo but appears to be dispensable for larval development. We wanted to test the idea that mel-28 has postembryonic roles that are buffered by the contributions of other genes. To find genes that act coordinately with mel-28, we did an RNA interference-based genetic interaction screen using mel-28 and wild-type larvae. We screened 18,364 clones and identified 65 genes that cause sterility in mel-28 but not wild-type worms. Some of these genes encode components of the nuclear pore. In addition we identified genes involved in dynein and dynactin function, vesicle transport, and cell-matrix attachments. By screening mel-28 larvae we have bypassed the requirement for mel-28 in the embryo, uncovering pleiotropic functions for mel-28 later in development that are normally provided by other genes. This work contributes toward revealing the gene networks that underlie cellular processes and reveals roles for a maternal-effect lethal gene later in development.

  8. Uncovering the lived experiences of junior and senior undergraduate female science majors

    Science.gov (United States)

    Adornato, Philip

    The following dissertation focuses on a case study that uses critical theory, social learning theory, identity theory, liberal feminine theory, and motivation theory to conduct a narrative describing the lived experience of females and their performance in two highly selective private university, where students can cross-register between school, while majoring in science, technology, engineering and mathematics (STEM). Through the use of narratives, the research attempts to shed additional light on the informal and formal science learning experiences that motivates young females to major in STEM in order to help increase the number of women entering STEM careers and retaining women in STEM majors. In the addition to the narratives, surveys were performed to encompass a larger audience while looking for themes and phenomena which explore what captivates and motivates young females' interests in science and continues to nurture and facilitate their growth throughout high school and college, and propel them into a major in STEM in college. The purpose of this study was to uncover the lived experiences of junior and senior undergraduate female science majors during their formal and informal education, their science motivation to learn science, their science identities, and any experiences in gender inequity they may have encountered. The findings have implications for young women deciding on future careers and majors through early exposure and guidance, understanding and recognizing what gender discrimination, and the positive effects of mentorships.

  9. Uncovering the inertia of dislocation motion and negative mechanical response in crystals.

    Science.gov (United States)

    Tang, Yizhe

    2018-01-09

    Dislocations are linear defects in crystals and their motion controls crystals' mechanical behavior. The dissipative nature of dislocation propagation is generally accepted although the specific mechanisms are still not fully understood. The inertia, which is undoubtedly the nature of motion for particles with mass, seems much less convincing for configuration propagation. We utilize atomistic simulations in conditions that minimize dissipative effects to enable uncovering of the hidden nature of dislocation motion, in three typical model metals Mg, Cu and Ta. We find that, with less/no dissipation, dislocation motion is under-damped and explicitly inertial at both low and high velocities. The inertia of dislocation motion is intrinsic, and more fundamental than the dissipative nature. The inertia originates from the kinetic energy imparted from strain energy and stored in the moving core. Peculiar negative mechanical response associated with the inertia is also discovered. These findings shed light on the fundamental nature of dislocation motion, reveal the underlying physics, and provide a new physical explanation for phenomena relevant to high-velocity dislocations.

  10. Newly Uncovered Large-Scale Component of the Northern Jet in R Aqr

    Science.gov (United States)

    Montez, Rodolfo; Karovska, Margarita; Nichols, Joy S.; Kashyap, Vinay

    2017-06-01

    R Aqr is a symbiotic system comprised a compact white dwarf and Mira giant star. The interaction of these stars is responsible for the presence of a two-sided jet structure that is seen across the electromagnetic spectrum. X-ray emission from the jet was first discovered in 2000 with an observation by the Chandra X-ray Observatory. Since then follow-up observations have traced the evolution of the X-ray emission from the jet and a central compact source. In X-rays, the NE jet is brighter than the SW jet, but the full extent of the SW jet was larger - before it began fading below the detection threshold. However, we have uncovered evidence for large-scale emission associated with the NE jet that matches the extent of the SW jet. The emission has escaped previous identification because it is near the detection threshold, but it has been present since the first 2000 observation and clearly evolves in subsequent observations. We present our study of the emission from this component of the NE jet, its relationship to multiwavelength observations, and how it impacts our interpretation of the jet-phenomenon in R Aqr.

  11. Seeing the forest through the trees: uncovering phenomic complexity through interactive network visualization.

    Science.gov (United States)

    Warner, Jeremy L; Denny, Joshua C; Kreda, David A; Alterovitz, Gil

    2015-03-01

    Our aim was to uncover unrecognized phenomic relationships using force-based network visualization methods, based on observed electronic medical record data. A primary phenotype was defined from actual patient profiles in the Multiparameter Intelligent Monitoring in Intensive Care II database. Network visualizations depicting primary relationships were compared to those incorporating secondary adjacencies. Interactivity was enabled through a phenotype visualization software concept: the Phenomics Advisor. Subendocardial infarction with cardiac arrest was demonstrated as a sample phenotype; there were 332 primarily adjacent diagnoses, with 5423 relationships. Primary network visualization suggested a treatment-related complication phenotype and several rare diagnoses; re-clustering by secondary relationships revealed an emergent cluster of smokers with the metabolic syndrome. Network visualization reveals phenotypic patterns that may have remained occult in pairwise correlation analysis. Visualization of complex data, potentially offered as point-of-care tools on mobile devices, may allow clinicians and researchers to quickly generate hypotheses and gain deeper understanding of patient subpopulations. © The Author 2014. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. Methods uncovering usability issues in medication-related alerting functions: results from a systematic review.

    Science.gov (United States)

    Marcilly, Romaric; Vasseur, Francis; Ammenwerth, Elske; Beuscart-Zephir, Marie-Catherine

    2014-01-01

    This paper aims at listing the methods used to evaluate the usability of medication-related alerting functions and at knowing what type of usability issues those methods allow to detect. A sub-analysis of data from this systematic review has been performed. Methods applied in the included papers were collected. Then, included papers were sorted in four types of evaluation: "expert evaluation", "user- testing/simulation", "on site observation" and "impact studies". The types of usability issues (usability flaws, usage problems and negative outcomes) uncovered by those evaluations were analyzed. Results show that a large set of methods are used. The largest proportion of papers uses "on site observation" evaluation. This is the only evaluation type for which every kind of usability flaws, usage problems and outcomes are detected. It is somehow surprising that, in a usability systematic review, most of the papers included use a method that is not often presented as a usability method. Results are discussed about the opportunity to provide usability information collected after the implementation of the technology during their design process, i.e. before their implementation.

  13. Uncovering molecular relaxation processes with nonlinear spectroscopies in the deep UV

    International Nuclear Information System (INIS)

    West, Brantley A.; Molesky, Brian P.; Giokas, Paul G.; Moran, Andrew M.

    2013-01-01

    Highlights: • We discuss the outlook for multidimensional spectroscopies in the deep UV. • Photophysics are examined in small DNA components at cryogenic temperatures. • Wavepacket motions are detected in ring-opening systems with 2DUV spectroscopy. • Measurements of electronic wavepacket motions in molecules are proposed. - Abstract: Nonlinear laser spectroscopies in the deep UV spectral range are motivated by studies of biological systems and elementary processes in small molecules. This perspective article discusses recent technical advances in this area with a particular emphasis on diffractive optic based approaches to four-wave mixing spectroscopies. Applications to two classes of systems illustrate present experimental capabilities. First, experiments on DNA components at cryogenic temperatures are used to uncover features of excited state potential energy surfaces and vibrational cooling mechanisms. Second, sub-200 fs internal conversion processes and coherent wavepacket motions are investigated in cyclohexadiene and α-terpinene. Finally, we propose new experimental directions that combine methods for producing few-cycle UV laser pulses in noble gases with incoherent detection methods (e.g., photoionization) in experiments with time resolution near a singlefemtosecond. These measurements are motivated by knowledge of extremely fast non-adiabatic dynamics and the resolution of electronic wavepacket motions in molecules

  14. MARS A Cosmic Stepping Stone Uncovering Humanity’s Cosmic Context

    CERN Document Server

    Nolan, Kevin

    2008-01-01

    The questions of our origin and cosmic abundance of life are among the most compelling facing humanity. We have determined much about the nature and origin of the Universe and our place in it, but with virtually all evidence of our origin long since gone from our world and an unimaginably vast Universe still to explore, defining answers are difficult to obtain. For all of the difficulties facing us however, the planet Mars may act as a ‘cosmic stepping stone’ in uncovering some of the answers. Although different today, the origin and early history of both Earth and Mars may have been similar enough to consider an origin to life on both. But because Mars’ planetary processes collapsed over three billion years ago – just as life was beginning to flourish on Earth – a significant and unique record of activity from that era perhaps relevant to the origin of life still resides there today. In recognition of this, both the US and Europe are currently engaged in one of the most ambitious programs of explor...

  15. Podoplanin regulates mammary stem cell function and tumorigenesis by potentiating Wnt/β-catenin signaling.

    Science.gov (United States)

    Bresson, Laura; Faraldo, Marisa M; Di-Cicco, Amandine; Quintanilla, Miguel; Glukhova, Marina A; Deugnier, Marie-Ange

    2018-02-21

    Stem cells (SCs) drive mammary development, giving rise postnatally to an epithelial bilayer composed of luminal and basal myoepithelial cells. Dysregulation of SCs is thought to be at the origin of certain breast cancers; however, the molecular identity of SCs and the factors regulating their function remain poorly defined. We identified the transmembrane protein podoplanin (Pdpn) as a specific marker of the basal compartment, including multipotent SCs, and found Pdpn localized at the basal-luminal interface. Embryonic deletion of Pdpn targeted to basal cells diminished basal and luminal SC activity and affected the expression of several Wnt/β-catenin signaling components in basal cells. Moreover, Pdpn loss attenuated mammary tumor formation in a mouse model of β-catenin-induced breast cancer, limiting tumor-initiating cell expansion and promoting molecular features associated with mesenchymal-to-epithelial cell transition. In line with the loss-of-function data, we demonstrated that mechanistically Pdpn enhances Wnt/β-catenin signaling in mammary basal cells. Overall, this study uncovers a role for Pdpn in mammary SC function and, importantly, identifies Pdpn as a new regulator of Wnt/β-catenin signaling, a key pathway in mammary development and tumorigenesis. © 2018. Published by The Company of Biologists Ltd.

  16. Global analysis of epigenetic regulation of gene expression in response to drought stress in Sorghum.

    Energy Technology Data Exchange (ETDEWEB)

    Reddy, Anireddy [Colorado State Univ., Fort Collins, CO (United States); Ben-Hur, Asa [Colorado State Univ., Fort Collins, CO (United States)

    2017-11-22

    Abiotic stresses including drought are major limiting factors of crop yields and cause significant crop losses. Acquisition of stress tolerance to abiotic stresses requires coordinated regulation of a multitude of biochemical and physiological changes, and most of these changes depend on alterations in gene expression. The goal of this work is to perform global analysis of differential regulation of gene expression and alternative splicing, and their relationship with chromatin landscape in drought sensitive and tolerant cultivars. our Iso-Seq study revealed transcriptome-wide full-length isoforms at an unprecedented scale with over 11000 novel splice isoforms. Additionally, we uncovered alternative polyadenylation sites of ~11000 expressed genes and many novel genes. Overall, Iso-Seq results greatly enhanced sorghum gene annotations that are not only useful in analyzing all our RNA-seq, ChIP-seq and ATAC-seq data but also serve as a great resource to the plant biology community. Our studies identified differentially expressed genes and splicing events that are correlated with the drought-resistant phenotype. An association between alternative splicing and chromatin accessibility was also revealed. Several computational tools developed here (TAPIS and iDiffIR) have been made freely available to the research community in analyzing alternative splicing and differential alternative splicing.

  17. Pnrc2 regulates 3'UTR-mediated decay of segmentation clock-associated transcripts during zebrafish segmentation.

    Science.gov (United States)

    Gallagher, Thomas L; Tietz, Kiel T; Morrow, Zachary T; McCammon, Jasmine M; Goldrich, Michael L; Derr, Nicolas L; Amacher, Sharon L

    2017-09-01

    Vertebrate segmentation is controlled by the segmentation clock, a molecular oscillator that regulates gene expression and cycles rapidly. The expression of many genes oscillates during segmentation, including hairy/Enhancer of split-related (her or Hes) genes, which encode transcriptional repressors that auto-inhibit their own expression, and deltaC (dlc), which encodes a Notch ligand. We previously identified the tortuga (tor) locus in a zebrafish forward genetic screen for genes involved in cyclic transcript regulation and showed that cyclic transcripts accumulate post-splicing in tor mutants. Here we show that cyclic mRNA accumulation in tor mutants is due to loss of pnrc2, which encodes a proline-rich nuclear receptor co-activator implicated in mRNA decay. Using an inducible in vivo reporter system to analyze transcript stability, we find that the her1 3'UTR confers Pnrc2-dependent instability to a heterologous transcript. her1 mRNA decay is Dicer-independent and likely employs a Pnrc2-Upf1-containing mRNA decay complex. Surprisingly, despite accumulation of cyclic transcripts in pnrc2-deficient embryos, we find that cyclic protein is expressed normally. Overall, we show that Pnrc2 promotes 3'UTR-mediated decay of developmentally-regulated segmentation clock transcripts and we uncover an additional post-transcriptional regulatory layer that ensures oscillatory protein expression in the absence of cyclic mRNA decay. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. A Legume TOR Protein Kinase Regulates Rhizobium Symbiosis and Is Essential for Infection and Nodule Development1[OPEN

    Science.gov (United States)

    Blanco, Lourdes; Quinto, Carmen

    2016-01-01

    The target of rapamycin (TOR) protein kinase regulates metabolism, growth, and life span in yeast, animals, and plants in coordination with nutrient status and environmental conditions. The nutrient-dependent nature of TOR functionality makes this kinase a putative regulator of symbiotic associations involving nutrient acquisition. However, TOR’s role in these processes remains to be understood. Here, we uncovered the role of TOR during the bean (Phaseolus vulgaris)-Rhizobium tropici (Rhizobium) symbiotic interaction. TOR was expressed in all tested bean tissues, with higher transcript levels in the root meristems and senesced nodules. We showed TOR promoter expression along the progressing infection thread and in the infected cells of mature nodules. Posttranscriptional gene silencing of TOR using RNA interference (RNAi) showed that this gene is involved in lateral root elongation and root cell organization and also alters the density, size, and number of root hairs. The suppression of TOR transcripts also affected infection thread progression and associated cortical cell divisions, resulting in a drastic reduction of nodule numbers. TOR-RNAi resulted in reduced reactive oxygen species accumulation and altered CyclinD1 and CyclinD3 expression, which are crucial factors for infection thread progression and nodule organogenesis. Enhanced expression of TOR-regulated ATG genes in TOR-RNAi roots suggested that TOR plays a role in the recognition of Rhizobium as a symbiont. Together, these data suggest that TOR plays a vital role in the establishment of root nodule symbiosis in the common bean. PMID:27698253

  19. Human immunodeficiency virus type 1 enhancer-binding protein 3 is essential for the expression of asparagine-linked glycosylation 2 in the regulation of osteoblast and chondrocyte differentiation.

    Science.gov (United States)

    Imamura, Katsuyuki; Maeda, Shingo; Kawamura, Ichiro; Matsuyama, Kanehiro; Shinohara, Naohiro; Yahiro, Yuhei; Nagano, Satoshi; Setoguchi, Takao; Yokouchi, Masahiro; Ishidou, Yasuhiro; Komiya, Setsuro

    2014-04-04

    Human immunodeficiency virus type 1 enhancer-binding protein 3 (Hivep3) suppresses osteoblast differentiation by inducing proteasomal degradation of the osteogenesis master regulator Runx2. In this study, we tested the possibility of cooperation of Hivep1, Hivep2, and Hivep3 in osteoblast and/or chondrocyte differentiation. Microarray analyses with ST-2 bone stroma cells demonstrated that expression of any known osteochondrogenesis-related genes was not commonly affected by the three Hivep siRNAs. Only Hivep3 siRNA promoted osteoblast differentiation in ST-2 cells, whereas all three siRNAs cooperatively suppressed differentiation in ATDC5 chondrocytes. We further used microarray analysis to identify genes commonly down-regulated in both MC3T3-E1 osteoblasts and ST-2 cells upon knockdown of Hivep3 and identified asparagine-linked glycosylation 2 (Alg2), which encodes a mannosyltransferase residing on the endoplasmic reticulum. The Hivep3 siRNA-mediated promotion of osteoblast differentiation was negated by forced Alg2 expression. Alg2 suppressed osteoblast differentiation and bone formation in cultured calvarial bone. Alg2 was immunoprecipitated with Runx2, whereas the combined transfection of Runx2 and Alg2 interfered with Runx2 nuclear localization, which resulted in suppression of Runx2 activity. Chondrocyte differentiation was promoted by Hivep3 overexpression, in concert with increased expression of Creb3l2, whose gene product is the endoplasmic reticulum stress transducer crucial for chondrogenesis. Alg2 silencing suppressed Creb3l2 expression and chondrogenesis of ATDC5 cells, whereas infection of Alg2-expressing virus promoted chondrocyte maturation in cultured cartilage rudiments. Thus, Alg2, as a downstream mediator of Hivep3, suppresses osteogenesis, whereas it promotes chondrogenesis. To our knowledge, this study is the first to link a mannosyltransferase gene to osteochondrogenesis.

  20. Neurokinin-1 receptor blocker CP-99 994 improved emesis induced by cisplatin via regulating the activity of gastric distention responsive neurons in the dorsal motor nucleus of vagus and enhancing gastric motility in rats.

    Science.gov (United States)

    Sun, X; Xu, L; Guo, F; Luo, W; Gao, S; Luan, X

    2017-10-01

    Nowadays, chemotherapy induced nausea and vomiting (CINV) is still common in patients with cancer. It was reported that substance P mediated CINV via neurokinin-1 (NK 1 ) receptor and antagonists of NK 1 receptor has been proved useful for treating CINV but the mechanism are not fully understood. This study aimed to examine the role of NK 1 receptor blocker, CP-99 994, when administrated into dorsal motor nucleus of vagus (DMNV), on the cisplatin-induced emesis in rats and the possible mechanism. Rats' kaolin intake, food intake, and bodyweight were recorded every day; gastric contraction activity was recorded in conscious rats through a force transducer implanted into the stomach; gastric emptying was monitored using the phenol red method; single unit extracellular firing in the DMNV were recorded. DMNV microinjection of CP-99 994 reduced the changes of increased kaolin consumption and suppressed food intake in cisplatin-treated rats; enhanced the gastric contraction activity dose-dependently in control and cisplatin-treated rats but enhanced gastric emptying only in cisplatin-treated rats; reduced the firing rate of gastric distention inhibited (GD-I) neurons but increased the firing rate of GD excited (GD-E) neurons in the DMNV. The effects of CP-99 994 on gastric motility and neuronal activity were stronger in cisplatin-treated rats than those of control rats. Our results suggested that CP-99 994 could improve emesis induced by cisplatin by regulating gastric motility and gastric related neuronal activity in the DMNV. © 2017 John Wiley & Sons Ltd.

  1. Enhancement of Cellular Antioxidant-Defence Preserves Diastolic Dysfunction via Regulation of Both Diastolic Zn2+ and Ca2+ and Prevention of RyR2-Leak in Hyperglycemic Cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Erkan Tuncay

    2014-01-01

    Full Text Available We examined whether cellular antioxidant-defence enhancement preserves diastolic dysfunction via regulation of both diastolic intracellular free Zn2+ and Ca2+ levels (Zn2+i and Ca2+i levels N-acetyl cysteine (NAC treatment (4 weeks of diabetic rats preserved altered cellular redox state and also prevented diabetes-induced tissue damage and diastolic dysfunction with marked normalizations in the resting Zn2+i and Ca2+i. The kinetic parameters of transient changes in Zn2+ and Ca2+ under electrical stimulation and the spatiotemporal properties of Zn2+ and Ca2+ sparks in resting cells are found to be normal in the treated diabetic group. Biochemical analysis demonstrated that the NAC treatment also antagonized hyperphosphorylation of cardiac ryanodine receptors (RyR2 and significantly restored depleted protein levels of both RyR2 and calstabin2. Incubation of cardiomyocytes with 10 µM ZnCl2 exerted hyperphosphorylation in RyR2 as well as higher phosphorphorylations in both PKA and CaMKII in a concentration-dependent manner, similar to hyperglycemia. Our present data also showed that a subcellular oxidative stress marker, NF-κB, can be activated if the cells are exposed directly to Zn2+. We thus for the first time report that an enhancement of antioxidant defence in diabetics via directly targeting heart seems to prevent diastolic dysfunction due to modulation of RyR2 macromolecular-complex thereby leading to normalized Ca2+i and Zn2+i in cardiomyocytes.

  2. NFAT5-Regulated Macrophage Polarization Supports the Proinflammatory Function of Macrophages and T Lymphocytes.

    Science.gov (United States)

    Tellechea, Mónica; Buxadé, Maria; Tejedor, Sonia; Aramburu, Jose; López-Rodríguez, Cristina

    2018-01-01

    Macrophages are exquisite sensors of tissue homeostasis that can rapidly switch between pro- and anti-inflammatory or regulatory modes to respond to perturbations in their microenvironment. This functional plasticity involves a precise orchestration of gene expression patterns whose transcriptional regulators have not been fully characterized. We had previously identified the transcription factor NFAT5 as an activator of TLR-induced responses, and in this study we explore its contribution to macrophage functions in different polarization settings. We found that both in classically and alternatively polarized macrophages, NFAT5 enhanced functions associated with a proinflammatory profile such as bactericidal capacity and the ability to promote Th1 polarization over Th2 responses. In this regard, NFAT5 upregulated the Th1-stimulatory cytokine IL-12 in classically activated macrophages, whereas in alternatively polarized ones it enhanced the expression of the pro-Th1 mediators Fizz-1 and arginase 1, indicating that it could promote proinflammatory readiness by regulating independent genes in differently polarized macrophages. Finally, adoptive transfer assays in vivo revealed a reduced antitumor capacity in NFAT5-deficient macrophages against syngeneic Lewis lung carcinoma and ID8 ovarian carcinoma cells, a defect that in the ID8 model was associated with a reduced accumulation of effector CD8 T cells at the tumor site. Altogether, detailed analysis of the effect of NFAT5 in pro- and anti-inflammatory macrophages uncovered its ability to regulate distinct genes under both polarization modes and revealed its predominant role in promoting proinflammatory macrophage functions. Copyright © 2017 by The American Association of Immunologists, Inc.

  3. FRUITFULL controls SAUR10 expression and regulates Arabidopsis growth and architecture

    NARCIS (Netherlands)

    Bemer, Marian; Mourik, van Hilda; Muiño, Jose M.; Ferrándiz, Cristina; Kaufmann, Kerstin; Angenent, Gerco C.

    2017-01-01

    MADS-domain transcription factors are well known for their roles in plant development and regulate sets of downstream genes that have been uncovered by high-throughput analyses. A considerable number of these targets are predicted to function in hormone responses or responses to environmental

  4. Mammalian target of rapamycin complex 2 regulates muscle glucose uptake during exercise in mice

    DEFF Research Database (Denmark)

    Kleinert, Maximilian; Parker, Benjamin L; Fritzen, Andreas Mæchel

    2017-01-01

    Exercise increases glucose uptake into insulin-resistant muscle. Thus, elucidating the exercise signalling network in muscle may uncover new therapeutic targets. mTORC2, a regulator of insulin-controlled glucose uptake, has been reported to interact with Rac1, which plays a role in exercise-induc...

  5. Sirt1 negatively regulates FcεRI-mediated mast cell activation through AMPK- and PTP1B-dependent processes.

    Science.gov (United States)

    Li, Xian; Lee, Youn Ju; Jin, Fansi; Park, Young Na; Deng, Yifeng; Kang, Youra; Yang, Ju Hye; Chang, Jae-Hoon; Kim, Dong-Young; Kim, Jung-Ae; Chang, Young-Chae; Ko, Hyun-Jeong; Kim, Cheorl-Ho; Murakami, Makoto; Chang, Hyeun Wook

    2017-07-25

    Sirt1, a key regulator of metabolism and longevity, has recently been implicated in the regulation of allergic reactions, although the underlying mechanism remains unclear. Here we show that Sirt1 negatively regulates FcεRI-stimulated mast cell activation and anaphylaxis through two mutually regulated pathways involving AMP-activated protein kinase (AMPK) and protein tyrosine phosphatase 1B (PTP1B). Mast cell-specific knockout of Sirt1 dampened AMPK-dependent suppression of FcεRI signaling, thereby augmenting mast cell activation both in vitro and in vivo. Sirt1 inhibition of FcεRI signaling also involved an alternative component, PTP1B, which attenuated the inhibitory AMPK pathway and conversely enhanced the stimulatory Syk pathway, uncovering a novel role of this phosphatase. Moreover, a Sirt1 activator resveratrol stimulated the inhibitory AMPK axis, with reciprocal suppression of the stimulatory PTP1B/Syk axis, thus potently inhibiting anaphylaxis. Overall, our results provide a molecular explanation for the beneficial role of Sirt1 in allergy and underscore a potential application of Sirt1 activators as a new class of anti-allergic agents.

  6. YB1/p32, a nuclear Y-box binding protein 1, is a novel regulator of myoblast differentiation that interacts with Msx1 homeoprotein

    Energy Technology Data Exchange (ETDEWEB)

    Song, Young Joon [Department of Biological Sciences, College of Natural Science, Inha University, 253 Yonghyun-dong, Nam-Gu, Incheon, Korea, 402-751 (Korea, Republic of); Lee, Hansol, E-mail: hlee@inha.ac.kr [Department of Biological Sciences, College of Natural Science, Inha University, 253 Yonghyun-dong, Nam-Gu, Incheon, Korea, 402-751 (Korea, Republic of)

    2010-02-15

    Precisely controlled cellular differentiation is essential for the proper development of vertebrate embryo and deregulated differentiation is a major cause of many human congenital diseases as well as cancer. Msx1 is a member of the homeoprotein family implicated in these processes, which inhibits the differentiation of skeletal muscle and other cell types, presumably by regulating transcription of target genes through interaction with other cellular factors. We presently show that YB1/p32, a nuclear Y-box binding protein 1, interacts with Msx1 homeoprotein and functions as a regulator of C2C12 myoblast differentiation. We demonstrate that YB1/p32 functionally interacts with Msx1 through its N-terminal region and colocalizes with Msx1 at the nuclear periphery. Moreover, we find that YB1/p32 is competent for inhibition of C2C12 myoblast differentiation, which is correlated with its activity as a negative regulator of MyoD gene expression and binding to the MyoD core enhancer region (CER). Furthermore, YB1/p32 cooperates with Msx1 in transcriptional repression and knocking down the expression of endogenous YB1 attenuates the effects of Msx1. Taken together, our study has uncovered a new function of YB1/p32, a regulator of skeletal muscle differentiation.

  7. YB1/p32, a nuclear Y-box binding protein 1, is a novel regulator of myoblast differentiation that interacts with Msx1 homeoprotein

    International Nuclear Information System (INIS)

    Song, Young Joon; Lee, Hansol

    2010-01-01

    Precisely controlled cellular differentiation is essential for the proper development of vertebrate embryo and deregulated differentiation is a major cause of many human congenital diseases as well as cancer. Msx1 is a member of the homeoprotein family implicated in these processes, which inhibits the differentiation of skeletal muscle and other cell types, presumably by regulating transcription of target genes through interaction with other cellular factors. We presently show that YB1/p32, a nuclear Y-box binding protein 1, interacts with Msx1 homeoprotein and functions as a regulator of C2C12 myoblast differentiation. We demonstrate that YB1/p32 functionally interacts with Msx1 through its N-terminal region and colocalizes with Msx1 at the nuclear periphery. Moreover, we find that YB1/p32 is competent for inhibition of C2C12 myoblast differentiation, which is correlated with its activity as a negative regulator of MyoD gene expression and binding to the MyoD core enhancer region (CER). Furthermore, YB1/p32 cooperates with Msx1 in transcriptional repression and knocking down the expression of endogenous YB1 attenuates the effects of Msx1. Taken together, our study has uncovered a new function of YB1/p32, a regulator of skeletal muscle differentiation.

  8. Resolution enhancement techniques in microscopy

    Science.gov (United States)

    Cremer, Christoph; Masters, Barry R.

    2013-05-01

    We survey the history of resolution enhancement techniques in microscopy and their impact on current research in biomedicine. Often these techniques are labeled superresolution, or enhanced resolution microscopy, or light-optical nanoscopy. First, we introduce the development of diffraction theory in its relation to enhanced resolution; then we explore the foundations of resolution as expounded by the astronomers and the physicists and describe the conditions for which they apply. Then we elucidate Ernst Abbe's theory of optical formation in the microscope, and its experimental verification and dissemination to the world wide microscope communities. Second, we describe and compare the early techniques that can enhance the resolution of the microscope. Third, we present the historical development of various techniques that substantially enhance the optical resolution of the light microscope. These enhanced resolution techniques in their modern form constitute an active area of research with seminal applications in biology and medicine. Our historical survey of the field of resolution enhancement uncovers many examples of reinvention, rediscovery, and independent invention and development of similar proposals, concepts, techniques, and instruments. Attribution of credit is therefore confounded by the fact that for understandable reasons authors stress the achievements from their own research groups and sometimes obfuscate their contributions and the prior art of others. In some cases, attribution of credit is also made more complex by the fact that long term developments are difficult to allocate to a specific individual because of the many mutual connections often existing between sometimes fiercely competing, sometimes strongly collaborating groups. Since applications in biology and medicine have been a major driving force in the development of resolution enhancing approaches, we focus on the contribution of enhanced resolution to these fields.

  9. Uncovering China’s transport CO2 emission patterns at the regional level

    International Nuclear Information System (INIS)

    Guo, Bin; Geng, Yong; Franke, Bernd; Hao, Han; Liu, Yaxuan; Chiu, Anthony

    2014-01-01

    With China’s rapid economic development, its transport sector has experienced a dramatic growth, leading to a large amount of related CO 2 emission. This paper aims to uncover China’s transport CO 2 emission patterns at the regional and provincial level. We first present the CO 2 emission features from transport sector in 30 Chinese provinces, including per capita emissions, emission intensities, and historical evolution of annual CO 2 emission. We then quantify the related driving forces by adopting both period-wise and time-series LMDI analysis. Results indicate that significant regional CO 2 emission disparities exist in China’s transport sector. The eastern region had higher total CO 2 emissions and per capita CO 2 emissions, but lower CO 2 emission intensities in its transport sector. The western region had higher CO 2 emission intensities and experienced a rapid CO 2 emission increase. The CO 2 emission increments in the eastern provinces were mainly contributed by both economic activity effect and population effect, while energy intensity partially offset the emission growth and energy structure had a marginal effect. However, in the central and western provinces, both economic activity effect and energy intensity effect induced the CO 2 emission increases, while the effects from population and energy structure change were limited. - Highlights: • The CO 2 emission features from transport sector in 30 Chinese provinces were presented. • The driving forces of CO 2 emissions from transport sector were quantified. • Regional disparities on China’s transport sector CO 2 emission exist. • Region-specific mitigation policies on transport sector CO 2 emission are needed

  10. Uncovering the Mechanisms Responsible for Why Language Learning May Promote Healthy Cognitive Aging

    Directory of Open Access Journals (Sweden)

    Mark Antoniou

    2017-12-01

    Full Text Available One of the great challenges facing humankind in the 21st century is preserving healthy brain function in our aging population. Individuals over 60 are the fastest growing age group in the world, and by 2050, it is estimated that the number of people over the age of 60 will triple. The typical aging process involves cognitive decline related to brain atrophy, especially in frontal brain areas and regions that subserve declarative memory, loss of synaptic connections, and the emergence of neuropathological symptoms associated with dementia. The disease-state of this age-related cognitive decline is Alzheimer’s disease and other dementias, which may cause older adults to lose their independence and rely on others to live safely, burdening family members and health care systems in the process. However, there are two lines of research that offer hope to those seeking to promote healthy cognitive aging. First, it has been observed that lifestyle variables such as cognitive leisure activities can moderate the risk of Alzheimer’s disease, which has led to the development of plasticity-based interventions for older adults designed to protect against the adverse effects of cognitive decline. Second, there is evidence that lifelong bilingualism acts as a safeguard in preserving healthy brain function, possibly delaying the incidence of dementia by several years. In previous work, we have suggested that foreign language learning programs aimed at older populations are an optimal solution for building cognitive reserve because language learning engages an extensive brain network that is known to overlap with the regions negatively affected by the aging process. Here, we will outline potential future lines of research that may uncover the mechanism responsible for the emergence of language learning related brain advantages, such as language typology, bi- vs. multi-lingualism, age of acquisition, and the elements that are likely to result in the largest

  11. Uncovering phenotypes of poor-pitch singing: the Sung Performance Battery (SPB)

    Science.gov (United States)

    Berkowska, Magdalena; Dalla Bella, Simone

    2013-01-01

    Singing is as natural as speaking for humans. Increasing evidence shows that the layman can carry a tune (e.g., when asked to sing a well-known song or to imitate single pitches, intervals and short melodies). Yet, important individual differences exist in the general population with regard to singing proficiency. Some individuals are particularly inaccurate or imprecise in producing or imitating pitch information (poor-pitch singers), thus showing a variety of singing phenotypes. Unfortunately, so far there is not a standard set of tasks for assessing singing proficiency in the general population, allowing to uncover and characterize individual profiles of poor-pitch singing. Different tasks and analysis methods are typically used in various experiments, making the comparison of the results across studies arduous. To fill this gap we propose here a new tool for assessing singing proficiency (the Sung Performance Battery, SPB). The SPB starts from the assessment of participants' vocal range followed by five tasks: (1) single-pitch matching, (2) pitch-interval matching, (3) novel-melody matching, (4) singing from memory of familiar melodies (with lyrics and on a syllable), and (5) singing of familiar melodies (with lyrics and on a syllable) at a slow tempo indicated by a metronome. Data analysis via acoustical methods provides objective measures of pitch accuracy and precision in terms of absolute and relative pitch. The SPB has been tested in a group of 50 occasional singers. The results indicate that the battery is useful for characterizing proficient singing and for detecting cases of inaccurate and/or imprecise singing. PMID:24151475

  12. RNA shotgun metagenomic sequencing of northern California (USA mosquitoes uncovers viruses, bacteria, and fungi

    Directory of Open Access Journals (Sweden)

    James Angus eChandler

    2015-03-01

    Full Text Available Mosquitoes, most often recognized for the microbial agents of disease they may carry, harbor diverse microbial communities that include viruses, bacteria, and fungi, collectively called the microbiota. The composition of the microbiota can directly and indirectly affect disease transmission through microbial interactions that could be revealed by its characterization in natural populations of mosquitoes. Furthermore, the use of shotgun metagenomic sequencing (SMS approaches co