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Sample records for elucidating key factors

  1. Transcriptome analysis elucidates key developmental components of bryozoan lophophore development

    PubMed Central

    Wong, Yue Him; Ryu, Taewoo; Seridi, Loqmane; Ghosheh, Yanal; Bougouffa, Salim; Qian, Pei-Yuan; Ravasi, Timothy

    2014-01-01

    The most recent phylogenomic study suggested that Bryozoa (Ectoprocta), Brachiopoda, and Phoronida are monophyletic, implying that the lophophore of bryozoans, phoronids and brachiopods is a synapomorphy. Understanding the molecular mechanisms of the lophophore development of the Lophophorata clade can therefore provide us a new insight into the formation of the diverse morphological traits in metazoans. In the present study, we profiled the transcriptome of the Bryozoan (Ectoproct) Bugula neritina during the swimming larval stage (SW) and the early (4 h) and late (24 h) metamorphic stages using the Illumina HiSeq2000 platform. Various genes that function in development, the immune response and neurogenesis showed differential expression levels during metamorphosis. In situ hybridization of 23 genes that participate in the Wnt, BMP, Notch, and Hedgehog signaling pathways revealed their regulatory roles in the development of the lophophore and the ancestrula digestive tract. Our findings support the hypothesis that developmental precursors of the lophophore and the ancestrula digestive tract are pre-patterned by the differential expression of key developmental genes according to their fate. This study provides a foundation to better understand the developmental divergence and/or convergence among developmental precursors of the lophophore of bryozoans, branchiopods and phoronids. PMID:25300304

  2. Transcriptome analysis elucidates key developmental components of bryozoan lophophore development.

    PubMed

    Wong, Yue Him; Ryu, Taewoo; Seridi, Loqmane; Ghosheh, Yanal; Bougouffa, Salim; Qian, Pei-Yuan; Ravasi, Timothy

    2014-01-01

    The most recent phylogenomic study suggested that Bryozoa (Ectoprocta), Brachiopoda, and Phoronida are monophyletic, implying that the lophophore of bryozoans, phoronids and brachiopods is a synapomorphy. Understanding the molecular mechanisms of the lophophore development of the Lophophorata clade can therefore provide us a new insight into the formation of the diverse morphological traits in metazoans. In the present study, we profiled the transcriptome of the Bryozoan (Ectoproct) Bugula neritina during the swimming larval stage (SW) and the early (4 h) and late (24 h) metamorphic stages using the Illumina HiSeq2000 platform. Various genes that function in development, the immune response and neurogenesis showed differential expression levels during metamorphosis. In situ hybridization of 23 genes that participate in the Wnt, BMP, Notch, and Hedgehog signaling pathways revealed their regulatory roles in the development of the lophophore and the ancestrula digestive tract. Our findings support the hypothesis that developmental precursors of the lophophore and the ancestrula digestive tract are pre-patterned by the differential expression of key developmental genes according to their fate. This study provides a foundation to better understand the developmental divergence and/or convergence among developmental precursors of the lophophore of bryozoans, branchiopods and phoronids. PMID:25300304

  3. Elucidation of Factors Effecting Enzymatic Saccharification using Transgenic Hardwoods

    NASA Astrophysics Data System (ADS)

    Min, Douyong

    Three groups of transgenic wood samples were used as starting materials to elucidate the recalcitrance of enzymatic saccharification with/without pretreatments. The first group of transgenic wood samples is low lignin P. trichocarpa. The second group is low xylan P. trichocarpa. The third one is 12 hybrid poplars which have different levels of S/V ratio and lignin content. Four pretreatments were carried out in this research including dilute sulfuric acid, green liquor, auto hydrolysis and ozone delignification. The behavior among pretreatments as a function of removal of lignin appears to be different. Lignin is the major factor of recalcitrance of the lignocellulosic material to ethanol conversion process. Xylan also plays key role in this process. In addition, the crude milled wood lignin was isolated from these three groups of transgenic samples. Lignin carbohydrate complexes was characterized by 1H-13C HMQC and 13C NMR. Thus the effect of LCCs on enzymatic saccharification was elucidated. High S/V ratio propels the lignin removal during pretreatments however; high S/V ratio retards the enzymatic saccharification on the lignocellulosic material without pretreatments. The level of LCCs linkages accounts for additional recalcitrance of the lignocellulosic material to ethanol conversion process. The amount of LCCs linkages is affected by xylan content, lignin content and S/V ratio.

  4. Factorizing RSA Keys

    NASA Astrophysics Data System (ADS)

    Blakey, Ed

    Factorization is notoriously difficult. Though the problem is not known to be NP-hard, neither efficient, algorithmic solution nor technologically practicable, quantum-computer solution has been found. This apparent complexity, which renders infeasible the factorization of sufficiently large values, makes secure the RSA cryptographic system.

  5. Key factors help programs succeed.

    PubMed

    Finger, W R

    1997-01-01

    The World Health Organization is coordinating a review (with the United Nations Population Fund and UNICEF) of key interventions designed to improve adolescent health services, focusing on the effectiveness of these efforts. Making services more available involves the attitude and training of providers, the logistics of clinic location and service, and the questions of privacy and confidentiality. Successful programs identify specific target groups defined by age, school status, marital status, and other social factors. In a recent evaluation of 70 projects focusing on adolescents, UNFPA found that almost none of them defined their target populations clearly. Marital status is particularly important, for the unmarried often face more obstacles to services. Providers should involve youth in planning and implementing reproductive health services and evaluating programs by working with youth focus groups and workshops. A review of the Family Health International's AIDS Control and Prevention (AIDSCAP) Project of 21 peer education projects in Africa, Asia, and Latin America showed that peer education is useful for providing HIV/AIDS information. In successful peer programming selection and training, skills building, effective provision of information and referrals, and minimal turnover are key elements. Involving community leaders, parents, teachers helps achieve the balance of needs and culture and traditions. A UNFPA analysis found that most projects did not involve parents and community groups. Sex education programs were particularly divisive. The accessibility of services depends on convenience of location, clinic hours, confidentiality, and style of services. The basic evaluation tool is simple observation. In 1992 an AIDS prevention project in Kenya used an outcome evaluation with interviews and found that the target audience had more positive behavior change. Sustaining good programs should also be included in the planning phase, as was done by the CORA project

  6. Helicopter training simulators: Key market factors

    NASA Technical Reports Server (NTRS)

    Mcintosh, John

    1992-01-01

    Simulators will gain an increasingly important role in training helicopter pilots only if the simulators are of sufficient fidelity to provide positive transfer of skills to the aircraft. This must be done within an economic model of return on investment. Although rotor pilot demand is still only a small percentage of overall pilot requirements, it will grow in significance. This presentation described the salient factors influencing the use of helicopter training simulators.

  7. Elucidating Sources and Factors Affecting Delivery of Nitrogen to Surface Waters of New York State

    NASA Astrophysics Data System (ADS)

    Golden, H. E.; Boyer, E. W.; Burns, D. A.; Elliott, E.; Kendall, C.; Butler, T.

    2005-12-01

    Rapid changes in power generation, transportation, and agriculture have appreciably altered nitrogen (N) cycling at regional scales, increasing N inputs to landscapes and surface waters. Numerous studies have linked this surplus N to a host of concerns, including eutrophication and violations in drinking water standards. Inputs of N nation-wide have increased during recent decades, primarily from the production and use of fertilizers, the planting of N-fixing crops, and the combustion of fossil fuels. The role of atmospheric N sources is of particular concern in New York, as rates of atmospheric N deposition in the northeast are among the highest in the nation. Our work aims to quantify nitrogen sources and fate in watersheds throughout the state. Further, we intend to elucidate factors controlling the retention and release of N to surface waters. We quantify nitrogen inputs through both measurement data (e.g., from wet and dry atmospheric deposition, precipitation, streamflow, water quality, and isotopic tracers) and from synoptic spatial databases (e.g., of terrain, land use, and fertilizer inputs). We present preliminary results from large catchments in contrasting spatial settings across the state (different land use configurations and atmospheric deposition gradients), illustrating the contribution of nitrogen sources to each region and factors affecting delivery to surface waters. Further, we present 30 years of temporal data from a large watershed (Fall Creek) in the Finger Lakes region of the state to demonstrate how hydrological and biogeochemical factors, over seasons and under varying hydrological regimes, combine to control N dynamics in surface waters. Our collective work provides information that is necessary to develop sound strategies for understanding and managing nutrients at regional scales.

  8. A genetic approach to elucidate the genotoxic pathway of monomethylarsonous acid suggests a key role for catalase

    EPA Science Inventory

    Although it is widely known that arsenic-contaminated drinking water causes many diseases, arsenic's exact mode of action (MOA) is not fully understood. Induction of oxidative stress has been proposed as an important key event in the toxic MOA of arsenic. Our studies are centered...

  9. A genetic approach to elucidate the genotoxic pathway of monomethylarsonousacid (MMAIII) suggests a key role for catalase

    EPA Science Inventory

    Arsenic-contaminated drinking water causes cancer, neuropathy, respiratory effects, diabetes, and cardiovascular disease. Its exact mode of action (MOA) is not fully understood. Oxidative stress has been proposed as a key event in the toxic MOA of arsenic. Our studies are centere...

  10. Key Factors of Circulation System Analysis and Design

    ERIC Educational Resources Information Center

    McGee, Rob

    1972-01-01

    Explained are basic concepts and components that are common to manual, machine-aided, and computer-based systems, and their significance as key factors in the analysis and design of academic library circulation systems is documented. (2 references) (Author)

  11. Key systemic and environmental risk factors for implant failure.

    PubMed

    Dawson, Dolphus R; Jasper, Samuel

    2015-01-01

    Dental implants are an important treatment option for patients interested in replacing lost or missing teeth. Although a robust body of literature has reviewed risk factors for tooth loss, the evidence for risk factors associated with dental implants is less well defined. This article focuses on key systemic risk factors relating to dental implant failure, as well as on perimucositis and peri-implantitis. PMID:25434557

  12. Beyond microarrays: Finding key transcription factors controlling signal transduction pathways

    PubMed Central

    Kel, Alexdander; Voss, Nico; Jauregui, Ruy; Kel-Margoulis, Olga; Wingender, Edgar

    2006-01-01

    Background Massive gene expression changes in different cellular states measured by microarrays, in fact, reflect just an "echo" of real molecular processes in the cells. Transcription factors constitute a class of the regulatory molecules that typically require posttranscriptional modifications or ligand binding in order to exert their function. Therefore, such important functional changes of transcription factors are not directly visible in the microarray experiments. Results We developed a novel approach to find key transcription factors that may explain concerted expression changes of specific components of the signal transduction network. The approach aims at revealing evidence of positive feedback loops in the signal transduction circuits through activation of pathway-specific transcription factors. We demonstrate that promoters of genes encoding components of many known signal transduction pathways are enriched by binding sites of those transcription factors that are endpoints of the considered pathways. Application of the approach to the microarray gene expression data on TNF-alpha stimulated primary human endothelial cells helped to reveal novel key transcription factors potentially involved in the regulation of the signal transduction pathways of the cells. Conclusion We developed a novel computational approach for revealing key transcription factors by knowledge-based analysis of gene expression data with the help of databases on gene regulatory networks (TRANSFAC® and TRANSPATH®). The corresponding software and databases are available at . PMID:17118134

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

    ERIC Educational Resources Information Center

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

    2014-01-01

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

  14. Key Factors that Influence Recruiting Young Chinese Students

    ERIC Educational Resources Information Center

    Wang, Zhenmin

    2007-01-01

    The discussion in this paper is based on the assumption that international education is equated to recruiting and educating international students, even though its true concept goes far beyond this narrow understanding. The purpose of this research is to look at the key factors that influence recruiting young Chinese students, and make sure all…

  15. Faculty perceptions of key factors in interprofessional education.

    PubMed

    Loversidge, Jacqueline; Demb, Ada

    2015-01-01

    Embedding interprofessional education (IPE) into academic programs presents structural, curricular and human factor challenges. Nurses and physicians comprise the dominant dyad in healthcare, and therefore nursing and medical faculty are key in guiding future IPE approaches. However, faculty experiences with IPE are rarely reported. This paper presents perceptions of medical and nursing faculty about key factors related to IPE for pre-licensure medical and nursing students. Semi-structured interviews with 32 faculty from three Midwest universities were analyzed thematically in this phenomenological study based on collaboration and cooperation theories. Findings clustered into six categories. Specific subthemes little discussed in the literature are addressed in detail. Study participants felt the most powerful interprofessional student experiences were authentic and faculty-facilitated, that constructive clinical environments were crucial, that curriculum design challenges included disparities between undergraduate and graduate education, and that leadership commitment to full-time and adjunct faculty engagement and development was imperative. PMID:25495176

  16. Cell division factors from crown gall tumors: a strategy for structural elucidation

    SciTech Connect

    Manning, K.S.

    1985-01-01

    Mitogenic compounds present in extracts of Vinca rosea crown gall tumor tissue were investigated. An isolation procedure, consisting of solvent partitions and reverse phase chromatography, has yielded a group of isomeric compounds which show activity in the tobacco pith bioassay. Initial characterizations revealed an unsaturated base, a sugar residue, a ..beta..-linked glucose, an allylic alcohol, and two methyl groups. A two part strategy of mass spectrometry (MS) in combination with proton nuclear magnetic resonance (/sup 1/H NMR) was envisioned. The aglycone structure would be determined by MS and the regiochemical relationships among the structural units would be defined by /sup 1/H NMR data. The utility of this approach was demonstrated by the structure assignment of a specific inhibitor of ..beta..-D-glucuronidase, 2(S)-carboxy-3(R),4(R),5(S)-trihydroxypiperidine. The relative stereochemistry of the hydroxyls was revealed by /sup 1/H NMR and the absolute configuration was deduced by a comparison of Cotton effects with a model compound. The use of /sup 1/H NMR to establish regiochemical relationships was investigated. Terpenes containing quaternary carbons and methyl groups were excellent models for the regiochemical problems presented by the mitogenic factors. This /sup 1/H NMR spectroscopy has been applied to the cell division factor structure problem. These data, with information from two dimensional nOe experiments, have defined some of the regio-relationships among the structural units present in the isolated factors.

  17. Biomolecular recognition principles for bionanocombinatorics: an integrated approach to elucidate enthalpic and entropic factors.

    PubMed

    Tang, Zhenghua; Palafox-Hernandez, J Pablo; Law, Wing-Cheung; Hughes, Zak E; Swihart, Mark T; Prasad, Paras N; Knecht, Marc R; Walsh, Tiffany R

    2013-11-26

    Bionanocombinatorics is an emerging field that aims to use combinations of positionally encoded biomolecules and nanostructures to create materials and devices with unique properties or functions. The full potential of this new paradigm could be accessed by exploiting specific noncovalent interactions between diverse palettes of biomolecules and inorganic nanostructures. Advancement of this paradigm requires peptide sequences with desired binding characteristics that can be rationally designed, based upon fundamental, molecular-level understanding of biomolecule-inorganic nanoparticle interactions. Here, we introduce an integrated method for building this understanding using experimental measurements and advanced molecular simulation of the binding of peptide sequences to gold surfaces. From this integrated approach, the importance of entropically driven binding is quantitatively demonstrated, and the first design rules for creating both enthalpically and entropically driven nanomaterial-binding peptide sequences are developed. The approach presented here for gold is now being expanded in our laboratories to a range of inorganic nanomaterials and represents a key step toward establishing a bionanocombinatorics assembly paradigm based on noncovalent peptide-materials recognition. PMID:24124916

  18. Five key factors determining pairwise correlations in visual cortex

    PubMed Central

    Sahani, Maneesh; Carandini, Matteo

    2015-01-01

    The responses of cortical neurons to repeated presentation of a stimulus are highly variable, yet correlated. These “noise correlations” reflect a low-dimensional structure of population dynamics. Here, we examine noise correlations in 22,705 pairs of neurons in primary visual cortex (V1) of anesthetized cats, during ongoing activity and in response to artificial and natural visual stimuli. We measured how noise correlations depend on 11 factors. Because these factors are themselves not independent, we distinguished their influences using a nonlinear additive model. The model revealed that five key factors play a predominant role in determining pairwise correlations. Two of these are distance in cortex and difference in sensory tuning: these are known to decrease correlation. A third factor is firing rate: confirming most earlier observations, it markedly increased pairwise correlations. A fourth factor is spike width: cells with a broad spike were more strongly correlated amongst each other. A fifth factor is spike isolation: neurons with worse isolation were more correlated, even if they were recorded on different electrodes. For pairs of neurons with poor isolation, this last factor was the main determinant of correlations. These results were generally independent of stimulus type and timescale of analysis, but there were exceptions. For instance, pairwise correlations depended on difference in orientation tuning more during responses to gratings than to natural stimuli. These results consolidate disjoint observations in a vast literature on pairwise correlations and point towards regularities of population coding in sensory cortex. PMID:26019310

  19. Identifying Key Hospital Service Quality Factors in Online Health Communities

    PubMed Central

    Jung, Yuchul; Hur, Cinyoung; Jung, Dain

    2015-01-01

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

  20. Elucidation of Genetic Interactions in the Yeast GATA-Factor Network Using Bayesian Model Selection

    PubMed Central

    Milias-Argeitis, Andreas; Oliveira, Ana Paula; Gerosa, Luca; Falter, Laura; Sauer, Uwe; Lygeros, John

    2016-01-01

    Understanding the structure and function of complex gene regulatory networks using classical genetic assays is an error-prone procedure that frequently generates ambiguous outcomes. Even some of the best-characterized gene networks contain interactions whose validity is not conclusively proven. Founded on dynamic experimental data, mechanistic mathematical models are able to offer detailed insights that would otherwise require prohibitively large numbers of genetic experiments. Here we attempt mechanistic modeling of the transcriptional network formed by the four GATA-factor proteins, a well-studied system of central importance for nitrogen-source regulation of transcription in the yeast Saccharomyces cerevisiae. To resolve ambiguities in the network organization, we encoded a set of five interactions hypothesized in the literature into a set of 32 mathematical models, and employed Bayesian model selection to identify the most plausible set of interactions based on dynamic gene expression data. The top-ranking model was validated on newly generated GFP reporter dynamic data and was subsequently used to gain a better understanding of how yeast cells organize their transcriptional response to dynamic changes of nitrogen sources. Our work constitutes a necessary and important step towards obtaining a holistic view of the yeast nitrogen regulation mechanisms; on the computational side, it provides a demonstration of how powerful Monte Carlo techniques can be creatively combined and used to address the great challenges of large-scale dynamical system inference. PMID:26967983

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

    NASA Astrophysics Data System (ADS)

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

    2016-08-01

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

  2. An Integrative Approach for Mapping Differentially Expressed Genes and Network Components Using Novel Parameters to Elucidate Key Regulatory Genes in Colorectal Cancer

    PubMed Central

    Sehgal, Manika; Gupta, Rajinder; Moussa, Ahmed; Singh, Tiratha Raj

    2015-01-01

    For examining the intricate biological processes concerned with colorectal cancer (CRC), a systems biology approach integrating several biological components and other influencing factors is essential to understand. We performed a comprehensive system level analysis for CRC which assisted in unravelling crucial network components and many regulatory elements through a coordinated view. Using this integrative approach, the perceptive of complexity hidden in a biological phenomenon is extensively simplified. The microarray analyses facilitated differential expression of 631 significant genes employed in the progression of disease and supplied interesting associated up and down regulated genes like jun, fos and mapk1. The transcriptional regulation of these genes was deliberated widely by examining transcription factors such as hnf4, nr2f1, znf219 and dr1 which directly influence the expression. Further, interactions of these genes/proteins were evaluated and crucial network motifs were detected to associate with the pathophysiology of CRC. The available standard statistical parameters such as z-score, p-value and significance profile were explored for the identification of key signatures from CRC pathway whereas a few novel parameters representing over-represented structures were also designed in the study. The applied approach revealed 5 key genes i.e. kras, araf, pik3r5, ralgds and akt3 via our novel designed parameters illustrating high statistical significance. These novel parameters can assist in scrutinizing candidate markers for diseases having known biological pathways. Further, investigating and targeting these proposed genes for experimental validations, instead being spellbound by the complicated pathway will certainly endow valuable insight in a well-timed systematic understanding of CRC. PMID:26222778

  3. That's why I take my ONS. Means-end chain as a novel approach to elucidate the personally relevant factors driving ONS consumption in nutritionally frail elderly users.

    PubMed

    den Uijl, Louise C; Kremer, Stefanie; Jager, Gerry; van der Stelt, Annelies J; de Graaf, Cees; Gibson, Peter; Godfrey, James; Lawlor, J Ben

    2015-06-01

    Oral nutritional supplements (ONS) are a recommended form of nutritional intervention for older malnourished persons when a 'food first' approach and/or food fortification prove ineffective. The efficacy of ONS will depend on, amongst other factors, whether persons do, or do not, consume their prescribed amount. Factors influencing ONS consumption can be product, context, or person related. Whereas product and context have received some attention, little is known about the person factors driving ONS consumption. In addition, the relative importance of the product, context, and person factors to ONS consumption is not known. Using the means-end chain (MEC) method, the current study elucidated personally relevant factors (product, context, and person factors) related to ONS consumption in two groups of older nutritionally frail ONS users: community-dwelling persons and care home residents with mainly somatic disorders. To our knowledge, the current work is the first to apply the MEC method to study older nutritionally frail ONS users. Forty ONS users (n = 20 per group) were recruited via healthcare professionals. The level of frailty was assessed using the FRAIL scale. Both groups were interviewed for 30 to 45 minutes using the soft laddering technique. The laddering data were analysed using LadderUX software™. The MEC method appeared to work well in both groups. The majority of the participants took ONS on their doctor's or dietician's prescription as they trusted their advice. The community-dwelling group took ONS to prolong their independence, whereas the care home group reported values that related more to small improvements in quality of life. In addition, care home residents perceived themselves as dependent on their caregiver for their ONS arrangements, whereas this dependence was not reported by community-dwelling persons. Key insights from this work will enable doctors and dieticians to customize their nutritional interventions to ONS users' personal

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

    SciTech Connect

    Buddemeier, B R; Dillon, M B

    2009-01-21

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

  5. Determination of specificity influencing residues for key transcription factor families

    PubMed Central

    Patel, Ronak Y.; Garde, Christian; D.Stormo, Gary

    2015-01-01

    Transcription factors (TFs) are major modulators of transcription and subsequent cellular processes. The binding of TFs to specific regulatory elements is governed by their specificity. Considering the gap between known TFs sequence and specificity, specificity prediction frameworks are highly desired. Key inputs to such frameworks are protein residues that modulate the specificity of TF under consideration. Simple measures like mutual information (MI) to delineate specificity influencing residues (SIRs) from alignment fail due to structural constraints imposed by the three-dimensional structure of protein. Structural restraints on the evolution of the amino-acid sequence lead to identification of false SIRs. In this manuscript we extended three methods (Direct Information, PSICOV and adjusted mutual information) that have been used to disentangle spurious indirect protein residue-residue contacts from direct contacts, to identify SIRs from joint alignments of amino-acids and specificity. We predicted SIRs forhomeodomain (HD), helix-loop-helix, LacI and GntR families of TFs using these methods and compared to MI. Using various measures, we show that the performance of these three methods is comparable but better than MI. Implication of these methods in specificity prediction framework is discussed. The methods are implemented as an R package and available along with the alignments at stormo.wustl.edu/SpecPred. PMID:26753103

  6. Spectroscopic Elucidation of the Inhibitory Mechanism of Cys2His2 Zinc Finger Transcription Factors by CobaltIII Schiff Base Complexes

    PubMed Central

    Heffern, Marie C.; Kurutz, Josh

    2014-01-01

    Transcription factors are key regulators in both normal and pathological cell processes. Affecting the activity of these proteins is a promising strategy for understanding gene regulation and developing effective therapeutics. CoIII Schiff base complexes ([Co(acacen)(L)2]+ where L = labile axial ligands) have been shown to be potent inhibitors of a number of zinc metalloproteins including Cys2His2 zinc finger transcription factors. Inhibition by [Co(acacen)(L)2]+ of the target protein is believed to occur through a dissociative exchange of the labile axial ligands for histidine (His) residues essential for function. Here, we report a series of spectroscopic investigations with model peptides of zinc fingers that elucidate the interaction between [Co(acacen)(L)2]+ complexes and zinc finger transcription factors. Observed changes in NMR chemical shifts and 2D 1H-1H NOESY NMR spectra demonstrate the preference of [Co(acacen)(L)2]+ complexes to coordinate His residues over other amino acids. The conformation of [Co(acacen)(L)2]+ upon His-coordination was characterized by 1H NMR, near-UV circular dichroism, and electronic absorption. These studies reveal that the resulting His-coordinated [Co(acacen)(L)2]+ complex possesses an octahedral structure. The effects of [Co(acacen)(L)2]+ complexes on the zinc finger structure were assessed by the degree of hydrogen bonding (probed by 2D NMR) and secondary structure profiles measured by far-UV circular dichroism. These structural studies demonstrate the ability of [Co(acacen)(L)2]+ complexes to disrupt the ββα structure of zinc fingers, resulting in primarily random coil conformations. A mechanism is described wherein [Co(acacen)(L)2]+ complexes inhibit zinc finger transcription factor activity through selectively coordinating His residues in the zinc finger via dissociative ligand exchange and disrupting the ββα structural motif required for gene regulation. PMID:24203451

  7. Organization of Anti-Phase Synchronization Pattern in Neural Networks: What are the Key Factors?

    PubMed Central

    Li, Dong; Zhou, Changsong

    2011-01-01

    Anti-phase oscillation has been widely observed in cortical neural network. Elucidating the mechanism underlying the organization of anti-phase pattern is of significance for better understanding more complicated pattern formations in brain networks. In dynamical systems theory, the organization of anti-phase oscillation pattern has usually been considered to relate to time delay in coupling. This is consistent to conduction delays in real neural networks in the brain due to finite propagation velocity of action potentials. However, other structural factors in cortical neural network, such as modular organization (connection density) and the coupling types (excitatory or inhibitory), could also play an important role. In this work, we investigate the anti-phase oscillation pattern organized on a two-module network of either neuronal cell model or neural mass model, and analyze the impact of the conduction delay times, the connection densities, and coupling types. Our results show that delay times and coupling types can play key roles in this organization. The connection densities may have an influence on the stability if an anti-phase pattern exists due to the other factors. Furthermore, we show that anti-phase synchronization of slow oscillations can be achieved with small delay times if there is interaction between slow and fast oscillations. These results are significant for further understanding more realistic spatiotemporal dynamics of cortico-cortical communications. PMID:22232576

  8. Elucidation of Xylem-Specific Transcription Factors and Absolute Quantification of Enzymes Regulating Cellulose Biosynthesis in Populus trichocarpa.

    PubMed

    Loziuk, Philip L; Parker, Jennifer; Li, Wei; Lin, Chien-Yuan; Wang, Jack P; Li, Quanzi; Sederoff, Ronald R; Chiang, Vincent L; Muddiman, David C

    2015-10-01

    Cellulose, the main chemical polymer of wood, is the most abundant polysaccharide in nature.1 The ability to perturb the abundance and structure of cellulose microfibrils is of critical importance to the pulp and paper industry as well as for the textile, wood products, and liquid biofuels industries. Although much has been learned at the transcript level about the biosynthesis of cellulose, a quantitative understanding at the proteome level has yet to be established. The study described herein sought to identify the proteins directly involved in cellulose biosynthesis during wood formation in Populus trichocarpa along with known xylem-specific transcription factors involved in regulating these key proteins. Development of an effective discovery proteomic strategy through a combination of subcellular fractionation of stem differentiating xylem tissue (SDX) with recently optimized FASP digestion protocols, StageTip fractionation, as well as optimized instrument parameters for global proteomic analysis using the quadrupole-orbitrap mass spectrometer resulted in the deepest proteomic coverage of SDX protein from P. trichocarpa with 9,146 protein groups being identified (1% FDR). Of these, 20 cellulosic/hemicellulosic enzymes and 43 xylem-specific transcription factor groups were identified. Finally, selection of surrogate peptides led to an assay for absolute quantification of 14 cellulosic proteins in SDX of P. trichocarpa. PMID:26325666

  9. Elucidating Article 45.6 of the International Code of Zoological Nomenclature: A dichotomous key for the determination of subspecific or infrasubspecific rank

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We present an overview of the difficulties sometimes encountered when determining whether a published name following a binomen is available or infrasubspecific and unavailable, following Article 45.6 of the International Code of Zoological Nomenclature (ICZN, 1999). We propose a dichotomous key that...

  10. Tendencies and Key Factors in the Health of School Students

    ERIC Educational Resources Information Center

    Rimashevskaia, N. M.; Shabunova, A. A.

    2013-01-01

    According to research data, in today's Russia 70 percent of children are born with various health risk factors, and this leads to a rapid deterioration of their health during their school years. The health of school students is getting worse as a consequence of the effect of a whole set of social and economic and psychological factors, and…

  11. Safety and reliability in industrial organizations - The key factors

    SciTech Connect

    Cooke, R.A. ); Sarkis, H.D. )

    1992-01-01

    A survey-based technique has been developed that measures and generates comparative data on important organizational, work group, and job-level variables that are directly related to on-the-job accidents. This paper describes the results of an analysis of data from more than 2,700 employees in the chemical, oil, construction, and wood products industries. These analyses indicate that several key variables are significantly related to accidents in the workplace.

  12. Succesful Lean Manufacturing Implementation: Internal Key Influencing Factors

    NASA Astrophysics Data System (ADS)

    Virginia, Iuga; Claudiu, Kifor

    2015-09-01

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

  13. Key Features of the TMD Soft-Factor Structure

    NASA Astrophysics Data System (ADS)

    Vladimirov, A.; Stefanis, N. G.

    2014-06-01

    We show that the geometry of the Wilson lines, entering the operator definition of the transverse-momentum dependent parton distributions and that of the soft factor, follows from the kinematics of the underlying physical process in conjunction with the gauge invariance of the QCD Lagrangian. We demonstrate our method in terms of concrete examples and determine the paths of the associated Wilson lines. The validation of the factorization theorem in our approach is postponed to future work.

  14. Ethylene, a key factor in the regulation of seed dormancy.

    PubMed

    Corbineau, Françoise; Xia, Qiong; Bailly, Christophe; El-Maarouf-Bouteau, Hayat

    2014-01-01

    Ethylene is an important component of the gaseous environment, and regulates numerous plant developmental processes including seed germination and seedling establishment. Dormancy, the inability to germinate in apparently favorable conditions, has been demonstrated to be regulated by the hormonal balance between abscisic acid (ABA) and gibberellins (GAs). Ethylene plays a key role in dormancy release in numerous species, the effective concentrations allowing the germination of dormant seeds ranging between 0.1 and 200 μL L(-1). Studies using inhibitors of ethylene biosynthesis or of ethylene action and analysis of mutant lines altered in genes involved in the ethylene signaling pathway (etr1, ein2, ain1, etr1, and erf1) demonstrate the involvement of ethylene in the regulation of germination and dormancy. Ethylene counteracts ABA effects through a regulation of ABA metabolism and signaling pathways. Moreover, ethylene insensitive mutants in Arabidopsis are more sensitive to ABA and the seeds are more dormant. Numerous data also show an interaction between ABA, GAs and ethylene metabolism and signaling pathways. It has been increasingly demonstrated that reactive oxygen species (ROS) may play a significant role in the regulation of seed germination interacting with hormonal signaling pathways. In the present review the responsiveness of seeds to ethylene will be described, and the key role of ethylene in the regulation of seed dormancy via a crosstalk between hormones and other signals will be discussed. PMID:25346747

  15. Ethylene, a key factor in the regulation of seed dormancy

    PubMed Central

    Corbineau, Françoise; Xia, Qiong; Bailly, Christophe

    2014-01-01

    Ethylene is an important component of the gaseous environment, and regulates numerous plant developmental processes including seed germination and seedling establishment. Dormancy, the inability to germinate in apparently favorable conditions, has been demonstrated to be regulated by the hormonal balance between abscisic acid (ABA) and gibberellins (GAs). Ethylene plays a key role in dormancy release in numerous species, the effective concentrations allowing the germination of dormant seeds ranging between 0.1 and 200 μL L-1. Studies using inhibitors of ethylene biosynthesis or of ethylene action and analysis of mutant lines altered in genes involved in the ethylene signaling pathway (etr1, ein2, ain1, etr1, and erf1) demonstrate the involvement of ethylene in the regulation of germination and dormancy. Ethylene counteracts ABA effects through a regulation of ABA metabolism and signaling pathways. Moreover, ethylene insensitive mutants in Arabidopsis are more sensitive to ABA and the seeds are more dormant. Numerous data also show an interaction between ABA, GAs and ethylene metabolism and signaling pathways. It has been increasingly demonstrated that reactive oxygen species (ROS) may play a significant role in the regulation of seed germination interacting with hormonal signaling pathways. In the present review the responsiveness of seeds to ethylene will be described, and the key role of ethylene in the regulation of seed dormancy via a crosstalk between hormones and other signals will be discussed. PMID:25346747

  16. The Human Factor: A Key to Excellence in Education.

    ERIC Educational Resources Information Center

    Mintzies, Paula; Hare, Isadora

    This document contends that efforts designed to determine how schools can educate children for the nation of tomorrow, by focusing primarily on curriculum issues, instruction, and teachers, may have overlooked the interpersonal factors which contribute to excellence and those human and social forces which may interfere with the attainment of…

  17. Key roles of necroptotic factors in promoting tumor growth.

    PubMed

    Liu, Xinjian; Zhou, Min; Mei, Ling; Ruan, Jiaying; Hu, Qian; Peng, Jing; Su, Hang; Liao, Hong; Liu, Shanling; Liu, WeiPing; Wang, He; Huang, Qian; Li, Fang; Li, Chuan-Yuan

    2016-04-19

    Necroptotic factors are generally assumed to play a positive role in tumor therapy by eliminating damaged tumor cells. Here we show that, contrary to expectation, necroptotic factors RIPK1, RIPK3, and MLKL promote tumor growth. We demonstrate that genetic knockout of necroptotic genes RIPK1, RIPK3, or MLKL in cancer cells significantly attenuated their abilities to grow in an anchorage-independent manner. In addition, they exhibited significantly enhanced radiosensitivity. The knockout cells also showed greatly reduced ability to form tumors in mice. Moreover, necrosulfonamide (NSA), a previously identified chemical inhibitor of necroptosis, could significantly delay tumor growth in a xenograft model. Mechanistically, we show that necroptoic factors play a significant role in maintaining the activity of NF-κB. Finally, we found that high levels of phosphorylated MLKL in human esophageal and colon cancers are associated with poor overall survival. Taken together, we conclude that pro-necroptic factors such as RIPK1, RIPK3, and MLKL may play a role in supporting tumor growth, and MLKL may be a promising target for cancer treatment. PMID:26959742

  18. Key roles of necroptotic factors in promoting tumor growth

    PubMed Central

    Liu, Xinjian; Zhou, Min; Mei, Ling; Ruan, Jiaying; Hu, Qian; Peng, Jing; Su, Hang; Liao, Hong; Liu, Shanling; Liu, WeiPing; Wang, He; Huang, Qian; Li, Fang; Li, Chuan-Yuan

    2016-01-01

    Necroptotic factors are generally assumed to play a positive role in tumor therapy by eliminating damaged tumor cells. Here we show that, contrary to expectation, necroptotic factors RIPK1, RIPK3, and MLKL promote tumor growth. We demonstrate that genetic knockout of necroptotic genes RIPK1, RIPK3, or MLKL in cancer cells significantly attenuated their abilities to grow in an anchorage-independent manner. In addition, they exhibited significantly enhanced radiosensitivity. The knockout cells also showed greatly reduced ability to form tumors in mice. Moreover, necrosulfonamide (NSA), a previously identified chemical inhibitor of necroptosis, could significantly delay tumor growth in a xenograft model. Mechanistically, we show that necroptoic factors play a significant role in maintaining the activity of NF-κB. Finally, we found that high levels of phosphorylated MLKL in human esophageal and colon cancers are associated with poor overall survival. Taken together, we conclude that pro-necroptic factors such as RIPK1, RIPK3, and MLKL may play a role in supporting tumor growth, and MLKL may be a promising target for cancer treatment. PMID:26959742

  19. Hypoxia-inducible factors as key regulators of tumor inflammation.

    PubMed

    Mamlouk, Soulafa; Wielockx, Ben

    2013-06-15

    Low levels of oxygen or hypoxia is often an obstacle in health, particularly in pathological disorders like cancer. The main family of transcription factors responsible for cell survival and adaptation under strenuous conditions of hypoxia are the "hypoxia-inducible factors" (HIFs). Together with prolyl hydroxylase domain enzymes (PHDs), HIFs regulates tumor angiogenesis, proliferation, invasion, metastasis, in addition to resistance to radiation and chemotherapy. Additionally, the entire HIF transcription cascade is involved in the "seventh" hallmark of cancer; inflammation. Studies have shown that hypoxia can influence tumor associated immune cells toward assisting in tumor proliferation, differentiation, vessel growth, distant metastasis and suppression of the immune response via cytokine expression alterations. These changes are not necessarily analogous to HIF's role in non-cancer immune responses, where hypoxia often encourages a strong inflammatory response. PMID:23055435

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

    NASA Astrophysics Data System (ADS)

    Serrano, Oscar; Ricart, Aurora M.; Lavery, Paul S.; Mateo, Miguel Angel; Arias-Ortiz, Ariane; Masque, Pere; Rozaimi, Mohammad; Steven, Andy; Duarte, Carlos M.

    2016-08-01

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

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

    NASA Astrophysics Data System (ADS)

    Serrano, O.; Ricart, A. M.; Lavery, P. S.; Mateo, M. A.; Arias-Ortiz, A.; Masque, P.; Steven, A.; Duarte, C. M.

    2015-11-01

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

  2. Key factors affecting urban runoff pollution under cold climatic conditions

    NASA Astrophysics Data System (ADS)

    Valtanen, Marjo; Sillanpää, Nora; Setälä, Heikki

    2015-10-01

    Urban runoff contains various pollutants and has the potential of deteriorating the quality of aquatic ecosystems. In this study our objective is to shed light on the factors that control the runoff water quality in urbanized catchments. The effects of runoff event characteristics, land use type and catchment imperviousness on event mass loads (EML) and event mean concentrations (EMC) were studied during warm and cold periods in three study catchments (6.1, 6.5 and 12.6 ha in size) in the city of Lahti, Finland. Runoff and rainfall were measured continuously for two years at each catchment. Runoff samples were taken for total nutrients (tot-P and tot-N), total suspended solids (TSS), heavy metals (Zn, Cr, Al, Co, Ni, Cu, Pb, Mn) and total organic carbon (TOC). Stepwise multiple linear regression analysis (SMLR) was used to identify general relationships between the following variables: event water quality, runoff event characteristics and catchment characteristics. In general, the studied variables explained 50-90% of the EMLs but only 30-60% of the EMCs, with runoff duration having an important role in most of the SMLR models. Mean runoff intensity or peak flow was also often included in the runoff quality models. Yet, the importance (being the first, second or third best) and role (negative or positive impact) of the explanatory variables varied between the cold and warm period. Land use type often explained cold period concentrations, but imperviousness alone explained EMCs weakly. As for EMLs, the influence of imperviousness and/or land use was season and pollutant dependent. The study suggests that pollutant loads can be - throughout the year - adequately predicted by runoff characteristics given that seasonal differences are taken into account. Although pollutant concentrations were sensitive to variation in seasonal and catchment conditions as well, the accurate estimation of EMCs would require a more complete set of explanatory factors than used in this

  3. A Simple Method for Discovering Druggable, Specific Glycosaminoglycan-Protein Systems. Elucidation of Key Principles from Heparin/Heparan Sulfate-Binding Proteins

    PubMed Central

    Sarkar, Aurijit; Desai, Umesh R.

    2015-01-01

    Glycosaminoglycans (GAGs) affect human physiology and pathology by modulating more than 500 proteins. GAG-protein interactions are generally assumed to be ionic and nonspecific, but specific interactions do exist. Here, we present a simple method to identify the GAG-binding site (GBS) on proteins that in turn helps predict high specific GAG–protein systems. Contrary to contemporary thinking, we found that the electrostatic potential at basic arginine and lysine residues neither identifies the GBS consistently, nor its specificity. GBSs are better identified by considering the potential at neutral hydrogen bond donors such as asparagine or glutamine sidechains. Our studies also reveal that an unusual constellation of ionic and non-ionic residues in the binding site leads to specificity. Nature engineers the local environment of Asn45 of antithrombin, Gln255 of 3-O-sulfotransferase 3, Gln163 and Asn167 of 3-O-sulfotransferase 1 and Asn27 of basic fibroblast growth factor in the respective GBSs to induce specificity. Such residues are distinct from other uncharged residues on the same protein structure in possessing a significantly higher electrostatic potential, resultant from the local topology. In contrast, uncharged residues on nonspecific GBSs such as thrombin and serum albumin possess a diffuse spread of electrostatic potential. Our findings also contradict the paradigm that GAG-binding sites are simply a collection of contiguous Arg/Lys residues. Our work demonstrates the basis for discovering specifically interacting and druggable GAG-protein systems based on the structure of protein alone, without requiring access to any structure-function relationship data. PMID:26488293

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

    PubMed

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

    2015-08-01

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

  5. Gemcitabine-Related Pneumonitis in Pancreas Adenocarcinoma—An Infrequent Event: Elucidation of Risk Factors and Management Implications

    PubMed Central

    Sahin, Ibrahim Halil; Geyer, Alexander I.; Kelly, Daniel W.; O’Reilly, Eileen Mary

    2016-01-01

    A total of 2440 pancreatic cancer patients who received gemcitabine treatment were screened for gemcitabine-related pneumonitis (GRP). The observed rate of GRP was 1.1%. History of smoking, alcohol use, and history of underlying lung disease were identified as possible risk factors of GRP. Early pulmonary consult and cessation of gemcitabine is recommended once clinical suspicion arises. Background Gemcitabine-related pneumonitis (GRP) has been reported relatively frequently for pancreas cancer in the literature; however, underlying risk factors and optimal management remain to be defined. We studied a cohort of patients with GRP and investigated potential predisposing factors in pancreatic cancer patients. Patients and Methods A total 2440 patients at Memorial Sloan Kettering Cancer Center were identified between January 1, 2000, and December 31, 2012, and were screened for grade 2 or higher GRP in an institutional tumor registry and using an ICD billing code database. Demographic and clinical information was extracted by electronic chart review. Results A total of 28 patients (1.1%) with GRP were identified. Incidence of grade 2, 3, and 4 reactions were 7 (25%), 18 (64%), and 3 (11%), respectively. No GRP-related mortality was observed. Twenty-one patients (75%) reported a history of cigarette smoking. Seventeen patients (61%) were alcohol users. Six patients (21%) were either regular or heavy drinkers. Most patients (93%) had either locally advanced or metastatic disease. Three patients (11%) underwent a diagnostic bronchoscopy, and in 1 patient a diagnosis of organizing pneumonia was established. Morbidity was significant; 3 patients (11%) required treatment in the intensive care unit. All hospitalized patients received steroid treatment. Conclusion GRP is relatively uncommon but incurs significant morbidity. Potential risk factors include advanced-stage disease, along with smoking and alcohol consumption and possibly underlying lung disease. We recommend a

  6. Elucidation of sigma factor-associated networks in Pseudomonas aeruginosa reveals a modular architecture with limited and function-specific crosstalk.

    PubMed

    Schulz, Sebastian; Eckweiler, Denitsa; Bielecka, Agata; Nicolai, Tanja; Franke, Raimo; Dötsch, Andreas; Hornischer, Klaus; Bruchmann, Sebastian; Düvel, Juliane; Häussler, Susanne

    2015-03-01

    Sigma factors are essential global regulators of transcription initiation in bacteria which confer promoter recognition specificity to the RNA polymerase core enzyme. They provide effective mechanisms for simultaneously regulating expression of large numbers of genes in response to challenging conditions, and their presence has been linked to bacterial virulence and pathogenicity. In this study, we constructed nine his-tagged sigma factor expressing and/or deletion mutant strains in the opportunistic pathogen Pseudomonas aeruginosa. To uncover the direct and indirect sigma factor regulons, we performed mRNA profiling, as well as chromatin immunoprecipitation coupled to high-throughput sequencing. We furthermore elucidated the de novo binding motif of each sigma factor, and validated the RNA- and ChIP-seq results by global motif searches in the proximity of transcriptional start sites (TSS). Our integrated approach revealed a highly modular network architecture which is composed of insulated functional sigma factor modules. Analysis of the interconnectivity of the various sigma factor networks uncovered a limited, but highly function-specific, crosstalk which orchestrates complex cellular processes. Our data indicate that the modular structure of sigma factor networks enables P. aeruginosa to function adequately in its environment and at the same time is exploited to build up higher-level functions by specific interconnections that are dominated by a participation of RpoN. PMID:25780925

  7. Elucidation of Sigma Factor-Associated Networks in Pseudomonas aeruginosa Reveals a Modular Architecture with Limited and Function-Specific Crosstalk

    PubMed Central

    Schulz, Sebastian; Eckweiler, Denitsa; Bielecka, Agata; Nicolai, Tanja; Franke, Raimo; Dötsch, Andreas; Hornischer, Klaus; Bruchmann, Sebastian; Düvel, Juliane; Häussler, Susanne

    2015-01-01

    Sigma factors are essential global regulators of transcription initiation in bacteria which confer promoter recognition specificity to the RNA polymerase core enzyme. They provide effective mechanisms for simultaneously regulating expression of large numbers of genes in response to challenging conditions, and their presence has been linked to bacterial virulence and pathogenicity. In this study, we constructed nine his-tagged sigma factor expressing and/or deletion mutant strains in the opportunistic pathogen Pseudomonas aeruginosa. To uncover the direct and indirect sigma factor regulons, we performed mRNA profiling, as well as chromatin immunoprecipitation coupled to high-throughput sequencing. We furthermore elucidated the de novo binding motif of each sigma factor, and validated the RNA- and ChIP-seq results by global motif searches in the proximity of transcriptional start sites (TSS). Our integrated approach revealed a highly modular network architecture which is composed of insulated functional sigma factor modules. Analysis of the interconnectivity of the various sigma factor networks uncovered a limited, but highly function-specific, crosstalk which orchestrates complex cellular processes. Our data indicate that the modular structure of sigma factor networks enables P. aeruginosa to function adequately in its environment and at the same time is exploited to build up higher-level functions by specific interconnections that are dominated by a participation of RpoN. PMID:25780925

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

    PubMed

    Chang, I-Pin; Lee, Tian-Fu; Lin, Tsung-Hung; Liu, Chuan-Ming

    2015-01-01

    Key agreements that use only password authentication are convenient in communication networks, but these key agreement schemes often fail to resist possible attacks, and therefore provide poor security compared with some other authentication schemes. To increase security, many authentication and key agreement schemes use smartcard authentication in addition to passwords. Thus, two-factor authentication and key agreement schemes using smartcards and passwords are widely adopted in many applications. Vaidya et al. recently presented a two-factor authentication and key agreement scheme for wireless sensor networks (WSNs). Kim et al. observed that the Vaidya et al. scheme fails to resist gateway node bypassing and user impersonation attacks, and then proposed an improved scheme for WSNs. This study analyzes the weaknesses of the two-factor authentication and key agreement scheme of Kim et al., which include vulnerability to impersonation attacks, lost smartcard attacks and man-in-the-middle attacks, violation of session key security, and failure to protect user privacy. An efficient and secure authentication and key agreement scheme for WSNs based on the scheme of Kim et al. is then proposed. The proposed scheme not only solves the weaknesses of previous approaches, but also increases security requirements while maintaining low computational cost. PMID:26633396

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

    PubMed Central

    Chang, I-Pin; Lee, Tian-Fu; Lin, Tsung-Hung; Liu, Chuan-Ming

    2015-01-01

    Key agreements that use only password authentication are convenient in communication networks, but these key agreement schemes often fail to resist possible attacks, and therefore provide poor security compared with some other authentication schemes. To increase security, many authentication and key agreement schemes use smartcard authentication in addition to passwords. Thus, two-factor authentication and key agreement schemes using smartcards and passwords are widely adopted in many applications. Vaidya et al. recently presented a two-factor authentication and key agreement scheme for wireless sensor networks (WSNs). Kim et al. observed that the Vaidya et al. scheme fails to resist gateway node bypassing and user impersonation attacks, and then proposed an improved scheme for WSNs. This study analyzes the weaknesses of the two-factor authentication and key agreement scheme of Kim et al., which include vulnerability to impersonation attacks, lost smartcard attacks and man-in-the-middle attacks, violation of session key security, and failure to protect user privacy. An efficient and secure authentication and key agreement scheme for WSNs based on the scheme of Kim et al. is then proposed. The proposed scheme not only solves the weaknesses of previous approaches, but also increases security requirements while maintaining low computational cost. PMID:26633396

  10. Elucidating the evolutionary conserved DNA-binding specificities of WRKY transcription factors by molecular dynamics and in vitro binding assays

    PubMed Central

    Brand, Luise H.; Fischer, Nina M.; Harter, Klaus; Kohlbacher, Oliver; Wanke, Dierk

    2013-01-01

    WRKY transcription factors constitute a large protein family in plants that is involved in the regulation of developmental processes and responses to biotic or abiotic stimuli. The question arises how stimulus-specific responses are mediated given that the highly conserved WRKY DNA-binding domain (DBD) exclusively recognizes the ‘TTGACY’ W-box consensus. We speculated that the W-box consensus might be more degenerate and yet undetected differences in the W-box consensus of WRKYs of different evolutionary descent exist. The phylogenetic analysis of WRKY DBDs suggests that they evolved from an ancestral group IIc-like WRKY early in the eukaryote lineage. A direct descent of group IIc WRKYs supports a monophyletic origin of all other group II and III WRKYs from group I by loss of an N-terminal DBD. Group I WRKYs are of paraphyletic descent and evolved multiple times independently. By homology modeling, molecular dynamics simulations and in vitro DNA–protein interaction-enzyme-linked immunosorbent assay with AtWRKY50 (IIc), AtWRKY33 (I) and AtWRKY11 (IId) DBDs, we revealed differences in DNA-binding specificities. Our data imply that other components are essentially required besides the W-box-specific binding to DNA to facilitate a stimulus-specific WRKY function. PMID:23975197

  11. Analysis of a Splice Array Experiment Elucidates Roles of Chromatin Elongation Factor Spt4–5 in Splicing

    PubMed Central

    2005-01-01

    Splicing is an important process for regulation of gene expression in eukaryotes, and it has important functional links to other steps of gene expression. Two examples of these linkages include Ceg1, a component of the mRNA capping enzyme, and the chromatin elongation factors Spt4–5, both of which have recently been shown to play a role in the normal splicing of several genes in the yeast Saccharomyces cerevisiae. Using a genomic approach to characterize the roles of Spt4–5 in splicing, we used splicing-sensitive DNA microarrays to identify specific sets of genes that are mis-spliced in ceg1, spt4, and spt5 mutants. In the context of a complex, nested, experimental design featuring 22 dye-swap array hybridizations, comprising both biological and technical replicates, we applied five appropriate statistical models for assessing differential expression between wild-type and the mutants. To refine selection of differential expression genes, we then used a robust model-synthesizing approach, Differential Expression via Distance Synthesis, to integrate all five models. The resultant list of differentially expressed genes was then further analyzed with regard to select attributes: we found that highly transcribed genes with long introns were most sensitive to spt mutations. QPCR confirmation of differential expression was established for the limited number of genes evaluated. In this paper, we showcase splicing array technology, as well as powerful, yet general, statistical methodology for assessing differential expression, in the context of a real, complex experimental design. Our results suggest that the Spt4–Spt5 complex may help coordinate splicing with transcription under conditions that present kinetic challenges to spliceosome assembly or function. PMID:16172632

  12. The Elucidation of the Interactome of 16 Arabidopsis bZIP Factors Reveals Three Independent Functional Networks

    PubMed Central

    Llorca, Carles Marco; Berendzen, Kenneth Wayne; Malik, Waqas Ahmed; Mahn, Stefan; Piepho, Hans-Peter; Zentgraf, Ulrike

    2015-01-01

    The function of the bZIP transcription factors is strictly dependent on their ability to dimerize. Heterodimerization has proven to be highly specific and is postulated to operate as a combinatorial mechanism allowing the generation of a large variety of dimers with unique qualities by specifically combining a small set of monomers; an assumption that has not yet been tested systematically. Here, the interaction pattern and the transactivation properties of 16 Arabidopsis thaliana bZIPs are examined in transiently transformed Arabidopsis protoplasts to deliver a perspective on the relationship between bZIP dimerization and function. An interaction matrix of bZIPs belonging to the C, G, H, and S1 bZIP groups was resolved by Bimolecular Fluorescent Complementation (BiFC) coupled to quantitative flow cytometric analysis, while an extensive GUS reporter gene assay was carried out to determine the effect of different bZIP pairs on the expression of four different known bZIP-targeted promoters. Statistical data treatment and complementary bioinformatic analysis were performed to substantiate the biological findings. According to these results, the 16 bZIPs interact in three isolated networks, within which their members dimerize non-specifically and exhibit a significant level of functional redundancy. A coherent explanation for these results is supported by in silico analysis of differences in the length, structure and composition of their leucine zippers and appears to explain their dimerization specificity and dynamics observed in vivo quite well. A model in which the bZIP networks act as functional units is proposed. PMID:26452049

  13. Teachers' Professional Development: What Are the Key Change Factors for Mathematics Teachers?

    ERIC Educational Resources Information Center

    Pehkonen, Erkki; Torner, Gunter

    1999-01-01

    Surveyed and interviewed 13 experienced German middle school mathematics teachers to examine key factors causing discontinuity in their professional development. Results included 49 statements about change that fell into four categories. Researchers extracted three change factors not reported in earlier literature: experiences and observations…

  14. Part II--Factors Associated with School Nurse Ratios: Key State Informants' Perceptions

    ERIC Educational Resources Information Center

    Maughan, Erin

    2009-01-01

    This paper is the second of a two-part series examining factors influencing school nurse to pupil staffing ratios. The paper reports data from a qualitative study exploring the social and political factors that potentially influence ratios. Interviews were conducted with 30 key state informants from these states. Content analysis of the data…

  15. Elucidation of a key position for acyltransfer activity in Candida parapsilosis lipase/acyltransferase (CpLIP2) and in Pseudozyma antarctica lipase A (CAL-A) by rational design.

    PubMed

    Jan, Anne-Hélène; Subileau, Maeva; Deyrieux, Charlotte; Perrier, Véronique; Dubreucq, Éric

    2016-02-01

    Performing transesterifications in aqueous media is becoming a priority challenge in lipid biotechnology in order to develop more eco-friendly and efficient biocatalytic processes in systems containing both polar and apolar substrates. In this context, our group has explored for several years the high potential of the lipase/acyltransferase CpLIP2 from Candida parapsilosis and of several of its homologs, that catalyze efficiently acyltransfer reactions in lipid/water media with high water activity (aw>0.9). The discovery of a new member of this group, CduLAc from Candida dubliniensis, with a higher acyltransferase activity than CpLIP2, has provided a new insight on structure-function relationships in this group. Indeed, the comparison of sequences and 3D models, especially of CpLIP2 and CduLAc, with those of the phylogenetically related lipase A from Pseudozyma antarctica (CAL-A), allowed elucidating a key structural determinant of the acyltransferase activity: serine S369 in CpLIP2 and its equivalents E370 in CAL-A and A366 in CduLAc. Mutants obtained by rational design at this key position showed significant changes in acyltransfer activity. Whereas mutation S369E resulted in an increase in the hydrolytic activity of CpLIP2, S369A increased alcoholysis. More strikingly, the single E370A mutation in CAL-A drastically increased the acyltransferase activity of this enzyme, giving it the character of a lipase/acyltransferase. Indeed, this single mutation lowered the methanol concentration for which the initial rates of alcoholysis and hydrolysis are equal from 2M in CAL-A down to 0.3M in its mutant, while the exceptional stability of the parental enzyme toward alcohol and temperature was conserved. PMID:26602447

  16. RM-DEMATEL: a new methodology to identify the key factors in PM2.5.

    PubMed

    Chen, Yafeng; Liu, Jie; Li, Yunpeng; Sadiq, Rehan; Deng, Yong

    2015-04-01

    Weather system is a relative complex dynamic system, the factors of the system are mutually influenced PM2.5 concentration. In this paper, a new method is proposed to quantify the influence on PM2.5 by other factors in the weather system and identify the most important factors for PM2.5 with limited resources. The relation map (RM) is used to figure out the direct relation matrix of 14 factors in PM2.5. The decision making trial and evaluation laboratory(DEMATEL) is applied to calculate the causal relationship and extent to a mutual influence of 14 factors in PM2.5. According to the ranking results of our proposed method, the most important key factors is sulfur dioxide (SO2) and nitrogen oxides (NO(X)). In addition, the other factors, the ambient maximum temperature (T(max)), concentration of PM10, and wind direction (W(dir)), are important factors for PM2.5. The proposed method can also be applied to other environment management systems to identify key factors. PMID:25728201

  17. Ethylene Response Factors: A Key Regulatory Hub in Hormone and Stress Signaling.

    PubMed

    Müller, Maren; Munné-Bosch, Sergi

    2015-09-01

    Ethylene is essential for many developmental processes and a key mediator of biotic and abiotic stress responses in plants. The ethylene signaling and response pathway includes Ethylene Response Factors (ERFs), which belong to the transcription factor family APETALA2/ERF. It is well known that ERFs regulate molecular response to pathogen attack by binding to sequences containing AGCCGCC motifs (the GCC box), a cis-acting element. However, recent studies suggest that several ERFs also bind to dehydration-responsive elements and act as a key regulatory hub in plant responses to abiotic stresses. Here, we review some of the recent advances in our understanding of the ethylene signaling and response pathway, with emphasis on ERFs and their role in hormone cross talk and redox signaling under abiotic stresses. We conclude that ERFs act as a key regulatory hub, integrating ethylene, abscisic acid, jasmonate, and redox signaling in the plant response to a number of abiotic stresses. PMID:26103991

  18. Factors that Influence Policy Decisions in Literacy: Perspectives of Key Policy Informants

    ERIC Educational Resources Information Center

    Mraz, Maryann E.

    2004-01-01

    The purpose of this study was to examine the perspectives of key policy informants on the factors that they believed influence policy decisions in literacy education. Participants were selected because they had significantly influenced, or had attempted to influence, policy decisions in literacy at either the national or state level.…

  19. Key Motivational Factors in the Retention of Three Generations of Public High School Mathematics Teachers

    ERIC Educational Resources Information Center

    Pospichal, Wendy

    2011-01-01

    Purpose: The purpose of this study was to describe and compare the similarities and differences between five key motivational factors: (a) new teacher induction, (b) noninduction mentor support in the early years of teaching, (c) salary and benefits, (d) working conditions, and (e) administrative support influential in retention of employment in…

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

    ERIC Educational Resources Information Center

    Hardin, Andrew M.; Looney, Clayton Arlen

    2012-01-01

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

  1. Understanding Reusability as a Key Factor for Open Education: A Review

    ERIC Educational Resources Information Center

    Chiappe, Andres; Arias, Vivian

    2015-01-01

    This article describes both the process and the results of an extensive literature review on "reusability" as one of the key factors for the creation of open content in the context of open and distance learning. Qualitative analysis of texts was made from 1992 to early 2014 in order to identify meanings associated with reusability and…

  2. Agri-Environmental Resource Management by Large-Scale Collective Action: Determining KEY Success Factors

    ERIC Educational Resources Information Center

    Uetake, Tetsuya

    2015-01-01

    Purpose: Large-scale collective action is necessary when managing agricultural natural resources such as biodiversity and water quality. This paper determines the key factors to the success of such action. Design/Methodology/Approach: This paper analyses four large-scale collective actions used to manage agri-environmental resources in Canada and…

  3. Key factors of readiness in the implementation of industrialised building system (IBS)

    NASA Astrophysics Data System (ADS)

    Tamrin, Norhidayah; Nawi, Mohd Nasrun Mohd; Nifa, Faizatul Akmar Abdul

    2016-08-01

    Although IBS has been introduced since the 1960, and many advantages that have identified for the implementation of IBS in Malaysia, yet the level of implementation of IBS still did not achieve the government target. Previous studies have been conducted to identify the factors that contribute to the lack of the implementation. From the previous studies, mostly the barriers of IBS implementation are rooted within the several semi-structured lack of readiness among industry players. The interview participants for this study are from the multidisciplinary IBS practitioners. This paper discusses the identified readiness with the objective to determine what the key factor of readiness in IBS implementation is and how far the factors influence the IBS activities. From the finding, the readiness factor was divided into three main factors which are knowledge, ability and planning.

  4. The structural elucidation of the Salmonella enterica subsp. enterica, reveals that it contains both O-factors 4 and 5 on the LPS antigen.

    PubMed

    De Castro, Cristina; Lanzetta, Rosa; Leone, Serena; Parrilli, Michelangelo; Molinaro, Antonio

    2013-04-01

    Spectroscopic investigation of the O-antigen from Salmonella enterica subsp. enterica revealed fine details on the acetylation pattern, the biological repeating unit and the polymerization degree. Acetylation at O-2 of the abequose residue, defined both O-factors 4 and 5 in the O-antigen chain of the lipopolysaccharide. NMR observation of the terminal non-reducing end of the polymer confirmed previous data regarding the biological repeating unit and showed an average polymerization degree of 5. The information about these structural elements might contribute to the understanding of key features of the biology of this pathogen, as phase variation and/or adaptation to the external environment. PMID:23419941

  5. Three-factor anonymous authentication and key agreement scheme for Telecare Medicine Information Systems.

    PubMed

    Arshad, Hamed; Nikooghadam, Morteza

    2014-12-01

    Nowadays, with comprehensive employment of the internet, healthcare delivery services is provided remotely by telecare medicine information systems (TMISs). A secure mechanism for authentication and key agreement is one of the most important security requirements for TMISs. Recently, Tan proposed a user anonymity preserving three-factor authentication scheme for TMIS. The present paper shows that Tan's scheme is vulnerable to replay attacks and Denial-of-Service attacks. In order to overcome these security flaws, a new and efficient three-factor anonymous authentication and key agreement scheme for TMIS is proposed. Security and performance analysis shows superiority of the proposed scheme in comparison with previously proposed schemes that are related to security of TMISs. PMID:25352490

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

    PubMed

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

    2015-01-01

    The study explores the perceptions of physicians and hospital managers regarding the key success factors (KSFs) of a clinical knowledge management system (CKMS). It aims to eliminate the perception gap and gain more insights for a successful CKMS.A survey was conducted in four medical centers in Taiwan. A total of 340 questionnaires, including 15 for hospital managers and 70 for physicians in each hospital, were administered. The effective response rates are 78.3% and 56.1% respectively. Partial least square (PLS) were used to analyze the data.The results identified six KSFs of CKMS including system software and hardware, knowledge quality, system quality, organizational factors, user satisfaction, and policy factors. User satisfaction and policy factors have direct effects on perceived CKMS performance. Knowledge quality is regarded as an antecedent to user satisfaction, while system quality is the antecedent to both user satisfaction and policy factors. System software and hardware was supported only by managers, and organizational factors were supported only by physicians.Among the factors, this study highlighted the policy factor. Besides, the study provides hospital managers additional insights into physician requirements for organizational support. Third, more physician participation and involvement are recommended when introducing and developing a CKMS. PMID:26444813

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

    PubMed

    Malin, Katrina; Littlejohn, Geoffrey Owen

    2016-09-01

    The clinical features of fibromyalgia are associated with various psychological factors, including stress. We examined the hypothesis that the path that psychological factors follow in influencing fibromyalgia symptoms is through their direct effect on stress. Ninety-eight females with ACR 1990 classified fibromyalgia completed the following questionnaires: The Big 5 Personality Inventory, Fibromyalgia Impact Questionnaire, Perceived Stress Scale, Profile of Mood States, Mastery Scale, and Perceived Control of Internal States Scale. SPSS (PASW version 22) was used to perform basic t tests, means, and standard deviations to show difference between symptom characteristics. Pathway analysis using structural equation modelling (Laavan) examined the effect of stress on the relationships between psychological factors and the elements that define the fibromyalgia phenotype. The preferred model showed that the identified path clearly linked the psychological variables of anxiety, neuroticism and mastery, but not internal control, to the three key elements of fibromyalgia, namely pain, fatigue and sleep (p < 0.001), via the person's perceived stress. Confusion, however, did not fit the preferred model. This study confirms that stress is a necessary link in the pathway between certain identified, established and significant psychological factors and key fibromyalgia symptoms. This has implications for the understanding of contributing mechanisms and the clinical care of patients with fibromyalgia. PMID:27245234

  8. Identifying the key factors affecting warning message dissemination in VANET real urban scenarios.

    PubMed

    Fogue, Manuel; Garrido, Piedad; Martinez, Francisco J; Cano, Juan-Carlos; Calafate, Carlos T; Manzoni, Pietro

    2013-01-01

    In recent years, new architectures and technologies have been proposed for Vehicular Ad Hoc networks (VANETs). Due to the cost and complexity of deploying such networks, most of these proposals rely on simulation. However, we find that most of the experiments made to validate these proposals tend to overlook the most important and representative factors. Moreover, the scenarios simulated tend to be very simplistic (highways or Manhattan-based layouts), which could seriously affect the validity of the obtained results. In this paper, we present a statistical analysis based on the 2k factorial methodology to determine the most representative factors affecting traffic safety applications under real roadmaps. Our purpose is to determine which are the key factors affecting Warning Message Dissemination in order to concentrate research tests on such parameters, thus avoiding unnecessary simulations and reducing the amount of simulation time required. Simulation results show that the key factors affecting warning messages delivery are the density of vehicles and the roadmap used. Based on this statistical analysis, we consider that VANET researchers must evaluate the benefits of their proposals using different vehicle densities and city scenarios, to obtain a broad perspective on the effectiveness of their solution. Finally, since city maps can be quite heterogeneous, we propose a roadmap profile classification to further reduce the number of cities evaluated. PMID:23604026

  9. Identifying the Key Factors Affecting Warning Message Dissemination in VANET Real Urban Scenarios

    PubMed Central

    Fogue, Manuel; Garrido, Piedad; Martinez, Francisco J.; Cano, Juan-Carlos; Calafate, Carlos T.; Manzoni, Pietro

    2013-01-01

    In recent years, new architectures and technologies have been proposed for Vehicular Ad Hoc networks (VANETs). Due to the cost and complexity of deploying such networks, most of these proposals rely on simulation. However, we find that most of the experiments made to validate these proposals tend to overlook the most important and representative factors. Moreover, the scenarios simulated tend to be very simplistic (highways or Manhattan-based layouts), which could seriously affect the validity of the obtained results. In this paper, we present a statistical analysis based on the 2k factorial methodology to determine the most representative factors affecting traffic safety applications under real roadmaps. Our purpose is to determine which are the key factors affecting Warning Message Dissemination in order to concentrate research tests on such parameters, thus avoiding unnecessary simulations and reducing the amount of simulation time required. Simulation results show that the key factors affecting warning messages delivery are the density of vehicles and the roadmap used. Based on this statistical analysis, we consider that VANET researchers must evaluate the benefits of their proposals using different vehicle densities and city scenarios, to obtain a broad perspective on the effectiveness of their solution. Finally, since city maps can be quite heterogeneous, we propose a roadmap profile classification to further reduce the number of cities evaluated. PMID:23604026

  10. Integrating candidate metabolites and biochemical factors to elucidate the action mechanism of Xue-sai-tong injection based on (1)H NMR metabolomics.

    PubMed

    Jiang, Miaomiao; Zhao, Xiaoping; Wang, Linli; Xu, Lei; Zhang, Yan; Li, Zheng

    2016-07-15

    A strategy of integrating candidate metabolites with crucial biochemical factors was proposed in this study to discover relevant biological functions for interpreting the action mechanism of Traditional Chinese Medicines (TCM). This approach was applied to Xue-Sai-Tong injection (XST) to reveal the action mechanism based on the metabolic response in an ischemia/reperfusion (I/R) rat model by analyzing NMR profile. Partial least squares discriminate analysis (PLS-DA) was used to compare metabolic profiles of serum samples and revealed nine metabolites altered by I/R injury could be restored to normal status (sham-operated group) under the therapy of XST. The pathway enrichment analysis suggested the metabolic changes were mainly involved in pyruvate metabolism, glycolysis, and citrate cycle. The functional roles of the candidate metabolites were further identified by Pearson correlation analysis with the key biochemical factors in serum. The results indicated pyruvate, succinate, acetate and lysine showed significant associations with the oxidative stress factors. Elevated level of pyruvate was found as an essential metabolic response for the major effect of XST against I/R injury by enhancing glycolysis and overcoming the induced reactive oxygen species (ROS). This metabolomics approach provides a better understanding of the mechanisms of TCM and helps to develop a holistic view of TCM efficacy. PMID:26862062

  11. A key genetic factor for fucosyllactose utilization affects infant gut microbiota development

    PubMed Central

    Matsuki, Takahiro; Yahagi, Kana; Mori, Hiroshi; Matsumoto, Hoshitaka; Hara, Taeko; Tajima, Saya; Ogawa, Eishin; Kodama, Hiroko; Yamamoto, Kazuya; Yamada, Takuji; Matsumoto, Satoshi; Kurokawa, Ken

    2016-01-01

    Recent studies have demonstrated that gut microbiota development influences infants' health and subsequent host physiology. However, the factors shaping the development of the microbiota remain poorly understood, and the mechanisms through which these factors affect gut metabolite profiles have not been extensively investigated. Here we analyse gut microbiota development of 27 infants during the first month of life. We find three distinct clusters that transition towards Bifidobacteriaceae-dominant microbiota. We observe considerable differences in human milk oligosaccharide utilization among infant bifidobacteria. Colonization of fucosyllactose (FL)-utilizing bifidobacteria is associated with altered metabolite profiles and microbiota compositions, which have been previously shown to affect infant health. Genome analysis of infants' bifidobacteria reveals an ABC transporter as a key genetic factor for FL utilization. Thus, the ability of bifidobacteria to utilize FL and the presence of FL in breast milk may affect the development of the gut microbiota in infants, and might ultimately have therapeutic implications. PMID:27340092

  12. A key genetic factor for fucosyllactose utilization affects infant gut microbiota development.

    PubMed

    Matsuki, Takahiro; Yahagi, Kana; Mori, Hiroshi; Matsumoto, Hoshitaka; Hara, Taeko; Tajima, Saya; Ogawa, Eishin; Kodama, Hiroko; Yamamoto, Kazuya; Yamada, Takuji; Matsumoto, Satoshi; Kurokawa, Ken

    2016-01-01

    Recent studies have demonstrated that gut microbiota development influences infants' health and subsequent host physiology. However, the factors shaping the development of the microbiota remain poorly understood, and the mechanisms through which these factors affect gut metabolite profiles have not been extensively investigated. Here we analyse gut microbiota development of 27 infants during the first month of life. We find three distinct clusters that transition towards Bifidobacteriaceae-dominant microbiota. We observe considerable differences in human milk oligosaccharide utilization among infant bifidobacteria. Colonization of fucosyllactose (FL)-utilizing bifidobacteria is associated with altered metabolite profiles and microbiota compositions, which have been previously shown to affect infant health. Genome analysis of infants' bifidobacteria reveals an ABC transporter as a key genetic factor for FL utilization. Thus, the ability of bifidobacteria to utilize FL and the presence of FL in breast milk may affect the development of the gut microbiota in infants, and might ultimately have therapeutic implications. PMID:27340092

  13. Review of key factors controlling engineered nanoparticle transport in porous media.

    PubMed

    Wang, Mei; Gao, Bin; Tang, Deshan

    2016-11-15

    Nanotechnology, an emerging technology, has witnessed rapid development in production and application. Engineered nanomaterials revolutionize the industry due to their unique structure and superior performance. The release of engineered nanoparticles (ENPs) into the environment, however, may pose risks to the environment and public health. To advance current understanding of environmental behaviors of ENPs, this work provides an introductory overview of ENP fate and transport in porous media. It systematically reviews the key factors controlling their fate and transport in porous media. It first provides a brief overview of common ENPs in the environment and their sources. The key factors that govern ENP transport in porous media are then categorized into three groups: (1) nature of ENPs affecting their transport in porous media, (2) nature of porous media affecting ENP transport, and (3) nature of flow affecting ENP transport in porous media. In each group, findings in recent literature on the specific governing factors of ENP transport in porous media are discussed in details. Finally, this work concludes with remarks on the importance of ENP transport in porous media and directions for future research. PMID:27427890

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

    PubMed

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

    2015-01-01

    Biological soil crusts (BSCs) are a widespread photosynthetic ground cover in arid and semiarid areas. They have many positive ecological functions, such as increasing soil stability, and reducing water and wind erosion. Using artificial technology to achieve the rapid development of BSCs is expected to become a low-cost and highly beneficial ecological restoration measure. In the present study, typical moss-dominated crusts in a region characterized by mobile dunes (Mu Us Sandland, China) were collected, and a 40-day cultivation experiment was performed to investigate key factors, including watering frequency, light intensity and a nutrient addition, which affect the rapid development of moss crusts and their optimal combination. The results demonstrated that watering frequency and illumination had a significant positive effect (P=0.049, three-factor ANOVA) and a highly significant, complicated effect (P=0.000, three-factor ANOVA), respectively, on the plant density of bryophytes, and a highly significant positive effect on the chlorophyll a and exopolysaccharide contents (P=0.000, P=0.000; P=0.000, P=0.000; one-way ANOVA). Knop nutrient solution did not have a significant positive but rather negative effect on the promotion of moss-dominated crust development (P=0.270, three-factor ANOVA). Moss-dominated crusts treated with the combination of moderate-intensity light (6,000 lx) + high watering frequency (1 watering/2 days) - Knop had the highest moss plant densities, while the treatment with high-intensity light (12,000 lx) + high watering frequency (1 watering/2 days) + Knop nutrient solution had higher chlorophyll a contents than that under other treatments. It is entirely feasible to achieve the rapid development of moss crusts under laboratory conditions by regulating key factors and creating the right environment. Future applications may seek to use cultured bryophytes to control erosion in vulnerable areas with urgent needs. PMID:26230324

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

    PubMed Central

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

    2015-01-01

    Biological soil crusts (BSCs) are a widespread photosynthetic ground cover in arid and semiarid areas. They have many positive ecological functions, such as increasing soil stability, and reducing water and wind erosion. Using artificial technology to achieve the rapid development of BSCs is expected to become a low-cost and highly beneficial ecological restoration measure. In the present study, typical moss-dominated crusts in a region characterized by mobile dunes (Mu Us Sandland, China) were collected, and a 40-day cultivation experiment was performed to investigate key factors, including watering frequency, light intensity and a nutrient addition, which affect the rapid development of moss crusts and their optimal combination. The results demonstrated that watering frequency and illumination had a significant positive effect (P=0.049, three-factor ANOVA) and a highly significant, complicated effect (P=0.000, three-factor ANOVA), respectively, on the plant density of bryophytes, and a highly significant positive effect on the chlorophyll a and exopolysaccharide contents (P=0.000, P=0.000; P=0.000, P=0.000; one-way ANOVA). Knop nutrient solution did not have a significant positive but rather negative effect on the promotion of moss-dominated crust development (P=0.270, three-factor ANOVA). Moss-dominated crusts treated with the combination of moderate-intensity light (6,000 lx) + high watering frequency (1 watering/2 days) - Knop had the highest moss plant densities, while the treatment with high-intensity light (12,000 lx) + high watering frequency (1 watering/2 days) + Knop nutrient solution had higher chlorophyll a contents than that under other treatments. It is entirely feasible to achieve the rapid development of moss crusts under laboratory conditions by regulating key factors and creating the right environment. Future applications may seek to use cultured bryophytes to control erosion in vulnerable areas with urgent needs. PMID:26230324

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

    PubMed

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

    2007-10-31

    The analytical process of lycopene extraction and photometrical determination was critically examined for raw tomato and processed tomato products by means of a 2 IV (15-10) Plackett-Burman experimental design in order to identify the key factors (KFs) involved. Fifteen apparent key factors (AKFs) reported in the literature were selected: sample weight (X1); volume of extraction solution (X2); antioxidant concentration (BHT, X3); neutralizing agent concentration (MgCO 3, X4); light presence during lycopene extraction (X5), homogenization velocity (X6) and time (X7), agitation time (X8), and temperature (X9) during the extraction process; water volume for separation of polar/nonpolar phases (X11); presence of inert atmosphere throughout the process (X12); time (X13), temperature (X14), and light presence (X10) during separation of phases and time delay for reading (X15). In general, higher lycopene concentrations in samples led to a higher number of key factors (KF). Thus, for raw tomato (lycopene range 1.22-2.29 mg/100 g) no KF were found, whereas for tomato sauce (lycopene range from 5.80 to 8.60 mg/100 g) one KF (X4) and for tomato paste (lycopene range from 35.80 to 51.27 mg/100 g) five KFs (X1, X2, X4, X11, and X12) were detected. For lycopene paste, X1 and X2 were identified as the KFs with the greatest impact on results, although in fact the X1/X2 ratio was the real cause. The results suggest that, with increased processing, the physical and chemical structure of lycopene becomes less important since the identified KFs explain almost 90% of variability in tomato paste but only 32% in raw tomato. PMID:17924704

  17. Analysis of Hypoxia-Inducible Factor-1α Expression Relative to Other Key Factors in Malignant Canine Mammary Tumours.

    PubMed

    Shin, J-I; Lim, H-Y; Kim, H-W; Seung, B-J; Sur, J-H

    2015-01-01

    Hypoxia-inducible factor (HIF)-1α plays important physiological roles, but is also of significance in carcinogenesis in man and animals. This study aimed to identify HIF-1α expression in malignant canine mammary tumours (CMTs) and to find correlations with other key factors by using immunohistochemistry (IHC). The histological classification, grading and evaluation of lymphatic invasion were achieved by examining sections stained by haematoxylin and eosin. Determination of molecular subtype, expression of HIF-1α, oestrogen receptor (OR), progesterone receptor (PR), human epidermal growth factor receptor (HER)-2, Ki67, vascular endothelial growth factor (VEGF) and E-cadherin was evaluated by IHC in 87 samples of malignant CMTs. HIF-1α expression correlated significantly with histological type, grade of cancer, negativity for OR and expression of Ki67 and VEGF. Lymphatic invasion, molecular subtype, PR, HER-2 and E-cadherin levels did not significantly correlate with HIF-1α expression. The results of this study imply that HIF-1α may potentially play a role in increased malignancy of CMTs, as it does in human breast cancer. PMID:26145724

  18. Factors Enabling Access to HIV Voluntary Counseling and Testing for Key Affected Populations in Thailand.

    PubMed

    Thepthien, Bang-on; Srivanichakorn, Supattra; Apipornchaisakul, Kanya

    2015-10-01

    The objective was to study the factors that enabled persons at risk of HIV to obtain voluntary counseling and testing (VCT) in Thailand. This research was a cross-sectional study and data were collected during May to July 2013 in 8, purposively selected provinces. The method for selecting respondents used time-location quota sampling to achieve a total sample of 751 persons. The proportion who had VCT in the year prior to the survey was 56%.The significant enabling factors associated with VCT were having someone encourage them to go for testing and receiving information about VCT In addition, other significant factors for female sex workers were self-assessed risk for HIV and having had risk behavior, and for men who have sex with men the factors were awareness of eligibility for VCT. Thus, in order to achieve the VCT target for higher risk populations by 2016, there should be special mechanisms to inform the different groups, along with improvements in outreach services to make VCT more convenient for key affected populations. PMID:26069165

  19. Master transcription factors and mediator establish super-enhancers at key cell identity genes.

    PubMed

    Whyte, Warren A; Orlando, David A; Hnisz, Denes; Abraham, Brian J; Lin, Charles Y; Kagey, Michael H; Rahl, Peter B; Lee, Tong Ihn; Young, Richard A

    2013-04-11

    Master transcription factors Oct4, Sox2, and Nanog bind enhancer elements and recruit Mediator to activate much of the gene expression program of pluripotent embryonic stem cells (ESCs). We report here that the ESC master transcription factors form unusual enhancer domains at most genes that control the pluripotent state. These domains, which we call super-enhancers, consist of clusters of enhancers that are densely occupied by the master regulators and Mediator. Super-enhancers differ from typical enhancers in size, transcription factor density and content, ability to activate transcription, and sensitivity to perturbation. Reduced levels of Oct4 or Mediator cause preferential loss of expression of super-enhancer-associated genes relative to other genes, suggesting how changes in gene expression programs might be accomplished during development. In other more differentiated cells, super-enhancers containing cell-type-specific master transcription factors are also found at genes that define cell identity. Super-enhancers thus play key roles in the control of mammalian cell identity. PMID:23582322

  20. Identification of Key Contributory Factors Responsible for Vascular Dysfunction in Idiopathic Recurrent Spontaneous Miscarriage

    PubMed Central

    Dutta, Mainak; Subramani, Elavarasan; Khalpada, Jaydeep; RoyChoudhury, Sourav; Chakravarty, Baidyanath; Chaudhury, Koel

    2013-01-01

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

  1. Surgical Ventricular Entry is a Key Risk Factor for Leptomeningeal Metastasis of High Grade Gliomas

    PubMed Central

    Roelz, Roland; Reinacher, Peter; Jabbarli, Ramazan; Kraeutle, Rainer; Hippchen, Beate; Egger, Karl; Weyerbrock, Astrid; Machein, Marcia

    2015-01-01

    Leptomeningeal metastasis (LM) of high grade gliomas (HGG) can lead to devastating disease courses. Understanding of risk factors for LM is important to identify patients at risk. We reviewed patient records and magnetic resonance imaging (MRI) of all patients with a first diagnosis of HGG who underwent surgery in our institution between 2008 and 2012. To assess the influence of potential risk factors for LM and the impact of LM on survival multivariate statistics were performed. 239 patients with a diagnosis of HGG and at least 6 months of MRI and clinical follow-up were included. LM occurred in 27 (11%) patients and was symptomatic in 17 (65%). A strong correlation of surgical entry to the ventricle and LM was found (HR: 8.1). Ventricular entry was documented in 137 patients (57%) and LM ensued in 25 (18%) of these. Only two (2%) of 102 patients without ventricular entry developed LM. Median overall survival of patients after diagnosis of LM (239 days) was significantly shorter compared to patients without LM (626 days). LM is a frequent complication in the course of disease of HGG and is associated with poor survival. Surgical entry to the ventricle is a key risk factor for LM. PMID:26635136

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

    NASA Astrophysics Data System (ADS)

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

    2012-12-01

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

  3. Transcription Factor RFX2 Is a Key Regulator of Mouse Spermiogenesis.

    PubMed

    Wu, Yujian; Hu, Xiangjing; Li, Zhen; Wang, Min; Li, Sisi; Wang, Xiuxia; Lin, Xiwen; Liao, Shangying; Zhang, Zhuqiang; Feng, Xue; Wang, Si; Cui, Xiuhong; Wang, Yanling; Gao, Fei; Hess, Rex A; Han, Chunsheng

    2016-01-01

    The regulatory factor X (RFX) family of transcription factors is crucial for ciliogenesis throughout evolution. In mice, Rfx1-4 are highly expressed in the testis where flagellated sperm are produced, but the functions of these factors in spermatogenesis remain unknown. Here, we report the production and characterization of the Rfx2 knockout mice. The male knockout mice were sterile due to the arrest of spermatogenesis at an early round spermatid step. The Rfx2-null round spermatids detached from the seminiferous tubules, forming large multinucleated giant cells that underwent apoptosis. In the mutants, formation of the flagellum was inhibited at its earliest stage. RNA-seq analysis identified a large number of cilia-related genes and testis-specific genes that were regulated by RFX2. Many of these genes were direct targets of RFX2, as revealed by chromatin immunoprecipitation-PCR assays. These findings indicate that RFX2 is a key regulator of the post-meiotic development of mouse spermatogenic cells. PMID:26853561

  4. Transcription Factor RFX2 Is a Key Regulator of Mouse Spermiogenesis

    PubMed Central

    Wu, Yujian; Hu, Xiangjing; Li, Zhen; Wang, Min; Li, Sisi; Wang, Xiuxia; Lin, Xiwen; Liao, Shangying; Zhang, Zhuqiang; Feng, Xue; Wang, Si; Cui, Xiuhong; Wang, Yanling; Gao, Fei; Hess, Rex A.; Han, Chunsheng

    2016-01-01

    The regulatory factor X (RFX) family of transcription factors is crucial for ciliogenesis throughout evolution. In mice, Rfx1-4 are highly expressed in the testis where flagellated sperm are produced, but the functions of these factors in spermatogenesis remain unknown. Here, we report the production and characterization of the Rfx2 knockout mice. The male knockout mice were sterile due to the arrest of spermatogenesis at an early round spermatid step. The Rfx2-null round spermatids detached from the seminiferous tubules, forming large multinucleated giant cells that underwent apoptosis. In the mutants, formation of the flagellum was inhibited at its earliest stage. RNA-seq analysis identified a large number of cilia-related genes and testis-specific genes that were regulated by RFX2. Many of these genes were direct targets of RFX2, as revealed by chromatin immunoprecipitation-PCR assays. These findings indicate that RFX2 is a key regulator of the post-meiotic development of mouse spermatogenic cells. PMID:26853561

  5. Key factors influencing rates of heterotrophic sulfate reduction in hydrothermal massive sulfide deposits

    NASA Astrophysics Data System (ADS)

    Frank, K. L.; Rogers, D.; Girguis, P. R.

    2012-12-01

    Despite sulfate reduction's ubiquity in marine systems, relatively little is known about how environmental or ecological factors influence rates of sulfate reduction. While numerous studies have considered how sulfate reduction and methanogenesis compete for reductants in natural and human-made systems, less is known about how temperature or metabolite concentration, such as sulfate and sulfide concentrations, affects rates of sulfate reduction. Here we use a factorial experimental design to evaluate the effects of key variables on sulfate reduction kinetics in sulfide deposits recovered from hydrothermal vents in the Main Endeavor Field, Juan de Fuca ridge. Microbial sulfate reduction rates were measured by 35-S tracer techniques over a range of environmentally relevant chemical conditions (pH, H2S, SO42-, and organic carbon concentrations) and temperatures (4, 50 and 90°C). Maximum sulfate reduction rates were observed at 50°C, and sulfate reduction rates had significant positive correlations with increasing sulfide, pH and sulfate. However, sulfate reduction rates did not correlate to exogenous dissolved organic carbon, implicating exogenous hydrogen or endogenous organic matter as the reductant (or even sulfur disproportionation). This research presents an opportunity to better understand the key variables that influence the rates of microbial sulfate reduction in hydrothermal environments and provides a framework for modeling sulfate reduction in mid-ocean ridge systems.

  6. A Secure Three-Factor User Authentication and Key Agreement Protocol for TMIS With User Anonymity.

    PubMed

    Amin, Ruhul; Biswas, G P

    2015-08-01

    Telecare medical information system (TMIS) makes an efficient and convenient connection between patient(s)/user(s) and doctor(s) over the insecure internet. Therefore, data security, privacy and user authentication are enormously important for accessing important medical data over insecure communication. Recently, many user authentication protocols for TMIS have been proposed in the literature and it has been observed that most of the protocols cannot achieve complete security requirements. In this paper, we have scrutinized two (Mishra et al., Xu et al.) remote user authentication protocols using smart card and explained that both the protocols are suffering against several security weaknesses. We have then presented three-factor user authentication and key agreement protocol usable for TMIS, which fix the security pitfalls of the above mentioned schemes. The informal cryptanalysis makes certain that the proposed protocol provides well security protection on the relevant security attacks. Furthermore, the simulator AVISPA tool confirms that the protocol is secure against active and passive attacks including replay and man-in-the-middle attacks. The security functionalities and performance comparison analysis confirm that our protocol not only provide strong protection on security attacks, but it also achieves better complexities along with efficient login and password change phase as well as session key verification property. PMID:26112322

  7. A key factor to the spin parameter of uniformly rotating compact stars: crust structure

    NASA Astrophysics Data System (ADS)

    Qi, Bin; Zhang, Nai-Bo; Sun, Bao-Yuan; Wang, Shou-Yu; Gao, Jian-Hua

    2016-04-01

    We study the dimensionless spin parameter j ≡ cJ/(GM2) of different kinds of uniformly rotating compact stars, including traditional neutron stars, hyperonic neutron stars and hybrid stars, based on relativistic mean field theory and the MIT bag model. It is found that jmax ∼ 0.7, which had been suggested in traditional neutron stars, is sustained for hyperonic neutron stars and hybrid stars with M > 0.5 M⊙. Not the interior but rather the crust structure of the stars is a key factor to determine jmax for three kinds of selected compact stars. Furthermore, a universal formula j = 0.63(f/fK) ‑ 0.42(f/fK)2 + 0.48(f/fK)3 is suggested to determine the spin parameter at any rotational frequency f smaller than the Keplerian frequency fK.

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

    PubMed

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

    2016-01-01

    Traumatic brain injury (TBI) has become a significant medical and social concern within the last 30 years. TBI has acute devastating effects, and in many cases, seems to initiate long-term neurodegeneration. With advances in medical technology, many people are now surviving severe brain injuries and their long term consequences. Post trauma effects include communication problems, sensory deficits, emotional and behavioral problems, physical complications and pain, increased suicide risk, dementia, and an increased risk for chronic CNS diseases, such as Alzheimer's disease (AD). In this review, we provide an introduction to TBI and hypothesize how it may lead to neurodegenerative disease in general and AD in particular. In addition, we discuss the evidence that supports the hypothesis that TBI may lead to AD. In particular, we focus on inflammatory responses as key processes in TBI-induced secondary injury, with emphasis on nuclear factor kappa B (NF-κB) signaling. PMID:26899581

  9. Neisseria meningitidis factor H-binding protein fHbp: a key virulence factor and vaccine antigen.

    PubMed

    Seib, Kate L; Scarselli, Maria; Comanducci, Maurizio; Toneatto, Daniela; Masignani, Vega

    2015-06-01

    Neisseria meningitidis is a leading cause of meningitis and sepsis worldwide. The first broad-spectrum multicomponent vaccine against serogroup B meningococcus (MenB), 4CMenB (Bexsero(®)), was approved by the EMA in 2013, for prevention of MenB disease in all age groups, and by the US FDA in January 2015 for use in adolescents. A second protein-based MenB vaccine has also been approved in the USA for adolescents (rLP2086, Trumenba(®)). Both vaccines contain the lipoprotein factor H-binding protein (fHbp). Preclinical studies demonstrated that fHbp elicits a robust bactericidal antibody response that correlates with the amount of fHbp expressed on the bacterial surface. fHbp is able to selectively bind human factor H, the key regulator of the alternative complement pathway, and this has important implications both for meningococcal pathogenesis and for vaccine design. Here, we review the functional and structural properties of fHbp, the strategies that led to the design of the two fHbp-based vaccines and the data generated during clinical studies. PMID:25704037

  10. Age at disease onset: a key factor for understanding psoriatic disease.

    PubMed

    Queiro, Rubén; Tejón, Patricia; Alonso, Sara; Coto, Pablo

    2014-07-01

    Psoriasis and PsA are immune-mediated diseases with a strong genetic component. More than 20 new loci have been recently linked to these diseases. However, interactions between these genes and the phenotypic traits of both diseases are poorly understood at present. Stratification of psoriatic disease according to the sex of the patients, genetic factors or age at onset has allowed in the last few years a better understanding of the principles governing the onset and progression of these processes. The age of onset of psoriasis has been used for decades as an appropriate descriptor to define two subpopulations of psoriatic patients (types I and II) whose clinical and immunogenetic characteristics have been very well differentiated. Moreover, in patients with PsA this distinction between type I and II psoriasis also seems equally operative. In patients with PsA expressing the HLA-C*06 antigen, the latency between the onset of psoriasis and onset of joint symptoms is longer than in those without this marker. It is also known that PsA tends to appear earlier in patients with HLA-B*27 positivity, and that these patients also show a shorter interval of time between the onset of cutaneous lesions and the onset of joint disease. This review highlights the growing importance of age at disease onset as a key stratification factor in worldwide clinical and genetic studies of psoriatic disease. PMID:24273020

  11. Short-term selective alleviation of glucotoxicity and lipotoxicity ameliorates the suppressed expression of key β-cell factors under diabetic conditions.

    PubMed

    Shimo, Naoki; Matsuoka, Taka-aki; Miyatsuka, Takeshi; Takebe, Satomi; Tochino, Yoshihiro; Takahara, Mitsuyoshi; Kaneto, Hideaki; Shimomura, Iichiro

    2015-11-27

    Alleviation of hyperglycaemia and hyperlipidemia improves pancreatic β-cell function in type 2 diabetes. However, the underlying molecular mechanisms are still not well clarified. In this study, we aimed to elucidate how the expression alterations of key β-cell factors are altered by the short-term selective alleviation of glucotoxicity or lipotoxicity. We treated db/db mice for one week with empagliflozin and/or bezafibrate to alleviate glucotoxicity and/or liptotoxicity, respectively. The gene expression levels of Pdx1 and Mafa, and their potential targets, insulin 1, Slc2a2, and Glp1r, were higher in the islets of empagliflozin-treated mice, and levels of insulin 2 were higher in mice treated with both reagents, than in untreated mice. Moreover, compared to the pretreatment levels, Mafa and insulin 1 expression increased in empagliflozin-treated mice, and Slc2a2 increased in combination-treated mice. In addition, empagliflozin treatment enhanced β-cell proliferation assessed by Ki-67 immunostaining. Our date clearly demonstrated that the one-week selective alleviation of glucotoxicity led to the better expression levels of the key β-cell factors critical for β-cell function over pretreatment levels, and that the alleviation of lipotoxicity along with glucotoxicity augmented the favorable effects under diabetic conditions. PMID:26471305

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

    SciTech Connect

    Iannuzzi, T.J.; Harrington, N.W.; Shear, N.M.; Curry, C.L.; Carlson-Lynch, H.; Henning, M.H.; Su, S.H.; Rabbe, D.E.

    1996-11-01

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

  13. Defining a protective epitope on factor H binding protein, a key meningococcal virulence factor and vaccine antigen.

    PubMed

    Malito, Enrico; Faleri, Agnese; Lo Surdo, Paola; Veggi, Daniele; Maruggi, Giulietta; Grassi, Eva; Cartocci, Elena; Bertoldi, Isabella; Genovese, Alessia; Santini, Laura; Romagnoli, Giacomo; Borgogni, Erica; Brier, Sébastien; Lo Passo, Carla; Domina, Maria; Castellino, Flora; Felici, Franco; van der Veen, Stijn; Johnson, Steven; Lea, Susan M; Tang, Christoph M; Pizza, Mariagrazia; Savino, Silvana; Norais, Nathalie; Rappuoli, Rino; Bottomley, Matthew J; Masignani, Vega

    2013-02-26

    Mapping of epitopes recognized by functional monoclonal antibodies (mAbs) is essential for understanding the nature of immune responses and designing improved vaccines, therapeutics, and diagnostics. In recent years, identification of B-cell epitopes targeted by neutralizing antibodies has facilitated the design of peptide-based vaccines against highly variable pathogens like HIV, respiratory syncytial virus, and Helicobacter pylori; however, none of these products has yet progressed into clinical stages. Linear epitopes identified by conventional mapping techniques only partially reflect the immunogenic properties of the epitope in its natural conformation, thus limiting the success of this approach. To investigate antigen-antibody interactions and assess the potential of the most common epitope mapping techniques, we generated a series of mAbs against factor H binding protein (fHbp), a key virulence factor and vaccine antigen of Neisseria meningitidis. The interaction of fHbp with the bactericidal mAb 12C1 was studied by various epitope mapping methods. Although a 12-residue epitope in the C terminus of fHbp was identified by both Peptide Scanning and Phage Display Library screening, other approaches, such as hydrogen/deuterium exchange mass spectrometry (MS) and X-ray crystallography, showed that mAb 12C1 occupies an area of ∼1,000 Å(2) on fHbp, including >20 fHbp residues distributed on both N- and C-terminal domains. Collectively, these data show that linear epitope mapping techniques provide useful but incomplete descriptions of B-cell epitopes, indicating that increased efforts to fully characterize antigen-antibody interfaces are required to understand and design effective immunogens. PMID:23396847

  14. The key sigma factor of transition phase, SigH, controls sporulation, metabolism, and virulence factor expression in Clostridium difficile.

    PubMed

    Saujet, Laure; Monot, Marc; Dupuy, Bruno; Soutourina, Olga; Martin-Verstraete, Isabelle

    2011-07-01

    Toxin synthesis in Clostridium difficile increases as cells enter into stationary phase. We first compared the expression profiles of strain 630E during exponential growth and at the onset of stationary phase and showed that genes involved in sporulation, cellular division, and motility, as well as carbon and amino acid metabolism, were differentially expressed under these conditions. We inactivated the sigH gene, which encodes an alternative sigma factor involved in the transition to post-exponential phase in Bacillus subtilis. Then, we compared the expression profiles of strain 630E and the sigH mutant after 10 h of growth. About 60% of the genes that were differentially expressed between exponential and stationary phases, including genes involved in motility, sporulation, and metabolism, were regulated by SigH, which thus appears to be a key regulator of the transition phase in C. difficile. SigH positively controls several genes required for sporulation. Accordingly, sigH inactivation results in an asporogeneous phenotype. The spo0A and CD2492 genes, encoding the master regulator of sporulation and one of its associated kinases, and the spoIIA operon were transcribed from a SigH-dependent promoter. The expression of tcdA and tcdB, encoding the toxins, and of tcdR, encoding the sigma factor required for toxin production, increased in a sigH mutant. Finally, SigH regulates the expression of genes encoding surface-associated proteins, such as the Cwp66 adhesin, the S-layer precursor, and the flagellum components. Among the 286 genes positively regulated by SigH, about 40 transcriptional units presenting a SigH consensus in their promoter regions are good candidates for direct SigH targets. PMID:21572003

  15. Hepatitis C virus suppresses Hepatocyte Nuclear Factor 4 alpha, a key regulator of hepatocellular carcinoma.

    PubMed

    Vallianou, Ioanna; Dafou, Dimitra; Vassilaki, Niki; Mavromara, Penelope; Hadzopoulou-Cladaras, Margarita

    2016-09-01

    Hepatitis C Virus (HCV) infection presents with a disturbed lipid profile and can evolve to hepatic steatosis and hepatocellular carcinoma (HCC). Hepatocyte Nuclear Factor 4 alpha (HNF4α) is the most abundant transcription factor in the liver, a key regulator of hepatic lipid metabolism and a critical determinant of Epithelial to Mesenchymal Transition and hepatic development. We have previously shown that transient inhibition of HNF4α initiates transformation of immortalized hepatocytes through a feedback loop consisting of miR-24, IL6 receptor (IL6R), STAT3, miR-124 and miR-629, suggesting a central role of HNF4α in HCC. However, the role of HNF4α in Hepatitis C Virus (HCV)-related hepatocarcinoma has not been evaluated and remains controversial. In this study, we provide strong evidence suggesting that HCV downregulates HNF4α expression at both transcriptional and translational levels. The observed decrease of HNF4α expression correlated with the downregulation of its downstream targets, HNF1α and MTP. Ectopic overexpression of HCV proteins also exhibited an inhibitory effect on HNF4α levels. The inhibition of HNF4α expression by HCV appeared to be mediated at transcriptional level as HCV proteins suppressed HNF4α gene promoter activity. HCV also up-regulated IL6R, activated STAT3 protein phosphorylation and altered the expression of acute phase genes. Furthermore, as HCV triggered the loss of HNF4α a consequent change of miR-24, miR-629 or miR-124 was observed. Our findings demonstrated that HCV-related HCC could be mediated through HNF4α-microRNA deregulation implying a possible role of HNF4α in HCV hepatocarcinogenesis. HCV inhibition of HNF4α could be sustained to promote HCC. PMID:27477312

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

    NASA Astrophysics Data System (ADS)

    Xia, Dehong; Jiang, Binfan; Xie, Yulei

    2016-06-01

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

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

    PubMed

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

    2013-01-01

    Critically ill patients frequently display unexplained or incompletely explained features of gastrointestinal (GI) dysfunction, including gastric stasis, ileus, and diarrhea. This makes nutrition delivery challenging, and may contribute to poor outcomes. The typical bowel dysfunction seen in severely ill patients includes retarded gastric emptying, unsynchronized intestinal motility, and intestinal hyperpermeability. These functional changes appear similar to the corticotropin-releasing factor (CRF)-mediated bowel dysfunctions associated with stress of various types and some GI disorders and diseases. CRF has been shown to be present within the GI tract and its action on CRF receptors within the gut have been shown to reduce gastric emptying, alter intestinal motility, and increase intestinal permeability. However, the precise role of CRF in the GI dysfunction in critical illness remains unclear. In this short review, we provide an update on GI dysfunction during stress and review the possible role of CRF in the aetiology of gut dysfunction. We suggest that activation of CRF signaling pathways in critical illness might be key to understanding the mechanisms underlying the gut dysfunction that impairs enteral feeding in the intensive care unit. PMID:23484741

  18. Prosthetic Abutment Height is a Key Factor in Peri-implant Marginal Bone Loss

    PubMed Central

    Galindo-Moreno, P.; León-Cano, A.; Ortega-Oller, I.; Monje, A.; Suárez, F.; ÓValle, F.; Spinato, S.; Catena, A.

    2014-01-01

    In this study, we analyzed the influence of prosthetic abutment height on marginal bone loss (MBL) around implants in the posterior maxilla. In this retrospective cohort study, the radiographically determined MBL was related to the height of the abutments of internal conical connection implants at 6 and 18 months post-loading. Data were gathered on age, sex, bone substratum, smoking habit, history of periodontitis, and prosthetic features, among other variables. A linear mixed model was used for statistical analysis. The study included 131 patients receiving 315 implants. MBL rates at 6 and 18 months were mainly affected by the abutment height but were also significantly influenced by the bone substratum, periodontitis, and smoking habit. MBL rates were higher for prosthetic abutment < 2 mm vs. ≥ 2 mm, for periodontal vs. non-periodontal patients, for grafted vs. pristine bone, and for a heavier smoking habit. The abutment height is a key factor in MBL. MBL rates followed a non-linear trend, with a greater MBL rate during the first 6 months post-loading than during the next 12 months. PMID:24621670

  19. Caudal, a key developmental regulator, is a DPE-specific transcriptional factor

    PubMed Central

    Juven-Gershon, Tamar; Hsu, Jer-Yuan; Kadonaga, James T.

    2008-01-01

    The regulation of gene transcription is critical for the proper development and growth of an organism. The transcription of protein-coding genes initiates at the RNA polymerase II core promoter, which is a diverse module that can be controlled by many different elements such as the TATA box and downstream core promoter element (DPE). To understand the basis for core promoter diversity, we explored potential biological functions of the DPE. We found that nearly all of the Drosophila homeotic (Hox) gene promoters, which lack TATA-box elements, contain functionally important DPE motifs that are conserved from Drosophila melanogaster to Drosophila virilis. We then discovered that Caudal, a sequence-specific transcription factor and key regulator of the Hox gene network, activates transcription with a distinct preference for the DPE relative to the TATA box. The specificity of Caudal activation for the DPE is particularly striking when a BREu core promoter motif is associated with the TATA box. These findings show that Caudal is a DPE-specific activator and exemplify how core promoter diversity can be used to establish complex regulatory networks. PMID:18923080

  20. Human Factors Engineering Program Review Model (NUREG-0711)Revision 3: Update Methodology and Key Revisions

    SciTech Connect

    OHara J. M.; Higgins, J.; Fleger, S.

    2012-07-22

    The U.S. Nuclear Regulatory Commission (NRC) reviews the human factors engineering (HFE) programs of applicants for nuclear power plant construction permits, operating licenses, standard design certifications, and combined operating licenses. The purpose of these safety reviews is to help ensure that personnel performance and reliability are appropriately supported. Detailed design review procedures and guidance for the evaluations is provided in three key documents: the Standard Review Plan (NUREG-0800), the HFE Program Review Model (NUREG-0711), and the Human-System Interface Design Review Guidelines (NUREG-0700). These documents were last revised in 2007, 2004 and 2002, respectively. The NRC is committed to the periodic update and improvement of the guidance to ensure that it remains a state-of-the-art design evaluation tool. To this end, the NRC is updating its guidance to stay current with recent research on human performance, advances in HFE methods and tools, and new technology being employed in plant and control room design. NUREG-0711 is the first document to be addressed. We present the methodology used to update NUREG-0711 and summarize the main changes made. Finally, we discuss the current status of the update program and the future plans.

  1. Molecular mobility of imidazoles in molten state as a key factor to enhance proton conductivity

    NASA Astrophysics Data System (ADS)

    Jarumaneeroj, Chatchai; Tashiro, Kohji; Chirachanchai, Suwabun

    2014-03-01

    A systematic study on alkyl urocanates related to the proton conductivity performances to clarify the role of molecular mobility and hydrogen bond in proton transfer is carried out. Depending on the methylene units, the melting (Tm) and degradation temperatures (Td) change remarkably. When methylene unit is four, C4U shows the lowest melting point (as low as 46 °C) and this suggests the favorable molecular mobility in the molten state. The short hydrogen bond distance and the short T1 relaxation time lead to a scheme of proton conductivity of C4U to be under a regular imidazole arrangement with highly active alkyl chain molecular motion. When C4U is in molten state, the proton transfer is under vehicle mechanism clarified by Volgel-Tammann-Fulcher (VTF) equation. By applying C4U as a proton conductive additive in a sulfonated poly(ether ether ketone) (SPEEK) membrane without any acid dopants, the proton conductivity in the heating process up to 170 °C continuously increases to be ∼104 times higher than that of the neat SPEEK. The present work not only demonstrates the thermal mobility as a key factor to govern the proton conductivity but also proposes the effective proton transfer of heterocyclic compounds based on the molten state.

  2. miR-122--a key factor and therapeutic target in liver disease.

    PubMed

    Bandiera, Simonetta; Pfeffer, Sébastien; Baumert, Thomas F; Zeisel, Mirjam B

    2015-02-01

    Being the largest internal organ of the human body with the unique ability of self-regeneration, the liver is involved in a wide variety of vital functions that require highly orchestrated and controlled biochemical processes. Increasing evidence suggests that microRNAs (miRNAs) are essential for the regulation of liver development, regeneration and metabolic functions. Hence, alterations in intrahepatic miRNA networks have been associated with liver disease including hepatitis, steatosis, cirrhosis and hepatocellular carcinoma (HCC). miR-122 is the most frequent miRNA in the adult liver, and a central player in liver biology and disease. Furthermore, miR-122 has been shown to be an essential host factor for hepatitis C virus (HCV) infection and an antiviral target, complementary to the standard of care using direct-acting antivirals or interferon-based treatment. This review summarizes our current understanding of the key role of miR-122 in liver physiology and disease, highlighting its role in HCC and viral hepatitis. We also discuss the perspectives of miRNA-based therapeutic approaches for viral hepatitis and liver disease. PMID:25308172

  3. On Key Factors Influencing Ductile Fractures of Dual Phase (DP) Steels

    SciTech Connect

    Sun, Xin; Choi, Kyoo Sil; Soulami, Ayoub; Liu, Wenning N.; Khaleel, Mohammad A.

    2009-11-25

    In this paper, we examine the key factors influencing ductile failure of various grades of dual phase (DP) steels using the microstructure-based modeling approach. Various microstructure-based finite element models are generated based on the actual microstructures of DP steels with different martensite volume fractions. These models are, then, used to investigate the influence of ductility of the constituent ferrite phase and also the influence of voids introduced in the ferrite phase on the overall ductility of DP steels. It is found that with volume fraction of martensite in the microstructure less than 15%, the overall ductility of the DP steels strongly depends on the ductility of the ferrite matrix, hence pre-existing micro voids in the microstructure significantly reduce the overall ductility of the steel. When the volume fraction of martensite is above 15%, the preexisting voids in the ferrite matrix does not significantly reduce the overall ductility of the DP steels, and the overall ductility is more influenced by the mechanical property disparity between the two phases. The applicability of the phase inhomogeneity driven ductile failure of DP steels is then discussed based on the obtained computational results for various grades of DP steels, and the experimentally obtained scanning electron microscopy (SEM) pictures of the corresponding grades of DP steels near fracture surface are used as evidence for result validations.

  4. Process and kinetics of azo dye decolourization in bioelectrochemical systems: effect of several key factors.

    PubMed

    Yang, Hou-Yun; He, Chuan-Shu; Li, Lei; Zhang, Jie; Shen, Jin-You; Mu, Yang; Yu, Han-Qing

    2016-01-01

    This study explored the influence of several key factors on the process and kinetics of azo dye decolourization in bioelectrochemical systems (BESs), including cathode potential, dissolved oxygen (DO) concentration of catholyte and biofilm formed on the cathode. The results show that azo dye methyl orange (MO) decolourization in the BES could be well described with the pseudo first-order kinetics. The MO decolourization efficiency increased from 0 to 94.90 ± 0.01% and correspondingly the reaction rate constant increased from 0 to 0.503 ± 0.001 h(-1) with the decrease in cathodic electrode potential from -0.2 to -0.8 V vs Ag/AgCl. On the contrary, DO concentration of the catholyte had a negative impact on MO decolourization in the BES. When DO concentration increased from zero to 5.80 mg L(-1), the MO decolourization efficiency decreased from 87.19 ± 4.73% to 27.77 ± 0.06% and correspondingly the reaction rate constant reduced from 0.207 ± 0.042 to 0.033 ± 0.007 h(-1). Additionally, the results suggest that the biofilm formed on the cathode could led to an adverse rather than a positive effect on azo dye decolourization in the BES in terms of efficiency and kinetics. PMID:27270398

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

    ERIC Educational Resources Information Center

    Pierce, Robert E.

    2012-01-01

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

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

    PubMed

    Salbu, Brit

    2016-01-01

    , ignoring sensitive history life stages of organisms and transgenerational effects. To link sources, ecosystem transfer and biological effects to future impact and risks, a series of models are usually interfaced, while uncertainty estimates are seldom given. The model predictions are, however, only valid within the boundaries of the overall uncertainties. Furthermore, the model predictions are only useful and relevant when uncertainties are estimated, communicated and understood. Among key factors contributing most to uncertainties, the present paper focuses especially on structure uncertainties (model bias or discrepancies) as aspects such as particle releases, ecosystem dynamics, mixed exposure, sensitive life history stages and transgenerational effects, are usually ignored in assessment models. Research focus on these aspects should significantly reduce the overall uncertainties in the impact and risk assessment of radioactive contaminated ecosystems. PMID:26546475

  7. Key Factors Controlling Space- and Time-Linked Rare Earth Element Distribution in Shallow Groundwaters

    NASA Astrophysics Data System (ADS)

    Dia, A.; Gruau, G.; Olivie-Lauquet, G.; Henin, O.; Petitjean, P.; Le Coz-Bouhnik, M.

    2001-12-01

    comparison of the different catchments shows that the spatial variability of the REE signatures between the hillslope DOC-poor groundwaters and the wetland DOC-rich groundwaters has to be the same whatever may be the climatic and geologic context. These results assess the key roles played in the REE transfer to hydrosystems by (i) the occurrence of organic compounds, acting as a trace-element carrier phase and (ii) redox condition changes. Finally, we propose that topography could be the ultimate key factor, through its ability to control the water table depth and therefore the organic colloids enrichment when groundwaters are flowing into organic-rich soil horizons.

  8. Process and kinetics of azo dye decolourization in bioelectrochemical systems: effect of several key factors

    PubMed Central

    Yang, Hou-Yun; He, Chuan-Shu; Li, Lei; Zhang, Jie; Shen, Jin-You; Mu, Yang; Yu, Han-Qing

    2016-01-01

    This study explored the influence of several key factors on the process and kinetics of azo dye decolourization in bioelectrochemical systems (BESs), including cathode potential, dissolved oxygen (DO) concentration of catholyte and biofilm formed on the cathode. The results show that azo dye methyl orange (MO) decolourization in the BES could be well described with the pseudo first-order kinetics. The MO decolourization efficiency increased from 0 to 94.90 ± 0.01% and correspondingly the reaction rate constant increased from 0 to 0.503 ± 0.001 h−1 with the decrease in cathodic electrode potential from −0.2 to −0.8 V vs Ag/AgCl. On the contrary, DO concentration of the catholyte had a negative impact on MO decolourization in the BES. When DO concentration increased from zero to 5.80 mg L−1, the MO decolourization efficiency decreased from 87.19 ± 4.73% to 27.77 ± 0.06% and correspondingly the reaction rate constant reduced from 0.207 ± 0.042 to 0.033 ± 0.007 h−1. Additionally, the results suggest that the biofilm formed on the cathode could led to an adverse rather than a positive effect on azo dye decolourization in the BES in terms of efficiency and kinetics. PMID:27270398

  9. Socioeconomic status, family background and other key factors influence the management of head lice in Norway.

    PubMed

    Rukke, Bjørn Arne; Soleng, Arnulf; Lindstedt, Heidi Heggen; Ottesen, Preben; Birkemoe, Tone

    2014-05-01

    How head lice infestations are managed by households is an important but generally neglected issue in head lice research. In the present study, we investigate actions taken against head lice by Norwegian households in association with socioeconomic status, family background, school-related variables and other key factors. Repeat questionnaires distributed to caretakers of the same elementary school children during a 2-year period enabled us to study both previous head lice management and any changes in this management through time. Households from 12 schools spanning the main socioeconomic variation found in Norway participated in the study. All students with active head lice infestation were treated in the four investigated periods. Most caretakers used a thorough head lice checking technique and informed others of own infestation. Checking frequency was low as most children were inspected less than monthly. The best determinant of increased checking frequency and thoroughness was personal experience with head lice. The increased awareness, however, seemed to be somewhat short-lived, as there was a decrease in checking frequency and thoroughness within 1 year after infestation. Personal experience with head lice also increased general knowledge related to the parasite. Parents born in developing countries checked their children for head lice more frequently, although less thoroughly, informed fewer contacts when infested, used pediculicides preventively more often and knew less about head lice than parents born in developed countries. Households with highly educated mothers had a lower checking frequency, but their knowledge and willingness to inform others was high. Single parents were more concerned about economic costs and kept children home from school longer while infested than other parents. As head lice management varied among socioeconomic groups and with parental background, differentiated advice should be considered in the control of head lice. The

  10. Key Residues Regulating the Reductase Activity of the Human Mitochondrial Apoptosis Inducing Factor.

    PubMed

    Villanueva, Raquel; Ferreira, Patricia; Marcuello, Carlos; Usón, Alejandro; Miramar, M Dolores; Peleato, M Luisa; Lostao, Anabel; Susin, Santos A; Medina, Milagros

    2015-08-25

    The human Apoptosis Inducing Factor (hAIF) is a bifunctional NAD(P)H-dependent flavoreductase involved in both mitochondrial energy metabolism and caspase-independent cell death. Even though several studies indicate that both functions are redox controlled by NADH binding, the exact role of hAIF as a reductase in healthy mitochondria remains unknown. Upon reduction by NADH, hAIF dimerizes and produces very stable flavin/nicotinamide charge transfer complexes (CTC), by stacking of the oxidized nicotinamide moiety of the NAD(+) coenzyme against the re-face of the reduced flavin ring of its FAD cofactor. Such complexes are critical to restrict the hAIF efficiency as a reductase. The molecular basis of the hAIF reductase activity is here investigated by analyzing the role played by residues contributing to the interaction of the FAD isoalloxazine ring and of the nicotinamide moiety of NADH at the active site. Mutations at K177 and E314 produced drastic effects on the hAIF ability to retain the FAD cofactor, indicating that these residues are important to set up the holo-enzyme active site conformation. Characterization of P173G hAIF indicates that the stacking of P173 against the isoalloxazine ring is relevant to determine the flavin environment and to modulate the enzyme affinity for NADH. Finally, the properties of the F310G and H454S hAIF mutants indicate that these two positions contribute to form a compact active site essential for NADH binding, CTC stabilization, and NAD(+) affinity for the reduced state of hAIF. These features are key determinants of the particular behavior of hAIF as a NADH-dependent oxidoreductase. PMID:26237213

  11. Soil physical properties: Key factors for successful reclamation of disturbed landscapes

    NASA Astrophysics Data System (ADS)

    Krümmelbein, Julia; Raab, Thomas

    2013-04-01

    The practice of open cast mining, e.g. for lignite, results in major landscape disturbances and especially affects soils because relocation and subsequent mixing of naturally developed soil horizons leads to areas with extremely altered soil properties compared to the undisturbed conditions. Various reclamation measures are applied to recover the reconstructed landscape for different land use options. Major parts of the post mining landscapes are used for agriculture, agroforestry or silviculture, the remaining voids of the coal mines fill successively with groundwater after mine closure and are or will be used mainly for touristic and leisure purposes. Small proportions of the post mining areas are left for natural succession, or habitats for endangered flora and fauna are initiated. In reclamation research, many studies have focused on soil chemical and biological constraints of post mining substrates and investigated factors such as unsuitable pH, in many cases very low pH, (poor) nutrient contents and (poor) biological activity. But the initial and developing soil physical parameters and functions are also key factors for the success of reclamation practices. The soil water and gas balance influence strongly the suitability of a site for the intended future land use. The mechanical stability of the soil determines the rigidity of the pore system against deforming forces and thereby the persistence of soil functions, such as water and air permeability over time. The amendment of unfavourable (initial) soil physical properties is in most cases more complex and time-consuming than e.g. optimization of pH or fertilization with nutrients. Moreover, regarding the suitability of a site e.g. as a habitat for plants or microorganisms, poor physical pre-conditions can turn substrates with perfect nutrient contents and composition and pH into infertile locations of very low productivity. We show results of an on-going field study where the effects of different

  12. Some Factors in Children's Identification of Key Words in Written Passages.

    ERIC Educational Resources Information Center

    Bruning, Roger; Kennedy, Dale

    For this study of children's selection of key words, children in the first, third, sixth, ninth and twelfth grades were asked to identify which words, in their judgment, were key words in written materials. Relationship of these choices to skilled readers, to words derived from passage analysis, and to random selections of hypothetical subjects…

  13. Biological activity in Technosols as a key factor of their structure

    NASA Astrophysics Data System (ADS)

    Watteau, Françoise; Villemin, Geneviève; Bouchard, Adeline; Monserié, Marie-France; Séré, Geoffroy; Schwartz, Christophe; Morel, Jean-Louis

    2010-05-01

    )availability. HAP also contributed to the aggregation of technogenic constituents in Technosol 1. The biological activity generated by the presence of exogenous organic matter is thus in short (0-2 years) and mean (30 years) terms, a key factor of the structuration and by there of the pedogenesis of Technosols.

  14. On the Security of a Two-Factor Authentication and Key Agreement Scheme for Telecare Medicine Information Systems.

    PubMed

    Arshad, Hamed; Teymoori, Vahid; Nikooghadam, Morteza; Abbassi, Hassan

    2015-08-01

    Telecare medicine information systems (TMISs) aim to deliver appropriate healthcare services in an efficient and secure manner to patients. A secure mechanism for authentication and key agreement is required to provide proper security in these systems. Recently, Bin Muhaya demonstrated some security weaknesses of Zhu's authentication and key agreement scheme and proposed a security enhanced authentication and key agreement scheme for TMISs. However, we show that Bin Muhaya's scheme is vulnerable to off-line password guessing attacks and does not provide perfect forward secrecy. Furthermore, in order to overcome the mentioned weaknesses, we propose a new two-factor anonymous authentication and key agreement scheme using the elliptic curve cryptosystem. Security and performance analyses demonstrate that the proposed scheme not only overcomes the weaknesses of Bin Muhaya's scheme, but also is about 2.73 times faster than Bin Muhaya's scheme. PMID:26084586

  15. A Comprehensive Test of General Strain Theory: Key Strains, Situational- and Trait-Based Negative Emotions, Conditioning Factors, and Delinquency

    ERIC Educational Resources Information Center

    Moon, Byongook; Morash, Merry; McCluskey, Cynthia Perez; Hwang, Hye-Won

    2009-01-01

    Using longitudinal data on South Korean youth, the authors addressed limitations of previous tests of general strain theory (GST), focusing on the relationships among key strains, situational- and trait-based negative emotions, conditioning factors, and delinquency. Eight types of strain previously shown most likely to result in delinquency,…

  16. Problem-Based Learning Environment in Basic Computer Course: Pre-Service Teachers' Achievement and Key Factors for Learning

    ERIC Educational Resources Information Center

    Efendioglu, Akin

    2015-01-01

    This experimental study aims to determine pre-service teachers' achievements and key factors that affect the learning process with regard to problem-based learning (PBL) and lecture-based computer course (LBCC) conditions. The research results showed that the pre-service teachers in the PBL group had significantly higher achievement scores than…

  17. Local Text Cohesion, Reading Ability and Individual Science Aspirations: Key Factors Influencing Comprehension in Science Classes

    ERIC Educational Resources Information Center

    Hall, Sophie S.; Kowalski, Rebecca; Paterson, Kevin B.; Basran, Jaskaran; Filik, Ruth; Maltby, John

    2015-01-01

    In response to the concern of the need to improve the scientific skills of school children, this study investigated the influence of text design (in terms of text cohesion) and individual differences, with the aim of identifying pathways to improving science education in early secondary school (Key Stage 3). One hundred and four secondary school…

  18. Key Factors to Instructors' Satisfaction of Learning Management Systems in Blended Learning

    ERIC Educational Resources Information Center

    Al-Busaidi, Kamla Ali; Al-Shihi, Hafedh

    2012-01-01

    Learning Management System (LMS) enables institutions to administer their educational resources, and support their traditional classroom education and distance education. LMS survives through instructors' continuous use, which may be to a great extent associated with their satisfaction of the LMS. Consequently, this study examined the key factors…

  19. Key factors influencing ADME properties of therapeutic proteins: A need for ADME characterization in drug discovery and development

    PubMed Central

    Tibbitts, Jay; Canter, David; Graff, Ryan; Smith, Alison; Khawli, Leslie A.

    2016-01-01

    abstract Protein therapeutics represent a diverse array of biologics including antibodies, fusion proteins, and therapeutic replacement enzymes. Since their inception, they have revolutionized the treatment of a wide range of diseases including respiratory, vascular, autoimmune, inflammatory, infectious, and neurodegenerative diseases, as well as cancer. While in vivo pharmacokinetic, pharmacodynamic, and efficacy studies are routinely carried out for protein therapeutics, studies that identify key factors governing their absorption, distribution, metabolism, and excretion (ADME) properties have not been fully investigated. Thorough characterization and in-depth study of their ADME properties are critical in order to support drug discovery and development processes for the production of safer and more effective biotherapeutics. In this review, we discuss the main factors affecting the ADME characteristics of these large macromolecular therapies. We also give an overview of the current tools, technologies, and approaches available to investigate key factors that influence the ADME of recombinant biotherapeutic drugs, and demonstrate how ADME studies will facilitate their future development. PMID:26636901

  20. The Promise of Virtual Teams: Identifying Key Factors in Effectiveness and Failure

    ERIC Educational Resources Information Center

    Horwitz, Frank M.; Bravington, Desmond; Silvis, Ulrik

    2006-01-01

    Purpose: The aim of the investigation is to identify enabling and disenabling factors in the development and operation of virtual teams; to evaluate the importance of factors such as team development, cross-cultural variables, leadership, communication and social cohesion as contributors to virtual team effectiveness. Design/methodology/approach:…

  1. From Loose Groups to Effective Teams: The Nine Key Factors of the Team Landscape.

    ERIC Educational Resources Information Center

    Sheard, A. G.; Kakabadse, A. P.

    2002-01-01

    A loose group of individuals working on a task differs from an effective team on nine factors: clearly defined goals, priorities, roles and responsibilities, self-awareness, leadership, group dynamics, communications, content, and infrastructure. Ways to eliminate barriers and speed formation of effective teams could be based on those factors.…

  2. Exercise-induced neuroprotective effects on neurodegenerative diseases: the key role of trophic factors.

    PubMed

    Campos, Carlos; Rocha, Nuno Barbosa F; Lattari, Eduardo; Paes, Flávia; Nardi, António E; Machado, Sérgio

    2016-06-01

    Age-related neurodegenerative disorders, like Alzheimer's or Parkinson's disease, are becoming a major issue to public health care. Currently, there is no effective pharmacological treatment to address cognitive impairment in these patients. Here, we aim to explore the role of exercise-induced trophic factor enhancement in the prevention or delay of cognitive decline in patients with neurodegenerative diseases. There is a significant amount of evidence from animal and human studies that links neurodegenerative related cognitive deficits with changes on brain and peripheral trophic factor levels. Several trials with elderly individuals and patients with neurodegenerative diseases report exercise induced cognitive improvements and changes on trophic factor levels including BDNF, IGF-I, among others. Further studies with healthy aging and clinical populations are needed to understand how diverse exercise interventions produce different variations in trophic factor signaling. Genetic profiles and potential confounders regarding trophic factors should also be addressed in future trials. PMID:27086703

  3. URI in athletes: are mucosal immunity and cytokine responses key risk factors?

    PubMed

    Gleeson, Michael; Bishop, Nicolette C

    2013-07-01

    Infection incidence among athletes is highest during periods of intensified training and competition and after strenuous long-distance events. Which aspects of depressed immune function are responsible for this increased infection risk are not known, but our hypothesis is that lower salivary immunoglobulin A (IgA) secretion and a higher antiinflammatory cytokine response to antigen exposure are key determinants of infection risk. PMID:23792489

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

    PubMed Central

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

    2012-01-01

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

  5. The physical size of transcription factors is key to transcriptional regulation in chromatin domains

    NASA Astrophysics Data System (ADS)

    Maeshima, Kazuhiro; Kaizu, Kazunari; Tamura, Sachiko; Nozaki, Tadasu; Kokubo, Tetsuro; Takahashi, Koichi

    2015-02-01

    Genetic information, which is stored in the long strand of genomic DNA as chromatin, must be scanned and read out by various transcription factors. First, gene-specific transcription factors, which are relatively small (˜50 kDa), scan the genome and bind regulatory elements. Such factors then recruit general transcription factors, Mediators, RNA polymerases, nucleosome remodellers, and histone modifiers, most of which are large protein complexes of 1-3 MDa in size. Here, we propose a new model for the functional significance of the size of transcription factors (or complexes) for gene regulation of chromatin domains. Recent findings suggest that chromatin consists of irregularly folded nucleosome fibres (10 nm fibres) and forms numerous condensed domains (e.g., topologically associating domains). Although the flexibility and dynamics of chromatin allow repositioning of genes within the condensed domains, the size exclusion effect of the domain may limit accessibility of DNA sequences by transcription factors. We used Monte Carlo computer simulations to determine the physical size limit of transcription factors that can enter condensed chromatin domains. Small gene-specific transcription factors can penetrate into the chromatin domains and search their target sequences, whereas large transcription complexes cannot enter the domain. Due to this property, once a large complex binds its target site via gene-specific factors it can act as a ‘buoy’ to keep the target region on the surface of the condensed domain and maintain transcriptional competency. This size-dependent specialization of target-scanning and surface-tethering functions could provide novel insight into the mechanisms of various DNA transactions, such as DNA replication and repair/recombination.

  6. The physical size of transcription factors is key to transcriptional regulation in chromatin domains.

    PubMed

    Maeshima, Kazuhiro; Kaizu, Kazunari; Tamura, Sachiko; Nozaki, Tadasu; Kokubo, Tetsuro; Takahashi, Koichi

    2015-02-18

    Genetic information, which is stored in the long strand of genomic DNA as chromatin, must be scanned and read out by various transcription factors. First, gene-specific transcription factors, which are relatively small (∼50 kDa), scan the genome and bind regulatory elements. Such factors then recruit general transcription factors, Mediators, RNA polymerases, nucleosome remodellers, and histone modifiers, most of which are large protein complexes of 1-3 MDa in size. Here, we propose a new model for the functional significance of the size of transcription factors (or complexes) for gene regulation of chromatin domains. Recent findings suggest that chromatin consists of irregularly folded nucleosome fibres (10 nm fibres) and forms numerous condensed domains (e.g., topologically associating domains). Although the flexibility and dynamics of chromatin allow repositioning of genes within the condensed domains, the size exclusion effect of the domain may limit accessibility of DNA sequences by transcription factors. We used Monte Carlo computer simulations to determine the physical size limit of transcription factors that can enter condensed chromatin domains. Small gene-specific transcription factors can penetrate into the chromatin domains and search their target sequences, whereas large transcription complexes cannot enter the domain. Due to this property, once a large complex binds its target site via gene-specific factors it can act as a 'buoy' to keep the target region on the surface of the condensed domain and maintain transcriptional competency. This size-dependent specialization of target-scanning and surface-tethering functions could provide novel insight into the mechanisms of various DNA transactions, such as DNA replication and repair/recombination. PMID:25563431

  7. Enhanced Production of Insulin-like Growth Factor I Protein in Escherichia coli by Optimization of Five Key Factors

    PubMed Central

    Ranjbari, Javad; Babaeipour, Valiollah; Vahidi, Hossein; Moghimi, Hamidreza; Mofid, Mohammad Reza; Namvaran, Mohammad Mehdi; Jafari, Sevda

    2015-01-01

    Human insulin-like growth factor I (hIGF-I) is a kind of growth factor with clinical significance in medicine. Up to now, E. coli expression system has been widely used as a host to produce rhIGF-1 with high yields. Batch cultures as non-continuous fermentations were carried out to overproduce rhIGF-I in E. coli. The major objective of this study is over- production of recombinant human insulin-like growth factor I (rhIGF-I) through a developed process by recruiting effective factors in order to achieve the most recombinant protein. In this study we investigated the effect of culture medium, induction temperature and amount of inducer on cell growth and IGF-1 production. Taguchi design of experiments (DOE) method was used as the statistical method. Analysis of experimental data showed that maximum production of rhIGF-I was occurred in 32y culture medium at 32 °C and 0.05 Mm IPTG. Under this condition, 0.694 g/L of rhIGF-I was produced as the inclusion bodies. Following optimization of these three factors, we have also optimized the amount of glucose and induction time in 5 liter top bench bioreactor. Full factorial design of experiment method was used for these two factors as the statistical method. 10 g/L and OD600=5 were selected as the optimum point of Glucose amount and induction time, respectively. Finally, we reached to a concentration of 1.26 g/L rhIGF-1 at optimum condition. PMID:26330880

  8. Enhanced Production of Insulin-like Growth Factor I Protein in Escherichia coli by Optimization of Five Key Factors.

    PubMed

    Ranjbari, Javad; Babaeipour, Valiollah; Vahidi, Hossein; Moghimi, Hamidreza; Mofid, Mohammad Reza; Namvaran, Mohammad Mehdi; Jafari, Sevda

    2015-01-01

    Human insulin-like growth factor I (hIGF-I) is a kind of growth factor with clinical significance in medicine. Up to now, E. coli expression system has been widely used as a host to produce rhIGF-1 with high yields. Batch cultures as non-continuous fermentations were carried out to overproduce rhIGF-I in E. coli. The major objective of this study is over- production of recombinant human insulin-like growth factor I (rhIGF-I) through a developed process by recruiting effective factors in order to achieve the most recombinant protein. In this study we investigated the effect of culture medium, induction temperature and amount of inducer on cell growth and IGF-1 production. Taguchi design of experiments (DOE) method was used as the statistical method. Analysis of experimental data showed that maximum production of rhIGF-I was occurred in 32y culture medium at 32 °C and 0.05 Mm IPTG. Under this condition, 0.694 g/L of rhIGF-I was produced as the inclusion bodies. Following optimization of these three factors, we have also optimized the amount of glucose and induction time in 5 liter top bench bioreactor. Full factorial design of experiment method was used for these two factors as the statistical method. 10 g/L and OD600=5 were selected as the optimum point of Glucose amount and induction time, respectively. Finally, we reached to a concentration of 1.26 g/L rhIGF-1 at optimum condition. PMID:26330880

  9. Understanding key factors of users' intentions to repurchase and recommend digital items in social virtual worlds.

    PubMed

    Kim, Byoungsoo

    2012-10-01

    Given to the remarkable profitability of digital items in social virtual worlds (SVWs), such as SecondLife, Cyworld, and Habbo Hotel, it has become crucial to understand SVW users' postadoption behaviors toward digital items. This study develops a theoretical framework to examine key antecedents of users' intentions to repurchase and recommend digital items. Data collected from 256 users of digital items were empirically tested against the research model. The analysis results indicate that both user satisfaction and a perceived value play an important role in establishing users' postadoption intentions about digital items. Moreover, the results clearly show what roles perceived usefulness, perceived enjoyment, and perceived fee play in SVW environments. PMID:22924676

  10. The T-box transcription factor 3 is a promising biomarker and a key regulator of the oncogenic phenotype of a diverse range of sarcoma subtypes.

    PubMed

    Willmer, T; Cooper, A; Sims, D; Govender, D; Prince, S

    2016-01-01

    Sarcomas represent a complex group of malignant neoplasms of mesenchymal origin and their heterogeneity poses a serious diagnostic and therapeutic challenge. There is therefore a need to elucidate the molecular mechanisms underpinning the pathogenesis of the more than 70 distinguishable sarcoma subtypes. The transcription factor TBX3, a critical developmental regulator, is overexpressed in several cancers of epithelial origin where it contributes to tumorigenesis by different molecular mechanisms. However, the status and role of TBX3 in sarcomas have not been reported. Here we show that a diverse subset of soft tissue and bone sarcoma cell lines and patient-derived sarcoma tissues express high levels of TBX3. We further explore the significance of this overexpression using a small interferring RNA approach and demonstrate that TBX3 promotes the migratory ability of chondrosarcoma, rhabdomyosarcoma and liposarcoma cells but inhibits fibrosarcoma cell migration. This suggested that TBX3 may play a key role in the development of different sarcoma subtypes by functioning as either an oncoprotein or as a brake to prevent tumour progression. To further explore this, TBX3 knockdown and overexpression cell culture models were established using chondrosarcoma and fibrosarcoma cells as representatives of each scenario, and the resulting cells were characterized with regard to key features of tumorigenesis. Results from in vitro and in vivo assays reveal that, while TBX3 promotes substrate-dependent and -independent cell proliferation, migration and tumour formation in chondrosarcoma cells, it discourages fibrosarcoma formation. Our findings provide novel evidence linking TBX3 to cancers of mesenchymal origin. Furthermore, we show that TBX3 may be a biomarker for the diagnosis of histologically dynamic sarcoma subtypes and that it impacts directly on their oncogenic phenotype. Indeed, we reveal that TBX3 may exhibit oncogene or tumour suppressor activity in sarcomas, which

  11. Risk factors for conduct disorder and delinquency: key findings from longitudinal studies.

    PubMed

    Murray, Joseph; Farrington, David P

    2010-10-01

    Conduct disorder (CD) and delinquency are behavioural problems involving violation of major rules, societal norms, and laws. The prevalence of CD and delinquency peaks in mid-to-late adolescence. Both show considerable continuity over time. The most important studies of CD and delinquency have prospective longitudinal designs, large community samples, repeated personal interviews, measures of many possible risk factors, and both self-reports and official measures of antisocial behaviour. The most important risk factors that predict CD and delinquency include impulsiveness, low IQ and low school achievement, poor parental supervision, punitive or erratic parental discipline, cold parental attitude, child physical abuse, parental conflict, disrupted families, antisocial parents, large family size, low family income, antisocial peers, high delinquency rate schools, and high crime neighbourhoods. However, for many risk factors, it is not known whether they have causal effects. Future research should examine changes in risk factors and changes in CD and delinquency to identify the risk factors that are causes and those that are merely markers of other risk mechanisms. PMID:20964942

  12. Belongingness in Early Secondary School: Key Factors that Primary and Secondary Schools Need to Consider.

    PubMed

    Vaz, Sharmila; Falkmer, Marita; Ciccarelli, Marina; Passmore, Anne; Parsons, Richard; Black, Melissa; Cuomo, Belinda; Tan, Tele; Falkmer, Torbjörn

    2015-01-01

    It is unknown if, and how, students redefine their sense of school belongingness after negotiating the transition to secondary school. The current study used longitudinal data from 266 students with, and without, disabilities who negotiated the transition from 52 primary schools to 152 secondary schools. The study presents the 13 most significant personal student and contextual factors associated with belongingness in the first year of secondary school. Student perception of school belongingness was found to be stable across the transition. No variability in school belongingness due to gender, disability or household-socio-economic status (SES) was noted. Primary school belongingness accounted for 22% of the variability in secondary school belongingness. Several personal student factors (competence, coping skills) and school factors (low-level classroom task-goal orientation), which influenced belongingness in primary school, continued to influence belongingness in secondary school. In secondary school, effort-goal orientation of the student and perception of their school's tolerance to disability were each associated with perception of school belongingness. Family factors did not influence belongingness in secondary school. Findings of the current study highlight the need for primary schools to foster belongingness among their students at an early age, and transfer students' belongingness profiles as part of the hand-over documentation. Most of the factors that influenced school belongingness before and after the transition to secondary are amenable to change. PMID:26372554

  13. Belongingness in Early Secondary School: Key Factors that Primary and Secondary Schools Need to Consider

    PubMed Central

    Vaz, Sharmila; Falkmer, Marita; Ciccarelli, Marina; Passmore, Anne; Parsons, Richard; Black, Melissa; Cuomo, Belinda; Tan, Tele; Falkmer, Torbjörn

    2015-01-01

    It is unknown if, and how, students redefine their sense of school belongingness after negotiating the transition to secondary school. The current study used longitudinal data from 266 students with, and without, disabilities who negotiated the transition from 52 primary schools to 152 secondary schools. The study presents the 13 most significant personal student and contextual factors associated with belongingness in the first year of secondary school. Student perception of school belongingness was found to be stable across the transition. No variability in school belongingness due to gender, disability or household-socio-economic status (SES) was noted. Primary school belongingness accounted for 22% of the variability in secondary school belongingness. Several personal student factors (competence, coping skills) and school factors (low-level classroom task-goal orientation), which influenced belongingness in primary school, continued to influence belongingness in secondary school. In secondary school, effort-goal orientation of the student and perception of their school’s tolerance to disability were each associated with perception of school belongingness. Family factors did not influence belongingness in secondary school. Findings of the current study highlight the need for primary schools to foster belongingness among their students at an early age, and transfer students’ belongingness profiles as part of the hand-over documentation. Most of the factors that influenced school belongingness before and after the transition to secondary are amenable to change. PMID:26372554

  14. MYC TRANSCRIPTION FACTORS: KEY REGULATORS BEHIND ESTABLISHMENT AND MAINTENANCE OF PLURIPOTENCY

    PubMed Central

    Smith, Keriayn; Dalton, Stephen

    2011-01-01

    Summary The interplay between transcription factors, epigenetic modifiers, chromatin remodelers and miRNAs form the foundation of a complex regulatory network required for establishment and maintenance of the pluripotent state. Recent work indicates that Myc transcription factors are essential elements of this regulatory system. Despite numerous reports however, aspects of how Myc controls self-renewal and pluripotency remain obscure. Here, we review evidence supporting the placement of Myc as a central regulator of the pluripotent state and discuss possible mechanisms of action. PMID:21082893

  15. Museum specimens reveal loss of pollen host plants as key factor driving wild bee decline in The Netherlands.

    PubMed

    Scheper, Jeroen; Reemer, Menno; van Kats, Ruud; Ozinga, Wim A; van der Linden, Giel T J; Schaminée, Joop H J; Siepel, Henk; Kleijn, David

    2014-12-01

    Evidence for declining populations of both wild and managed bees has raised concern about a potential global pollination crisis. Strategies to mitigate bee loss generally aim to enhance floral resources. However, we do not really know whether loss of preferred floral resources is the key driver of bee decline because accurate assessment of host plant preferences is difficult, particularly for species that have become rare. Here we examine whether population trends of wild bees in The Netherlands can be explained by trends in host plants, and how this relates to other factors such as climate change. We determined host plant preference of bee species using pollen loads on specimens in entomological collections that were collected before the onset of their decline, and used atlas data to quantify population trends of bee species and their host plants. We show that decline of preferred host plant species was one of two main factors associated with bee decline. Bee body size, the other main factor, was negatively related to population trend, which, because larger bee species have larger pollen requirements than smaller species, may also point toward food limitation as a key factor driving wild bee loss. Diet breadth and other potential factors such as length of flight period or climate change sensitivity were not important in explaining twentieth century bee population trends. These results highlight the species-specific nature of wild bee decline and indicate that mitigation strategies will only be effective if they target the specific host plants of declining species. PMID:25422416

  16. On the Factor Structure of the Beck Depression Inventory-II: G Is the Key

    ERIC Educational Resources Information Center

    Brouwer, Danny; Meijer, Rob R.; Zevalkink, Jolien

    2013-01-01

    The Beck Depression Inventory-II (BDI-II; Beck, Steer, & Brown, 1996) is intended to measure severity of depression, and because items represent a broad range of depressive symptoms, some multidimensionality exists. In recent factor-analytic studies, there has been a debate about whether the BDI-II can be considered as one scale or whether…

  17. Students' Understanding of Large Numbers as a Key Factor in Their Understanding of Geologic Time

    ERIC Educational Resources Information Center

    Cheek, Kim A.

    2012-01-01

    An understanding of geologic time is comprised of 2 facets. Events in Earth's history can be placed in relative and absolute temporal succession on a vast timescale. Rates of geologic processes vary widely, and some occur over time periods well outside human experience. Several factors likely contribute to an understanding of geologic time, one of…

  18. Key Factors in Smoking Cessation Intervention among 15-16-Year-Olds

    ERIC Educational Resources Information Center

    Heikkinen, Anna Maria; Broms, Ulla; Pitkaniemi, Janne; Koskenvuo, Markku; Meurman, Jukka

    2009-01-01

    The authors aimed to investigate factors associated with smoking cessation among adolescents after tobacco intervention. They examined smokers (n = 127) from one birth cohort (n = 545) in the city of Kotka in Finland. These smokers were randomized in 3 intervention groups the dentist (n = 44) and the school nurse (n = 42 groups), and a control…

  19. Key recovery factors for the August 24, 2014, South Napa earthquake

    USGS Publications Warehouse

    Hudnut, Kenneth W.; Brocher, Thomas M.; Prentice, Carol S.; Boatwright, John; Brooks, Benjamin A.; Aagaard, Brad T.; Blair, James Luke; Fletcher, Joe B.; Erdem, Jemile E.; Wicks, Charles W., Jr.; Murray, Jessica R.; Pollitz, Fred F.; Langbein, John O.; Svarc, Jerry L.; Schwartz, David P.; Ponti, Daniel J.; Hecker, Suzanne; DeLong, Stephen B.; Rosa, Carla M.; Jones, Brenda; Lamb, Rynn; Rosinski, Anne M.; McCrink, Timothy P.; Dawson, Timothy E.; Seitz, Gordon G.; Rubin, Ron S.; Glennie, Craig; Hauser, Darren; Ericksen, Todd; Mardock, Dan; Hoirup, Don F.; Bray, Jonathan D.

    2014-01-01

    Through discussions between the Federal Emergency Management Agency (FEMA) and the U.S. Geological Survey (USGS) following the South Napa earthquake, it was determined that several key decision points would be faced by FEMA for which additional information should be sought and provided by USGS and its partners. This report addresses the four tasks that were agreed to. These tasks are (1) assessment of ongoing fault movement (called afterslip) especially in the Browns Valley residential neighborhood, (2) assessment of the shaking pattern in the downtown area of the City of Napa, (3) improvement of information on the fault hazards posed by the West Napa Fault System (record of past earthquakes and slip rate, for example), and (4) imagery acquisition and data processing to provide overall geospatial information support to FEMA.

  20. Oxidative stress--a key emerging impact factor in health, ageing, lifestyle and aesthetics.

    PubMed

    Kandola, K; Bowman, A; Birch-Machin, M A

    2015-12-01

    Oxidative stress is the resultant damage that arises due to redox imbalances, more specifically an increase in destructive free radicals and reduction in protection from antioxidants and the antioxidant defence pathways. Oxidation of lipids by reactive oxygen species (ROS) can damage cellular structures and result in premature cell death. At low levels, ROS-induced oxidative stress can be prevented through the action of antioxidants, however, when ROS are present in excess, inflammation and cytotoxicity eventually results leading to cellular oxidative stress damage. Increasing evidence for the role of oxidative stress in various diseases including neurological, dermatological, and cardiovascular diseases is now emerging. Mitochondria are the principal source (90%) of ROS in the cell, with superoxide radicals being generated when molecular oxygen is combined with free electrons. Given the key role of mitochondria in the generation of cellular oxidative stress it is worth considering this organelle and the process in more detail and to provide methods of intervention. PMID:26574299

  1. Key factors limiting the open circuit voltage of n(+)pp(+) indium phosphide solar cells

    NASA Technical Reports Server (NTRS)

    Goradia, Chandra; Thesling, William; Weinberg, Irving

    1990-01-01

    Solar cells made from gallium arsenide (Gaas), with a room temperature bandgap of E(sub g) = 1.43 eV have exhibited the best measured open circuit voltage (V sub oc) of 1.05 V at 1 AM0, 25 C. The material InP is in many ways similar to GaAs. A simple calculation comparing InP to GaAs then shows that solar cells made from InP, with E(sub g) = 1.35 at 300 K, should exhibit the best measured V sub oc of approximately 950 mV at 1 AM0, 300 K. However, to date, the best measured V sub oc for InP solar cells made by any fabrication method is 899 mV at AM1.5, 25 C which would translate to 912 mV at 1 AM0, 25 C. The V sub oc of an n(+)pp(+) InP solar cell is governed by several factors. Of these, some factors, such as the thickness and doping of the emitter and base regions, are easily controlled and can be adjusted to desired values dictated by a good performance optimizing model. Such factors were not considered. There are other factors which also govern V sub oc, and their values are not so easily controlled. The primary ones among these are (1) the indirect or Hall-Shockley-Read lifetimes in the various regions of the cell, (2) the low-doping intrinsic carrier concentration n(sub i) of the InP material, (3) the heavy doping factors in the emitter and BSF regions, and (4) the front surface recombination velocity S(sub F). The influence of these latter factors on the V sub oc of the n(+)pp(+) InP solar cell and the results were used to produce a near-optimum design of the n(+)pp(+) InP solar cell.

  2. Key factors limiting the open circuit voltage of n(+)pp(+) indium phosphide solar cells

    NASA Technical Reports Server (NTRS)

    Goradia, Chandra; Thesling, William; Weinberg, Irving

    1991-01-01

    Solar cells made from gallium arsenide (GaAs), with a room temperature bandgap of E(sub g) = 1.43 eV have exhibited the best measured open circuit voltage (V sub OC) of 1.05 V at 1 AMO, 25 C. The material InP is in many ways similar to GaAs. A simple calculation comparing InP to GaAs then shows that solar cells made from InP, with E(sub g) = 1.35 at 300 K, should exhibit the best measured (V sub OC) of approximately 950 mV at 1 AMO, 300 K. However, to date, the best measured V(sub OC) for InP solar cells made by any fabrication method is 899 mV at AM1.5, 25 C which would translate to 912 mV at 1 AMO, 25 C. The V(sub OC) of an n(+)pp(+) InP solar cell is governed by several factors. Of these, some factors, such as the thickness and doping of the emitter and base regions, are easily controlled and can be adjusted to desired values dictated by a good performance optimizing model. Such factors were not considered. There are other factors which also govern V(sub OC), and their values are not so easily controlled. The primary ones among these are (1) the indirect or Hall-Shockley-Read lifetimes in the various regions of the cell, (2) the low-doping intrinsic carrier concentration n(sub i) of the InP material, (3) the heavy doping factors in the emitter and BSF regions, and (4) the front surface recombination velocity S(sub F). The influence of these latter factors on the V(sub OC) of the n(+)pp(+) InP solar cell and the results were used to produce a near-optimum design of the n(+)pp(+) InP solar cell.

  3. Key facts and hot spots on tumor necrosis factor receptor-associated periodic syndrome.

    PubMed

    Rigante, Donato; Lopalco, Giuseppe; Vitale, Antonio; Lucherini, Orso Maria; De Clemente, Caterina; Caso, Francesco; Emmi, Giacomo; Costa, Luisa; Silvestri, Elena; Andreozzi, Laura; Iannone, Florenzo; Galeazzi, Mauro; Cantarini, Luca

    2014-09-01

    Tumor necrosis factor receptor-associated periodic syndrome (TRAPS), formerly known as familial Hibernian fever, is the most common autosomal dominant autoinflammatory disease, resulting from mutations in the TNFRSF1A gene, encoding the 55-kD tumor necrosis factor receptor. The pathophysiologic mechanism of TRAPS remains ambiguous and only partially explained. The onset age of the syndrome is variable and the clinical scenery is characterized by recurrent episodes of high-grade fever that typically lasts 1-3 weeks, associated with migrating myalgia, pseudocellulitis, diffuse abdominal pain, appendicitis-like findings, ocular inflammatory signs, and risk of long-term amyloidosis. Fever episodes are responsive to high-dose corticosteroids, but different classes of drugs have been reported to be ineffective. The use of etanercept is unable to control systemic inflammation, while interleukin-1 blockade has been shown as effective in the control of disease activity in many patients reported so far. PMID:24935411

  4. Soil Surface Structure: A key factor for the degree of soil water repellency

    NASA Astrophysics Data System (ADS)

    Ahn, S.; Doerr, S. H.; Douglas, P.; Bryant, R.; Hamlett, C.; McHale, G.; Newton, M.; Shirtcliffe, N.

    2012-04-01

    Despite of considerable efforts, the degree of water repellency has not always been fully explained by chemical property of soil (termed hydrophobicity). That might be because the structure of a soil surface was not considered properly, which is another main factor determining the severity of soil water repellency. Surface structure has only recently been considered in soil science, whilst it has been paid attention for several decades in materials science due to its relevance to industrial applications. In this contribution, comparison of critical contact angles measured on different surface structures (made with glass beads, glass shards and beach sands) is presented and the effect of surface structure on manifestation of soil water repellency is discussed in terms of several different variables such as the individual particles shape, and areal and structural factors of the actual surface.

  5. Negative thinking: a key factor in depressive symptoms in Thai adolescents.

    PubMed

    Charoensuk, Sukjai

    2007-01-01

    Negative thinking, self-esteem, parental bonding, and everyday stressors are factors related to depressive symptoms in studies conducted in the United States, but they have been rarely explored in Thailand. An understanding of factors influencing depressive symptoms in Thai youth will lead to the development of interventions to decrease depressive symptoms among this age group. The purpose of this study was to examine the effects of parental bonding, everyday stressors, self-esteem, and negative thinking on depressive symptoms among Thai adolescents. A random sample of 812 high school students in Chon Buri, Thailand, participated in the study. The prevalence of depressive symptoms varied from 20-21% depending on the measures used. Negative thinking was the best predictor of depressive symptoms in Thai adolescents. Negative thinking also mediated the effects of parental bonding, everyday stressors, and self-esteem on depressive symptoms. PMID:17130007

  6. Key factors contributing to accident severity rate in construction industry in Iran: a regression modelling approach.

    PubMed

    Soltanzadeh, Ahmad; Mohammadfam, Iraj; Moghimbeigi, Abbas; Ghiasvand, Reza

    2016-03-01

    Construction industry involves the highest risk of occupational accidents and bodily injuries, which range from mild to very severe. The aim of this cross-sectional study was to identify the factors associated with accident severity rate (ASR) in the largest Iranian construction companies based on data about 500 occupational accidents recorded from 2009 to 2013. We also gathered data on safety and health risk management and training systems. Data were analysed using Pearson's chi-squared coefficient and multiple regression analysis. Median ASR (and the interquartile range) was 107.50 (57.24- 381.25). Fourteen of the 24 studied factors stood out as most affecting construction accident severity (p<0.05). These findings can be applied in the design and implementation of a comprehensive safety and health risk management system to reduce ASR. PMID:27092639

  7. K-factor greater than 1 - The key for stable amplifiers

    NASA Astrophysics Data System (ADS)

    Gutierrez, Ray

    1989-09-01

    A review is given of stability problems encountered with amplifiers, and attention is given to the K-factor, which is a measure of the oscillatory tendency of any network at a specific frequency and for the conditions represented by the particular S-parameter values. The K-factor equation is reviewed for both conditionally stable (K less than or equal to one) and unconditionally stable (K greater than one) networks, and the three different degrees of stability are outlined in a discussion of stability circles. In addition, a review is given of some circuit configurations that are used to improve amplifier performance at the expense of stability, and a quick alternative is presented for measuring amplifier stability over broad bandwidths using a scalar analyzer.

  8. A structured elicitation method to identify key direct risk factors for the management of natural resources.

    PubMed

    Smith, Michael; Wallace, Ken; Lewis, Loretta; Wagner, Christian

    2015-11-01

    The high level of uncertainty inherent in natural resource management requires planners to apply comprehensive risk analyses, often in situations where there are few resources. In this paper, we demonstrate a broadly applicable, novel and structured elicitation approach to identify important direct risk factors. This new approach combines expert calibration and fuzzy based mathematics to capture and aggregate subjective expert estimates of the likelihood that a set of direct risk factors will cause management failure. A specific case study is used to demonstrate the approach; however, the described methods are widely applicable in risk analysis. For the case study, the management target was to retain all species that characterise a set of natural biological elements. The analysis was bounded by the spatial distribution of the biological elements under consideration and a 20-year time frame. Fourteen biological elements were expected to be at risk. Eleven important direct risk factors were identified that related to surrounding land use practices, climate change, problem species (e.g., feral predators), fire and hydrological change. In terms of their overall influence, the two most important risk factors were salinisation and a lack of water which together pose a considerable threat to the survival of nine biological elements. The described approach successfully overcame two concerns arising from previous risk analysis work: (1) the lack of an intuitive, yet comprehensive scoring method enabling the detection and clarification of expert agreement and associated levels of uncertainty; and (2) the ease with which results can be interpreted and communicated while preserving a rich level of detail essential for informed decision making. PMID:27441228

  9. The transcription factor Pokemon: a new key player in cancer pathogenesis.

    PubMed

    Maeda, Takahiro; Hobbs, Robin M; Pandolfi, Pier Paolo

    2005-10-01

    Learning how critical cell regulatory pathways are controlled may lead to new opportunities for cancer treatment. We recently identified the transcription factor Pokemon as a central regulator of the important tumor suppressor ARF. Pokemon is overexpressed in multiple human cancers and cells lacking Pokemon are refractory to oncogenic transformation. These findings suggest that Pokemon may offer an effective new target for cancer therapeutics. PMID:16204018

  10. Key factors for a successful implementation of personalized e-health services.

    PubMed

    Griebel, Lena; Sedlmayr, Brita; Prokosch, Hans-Ulrich; Criegee-Rieck, Manfred; Sedlmayr, Martin

    2013-01-01

    Personalized e-health services hold many promises, e.g. the improvement of health care quality or the reduction of costs. However, such services can't tap their full potential if they will not be used. That's why it is essential to understand what brings potential users to accept them. In the literature many acceptance models exist that predict the usage of innovations, but none of them specifically refers to the adoption of e-health services. Therefore we combined the Unified Theory of Acceptance and Use of Technology (UTAUT) and the e-health literacy concept and enhanced the resulting model with additional factors. MEDLINE® was searched; 75 studies were included for final analysis. Apart from the UTAUT variables and e-health literacy, 10 additional factors were identified: anxiety, trust, attitude toward using, computer self-efficacy, perceived system quality, search strategy, user's condition, health specific knowledge, Internet dependency and satisfaction with medical care. Future research will include the devolvement of an instrument for assessing these factors and testing the initial research model in an international context. PMID:23920739

  11. Comparative “-omics” in Mycoplasma pneumoniae Clinical Isolates Reveals Key Virulence Factors

    PubMed Central

    Lluch-Senar, Maria; Cozzuto, Luca; Cano, Jaime; Delgado, Javier; Llórens-Rico, Verónica; Pereyre, Sabine; Bebear, Cécile; Serrano, Luis

    2015-01-01

    The human respiratory tract pathogen M. pneumoniae is one of the best characterized minimal bacterium. Until now, two main groups of clinical isolates of this bacterium have been described (types 1 and 2), differing in the sequence of the P1 adhesin gene. Here, we have sequenced the genomes of 23 clinical isolates of M. pneumoniae. Studying SNPs, non-synonymous mutations, indels and genome rearrangements of these 23 strains and 4 previously sequenced ones, has revealed new subclasses in the two main groups, some of them being associated with the country of isolation. Integrative analysis of in vitro gene essentiality and mutation rates enabled the identification of several putative virulence factors and antigenic proteins; revealing recombination machinery, glycerol metabolism and peroxide production as possible factors in the genetics and physiology of these pathogenic strains. Additionally, the transcriptomes and proteomes of two representative strains, one from each of the two main groups, have been characterized to evaluate the impact of mutations on RNA and proteins levels. This study has revealed that type 2 strains show higher expression levels of CARDS toxin, a protein recently shown to be one of the major factors of inflammation. Thus, we propose that type 2 strains could be more toxigenic than type 1 strains of M. pneumoniae. PMID:26335586

  12. Academic mobility as a key factor of quality assurance in tertiary education

    NASA Astrophysics Data System (ADS)

    Voroshilova, Anna A.

    2015-01-01

    Academic mobility of both faculty and students forms a critical element of the international dimension of higher education and is one of the most important factors of quality assurance of higher education institutions worldwide. Internationalization and globalization of Russian higher education system is having one of the major impacts on the quality management and assurance. Faculty and student mobility figures are now one of the core factors for obtaining state accreditation for Russian universities as well as an important indicator showing the university success and prestige. The aim of the paper is a closer look at the perspectives and results of the academic mobility, the factors stimulating and discouraging mobility, and the outcomes of the mobility influencing the education in Russian universities. Siberian State Aerospace University has had more than 10 years experience in organizing student mobility. Most of the problems in carrying out international activities are common for the whole Russia but still there are some peculiarities featuring technical universities situated in the centre of Russia.

  13. Interferon regulatory factor 3 is a key regulation factor for inducing the expression of SAMHD1 in antiviral innate immunity

    PubMed Central

    Yang, Shen; Zhan, Yuan; Zhou, Yanjun; Jiang, Yifeng; Zheng, Xuchen; Yu, Lingxue; Tong, Wu; Gao, Fei; Li, Liwei; Huang, Qinfeng; Ma, Zhiyong; Tong, Guangzhi

    2016-01-01

    SAMHD1 is a type I interferon (IFN) inducible host innate immunity restriction factor that inhibits an early step of the viral life cycle. The underlying mechanisms of SAMHD1 transcriptional regulation remains elusive. Here, we report that inducing SAMHD1 upregulation is part of an early intrinsic immune response via TLR3 and RIG-I/MDA5 agonists that ultimately induce the nuclear translocation of the interferon regulation factor 3 (IRF3) protein. Further studies show that IRF3 plays a major role in upregulating endogenous SAMHD1 expression in a mechanism that is independent of the classical IFN-induced JAK-STAT pathway. Both overexpression and activation of IRF3 enhanced the SAMHD1 promoter luciferase activity, and activated IRF3 was necessary for upregulating SAMHD1 expression in a type I IFN cascade. We also show that the SAMHD1 promoter is a direct target of IRF3 and an IRF3 binding site is sufficient to render this promoter responsive to stimulation. Collectively, these findings indicate that upregulation of endogenous SAMHD1 expression is attributed to the phosphorylation and nuclear translocation of IRF3 and we suggest that type I IFN induction and induced SAMHD1 expression are coordinated. PMID:27411355

  14. Key Factors and Timing Patterns in the Tennis Forehand of Different Skill Levels

    PubMed Central

    Landlinger, Johannes; Lindinger, Stefan; Stöggl, Thomas; Wagner, Herbert; Müller, Erich

    2010-01-01

    The main purpose of the present study was to quantify and compare selected kinematic variables and their timing during the tennis forehand of different skill levels. An eight-camera 400 Hz, Vicon motion analysis system recorded kinematic data of six ATP- professionals (elite) and seven high performance (HP) players when shots were played cross court and down the line. Timing of the maximum angles, linear and angular velocities was measured prior to and after impact. A total of twelve strokes per subject were analyzed from the beginning to the end of horizontal racquet movement. Significant differences (p < 0.01) and large effect sizes were observed between elite and HP players in the timing of maximum pelvis (-0.075 ± 0.008 vs. -0.093 ± 0.012 s) and trunk angular velocities (-0.057 ± 0.004 vs. -0.075 ± 0.011 s) before impact. The elite group showed a tendency (p < 0.05) towards higher peak horizontal shoulder (3.0 ± 0.4 vs. 2.5 ± 0.4 m·s-1) and racquet velocities (33.1 ± 2.4 vs. 31.1 ± 1.9 m·s-1) compared to the HP players. Depending on the situation (cross court vs. down the line), different peak hip, racquet and separation angles were found for both groups. Similar peak values were detected between groups for maximum angular velocities and displacement of key variables that had been selected for analysis. The findings of this study can be vital for successful player development, improved performance or injury prevention. The later occurrence of maximum angular pelvis and trunk rotations were the main reasons for the tendency towards higher horizontal shoulder and racquet velocities in the elite group. Key points Different timing of maximum angular pelvis and trunk rotations separated the elite from the high performance players. The elite group tended to reach higher horizontal shoulder and racquet velocities than the high performance group. In addition to maximum angular velocities, maximum racquet, shoulder, and hip alignment angles were similar

  15. Key factors limiting carbon nanotube yarn strength: exploring processing-structure-property relationships.

    PubMed

    Beese, Allison M; Wei, Xiaoding; Sarkar, Sourangsu; Ramachandramoorthy, Rajaprakash; Roenbeck, Michael R; Moravsky, Alexander; Ford, Matthew; Yavari, Fazel; Keane, Denis T; Loutfy, Raouf O; Nguyen, SonBinh T; Espinosa, Horacio D

    2014-11-25

    Studies of carbon nanotube (CNT) based composites have been unable to translate the extraordinary load-bearing capabilities of individual CNTs to macroscale composites such as yarns. A key challenge lies in the lack of understanding of how properties of filaments and interfaces across yarn hierarchical levels govern the properties of macroscale yarns. To provide insight required to enable the development of superior CNT yarns, we investigate the fabrication-structure-mechanical property relationships among CNT yarns prepared by different techniques and employ a Monte Carlo based model to predict upper bounds on their mechanical properties. We study the correlations between different levels of alignment and porosity and yarn strengths up to 2.4 GPa. The uniqueness of this experimentally informed modeling approach is the model's ability to predict when filament rupture or interface sliding dominates yarn failure based on constituent mechanical properties and structural organization observed experimentally. By capturing this transition and predicting the yarn strengths that could be obtained under ideal fabrication conditions, the model provides critical insights to guide future efforts to improve the mechanical performance of CNT yarn systems. This multifaceted study provides a new perspective on CNT yarn design that can serve as a foundation for the development of future composites that effectively exploit the superior mechanical performance of CNTs. PMID:25353651

  16. Crystallographic orientation and electrode nature are key factors for electric current generation by Geobacter sulfurreducens.

    PubMed

    Maestro, Beatriz; Ortiz, Juan M; Schrott, Germán; Busalmen, Juan P; Climent, Víctor; Feliu, Juan M

    2014-08-01

    We have investigated the influence of electrode material and crystallographic structure on electron transfer and biofilm formation of Geobacter sulfurreducens. Single-crystal gold-Au(110), Au(111), Au(210)-and platinum-Pt(100), Pt(110), Pt(111), Pt(210)-electrodes were tested and compared to graphite rods. G. sulfurreducens electrochemically interacts with all these materials with different attachment kinetics and final current production, although redox species involved in the electron transfer to the anode are virtually the same in all cases. Initial bacterial colonization was fastest on graphite up to the monolayer level, whereas gold electrodes led to higher final current densities. Crystal geometry was shown to have an important influence, with Au(210) sustaining a current density of up to 1442±101μAcm(-2) at the steady state, over Au(111) with 961±94μAcm(-2) and Au(110) with 944±89μAcm(-2). On the other hand, the platinum electrodes displayed the lowest performances, including Pt(210). Our results indicate that both crystal geometry and electrode material are key parameters for the efficient interaction of bacteria with the substrate and should be considered for the design of novel materials and microbial devices to optimize energy production. PMID:24642203

  17. Key Factors Influencing Rates of Heterotrophic Sulfate Reduction in Hydrothermal Massive Sulfide Deposits

    NASA Astrophysics Data System (ADS)

    Frank, K. L.; Rogers, K. L.; Rogers, D.; Johnston, D. T.; Girguis, P. R.

    2015-12-01

    Hydrothermal vents are thermally and geochemically dynamic habitats, and the organisms therein are subject to steep fluctuations in temperature and chemistry. To date, the influence of these environmental dynamics on microbial sulfate reduction has not been well constrained. Here, via multivariate experiments, we evaluate the effects of key environmental variables (temperature, pH, H2S, SO42-, DOC) on sulfate reduction rates and metabolic energy yields in a hydrothermal flange recovered from the Grotto vent in the Main Endeavor Field, Juan de Fuca ridge. Sulfate reduction was measured in batch reactions across a range of physico-chemical conditions. Temperature and pH were the strongest stimuli and maximum sulfate reduction rates were observed at 50°C and pH 6, suggesting that the in situ community of sulfate reducing organisms at Grotto may be most active in a slightly acidic and moderate thermal/chemical regime. At pH 4, sulfate reduction rates increased with sulfide concentrations most likely due to the mitigation of metal toxicity. While substrate concentrations also influenced sulfate reduction rates, energy-rich conditions muted the effect of metabolic energetics on sulfate reduction rates. We posit that variability in sulfate reduction rates reflect the response of the active microbial consortia to environmental constraints on in situ microbial physiology, toxicity, and the type and extent of energy limitation. These experiments help to constrain models of the spatial contribution of heterotrophic sulfate within the complex gradients inherent to hydrothermal deposits.

  18. Krüppel-like Factor 15 (KLF15) Is a Key Regulator of Podocyte Differentiation*

    PubMed Central

    Mallipattu, Sandeep K.; Liu, Ruijie; Zheng, Feng; Narla, Goutham; Ma'ayan, Avi; Dikman, Steven; Jain, Mukesh K.; Saleem, Moin; D'Agati, Vivette; Klotman, Paul; Chuang, Peter Y.; He, John C.

    2012-01-01

    Podocyte injury resulting from a loss of differentiation is the hallmark of many glomerular diseases. We previously showed that retinoic acid (RA) induces podocyte differentiation via stimulation of the cAMP pathway. However, many podocyte maturity markers lack binding sites for RA-response element or cAMP-response element (CREB) in their promoter regions. We hypothesized that transcription factors induced by RA and downstream of CREB mediate podocyte differentiation. We performed microarray gene expression studies in human podocytes treated with and without RA to identify differentially regulated genes. In comparison with known CREB target genes, we identified Krüppel-like factor 15 (KLF15), a kidney-enriched nuclear transcription factor, that has been previously shown to mediate cell differentiation. We confirmed that RA increased KLF15 expression in both murine and human podocytes. Overexpression of KLF15 stimulated expression of differentiation markers in both wild-type and HIV-1-infected podocytes. Also, KLF15 binding to the promoter regions of nephrin and podocin was increased in RA-treated podocytes. Although KLF15−/− mice at base line had minimal phenotype, lipopolysaccharide- or adriamycin-treated KLF15−/− mice had a significant increase in proteinuria and podocyte foot process effacement with a reduction in the expression of podocyte differentiation markers as compared with the wild-type treated mice. Finally, KLF15 expression was reduced in glomeruli isolated from HIV transgenic mice as well as in kidney biopsies from patients with HIV-associated nephropathy and idiopathic focal segmental glomerulosclerosis. These results indicate a critical role of KLF15 in mediating podocyte differentiation and in protecting podocytes against injury. PMID:22493483

  19. Macrophage Migration Inhibitory Factor (MIF): A Key Player in Protozoan Infections

    PubMed Central

    de Dios Rosado, Juan; Rodriguez-Sosa, Miriam

    2011-01-01

    Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine produced by the pituitary gland and multiple cell types, including macrophages (Mø), dendritic cells (DC) and T-cells. Upon releases MIF modulates the expression of several inflammatory molecules, such as TNF-α, nitric oxide and cyclooxygenase 2 (COX-2). These important MIF characteristics have prompted investigators to study its role in parasite infections. Several reports have demonstrated that MIF plays either a protective or deleterious role in the immune response to different pathogens. Here, we review the role of MIF in the host defense response to some important protozoan infections. PMID:22110378

  20. Deterministic Polynomial Time Equivalence between Factoring and Key-Recovery Attack on Takagi's RSA

    NASA Astrophysics Data System (ADS)

    Kunihiro, Noboru; Kurosawa, Kaoru

    For RSA, May showed a deterministic polynomial time equivalence of computing d to factoring N(=pq). On the other hand, Takagi showed a variant of RSA such that the decryption algorithm is faster than the standard RSA, where N=prq while ed=1 mod (p-1)(q-1). In this paper, we show that a deterministic polynomial time equivalence also holds in this variant. The coefficient matrix T to which LLL algorithm is applied is no longer lower triangular, and hence we develop a new technique to overcome this problem.

  1. Hepatocyte Nuclear Factor 4 Alpha Is a Key Factor Related to Depression and Physiological Homeostasis in the Mouse Brain

    PubMed Central

    Yamanishi, Kyosuke; Doe, Nobutaka; Sumida, Miho; Watanabe, Yuko; Yoshida, Momoko; Yamamoto, Hideyuki; Xu, Yunfeng; Li, Wen; Yamanishi, Hiromichi; Okamura, Haruki; Matsunaga, Hisato

    2015-01-01

    Major depressive disorder (MDD) is a common psychiatric disorder that involves marked disabilities in global functioning, anorexia, and severe medical comorbidities. MDD is associated with not only psychological and sociocultural problems, but also pervasive physical dysfunctions such as metabolic, neurobiological and immunological abnormalities. Nevertheless, the mechanisms underlying the interactions between these factors have yet to be determined in detail. The aim of the present study was to identify the molecular mechanisms responsible for the interactions between MDD and dysregulation of physiological homeostasis, including immunological function as well as lipid metabolism, coagulation, and hormonal activity in the brain. We generated depression-like behavior in mice using chronic mild stress (CMS) as a model of depression. We compared the gene expression profiles in the prefrontal cortex (PFC) of CMS and control mice using microarrays. We subsequently categorized genes using two web-based bioinformatics applications: Ingenuity Pathway Analysis and The Database for Annotation, Visualization, and Integrated Discovery. We then confirmed significant group-differences by analyzing mRNA and protein expression levels not only in the PFC, but also in the thalamus and hippocampus. These web tools revealed that hepatocyte nuclear factor 4 alpha (Hnf4a) may exert direct effects on various genes specifically associated with amine synthesis, such as genes involved in serotonin metabolism and related immunological functions. Moreover, these genes may influence lipid metabolism, coagulation, and hormonal activity. We also confirmed the significant effects of Hnf4a on both mRNA and protein expression levels in the brain. These results suggest that Hnf4a may have a critical influence on physiological homeostasis under depressive states, and may be associated with the mechanisms responsible for the interactions between MDD and the dysregulation of physiological homeostasis

  2. The Grp170 nucleotide exchange factor executes a key role during ERAD of cellular misfolded clients

    PubMed Central

    Inoue, Takamasa; Tsai, Billy

    2016-01-01

    When a protein misfolds in the endoplasmic reticulum (ER), it retrotranslocates to the cytosol and is degraded by the proteasome via a pathway called ER-associated degradation (ERAD). To initiate ERAD, ADP-BiP is often recruited to the misfolded client, rendering it soluble and translocation competent. How the misfolded client is subsequently released from BiP so that it undergoes retrotranslocation, however, remains enigmatic. Here we demonstrate that the ER-resident nucleotide exchange factor (NEF) Grp170 plays an important role during ERAD of the misfolded glycosylated client null Hong Kong (NHK). As a NEF, Grp170 triggers nucleotide exchange of BiP to generate ATP-BiP. ATP-BiP disengages from NHK, enabling it to retrotranslocate to the cytosol. We demonstrate that Grp170 binds to Sel1L, an adapter of the transmembrane Hrd1 E3 ubiquitin ligase postulated to be the retrotranslocon, and links this interaction to Grp170’s function during ERAD. More broadly, Grp170 also promotes degradation of the nonglycosylated transthyretin (TTR) D18G misfolded client. Our findings thus establish a general function of Grp170 during ERAD and suggest that positioning this client-release factor at the retrotranslocation site may afford a mechanism to couple client release from BiP and retrotranslocation. PMID:27030672

  3. Identifying Key Factors in Homeowner's Adoption of Water Quality Best Management Practices

    NASA Astrophysics Data System (ADS)

    Brehm, Joan M.; Pasko, Danielle K.; Eisenhauer, Brian W.

    2013-07-01

    The recognition of the significance of the residential environment in contributing to non-point source (NPS) pollution and the inherently dispersed nature of NPS pollution itself that presents significant challenges to effective regulation has led to the creation and dissemination of best management practices (BMPs) that can reduce the impacts of NPS pollution (Environmental Protection Agency US, Protecting water quality from urban runoff, http://www.epa.gov/npdes/pubs/nps_urban-facts_final.pdf, 2003). However, very few studies have examined the factors that influence the adoption of BMPs by residential homeowners, despite the fact that residential environments have been identified as one of the most significant contributors to NPS pollution. Given this need, the purpose of this project was to explore how demographic and knowledge-based factors predict adoption of residential BMPs in an urbanizing watershed in Northern Illinois using statistical analyses of survey data collected as part of a watershed planning process. The findings indicate that broad knowledge of BMPs is the strongest predictor of use for a specific BMP. Knowledge of BMPs is strongly correlated with their use, which reinforces the need for educational programs, even among those assumed to be knowledgeable about BMPs.

  4. Key Factors Influencing Rates of Heterotrophic Sulfate Reduction in Active Seafloor Hydrothermal Massive Sulfide Deposits

    PubMed Central

    Frank, Kiana L.; Rogers, Karyn L.; Rogers, Daniel R.; Johnston, David T.; Girguis, Peter R.

    2015-01-01

    Hydrothermal vents are thermally and geochemically dynamic habitats, and the organisms therein are subject to steep gradients in temperature and chemistry. To date, the influence of these environmental dynamics on microbial sulfate reduction has not been well constrained. Here, via multivariate experiments, we evaluate the effects of key environmental variables (temperature, pH, H2S, SO42−, DOC) on sulfate reduction rates and metabolic energy yields in material recovered from a hydrothermal flange from the Grotto edifice in the Main Endeavor Field, Juan de Fuca Ridge. Sulfate reduction was measured in batch reactions across a range of physico-chemical conditions. Temperature and pH were the strongest stimuli, and maximum sulfate reduction rates were observed at 50°C and pH 6, suggesting that the in situ community of sulfate-reducing organisms in Grotto flanges may be most active in a slightly acidic and moderate thermal/chemical regime. At pH 4, sulfate reduction rates increased with sulfide concentrations most likely due to the mitigation of metal toxicity. While substrate concentrations also influenced sulfate reduction rates, energy-rich conditions muted the effect of metabolic energetics on sulfate reduction rates. We posit that variability in sulfate reduction rates reflect the response of the active microbial consortia to environmental constraints on in situ microbial physiology, toxicity, and the type and extent of energy limitation. These experiments help to constrain models of the spatial contribution of heterotrophic sulfate reduction within the complex gradients inherent to seafloor hydrothermal deposits. PMID:26733984

  5. Hiring and Retention: Key Factors in Increasing Gender Diversity in the Geosciences

    NASA Astrophysics Data System (ADS)

    Holmes, M.; O'Connell, S.; Frey, C.

    2004-12-01

    Graduation and hiring data of geoscientists over the last ten years indicate that the largest leak in the academic pipeline for women geoscientists is at hiring into tenure-track positions. Anecdotal explanations for this leak generally cite a lack of females in the applicant pool, but women in tenure-track positions anecdotally cite a lack of family-friendly practices by academic departments. Both ideas are currently being tested via surveys of geoscience departments. Is there a way to attract more women to the field to increase the applicant pool? Results of focus groups of geoscientists indicate that both men and women are attracted into the field of geosciences by the same types of events: over one-third became a geoscientist by randomly walking into an undergraduate class and finding themselves captivated by the topic and/or a dynamic instructor. The subject matter itself attracts another one-fourth, and family members encourage another one-fifth of geoscientists to initially enter the field. Slightly more women cite the first attractor of undergraduate class, but the principal draw for our future workforce, male and female, is good instruction of freshman courses. Retention of women in academia is another key issue. The proportion that considers leaving after working towards one or more degrees is highly skewed by gender: one-half of female and only one-third of male geoscientists considered leaving the field at some time in their career. The reasons for considering leaving also differ by gender. Males cite financial issues, including an uncertain job market. Females cite two principal reasons for considering leaving: family issues and difficulties with a graduate advisor. Strategies currently exist for "family issues", including stop-the-clock (of tenure for family needs), assignment shift, on-campus daycare facilities, and unflinching administrative support for such practices. Graduate advising is a learnable skill, and more attention needs to be paid to

  6. Granuloma Encapsulation Is a Key Factor for Containing Tuberculosis Infection in Minipigs

    PubMed Central

    Vilaplana, Cristina; Tapia, Gustavo; Díaz, Jorge; Fort, María; Cáceres, Neus; Pinto, Sergio; Caylà, Joan; Corner, Leigh; Domingo, Mariano; Cardona, Pere-Joan

    2010-01-01

    A transthoracic infection involving a low dose of Mycobacterium tuberculosis has been used to establish a new model of infection in minipigs. The 20-week monitoring period showed a marked Th1 response and poor humoral response for the whole infection. A detailed histopathological analysis was performed after slicing the formalin-fixed whole lungs of each animal. All lesions were recorded and classified according to their microscopic aspect, their relationship with the intralobular connective network and their degree of maturity in order to obtain a dissemination ratio (DR) between recent and old lesions. CFU counts and evolution of the DR with time showed that the proposed model correlated with a contained infection, decreasing from week 9 onwards. These findings suggest that the infection induces an initial Th1 response, which is followed by local fibrosis and encapsulation of the granulomas, thereby decreasing the onset of new lesions. Two therapeutic strategies were applied in order to understand how they could influence the model. Thus, chemotherapy with isoniazid alone helped to decrease the total number of lesions, despite the increase in DR after week 9, with similar kinetics to those of the control group, whereas addition of a therapeutic M. tuberculosis fragment-based vaccine after chemotherapy increased the Th1 and humoral responses, as well as the number of lesions, but decreased the DR. By providing a local pulmonary structure similar to that in humans, the mini-pig model highlights new aspects that could be key to a better understanding tuberculosis infection control in humans. PMID:20386605

  7. Key Factors Influencing Rates of Heterotrophic Sulfate Reduction in Active Seafloor Hydrothermal Massive Sulfide Deposits.

    PubMed

    Frank, Kiana L; Rogers, Karyn L; Rogers, Daniel R; Johnston, David T; Girguis, Peter R

    2015-01-01

    Hydrothermal vents are thermally and geochemically dynamic habitats, and the organisms therein are subject to steep gradients in temperature and chemistry. To date, the influence of these environmental dynamics on microbial sulfate reduction has not been well constrained. Here, via multivariate experiments, we evaluate the effects of key environmental variables (temperature, pH, H2S, [Formula: see text], DOC) on sulfate reduction rates and metabolic energy yields in material recovered from a hydrothermal flange from the Grotto edifice in the Main Endeavor Field, Juan de Fuca Ridge. Sulfate reduction was measured in batch reactions across a range of physico-chemical conditions. Temperature and pH were the strongest stimuli, and maximum sulfate reduction rates were observed at 50°C and pH 6, suggesting that the in situ community of sulfate-reducing organisms in Grotto flanges may be most active in a slightly acidic and moderate thermal/chemical regime. At pH 4, sulfate reduction rates increased with sulfide concentrations most likely due to the mitigation of metal toxicity. While substrate concentrations also influenced sulfate reduction rates, energy-rich conditions muted the effect of metabolic energetics on sulfate reduction rates. We posit that variability in sulfate reduction rates reflect the response of the active microbial consortia to environmental constraints on in situ microbial physiology, toxicity, and the type and extent of energy limitation. These experiments help to constrain models of the spatial contribution of heterotrophic sulfate reduction within the complex gradients inherent to seafloor hydrothermal deposits. PMID:26733984

  8. Maternal effects and range expansion: a key factor in a dynamic process?

    PubMed Central

    Duckworth, Renée A.

    2009-01-01

    generated in newly colonized populations. More generally, these results suggest that, as a key source of variation in colonizing phenotypes, maternal effects are of crucial importance for understanding the dynamics of range expansion. PMID:19324612

  9. Syntactic Computation in the Human Brain: The Degree of Merger as a Key Factor

    PubMed Central

    Ohta, Shinri; Fukui, Naoki; Sakai, Kuniyoshi L.

    2013-01-01

    Our goal of this study is to characterize the functions of language areas in most precise terms. Previous neuroimaging studies have reported that more complex sentences elicit larger activations in the left inferior frontal gyrus (L. F3op/F3t), although the most critical factor still remains to be identified. We hypothesize that pseudowords with grammatical particles and morphosyntactic information alone impose a construction of syntactic structures, just like normal sentences, and that “the Degree of Merger” (DoM) in recursively merged sentences parametrically modulates neural activations. Using jabberwocky sentences with distinct constructions, we fitted various parametric models of syntactic, other linguistic, and nonlinguistic factors to activations measured with functional magnetic resonance imaging. We demonstrated that the models of DoM and “DoM+number of Search (searching syntactic features)” were the best to explain activations in the L. F3op/F3t and supramarginal gyrus (L. SMG), respectively. We further introduced letter strings, which had neither lexical associations nor grammatical particles, but retained both matching orders and symbol orders of sentences. By directly contrasting jabberwocky sentences with letter strings, localized activations in L. F3op/F3t and L. SMG were indeed independent of matching orders and symbol orders. Moreover, by using dynamic causal modeling, we found that the model with a inhibitory modulatory effect for the bottom-up connectivity from L. SMG to L. F3op/F3t was the best one. For this best model, the top-down connection from L. F3op/F3t to L. SMG was significantly positive. By using diffusion-tensor imaging, we confirmed that the left dorsal pathway of the superior longitudinal and arcuate fasciculi consistently connected these regions. Lastly, we established that nonlinguistic order-related and error-related factors significantly activated the right (R.) lateral premotor cortex and R. F3op/F3t, respectively

  10. KEY FACTORS THAT INFLUENCE THE PERFORMANCE PROPERTIES OF ARP/MCU SALTSTONE MIXES

    SciTech Connect

    Harbour, J.; Edwards, T.; Williams, V.

    2009-10-05

    At the Saltstone Production Facility (SPF), decontaminated salt solution (DSS) is combined with premix (a cementitious mixture of portland cement (PC), blast furnace slag (BFS) and Class F fly ash (FA)) in a Readco mixer to produce fresh (uncured) Saltstone. After transfer to the Saltstone Disposal Facility (SDF) the hydration reactions initiated during the contact of the premix and salt solution continue during the curing period to produce the hardened waste form product. The amount of heat generated from hydration and the resultant temperature increase in the vaults depend on the composition of the decontaminated salt solution being dispositioned as well as the grout formulation (mix design). This report details the results from Task 3 of the Saltstone Variability Study for FY09 which was performed to identify, and quantify when possible, those factors that drive the performance properties of the projected ARP/MCU Batches. A baseline ARP/MCU mix (at 0.60 water to cementitious materials (w/cm) ratio) was established and consisted of the normal premix composition and a salt solution that was an average of the projected compositions of the last three ARP/MCU batches developed by T. A. Le. This task introduced significant variation in (1) wt % slag, w/cm ratio, and wt % portland cement about the baseline mix and (2) the temperature of curing in order to better assess the dependence of the performance properties on these factors. Two separate campaigns, designated Phase 10 and Phase 11, were carried out under Task 3. Experimental designs and statistical analyses were used to search for correlation among properties and to develop linear models to predict property values based on factors such as w/cm ratio, slag concentration, and portland cement concentration. It turns out that the projected salt compositions contained relatively high amounts of aluminate (0.22 M) even though no aluminate was introduced due to caustic aluminate removal from High Level Waste. Previous

  11. Study on the Key Factor Parameters to Increase Productivity in Construction and Manufacturing Industries.

    NASA Astrophysics Data System (ADS)

    Almazyed, K.; Alaswad, A.; Olabi, A. G.

    2016-02-01

    Proper management of human and non-human resources in construction and manufacturing projects can give-in considerable savings in time and cost. Construction and Manufacturing industry faces issues in connection with problems related with productivity and the problems are usually connected with performance of employees. The performance of employees is affected by many factors. In this paper a survey was made on respondents who are employed various projects of Saudi Arabia. The researcher developed a theoretical framework from the existing research which was used as a Model to collect and analyze the field data to test the hypothesis. In this research activity three predictors (commitment, job satisfaction and job performance) for determining the change in productivity. The results highlight that commitment and job performance (respectively) are the two predictors which are explaining 37% of variation in the productivity of the companies. The results also show that Job Satisfaction has no role in the prediction of productivity.

  12. Olive (Olea europaea L.) tree nitrogen status is a key factor for olive oil quality.

    PubMed

    Erel, Ran; Kerem, Zohar; Ben-Gal, Alon; Dag, Arnon; Schwartz, Amnon; Zipori, Isaac; Basheer, Loai; Yermiyahu, Uri

    2013-11-27

    The influence of macronutrient status on olive oil properties was studied for three years. Data were analyzed by a multivariate model considering N, P, K, and fruiting year as explanatory factors. Oil quality parameters were primarily associated with N concentration in leaves and fruits which increased with N in irrigation solution. The effect of P on oil quality was mainly indirect since increased P availability increased N accumulation. The potassium level had negligible effects. The oil phenolic content decreased linearly as a function of increased leaf N, indicating protein-phenol competition in leaves. The overall saturation level of the fatty acids decreased with fruit N, resulting in increased polyunsaturated fatty acids. Free fatty acids increased with increased levels of fruit N. High fruit load tended to reduce fruit N and subsequently improve oil quality. The effect of N on oil properties depended solely on its concentration in leaves or fruits, regardless of the cause. PMID:24245487

  13. A Key Role for Leukemia Inhibitory Factor in C26 Cancer Cachexia.

    PubMed

    Seto, Danielle N; Kandarian, Susan C; Jackman, Robert W

    2015-08-01

    Cachexia is an exacerbating event in many types of cancer that is strongly associated with a poor prognosis. We have identified cytokine, signaling, and transcription factors that are required for cachexia in the mouse C26 colon carcinoma model of cancer. C2C12 myotubes treated with conditioned medium from C26 cancer cells induced atrophy and activated a STAT-dependent reporter gene but not reporter genes dependent on SMAD, FOXO, C/EBP, NF-κB, or AP-1. Of the gp130 family members IL-11, IL-6, oncostatin M (OSM), and leukemia inhibitory factor (LIF), only OSM and LIF were sufficient to activate the STAT reporter in myotubes. LIF was elevated in C26 conditioned medium (CM), but IL-6, OSM, TNFα, and myostatin were not. A LIF-blocking antibody abolished C26 CM-induced STAT reporter activation, STAT3 phosphorylation, and myotube atrophy but blocking antibodies to IL-6 or OSM did not. JAK2 inhibitors also blocked C26 CM-induced STAT reporter activation, STAT3 phosphorylation, and atrophy in myotubes. LIF at levels found in the C26 CM was sufficient for STAT reporter activation and atrophy in myotubes. In vivo, an increase in serum LIF preceded the increase in IL-6 in mice with C26 tumors. Overexpression of a dominant negative Stat3Cβ-EGFP gene in myotubes and in mouse muscle blocked the atrophy caused by C26 CM or C26 tumors, respectively. Taken together, these data support an important role of LIF-JAK2-STAT3 in C26 cachexia and point to a therapeutic approach for at least some types of cancer cachexia. PMID:26092726

  14. Identification of Transcriptional Factors and Key Genes in Primary Osteoporosis by DNA Microarray

    PubMed Central

    Xie, Wengui; Ji, Lixin; Zhao, Teng; Gao, Pengfei

    2015-01-01

    Background A number of genes have been identified to be related with primary osteoporosis while less is known about the comprehensive interactions between regulating genes and proteins. We aimed to identify the differentially expressed genes (DEGs) and regulatory effects of transcription factors (TFs) involved in primary osteoporosis. Material/Methods The gene expression profile GSE35958 was obtained from Gene Expression Omnibus database, including 5 primary osteoporosis and 4 normal bone tissues. The differentially expressed genes between primary osteoporosis and normal bone tissues were identified by the same package in R language. The TFs of these DEGs were predicted with the Essaghir A method. DAVID (The Database for Annotation, Visualization and Integrated Discovery) was applied to perform the GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis of DEGs. After analyzing regulatory effects, a regulatory network was built between TFs and the related DEGs. Results A total of 579 DEGs was screened, including 310 up-regulated genes and 269 down-regulated genes in primary osteoporosis samples. In GO terms, more up-regulated genes were enriched in transcription regulator activity, and secondly in transcription factor activity. A total 10 significant pathways were enriched in KEGG analysis, including colorectal cancer, Wnt signaling pathway, Focal adhesion, and MAPK signaling pathway. Moreover, total 7 TFs were enriched, of which CTNNB1, SP1, and TP53 regulated most up-regulated DEGs. Conclusions The discovery of the enriched TFs might contribute to the understanding of the mechanism of primary osteoporosis. Further research on genes and TFs related to the WNT signaling pathway and MAPK pathway is urgent for clinical diagnosis and directing treatment of primary osteoporosis. PMID:25957414

  15. Security analysis and improvements of two-factor mutual authentication with key agreement in wireless sensor networks.

    PubMed

    Kim, Jiye; Lee, Donghoon; Jeon, Woongryul; Lee, Youngsook; Won, Dongho

    2014-01-01

    User authentication and key management are two important security issues in WSNs (Wireless Sensor Networks). In WSNs, for some applications, the user needs to obtain real-time data directly from sensors and several user authentication schemes have been recently proposed for this case. We found that a two-factor mutual authentication scheme with key agreement in WSNs is vulnerable to gateway node bypassing attacks and user impersonation attacks using secret data stored in sensor nodes or an attacker's own smart card. In this paper, we propose an improved scheme to overcome these security weaknesses by storing secret data in unique ciphertext form in each node. In addition, our proposed scheme should provide not only security, but also efficiency since sensors in a WSN operate with resource constraints such as limited power, computation, and storage space. Therefore, we also analyze the performance of the proposed scheme by comparing its computation and communication costs with those of other schemes. PMID:24721764

  16. Security Analysis and Improvements of Two-Factor Mutual Authentication with Key Agreement in Wireless Sensor Networks

    PubMed Central

    Kim, Jiye; Lee, Donghoon; Jeon, Woongryul; Lee, Youngsook; Won, Dongho

    2014-01-01

    User authentication and key management are two important security issues in WSNs (Wireless Sensor Networks). In WSNs, for some applications, the user needs to obtain real-time data directly from sensors and several user authentication schemes have been recently proposed for this case. We found that a two-factor mutual authentication scheme with key agreement in WSNs is vulnerable to gateway node bypassing attacks and user impersonation attacks using secret data stored in sensor nodes or an attacker's own smart card. In this paper, we propose an improved scheme to overcome these security weaknesses by storing secret data in unique ciphertext form in each node. In addition, our proposed scheme should provide not only security, but also efficiency since sensors in a WSN operate with resource constraints such as limited power, computation, and storage space. Therefore, we also analyze the performance of the proposed scheme by comparing its computation and communication costs with those of other schemes. PMID:24721764

  17. Platelet-Derived Growth Factor: A Key Factor in the Pathogenesis of Graves' Ophthalmopathy and Potential Target for Treatment

    PubMed Central

    Virakul, Sita; van Steensel, Leendert; Dalm, Virgil A.S.H.; Paridaens, Dion; van Hagen, P. Martin; Dik, Willem A.

    2014-01-01

    Activation of orbital fibroblasts resulting in excessive proliferation, cytokine and hyaluronan production and differentiation into adipocytes, is a main determinant of orbital tissue inflammation and tissue expansion in Graves' ophthalmopathy (GO). During the last years we have shown that the platelet-derived growth factor (PDGF) isoforms PDGF-AA, PDGF-AB and PDGF-BB are increased in orbital tissue from GO patients with active and inactive disease. These PDGF isoforms exhibit the capacity to stimulate proliferation, hyaluronan and cytokine/chemokine production by orbital fibroblasts. Moreover, PDGF-AB and PDGF-BB increase thyroid stimulating hormone receptor (TSHR) expression by orbital fibroblasts, which enhances the orbital fibroblast activating capacity of the THSR stimulatory autoantibodies present in Graves' disease (GD) patients. Of these PDGF isoforms PDGF-BB exhibits the strongest orbital fibroblast activating effects, which is likely related to its ability to bind both the PDGF-receptor (PDGF-R)α and PDGF-Rβ chains. Thus the PDGF-system fulfills important roles in orbital fibroblast activation in both active and inactive GO, which supports a therapeutic rationale for blocking PDGF signaling in GO. Tyrosine kinase inhibitors (TKIs) may be candidates to target PDGF signaling. Of several TKIs tested dasatinib exhibited the highest potency to block PDGF-R signaling in orbital fibroblasts and may represent a promising compound for the treatment of GO as it was effective at low dosage and is associated with less side effects compared to imatinib mesylate and nilotinib. In this review the contribution of PDGF to the pathophysiology of GO as well as therapeutic approaches to target this PDGF-system will be addressed. PMID:25759797

  18. Key factors controlling microbial community response after a fire: importance of severity and recurrence

    NASA Astrophysics Data System (ADS)

    Lombao, Alba; Barreiro, Ana; Martín, Ángela; Díaz-Raviña, Montserrat

    2015-04-01

    Microorganisms play an important role in forest ecosystems, especially after fire when vegetation is destroyed and soil is bared. Fire severity and recurrence might be one of main factors controlling the microbial response after a wildfire but information about this topic is scarce. The aim of this study is to evaluate the influence of fire regimen (recurrence and severity) on soil microbial community structure by means of the analysis of phospholipid fatty acid (PLFA). The study was performed with unburned and burned samples collected from the top layer of a soil affected by a high severity fire (Laza, NW Spain) heated under laboratory conditions at different temperatures (50°C, 75°C, 100°C, 125°C, 150°C, 175°C, 200°C, 300°C) to simulate different fire intensities; the process was repeated after further soil recovery (1 month incubation) to simulate fire recurrence. The soil temperature was measured with thermocouples and used to calculate the degree-hours as estimation of the amount of heat supplied to the samples (fire severity). The PLFA analysis was used to estimate total biomass and the biomass of specific groups (bacteria, fungi, gram-positive bacteria and gram-negative bacteria) as well as microbial community structure (PLFA pattern) and PLFA data were analyzed by means of principal component analysis (PCA) in order to identify main factors determining microbial community structure. The results of PCA, performed with the whole PLFA data set, showed that first component explained 35% of variation and clearly allow us to differentiate unburned samples from the corresponding burned samples, while the second component, explaining 16% of variation, separated samples according the heating temperature. A marked impact of fire regimen on soil microorganisms was detected; the microbial community response varied depending on previous history of soil heating and the magnitude of changes in the PLFA pattern was related to the amount of heat supplied to the

  19. Zinc regulates a key transcriptional pathway for epileptogenesis via metal-regulatory transcription factor 1.

    PubMed

    van Loo, Karen M J; Schaub, Christina; Pitsch, Julika; Kulbida, Rebecca; Opitz, Thoralf; Ekstein, Dana; Dalal, Adam; Urbach, Horst; Beck, Heinz; Yaari, Yoel; Schoch, Susanne; Becker, Albert J

    2015-01-01

    Temporal lobe epilepsy (TLE) is the most common focal seizure disorder in adults. In many patients, transient brain insults, including status epilepticus (SE), are followed by a latent period of epileptogenesis, preceding the emergence of clinical seizures. In experimental animals, transcriptional upregulation of CaV3.2 T-type Ca(2+)-channels, resulting in an increased propensity for burst discharges of hippocampal neurons, is an important trigger for epileptogenesis. Here we provide evidence that the metal-regulatory transcription factor 1 (MTF1) mediates the increase of CaV3.2 mRNA and intrinsic excitability consequent to a rise in intracellular Zn(2+) that is associated with SE. Adeno-associated viral (rAAV) transfer of MTF1 into murine hippocampi leads to increased CaV3.2 mRNA. Conversely, rAAV-mediated expression of a dominant-negative MTF1 abolishes SE-induced CaV3.2 mRNA upregulation and attenuates epileptogenesis. Finally, data from resected human hippocampi surgically treated for pharmacoresistant TLE support the Zn(2+)-MTF1-CaV3.2 cascade, thus providing new vistas for preventing and treating TLE. PMID:26498180

  20. Corticotropin Releasing Factor: A Key Role in the Neurobiology of Addiction

    PubMed Central

    Zorrilla, Eric P.; Logrip, Marian L.; Koob, George F.

    2014-01-01

    Drug addiction is a chronically relapsing disorder characterized by loss of control over intake and dysregulation of stress-related brain emotional systems. Since the discovery by Wylie Vale and his colleagues of corticotropin-releasing factor (CRF) and the structurally-related urocortins, CRF systems have emerged as mediators of the body’s response to stress. Relatedly, CRF systems have a prominent role in driving addiction via actions in the central extended amygdala, producing anxiety-like behavior, reward deficits, excessive, compulsive-like drug self-administration and stress-induced reinstatement of drug seeking. CRF neuron activation in the medial prefrontal cortex may also contribute to the loss of control. Polymorphisms in CRF system molecules are associated with drug use phenotypes in humans, often in interaction with stress history. Drug discovery efforts have yielded brain-penetrant CRF1 antagonists with activity in preclinical models of addiction.. The results support the hypothesis that brain CRF-CRF1 systems contribute to the etiology and maintenance of addiction. PMID:24456850

  1. Leptin in early life: a key factor for the development of the adult metabolic profile.

    PubMed

    Granado, Miriam; Fuente-Martín, Esther; García-Cáceres, Cristina; Argente, Jesús; Chowen, Julie A

    2012-01-01

    Leptin levels during the perinatal period are important for the development of metabolic systems involved in energy homeostasis. In rodents, there is a postnatal leptin surge, with circulating leptin levels increasing around postnatal day (PND) 5 and peaking between PND 9 and PND 10. At this time circulating leptin acts as an important trophic factor for the development of hypothalamic circuits that control energy homeostasis and food seeking and reward behaviors. Blunting the postnatal leptin surge results in long-term leptin insensitivity and increased susceptibility to diet-induced obesity during adulthood. Pharmacologically increased leptin levels in the postnatal period also have long-term effects on metabolism. Nevertheless, this effect is controversial as postnatal hyperleptinemia is reported to both increase and decrease the predisposition to obesity in adulthood. The different effects reported in the literature could be explained by the different moments at which this hormone was administered, suggesting that modifications of the neonatal leptin surge at specific time points could selectively affect the development of central and peripheral systems that are undergoing modifications at this moment resulting in different metabolic and behavioral outcomes. In addition, maternal nutrition and the hormonal environment during pregnancy and lactation may also modulate the offspring's response to postnatal modifications in leptin levels. This review highlights the importance of leptin levels during the perinatal period in the development of metabolic systems that control energy homeostasis and how modifications of these levels may induce long-lasting and potentially irreversible effects on metabolism. PMID:22433625

  2. Zinc regulates a key transcriptional pathway for epileptogenesis via metal-regulatory transcription factor 1

    PubMed Central

    van Loo, Karen M. J.; Schaub, Christina; Pitsch, Julika; Kulbida, Rebecca; Opitz, Thoralf; Ekstein, Dana; Dalal, Adam; Urbach, Horst; Beck, Heinz; Yaari, Yoel; Schoch, Susanne; Becker, Albert J.

    2015-01-01

    Temporal lobe epilepsy (TLE) is the most common focal seizure disorder in adults. In many patients, transient brain insults, including status epilepticus (SE), are followed by a latent period of epileptogenesis, preceding the emergence of clinical seizures. In experimental animals, transcriptional upregulation of CaV3.2 T-type Ca2+-channels, resulting in an increased propensity for burst discharges of hippocampal neurons, is an important trigger for epileptogenesis. Here we provide evidence that the metal-regulatory transcription factor 1 (MTF1) mediates the increase of CaV3.2 mRNA and intrinsic excitability consequent to a rise in intracellular Zn2+ that is associated with SE. Adeno-associated viral (rAAV) transfer of MTF1 into murine hippocampi leads to increased CaV3.2 mRNA. Conversely, rAAV-mediated expression of a dominant-negative MTF1 abolishes SE-induced CaV3.2 mRNA upregulation and attenuates epileptogenesis. Finally, data from resected human hippocampi surgically treated for pharmacoresistant TLE support the Zn2+-MTF1-CaV3.2 cascade, thus providing new vistas for preventing and treating TLE. PMID:26498180

  3. Protein Adsorption Patterns and Analysis on IV Nanoemulsions—The Key Factor Determining the Organ Distribution

    PubMed Central

    Keck, Cornelia M.; Jansch, Mirko; Müller, Rainer H.

    2012-01-01

    Intravenous nanoemulsions have been on the market for parenteral nutrition since the 1950s; meanwhile, they have also been used successfully for IV drug delivery. To be well tolerable, the emulsions should avoid uptake by the MPS cells of the body; for drug delivery, they should be target-specific. The organ distribution is determined by the proteins adsorbing them after injection from the blood (protein adsorption pattern), typically analyzed by two-dimensional polyacrylamide gel electrophoresis, 2-D PAGE. The article reviews the 2-D PAGE method, the analytical problems to be faced and the knowledge available on how the composition of emulsions affects the protein adsorption patterns, e.g., the composition of the oil phase, stabilizer layer and drug incorporation into the interface or oil core. Data were re-evaluated and compared, and the implications for the in vivo distribution are discussed. Major results are that the interfacial composition of the stabilizer layer is the main determining factor and that this composition can be modulated by simple processes. Drug incorporation affects the pattern depending on the localization of the drug (oil core versus interface). The data situation regarding in vivo effects is very limited; mainly, it has to be referred to in the in vivo data of polymeric nanoparticles. As a conclusion, determination of the protein adsorption patterns can accelerate IV nanoemulsion formulation development regarding optimized organ distribution and related pharmacokinetics. PMID:24300396

  4. Key factors in work engagement and job motivation of teaching faculty at a university medical centre.

    PubMed

    van den Berg, B A M; Bakker, Arnold B; Ten Cate, Th J

    2013-11-01

    This study reports about teacher motivation and work engagement in a Dutch University Medical Centre (UMC). We examined factors affecting the motivation for teaching in a UMC, the engagement of UMC Utrecht teaching faculty in their work, and their engagement in teaching compared with engagement in patient care and research. Based on a pilot study within various departments at the UMCU, a survey on teaching motivation and work engagement was developed and sent to over 600 UMCU teachers. About 50 % responded. Work engagement was measured by the Utrecht Work Engagement Scale, included in this survey. From a list of 22 pre-defined items, 5 were marked as most motivating: teaching about my own speciality, noticeable appreciation for teaching by my direct superior, teaching small groups, feedback on my teaching performance, and freedom to determine what I teach. Feedback on my teaching performance showed the strongest predictive value for teaching engagement. Engagement scores were relatively favourable, but engagement with patient care was higher than with research and teaching. Task combinations appear to decrease teaching engagement. Our results match with self-determination theory and the job demands-resources model, and challenge the policy to combine teaching with research and patient care. PMID:24037742

  5. Research on key factors in the digital shearing speckle pattern interferometry

    NASA Astrophysics Data System (ADS)

    Feng, Ziang; Gao, Zhan; Zhang, Xiaoqiong; Wang, Shengjia

    2015-08-01

    Digital shearing speckle pattern interferometry (DSSPI) is a powerful tool in the measurement of strain, residual stress and the non-destructive testing (NDT). It is widely used in the fields of wood testing, tire inspection and aerospace, etc. The DSSPI system based on the Wollaston prism is attractive because of its compact arrangement, high immunity to disturbance, and, most of all, the ability to measure strain directly. It could show the strain distribution of the measured object by producing fringe patterns. In conventional DSSPI systems, phase-shifting devices are commonly adopted to extract phase information from the fringe patterns, which means dynamical measurement cannot be realized. In this paper, the principle of a novel DSSPI system based on the temporal analysis is presented. Phase information is extracted with the Fourier Transform method instead of the phase-shifting devices in this system. In this way, dynamical measurement is realized. The measuring accuracy is mostly determined by the quality of the fringe patterns (the fringe width and the contrast ratio). There are several factors that influence the quality of the fringe patterns. Here we mainly discuss the influence of the shearing distance and the polarization state. The preliminary experiments with different shearing distances and polarization states are conducted. The ideal shearing distance and polarization state are suggested.

  6. Physiologically-based toxicokinetic models help identifying the key factors affecting contaminant uptake during flood events.

    PubMed

    Brinkmann, Markus; Eichbaum, Kathrin; Kammann, Ulrike; Hudjetz, Sebastian; Cofalla, Catrina; Buchinger, Sebastian; Reifferscheid, Georg; Schüttrumpf, Holger; Preuss, Thomas; Hollert, Henner

    2014-07-01

    As a consequence of global climate change, we will be likely facing an increasing frequency and intensity of flood events. Thus, the ecotoxicological relevance of sediment re-suspension is of growing concern. It is vital to understand contaminant uptake from suspended sediments and relate it to effects in aquatic biota. Here we report on a computational study that utilizes a physiologically based toxicokinetic model to predict uptake, metabolism and excretion of sediment-borne pyrene in rainbow trout (Oncorhynchus mykiss). To this end, data from two experimental studies were compared with the model predictions: (a) batch re-suspension experiments with constant concentration of suspended particulate matter at two different temperatures (12 and 24°C), and (b) simulated flood events in an annular flume. The model predicted both the final concentrations and the kinetics of 1-hydroxypyrene secretion into the gall bladder of exposed rainbow trout well. We were able to show that exhaustive exercise during exposure in simulated flood events can lead to increased levels of biliary metabolites and identified cardiac output and effective respiratory volume as the two most important factors for contaminant uptake. The results of our study clearly demonstrate the relevance and the necessity to investigate uptake of contaminants from suspended sediments under realistic exposure scenarios. PMID:24727214

  7. Dynamic Transcription Factor Activity Profiles Reveal Key Regulatory Interactions During Megakaryocytic and Erythroid Differentiation

    PubMed Central

    Duncan, Mark T.; Shin, Seungjin; Wu, Jia J.; Mays, Zachary; Weng, Stanley; Bagheri, Neda; Miller, William M.; Shea, Lonnie D.

    2014-01-01

    The directed differentiation toward erythroid (E) or megakaryocytic (MK) lineages by the MK-E progenitor (MEP) could enhance the ex vivo generation of red blood cells and platelets for therapeutic transfusions. The lineage choice at the MEP bifurcation is controlled in large part by activity within the intracellular signal transduction network, the output of which determines the activity of transcription factors (TFs) and ultimately gene expression. Although many TFs have been implicated, E or MK differentiation is a complex process requiring multiple days, and the dynamics of TF activities during commitment and terminal maturation are relatively unexplored. Herein, we applied a living cell array for the large-scale, dynamic quantification of TF activities during MEP bifurcation. A panel of hematopoietic TFs (GATA-1, GATA-2, SCL/TAL1, FLI-1, NF-E2, PU.1, c-Myb) was characterized during E and MK differentiation of bipotent K562 cells. Dynamic TF activity profiles associated with differentiation towards each lineage were identified, and validated with previous reports. From these activity profiles, we show that GATA-1 is an important hub during early hemin- and PMA-induced differentiation, and reveal several characteristic TF interactions for E and MK differentiation that confirm regulatory mechanisms documented in the literature. Additionally, we highlight several novel TF interactions at various stages of E and MK differentiation. Furthermore, we investigated the mechanism by which nicotinamide (NIC) promoted terminal MK maturation using an MK-committed cell line, CHRF-288-11 (CHRF). Concomitant with its enhancement of ploidy, NIC strongly enhanced the activity of three TFs with known involvement in terminal MK maturation: FLI-1, NF-E2, and p53. Dynamic profiling of TF activity represents a novel tool to complement traditional assays focused on mRNA and protein expression levels to understand progenitor cell differentiation. PMID:24853077

  8. Key geochemical factors regulating Mn(IV)-catalyzed anaerobic nitrification in coastal marine sediments

    NASA Astrophysics Data System (ADS)

    Lin, Hui; Taillefert, Martial

    2014-05-01

    The reduction of Mn(IV) oxides coupled to the anaerobic oxidation of NH4+ has been proposed for more than a decade to contribute to the fixed nitrogen pool in marine sediments, yet the existence of this process is still under debate. In this study, surface sediments from an intertidal salt marsh were incubated with MnO2 in the presence of elevated concentrations of NH4+ to test the hypothesis that the reduction of Mn(IV) oxides catalyzes anaerobic NH4+ oxidation to NO2- or NO3-. Geochemical factors such as the ratio of Mn(IV) to NH4+, the type of Mn(IV) oxides (amorphous or colloidal MnO2), and the redox potential of the sediment significantly affect the activity of anaerobic nitrification. Incubations show that the net production of NO3- is stimulated under anaerobic conditions with external addition of colloidal but not amorphous MnO2 and is facilitated by the presence of high concentrations of NH4+. Mass balance calculations demonstrate that anaerobic NH4+ oxidation contributes to the net consumption of NH4+, providing another piece of evidence for the occurrence of Mn(IV)-catalyzed anaerobic nitrification in coastal marine sediments. Finally, anaerobic nitrification is stimulated by the amendment of small concentrations of NO3- or the absence of sulfate reduction, suggesting that moderately reducing conditions favor anaerobic NH4+ oxidation. Overall, these findings suggest that Mn(IV)-catalyzed anaerobic nitrification in suboxic sediments with high N/Mn concentration ratios and highly reactive manganese oxides may be an important source of NO2- and NO3- for subsequent marine nitrogen loss via denitrification or anammox.

  9. Dynamic transcription factor activity profiles reveal key regulatory interactions during megakaryocytic and erythroid differentiation.

    PubMed

    Duncan, Mark T; Shin, Seungjin; Wu, Jia J; Mays, Zachary; Weng, Stanley; Bagheri, Neda; Miller, William M; Shea, Lonnie D

    2014-10-01

    The directed differentiation toward erythroid (E) or megakaryocytic (MK) lineages by the MK-E progenitor (MEP) could enhance the ex vivo generation of red blood cells and platelets for therapeutic transfusions. The lineage choice at the MEP bifurcation is controlled in large part by activity within the intracellular signal transduction network, the output of which determines the activity of transcription factors (TFs) and ultimately gene expression. Although many TFs have been implicated, E or MK differentiation is a complex process requiring multiple days, and the dynamics of TF activities during commitment and terminal maturation are relatively unexplored. Herein, we applied a living cell array for the large-scale, dynamic quantification of TF activities during MEP bifurcation. A panel of hematopoietic TFs (GATA-1, GATA-2, SCL/TAL1, FLI-1, NF-E2, PU.1, c-Myb) was characterized during E and MK differentiation of bipotent K562 cells. Dynamic TF activity profiles associated with differentiation towards each lineage were identified, and validated with previous reports. From these activity profiles, we show that GATA-1 is an important hub during early hemin- and PMA-induced differentiation, and reveal several characteristic TF interactions for E and MK differentiation that confirm regulatory mechanisms documented in the literature. Additionally, we highlight several novel TF interactions at various stages of E and MK differentiation. Furthermore, we investigated the mechanism by which nicotinamide (NIC) promoted terminal MK maturation using an MK-committed cell line, CHRF-288-11 (CHRF). Concomitant with its enhancement of ploidy, NIC strongly enhanced the activity of three TFs with known involvement in terminal MK maturation: FLI-1, NF-E2, and p53. Dynamic profiling of TF activity represents a novel tool to complement traditional assays focused on mRNA and protein expression levels to understand progenitor cell differentiation. PMID:24853077

  10. Transition of basaltic lava from pahoehoe to aa, Kilauea Volcano, Hawaii: Field observations and key factors

    USGS Publications Warehouse

    Peterson, D.W.; Tilling, R.I.

    1980-01-01

    Nearly all Hawaiian basaltic lava erupts as pahoehoe, and some changes to aa during flowage and cooling; factors governing the transition involve certain critical relations between viscosity and rate of shear strain. If the lava slows, cools, and stops in direct response to concomitant increase in viscosity before these critical relations are reached, it remains pahoehoe. But, if flow mechanics (flow rate, flow dimensions, slope, momentum, etc.) impel the lava to continue to move and deform even after it has become highly viscous, the critical relations may be reached and the lava changes to aa. Typical modes of transition from pahoehoe to aa include: (1) spontaneous formation of relatively stiff clots in parts of the flowing lava where shear rate is highest; these clots grow into discrete, rough, sticky masses to which the remaining fluid lava incrementally adheres; (2) fragmentation and immersion of solid or semi-solid surface crusts of pahoehoe by roiling movements of the flow, forming cores of discrete, tacky masses; (3) sudden renewed movement of lava stored and cooled within surface reservoirs to form clots. The masses, fragments, and clots in these transition modes are characterized by spinose, granulated surfaces; as flow movement continues, the masses and fragments aggregate, fracture, and grind together, completing the transition to aa. Observations show that the critical relation between viscosity and rate of shear strain is inverse: if viscosity is low, a high rate of shear is required to begin the transition to aa; conversely, if viscosity is high, a much lower rate of shear will induce the transition. These relations can be demonstrated qualitatively with simple graphs, which can be used to examine the flow history of any selected finite lava element by tracing the path represented by its changing viscosity and shear rate. A broad, diffuse "transition threshold zone" in these graphs portrays the inverse critical relation between viscosity and shear

  11. Mechanisms of fertilization elucidated by gene-manipulated animals

    PubMed Central

    Okabe, Masaru

    2015-01-01

    Capacitation and the acrosome reaction are key phenomena in mammalian fertilization. These phenomena were found more than 60 years ago. However, fundamental questions regarding the nature of capacitation and the timing of the acrosome reaction remain unsolved. Factors were postulated over time, but as their roles were not verified by gene-disruption experiments, widely accepted notions concerning the mechanism of fertilization are facing modifications. Today, although in vitro fertilization systems remain our central research tool, the importance of in vivo observations must be revisited. Here, primarily focusing on our own research, I summarize how in vivo observations using gene-manipulated animals have elucidated new concepts in the mechanisms of fertilization. PMID:25851662

  12. Transcription Factor ATAF1 in Arabidopsis Promotes Senescence by Direct Regulation of Key Chloroplast Maintenance and Senescence Transcriptional Cascades.

    PubMed

    Garapati, Prashanth; Xue, Gang-Ping; Munné-Bosch, Sergi; Balazadeh, Salma

    2015-07-01

    Senescence represents a fundamental process of late leaf development. Transcription factors (TFs) play an important role for expression reprogramming during senescence; however, the gene regulatory networks through which they exert their functions, and their physiological integration, are still largely unknown. Here, we identify the Arabidopsis (Arabidopsis thaliana) abscisic acid (ABA)- and hydrogen peroxide-activated TF Arabidopsis thaliana activating factor1 (ATAF1) as a novel upstream regulator of senescence. ATAF1 executes its physiological role by affecting both key chloroplast maintenance and senescence-promoting TFs, namely GOLDEN2-LIKE1 (GLK1) and ORESARA1 (Arabidopsis NAC092), respectively. Notably, while ATAF1 activates ORESARA1, it represses GLK1 expression by directly binding to their promoters, thereby generating a transcriptional output that shifts the physiological balance toward the progression of senescence. We furthermore demonstrate a key role of ATAF1 for ABA- and hydrogen peroxide-induced senescence, in accordance with a direct regulatory effect on ABA homeostasis genes, including nine-CIS-epoxycarotenoid dioxygenase3 involved in ABA biosynthesis and ABC transporter G family member40, encoding an ABA transport protein. Thus, ATAF1 serves as a core transcriptional activator of senescence by coupling stress-related signaling with photosynthesis- and senescence-related transcriptional cascades. PMID:25953103

  13. Key factors influencing adoption of an innovation in primary health care: a qualitative study based on implementation theory

    PubMed Central

    2010-01-01

    Background Bridging the knowledge-to-practice gap in health care is an important issue that has gained interest in recent years. Implementing new methods, guidelines or tools into routine care, however, is a slow and unpredictable process, and the factors that play a role in the change process are not yet fully understood. There is a number of theories concerned with factors predicting successful implementation in various settings, however, this issue is insufficiently studied in primary health care (PHC). The objective of this article was to apply implementation theory to identify key factors influencing the adoption of an innovation being introduced in PHC in Sweden. Methods A qualitative study was carried out with staff at six PHC units in Sweden where a computer-based test for lifestyle intervention had been implemented. Two different implementation strategies, implicit or explicit, were used. Sixteen focus group interviews and two individual interviews were performed. In the analysis a theoretical framework based on studies of implementation in health service organizations, was applied to identify key factors influencing adoption. Results The theoretical framework proved to be relevant for studies in PHC. Adoption was positively influenced by positive expectations at the unit, perceptions of the innovation being compatible with existing routines and perceived advantages. An explicit implementation strategy and positive opinions on change and innovation were also associated with adoption. Organizational changes and staff shortages coinciding with implementation seemed to be obstacles for the adoption process. Conclusion When implementation theory obtained from studies in other areas was applied in PHC it proved to be relevant for this particular setting. Based on our results, factors to be taken into account in the planning of the implementation of a new tool in PHC should include assessment of staff expectations, assessment of the perceived need for the

  14. CENP-C and CENP-I are key connecting factors for kinetochore and CENP-A assembly

    PubMed Central

    Shono, Nobuaki; Ohzeki, Jun-ichirou; Otake, Koichiro; Martins, Nuno M. C.; Nagase, Takahiro; Kimura, Hiroshi; Larionov, Vladimir; Earnshaw, William C.; Masumoto, Hiroshi

    2015-01-01

    ABSTRACT Although it is generally accepted that chromatin containing the histone H3 variant CENP-A is an epigenetic mark maintaining centromere identity, the pathways leading to the formation and maintenance of centromere chromatin remain unclear. We previously generated human artificial chromosomes (HACs) whose centromeres contain a synthetic alpha-satellite (alphoid) DNA array containing the tetracycline operator (alphoidtetO). We also obtained cell lines bearing the alphoidtetO array at ectopic integration sites on chromosomal arms. Here, we have examined the regulation of CENP-A assembly at centromeres as well as de novo assembly on the ectopic arrays by tethering tetracycline repressor (tetR) fusions of substantial centromeric factors and chromatin modifiers. This analysis revealed four classes of factors that influence CENP-A assembly. Interestingly, many kinetochore structural components induced de novo CENP-A assembly at the ectopic site. We showed that these components work by recruiting CENP-C and subsequently recruiting M18BP1. Furthermore, we found that CENP-I can also recruit M18BP1 and, as a consequence, enhances M18BP1 assembly on centromeres in the downstream of CENP-C. Thus, we suggest that CENP-C and CENP-I are key factors connecting kinetochore to CENP-A assembly. PMID:26527398

  15. CENP-C and CENP-I are key connecting factors for kinetochore and CENP-A assembly.

    PubMed

    Shono, Nobuaki; Ohzeki, Jun-ichirou; Otake, Koichiro; Martins, Nuno M C; Nagase, Takahiro; Kimura, Hiroshi; Larionov, Vladimir; Earnshaw, William C; Masumoto, Hiroshi

    2015-12-15

    Although it is generally accepted that chromatin containing the histone H3 variant CENP-A is an epigenetic mark maintaining centromere identity, the pathways leading to the formation and maintenance of centromere chromatin remain unclear. We previously generated human artificial chromosomes (HACs) whose centromeres contain a synthetic alpha-satellite (alphoid) DNA array containing the tetracycline operator (alphoid(tetO)). We also obtained cell lines bearing the alphoid(tetO) array at ectopic integration sites on chromosomal arms. Here, we have examined the regulation of CENP-A assembly at centromeres as well as de novo assembly on the ectopic arrays by tethering tetracycline repressor (tetR) fusions of substantial centromeric factors and chromatin modifiers. This analysis revealed four classes of factors that influence CENP-A assembly. Interestingly, many kinetochore structural components induced de novo CENP-A assembly at the ectopic site. We showed that these components work by recruiting CENP-C and subsequently recruiting M18BP1. Furthermore, we found that CENP-I can also recruit M18BP1 and, as a consequence, enhances M18BP1 assembly on centromeres in the downstream of CENP-C. Thus, we suggest that CENP-C and CENP-I are key factors connecting kinetochore to CENP-A assembly. PMID:26527398

  16. CR6-interacting factor 1 is a key regulator in Aβ-induced mitochondrial disruption and pathogenesis of Alzheimer's disease

    PubMed Central

    Byun, J; Son, S M; Cha, M-Y; Shong, M; Hwang, Y J; Kim, Y; Ryu, H; Moon, M; Kim, K-S; Mook-Jung, I

    2015-01-01

    Mitochondrial dysfunction, often characterized by massive fission and other morphological abnormalities, is a well-known risk factor for Alzheimer's disease (AD). One causative mechanism underlying AD-associated mitochondrial dysfunction is thought to be amyloid-β (Aβ), yet the pathways between Aβ and mitochondrial dysfunction remain elusive. In this study, we report that CR6-interacting factor 1 (Crif1), a mitochondrial inner membrane protein, is a key player in Aβ-induced mitochondrial dysfunction. Specifically, we found that Crif1 levels were downregulated in the pathological regions of Tg6799 mice brains, wherein overexpressed Aβ undergoes self-aggregation. Downregulation of Crif1 was similarly observed in human AD brains as well as in SH-SY5Y cells treated with Aβ. In addition, knockdown of Crif1, using RNA interference, induced mitochondrial dysfunction with phenotypes similar to those observed in Aβ-treated cells. Conversely, Crif1 overexpression prevented Aβ-induced mitochondrial dysfunction and cell death. Finally, we show that Aβ-induced downregulation of Crif1 is mediated by enhanced reactive oxygen species (ROS) and ROS-dependent sumoylation of the transcription factor specificity protein 1 (Sp1). These results identify the ROS-Sp1-Crif1 pathway to be a new mechanism underlying Aβ-induced mitochondrial dysfunction and suggest that ROS-mediated downregulation of Crif1 is a crucial event in AD pathology. We propose that Crif1 may serve as a novel therapeutic target in the treatment of AD. PMID:25361083

  17. Capturing the wide variety of impaired fracture healing phenotypes in Neurofibromatosis Type 1 with eight key factors: a computational study

    PubMed Central

    Carlier, A.; Brems, H.; Ashbourn, J. M. A.; Nica, I.; Legius, E.; Geris, L.

    2016-01-01

    Congenital pseudarthrosis of the tibia (CPT) is a rare disease which normally presents itself during early childhood by anterolateral bowing of the tibia and spontaneous tibial fractures. Although the exact etiology of CPT is highly debated, 40–80% of CPT patients are carriers of a mutation in the Neurofibromatosis Type 1 (NF1) gene, which can potentially result in an altered phenotype of the skeletal cells and impaired bone healing. In this study we use a computational model of bone regeneration to examine the effect of the Nf1 mutation on bone fracture healing by altering the parameter values of eight key factors which describe the aberrant cellular behaviour of Nf1 haploinsufficient and Nf1 bi-allelically inactivated cells. We show that the computational model is able to predict the formation of a hamartoma as well as a wide variety of CPT phenotypes through different combinations of altered parameter values. A sensitivity analysis by “Design of Experiments” identified the impaired endochondral ossification process and increased infiltration of fibroblastic cells as key contributors to the degree of severity of CPT. Hence, the computational model results have added credibility to the experimental hypothesis of a genetic cause (i.e. Nf1 mutation) for CPT. PMID:26822862

  18. A new player in X identification: the CLAMP protein is a key factor in Drosophila dosage compensation

    PubMed Central

    Soruco, Marcela M. L.

    2016-01-01

    Dosage compensation adjusts the expression levels of genes on one or both targeted sex chromosomes in heterogametic species. This process results in the normalized transcriptional output of important and essential gene families encoded on multiple chromosomes. The mechanisms of dosage compensation have been studied in many model organisms, including Drosophila melanogaster (fly), Caenorhabditis elegans (worm), and Mus musculus (mouse). Although the mechanisms of dosage compensations differ among these species, all of these processes rely on the initial discrimination of the X chromosome from autosomes. Recently, a new paradigm for how the X chromosome is targeted for regulation was identified in Drosophila. This mechanism involves a newly identified zinc finger protein, CLAMP. Here, we review important factors involved in dosage compensation across species with special focus on the fly. Understanding how the newly identified CLAMP protein is involved in X targeting in the fly could provide key insights into how the X chromosome is initially identified across species. PMID:25102930

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

    PubMed

    Ly, Donald L; Waheed, Faiza; Lodyga, Monika; Speight, Pam; Masszi, András; Nakano, Hiroyasu; Hersom, Maria; Pedersen, Stine F; Szászi, Katalin; Kapus, András

    2013-01-15

    Hyperosmotic stress initiates several adaptive responses, including the remodeling of the cytoskeleton. Besides maintaining structural integrity, the cytoskeleton has emerged as an important regulator of gene transcription. Myocardin-related transcription factor (MRTF), an actin-regulated coactivator of serum response factor, is a major link between the actin skeleton and transcriptional control. We therefore investigated whether MRTF is regulated by hyperosmotic stress. Here we show that hypertonicity induces robust, rapid, and transient translocation of MRTF from the cytosol to the nucleus in kidney tubular cells. We found that the hyperosmolarity-triggered MRTF translocation is mediated by the RhoA/Rho kinase (ROK) pathway. Moreover, the Rho guanine nucleotide exchange factor GEF-H1 is activated by hyperosmotic stress, and it is a key contributor to the ensuing RhoA activation and MRTF translocation, since siRNA-mediated GEF-H1 downregulation suppresses these responses. While the osmotically induced RhoA activation promotes nuclear MRTF accumulation, the concomitant activation of p38 MAP kinase mitigates this effect. Moderate hyperosmotic stress (600 mosM) drives MRTF-dependent transcription through the cis-element CArG box. Silencing or pharmacological inhibition of MRTF prevents the osmotic stimulation of CArG-dependent transcription and renders the cells susceptible to osmotic shock-induced structural damage. Interestingly, strong hyperosmolarity promotes proteasomal degradation of MRTF, concomitant with apoptosis. Thus, MRTF is an osmosensitive and osmoprotective transcription factor, whose intracellular distribution is regulated by the GEF-H1/RhoA/ROK and p38 pathways. However, strong osmotic stress destabilizes MRTF, concomitant with apoptosis, implying that hyperosmotically induced cell death takes precedence over epithelial-myofibroblast transition, a potential consequence of MRTF-mediated phenotypic reprogramming. PMID:23054059

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

    SciTech Connect

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

    2015-04-23

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

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

    DOE PAGESBeta

    Dogan, Nergiz; Wu, Weisheng; Morrissey, Christapher S.; Chen, Kuan-Bei; Stonestrom, Aaron; Long, Maria; Keller, Cheryl A.; Cheng, Yong; Jain, Deepti; Visel, Axel; et al

    2015-04-23

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

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

    PubMed Central

    Ly, Donald L.; Waheed, Faiza; Lodyga, Monika; Speight, Pam; Masszi, András; Nakano, Hiroyasu; Hersom, Maria; Pedersen, Stine F.; Szászi, Katalin

    2013-01-01

    Hyperosmotic stress initiates several adaptive responses, including the remodeling of the cytoskeleton. Besides maintaining structural integrity, the cytoskeleton has emerged as an important regulator of gene transcription. Myocardin-related transcription factor (MRTF), an actin-regulated coactivator of serum response factor, is a major link between the actin skeleton and transcriptional control. We therefore investigated whether MRTF is regulated by hyperosmotic stress. Here we show that hypertonicity induces robust, rapid, and transient translocation of MRTF from the cytosol to the nucleus in kidney tubular cells. We found that the hyperosmolarity-triggered MRTF translocation is mediated by the RhoA/Rho kinase (ROK) pathway. Moreover, the Rho guanine nucleotide exchange factor GEF-H1 is activated by hyperosmotic stress, and it is a key contributor to the ensuing RhoA activation and MRTF translocation, since siRNA-mediated GEF-H1 downregulation suppresses these responses. While the osmotically induced RhoA activation promotes nuclear MRTF accumulation, the concomitant activation of p38 MAP kinase mitigates this effect. Moderate hyperosmotic stress (600 mosM) drives MRTF-dependent transcription through the cis-element CArG box. Silencing or pharmacological inhibition of MRTF prevents the osmotic stimulation of CArG-dependent transcription and renders the cells susceptible to osmotic shock-induced structural damage. Interestingly, strong hyperosmolarity promotes proteasomal degradation of MRTF, concomitant with apoptosis. Thus, MRTF is an osmosensitive and osmoprotective transcription factor, whose intracellular distribution is regulated by the GEF-H1/RhoA/ROK and p38 pathways. However, strong osmotic stress destabilizes MRTF, concomitant with apoptosis, implying that hyperosmotically induced cell death takes precedence over epithelial-myofibroblast transition, a potential consequence of MRTF-mediated phenotypic reprogramming. PMID:23054059

  3. Ruguo key genes and tumor driving factors identification of bladder cancer based on the RNA-seq profile

    PubMed Central

    Zhang, Minglei; Li, Hongyan; Zou, Di; Gao, Ji

    2016-01-01

    Aim This study aimed to select several signature genes associated with bladder cancer, thus to investigate the possible mechanism in bladder cancer. Methods The mRNA expression profile data of GSE31614, including ten bladder tissues and ten control samples, was downloaded from the Gene Expression Omnibus. The differentially expressed genes (DEGs) in bladder cancer samples compared with the control samples were screened using the Student’s t-test method. Functional analysis for the DEGs was analyzed using the Database for Annotation, Visualization, and Integrated Discovery from the Gene Ontology database, followed by the transcription function annotation of DEGs from Tumor-Associated Gene database. Motifs of genes that had transcription functions in promoter region were analyzed using the Seqpos. Results A total of 1,571 upregulated and 1,507 downregulated DEGs in the bladder cancer samples were screened. ELF3 and MYBL2 involved in cell cycle and DNA replication were tumor suppressors. MEG3, APEX1, and EZH2 were related with the cell epigenetic regulation in bladder cancer. Moreover, HOXB9 and EN1 that have their own motif were the transcription factors. Conclusion Our study has identified several key genes involved in bladder cancer. ELF3 and MYBL2 are tumor suppressers, HOXB9 and EN1 are the main regulators, while MEG3, APEX1, and EZH2 are driving factors for bladder cancer progression. PMID:27217782

  4. Nutrient depletion as a key factor for manipulating gene expression and product formation in different branches of the flavonoid pathway.

    PubMed

    Lillo, Cathrine; Lea, Unni S; Ruoff, Peter

    2008-05-01

    The content of flavonoids increases in response to nitrogen and phosphorus depletion in plants. Manipulation of these macronutrients may therefore be used to control the levels of desirable compounds and improve plant quality. Key enzymes in the shikimate pathway, which feeds precursors into the flavonoid pathway, are regulated post-translationally by feedback from aromatic amino acids, and possibly by redox control through photosynthesis. Use of microarrays for global transcript analysis in Arabidopsis has revealed that transcript levels are less influenced by mineral nutrients in the shikimate pathway compared with the flavonoid pathway. The responses in the shikimate pathway appear complex, whereas in the flavonoid pathway, a single gene often responds similarly to mineral depletion, high light intensity and sucrose. MYB [production of anthocyanin pigment 1 (PAP1)/production of anthocyanin pigment 2 (PAP2)] and bHLH [GLABRA3 (GL3)] transcription factors are important for the nutrient depletion response. PAP1/2 stimulate gross activation of the flavonoid pathway, and different investigations support merging signal transduction chains for various abiotic treatments on PAP1/2. Flavonol synthase is not part of the PAP1/2 regulon, and expression is mainly enhanced by high light intensity and sucrose, not mineral depletion. Nevertheless, both cyanidin and flavonol derivatives increase in response to nitrogen depletion. Kaempferols are the dominating flavonols in Arabidopsis leaves under normal cultivation conditions, but quercetin accumulation can be triggered by nitrogen depletion in combination with other abiotic factors. PMID:18031469

  5. Screening Active Components from Yu-Ping-Feng-San for Regulating Initiative Key Factors in Allergic Sensitization

    PubMed Central

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

    2014-01-01

    Yu-ping-feng-san (YPFS) is a Chinese medical formula that is used clinically for allergic diseases and characterized by reducing allergy relapse. Our previous studies demonstrated that YPFS efficiently inhibited T helper 2 cytokines in allergic inflammation. The underlying mechanisms of action of YPFS and its effective components remain unclear. In this study, it was shown that YPFS significantly inhibited production of thymic stromal lymphopoietin (TSLP), an epithelial cell-derived initiative factor in allergic inflammation, in vitro and in vivo. A method of human bronchial epithelial cell (16HBE) binding combined with HPLC-MS (named 16HBE-HPLC-MS) was established to explore potential active components of YPFS. The following five components bound to 16HBE cells: calycosin-7-glucoside, ononin, claycosin, sec-o-glucosylhamaudol and formononetin. Serum from YPFS-treated mice was analyzed and three major components were detected claycosin, formononetin and cimifugin. Among these, claycosin and formononetin were detected by 16HBE-HPLC-MS and in the serum of YPFS-treated mice. Claycosin and formononetin decreased the level of TSLP markedly at the initial stage of allergic inflammation in vivo. Nuclear factor (NF)-κB, a key transcription factor in TSLP production, was also inhibited by claycosin and formononetin, either in terms of transcriptional activation or its nuclear translocation in vitro. Allergic inflammation was reduced by claycosin and formononetin when they are administered only at the initial stage in a murine model of atopic contact dermatitis. Thus, epithelial cell binding combined with HPLC-MS is a valid method for screening active components from complex mixtures of Chinese medicine. It was demonstrated that the compounds screened from YPFS significantly attenuated allergic inflammation probably by reducing TSLP production via regulating NF-κB activation. PMID:25198676

  6. Determination of Key Environmental Factors Responsible for Distribution Patterns of Fiddler Crabs in a Tropical Mangrove Ecosystem

    PubMed Central

    Mokhtari, Mohammad; Ghaffar, Mazlan Abd; Usup, Gires; Cob, Zaidi Che

    2015-01-01

    In tropical regions, different species of fiddler crabs coexist on the mangrove floor, which sometimes makes it difficult to define species-specific habitat by visual inspection. The aim of this study is to find key environmental parameters which affect the distribution of fiddler crabs and to determine the habitats in which each species was most abundant. Crabs were collected from 19 sites within the mudflats of Sepang-Lukut mangrove forest. Temperature, porewater salinity, organic matter, water content, carbon and nitrogen content, porosity, chlorophyll content, pH, redox potential, sediment texture and heavy metals were determined in each 1 m2 quadrate. Pearson correlation indicated that all sediment properties except pH and redox potential were correlated with sediment grain size. Canonical correspondence analysis (CCA) indicated that Uca paradussumieri was negatively correlated with salinity and redox potential. Sand dwelling species, Uca perplexa and Uca annulipes, were highly dependent on the abundance of 250 μm and 150 μm grain size particles in the sediment. Canonical Discriminative Analysis (CDA) indicated that variation in sediment grain size best explained where each crab species was most abundant. Moreover, U. paradussumieri commonly occupies muddy substrates of low shore, while U. forcipata lives under the shade of mangrove trees. U. annulipes and U. perplexa with the high number of spoon tipped setae on their second maxiliped are specialized to feed on the sandy sediments. U. rosea and U. triangularis are more common on muddy sediment with high sediment density. In conclusion, sediment grain size that influences most sediment properties acts as a main factor responsible for sediment heterogeneity. In this paper, the correlation between fiddler crab species and environmental parameters, as well as the interaction between sediment characteristics, was explained in order to define the important environmental factors in fiddler crab distributions. PMID

  7. Identification of Key Factors Involved in the Biosorption of Patulin by Inactivated Lactic Acid Bacteria (LAB) Cells

    PubMed Central

    Wang, Ling; Wang, Zhouli; Yuan, Yahong; Cai, Rui; Niu, Chen; Yue, Tianli

    2015-01-01

    The purpose of this study was to identify the key factors involved in patulin adsorption by heat-inactivated lactic acid bacteria (LAB) cells. For preventing bacterial contamination, a sterilization process was involved in the adsorption process. The effects of various physical, chemical, and enzymatic pre-treatments, simultaneous treatments, and post-treatments on the patulin adsorption performances of six LAB strains were evaluated. The pre-treated cells were characterized by scanning electron microscopy (SEM). Results showed that the removal of patulin by viable cells was mainly based on adsorption or degradation, depending on the specific strain. The adsorption abilities were widely increased by NaOH and esterification pre-treatments, and reduced by trypsin, lipase, iodate, and periodate pre-treatments. Additionally, the adsorption abilities were almost maintained at pH 2.2–4.0, and enhanced significantly at pH 4.0–6.0. The effects of sodium and magnesium ions on the adsorption abilities at pH 4 were slight and strain-specific. A lower proportion of patulin was released from the strain with higher adsorption ability. Analyses revealed that the physical structure of peptidoglycan was not a principal factor. Vicinal OH and carboxyl groups were not involved in patulin adsorption, while alkaline amino acids, thiol and ester compounds were important for patulin adsorption. Additionally, besides hydrophobic interaction, electrostatic interaction also participated in patulin adsorption, which was enhanced with the increase in pH (4.0–6.0). PMID:26581099

  8. Determination of key environmental factors responsible for distribution patterns of fiddler crabs in a tropical mangrove ecosystem.

    PubMed

    Mokhtari, Mohammad; Ghaffar, Mazlan Abd; Usup, Gires; Cob, Zaidi Che

    2015-01-01

    In tropical regions, different species of fiddler crabs coexist on the mangrove floor, which sometimes makes it difficult to define species-specific habitat by visual inspection. The aim of this study is to find key environmental parameters which affect the distribution of fiddler crabs and to determine the habitats in which each species was most abundant. Crabs were collected from 19 sites within the mudflats of Sepang-Lukut mangrove forest. Temperature, porewater salinity, organic matter, water content, carbon and nitrogen content, porosity, chlorophyll content, pH, redox potential, sediment texture and heavy metals were determined in each 1 m2 quadrate. Pearson correlation indicated that all sediment properties except pH and redox potential were correlated with sediment grain size. Canonical correspondence analysis (CCA) indicated that Uca paradussumieri was negatively correlated with salinity and redox potential. Sand dwelling species, Uca perplexa and Uca annulipes, were highly dependent on the abundance of 250 μm and 150 μm grain size particles in the sediment. Canonical Discriminative Analysis (CDA) indicated that variation in sediment grain size best explained where each crab species was most abundant. Moreover, U. paradussumieri commonly occupies muddy substrates of low shore, while U. forcipata lives under the shade of mangrove trees. U. annulipes and U. perplexa with the high number of spoon tipped setae on their second maxiliped are specialized to feed on the sandy sediments. U. rosea and U. triangularis are more common on muddy sediment with high sediment density. In conclusion, sediment grain size that influences most sediment properties acts as a main factor responsible for sediment heterogeneity. In this paper, the correlation between fiddler crab species and environmental parameters, as well as the interaction between sediment characteristics, was explained in order to define the important environmental factors in fiddler crab distributions. PMID

  9. Identifying key processes in the hydrochemistry of a basin through the combined use of factor and regression models

    NASA Astrophysics Data System (ADS)

    Yidana, Sandow Mark; Banoeng-Yakubo, Bruce; Sakyi, Patrick Asamoah

    2012-04-01

    An innovative technique of measuring the intensities of major sources of variation in the hydrochemistry of (ground) water in a basin has been developed. This technique, which is based on the combination of R-mode factor and multiple regression analyses, can be used to measure the degrees of influence of the major sources of variation in the hydrochemistry without measuring the concentrations of the entire set of physico-chemical parameters which are often used to characterize water systems. R-mode factor analysis was applied to the data of 13 physico-chemical parameters and 50 samples in order to determine the major sources of variation in the hydrochemistry of some aquifers in the western region of Ghana. In this study, three sources of variation in the hydrochemistry were distinguished: the dissolution of chlorides and sulfates of the major cations, carbonate mineral dissolution, and silicate mineral weathering. Two key parameters were identified with each of the processes and multiple regression models were developed for each process. These models were tested and found to predict these processes quite accurately, and can be applied anywhere within the terrain. This technique can be reliably applied in areas where logistical constraints limit water sampling for whole basin hydrochemical characterization. Q-mode hierarchical cluster analysis (HCA) applied to the data revealed three major groundwater associations distinguished on the basis of the major causes of variation in the hydrochemistry. The three groundwater types represent Na-HCO3, Ca-HCO3, and Na-Cl groundwater types. Silicate stability diagrams suggest that all these groundwater types are mainly stable in the kaolinite and montmorillonite fields suggesting moderately restricted flow conditions.

  10. Study of key factors influencing dust emission: An assessment of GEOS-Chem and DEAD simulations with observations

    NASA Astrophysics Data System (ADS)

    Bartlett, Kevin S.

    Mineral dust aerosols can impact air quality, climate change, biological cycles, tropical cyclone development and flight operations due to reduced visibility. Dust emissions are primarily limited to the extensive arid regions of the world, yet can negatively impact local to global scales, and are extremely complex to model accurately. Within this dissertation, the Dust Entrainment And Deposition (DEAD) model was adapted to run, for the first known time, using high temporal (hourly) and spatial (0.3°x0.3°) resolution data to methodically interrogate the key parameters and factors influencing global dust emissions. The dependence of dust emissions on key parameters under various conditions has been quantified and it has been shown that dust emissions within DEAD are largely determined by wind speeds, vegetation extent, soil moisture and topographic depressions. Important findings were that grid degradation from 0.3ºx0.3º to 1ºx1º, 2ºx2.5º, and 4°x5° of key meteorological, soil, and surface input parameters greatly reduced emissions approximately 13% and 29% and 64% respectively, as a result of the loss of sub grid detail within these key parameters at coarse grids. After running high resolution DEAD emissions globally for 2 years, two severe dust emission cases were chosen for an in-depth investigation of the root causes of the events and evaluation of the 2°x2.5° Goddard Earth Observing System (GEOS)-Chem and 0.3°x0.3° DEAD model capabilities to simulate the events: one over South West Asia (SWA) in June 2008 and the other over the Middle East in July 2009. The 2 year lack of rain over SWA preceding June 2008 with a 43% decrease in mean rainfall, yielded less than normal plant growth, a 28% increase in Aerosol Optical Depth (AOD), and a 24% decrease in Meteorological Aerodrome Report (METAR) observed visibility (VSBY) compared to average years. GEOS-Chem captured the observed higher AOD over SWA in June 2008. More detailed comparisons of GEOS

  11. Research on Key Factors and Their Interaction Effects of Electromagnetic Force of High-Speed Solenoid Valve

    PubMed Central

    Fan, Liyun; Xu, De; Ma, Xiuzhen; Song, Enzhe

    2014-01-01

    Analysis consisting of numerical simulations along with lab experiments of interaction effects between key parameters on the electromagnetic force based on response surface methodology (RSM) has been also proposed to optimize the design of high-speed solenoid valve (HSV) and improve its performance. Numerical simulation model of HSV has been developed in Ansoft Maxwell environment and its accuracy has been validated through lab experiments. Effect of change of core structure, coil structure, armature structure, working air gap, and drive current on the electromagnetic force of HSV has been analyzed through simulation model and influence rules of various parameters on the electromagnetic force have been established. The response surface model of the electromagnetic force has been utilized to analyze the interaction effect between major parameters. It has been concluded that six interaction factors including working air gap with armature radius, drive current with armature thickness, coil turns with side pole radius, armature thickness with its radius, armature thickness with side pole radius, and armature radius with side pole radius have significant influence on the electromagnetic force. Optimal match values between coil turns and side pole radius; armature thickness and side pole radius; and armature radius and side pole radius have also been determined. PMID:25243217

  12. A host basal transcription factor is a key component for infection of rice by TALE-carrying bacteria

    PubMed Central

    Yuan, Meng; Ke, Yinggen; Huang, Renyan; Ma, Ling; Yang, Zeyu; Chu, Zhaohui; Xiao, Jinghua; Li, Xianghua; Wang, Shiping

    2016-01-01

    Transcription activator-like effectors (TALEs) are sequence-specific DNA binding proteins found in a range of plant pathogenic bacteria, where they play important roles in host-pathogen interactions. However, it has been unclear how TALEs, after they have been injected into the host cells, activate transcription of host genes required for infection success. Here, we show that the basal transcription factor IIA gamma subunit TFIIAγ5 from rice is a key component for infection by the TALE-carrying bacterium Xanthomonas oryzae pv. oryzae, the causal agent for bacterial blight. Direct interaction of several TALEs with TFIIAγ5 is required for activation of disease susceptibility genes. Conversely, reduced expression of the TFIIAγ5 host gene limits the induction of susceptibility genes and thus decreases bacterial blight symptoms. Suppression or mutation of TFIIAγ5 can also reduce bacterial streak, another devastating disease of rice caused by TALE-carrying X. oryzae pv. oryzicola. These results have important implications for formulating a widely applicable strategy with which to improve resistance of plants to TALE-carrying pathogens. DOI: http://dx.doi.org/10.7554/eLife.19605.001 PMID:27472897

  13. Proton Gradients as a Key Physical Factor in the Evolution of the Forced Transport Mechanism Across the Lipid Membrane

    NASA Astrophysics Data System (ADS)

    Strbak, Oliver; Kanuchova, Zuzana; Krafcik, Andrej

    2016-04-01

    A critical phase in the transition from prebiotic chemistry to biological evolution was apparently an asymmetric ion flow across the lipid membrane. Due to imbalance in the ion flow, the early lipid vesicles could selectively take the necessary molecules from the environment, and release the side-products from the vesicle. Natural proton gradients played a definitively crucial role in this process, since they remain the basis of energy transfer in the present-day cells. On the basis of this supposition, and the premise of the early vesicle membrane's impermeability to protons, we have shown that the emergence of the proton gradient in the lipid vesicle could be a key physical factor in the evolution of the forced transport mechanism (pore formation and active transport) across the lipid bilayer. This driven flow of protons across the membrane is the result of the electrochemical proton gradient and osmotic pressures on the integrity of the lipid vesicle. At a critical number of new lipid molecules incorporated into the vesicle, the energies associated with the creation of the proton gradient exceed the bending stiffness of the lipid membrane, and overlap the free energy of the lipid bilayer pore formation.

  14. A Genome-wide Regulatory Network Identifies Key Transcription Factors for Memory CD8+ T Cell Development

    PubMed Central

    Hu, Guangan; Chen, Jianzhu

    2014-01-01

    Memory CD8+ T cell development is defined by the expression of a specific set of memory signature genes (MSGs). Despite recent progress, many components of the transcriptional control of memory CD8+ T cell development are still unknown. To identify transcription factors (TFs) and their interactions in memory CD8+ T cell development, we construct a genome-wide regulatory network and apply it to identify key TFs that regulate MSGs. Most of the known TFs in memory CD8+ T cell development are rediscovered and about a dozen new TFs are also identified. Sox4, Bhlhe40, Bach2 and Runx2 are experimentally verified and Bach2 is further shown to promote both development and recall proliferation of memory CD8+ T cells through Prdm1 and Id3. Gene perturbation study identifies the mode of interactions among the TFs with Sox4 as a hub. The identified TFs and insights into their interactions should facilitate further dissection of molecular mechanisms underlying memory CD8+ T cell development. PMID:24335726

  15. A host basal transcription factor is a key component for infection of rice by TALE-carrying bacteria.

    PubMed

    Yuan, Meng; Ke, Yinggen; Huang, Renyan; Ma, Ling; Yang, Zeyu; Chu, Zhaohui; Xiao, Jinghua; Li, Xianghua; Wang, Shiping

    2016-01-01

    Transcription activator-like effectors (TALEs) are sequence-specific DNA binding proteins found in a range of plant pathogenic bacteria, where they play important roles in host-pathogen interactions. However, it has been unclear how TALEs, after they have been injected into the host cells, activate transcription of host genes required for infection success. Here, we show that the basal transcription factor IIA gamma subunit TFIIAγ5 from rice is a key component for infection by the TALE-carrying bacterium Xanthomonas oryzae pv. oryzae, the causal agent for bacterial blight. Direct interaction of several TALEs with TFIIAγ5 is required for activation of disease susceptibility genes. Conversely, reduced expression of the TFIIAγ5 host gene limits the induction of susceptibility genes and thus decreases bacterial blight symptoms. Suppression or mutation of TFIIAγ5 can also reduce bacterial streak, another devastating disease of rice caused by TALE-carrying X. oryzae pv. oryzicola. These results have important implications for formulating a widely applicable strategy with which to improve resistance of plants to TALE-carrying pathogens. PMID:27472897

  16. Two separate key enzymes and two pathway-specific transcription factors are involved in fusaric acid biosynthesis in Fusarium fujikuroi.

    PubMed

    Studt, Lena; Janevska, Slavica; Niehaus, Eva-Maria; Burkhardt, Immo; Arndt, Birgit; Sieber, Christian M K; Humpf, Hans-Ulrich; Dickschat, Jeroen S; Tudzynski, Bettina

    2016-03-01

    Fusaric acid (FSA) is a mycotoxin produced by several fusaria, including the rice pathogen Fusarium fujikuroi. Genes involved in FSA biosynthesis were previously identified as a cluster containing a polyketide synthase (PKS)-encoding (FUB1) and four additional genes (FUB2-FUB5). However, the biosynthetic steps leading to FSA as well as the origin of the nitrogen atom, which is incorporated into the polyketide backbone, remained unknown. In this study, seven additional cluster genes (FUB6-FUB12) were identified via manipulation of the global regulator FfSge1. The extended FUB gene cluster encodes two Zn(II)2 Cys6 transcription factors: Fub10 positively regulates expression of all FUB genes, whereas Fub12 is involved in the formation of the two FSA derivatives, i.e. dehydrofusaric acid and fusarinolic acid, serving as a detoxification mechanism. The major facilitator superfamily transporter Fub11 functions in the export of FSA out of the cell and is essential when FSA levels become critical. Next to Fub1, a second key enzyme was identified, the non-canonical non-ribosomal peptide synthetase Fub8. Chemical analyses of generated mutant strains allowed for the identification of a triketide as PKS product and the proposition of an FSA biosynthetic pathway, thereby unravelling the unique formation of a hybrid metabolite consisting of this triketide and an amino acid moiety. PMID:26662839

  17. Polyacrylamide grafted cellulose as an eco-friendly flocculant: Key factors optimization of flocculation to surfactant effluent.

    PubMed

    Zhu, Hangcheng; Zhang, Yong; Yang, Xiaogang; Shao, Lan; Zhang, Xiumei; Yao, Juming

    2016-01-01

    The discharge of effluents from surfactant manufacturers is giving rise to increasingly serious environmental problems. In order to develop the eco-friendly flocculation materials to achieve effective removal of pollutants from the surfactant effluents, the bamboo pulp cellulose from Phyllostachys heterocycla is employed as the skeleton material to synthesize an eco-friendly bamboo pulp cellulose-g-polyacrylamide (BPC-g-PAM) for flocculation. The BPC-g-PAM is used with the metal ions as the coagulant to treat the effluent from a surfactant manufacturer. The response surface methodology coupled with Box-behnken design is employed to optimize the key factors of coagulation-flocculation. The results show that the combination of Fe(3+) with BPC-g-PAM achieves the best coagulation-flocculation performance like, the fast treatment time, minimum coagulant and BPC-g-PAM dosages compared with the other two combinations of Al(3+) with BPC-g-PAM and Ca(2+) with BPC-g-PAM. Therefore, the combination of Fe(3+) with BPC-g-PAM is expected to promote its application for the pollution control in the surfactant manufacturers. PMID:26453862

  18. Key Factors in the Rise of Mass Popular Education and Their Relevance for Education in Southern Africa in the Twenty-First Century.

    ERIC Educational Resources Information Center

    van Niekerk, E. J.

    This paper identifies the historical factors that played a key role in the rise of mass popular education and describes how these factors relate to education in Southern Africa in the 21st century. The broad overview of developments since the Renaissance begins with the Protestant Reformation, which established a theoretical basis for elementary…

  19. Maintaining the momentum: Key factors influencing acceptance of influenza vaccination among pregnant women following the H1N1 pandemic

    PubMed Central

    Halperin, Beth A; MacKinnon-Cameron, Donna; McNeil, Shelly; Kalil, Jennifer; Halperin, Scott A

    2015-01-01

    This survey study compared pre- and post-pandemic knowledge, attitudes, beliefs, and intended behaviors of pregnant women regarding influenza vaccination (seasonal and/or pandemic) during pregnancy in order to determine key factors influencing their decision to adhere to influenza vaccine recommendations. Only 36% of 662 pre-pandemic respondents knew that influenza was more severe in pregnant women, compared to 62% of the 159 post-pandemic respondents. Of the pre-pandemic respondents, 41% agreed or strongly agreed that that it was safer to wait until after the first 3 months to receive the seasonal influenza vaccine, whereas 23% of the post-pandemic cohort agreed or strongly agreed; 32% of pre-pandemic participants compared to 11% of post-pandemic respondents felt it was best to avoid all vaccines while pregnant. Despite 61% of the pre-pandemic cohort stating that they would have the vaccine while pregnant if their doctor recommended it and 54% citing their doctor/nurse as their primary source of vaccine information, only 20% said their doctor discussed influenza vaccination during their pregnancy, compared to 77% of the post-pandemic respondents who reported having this conversation. Women whose doctors discussed influenza vaccine during pregnancy had higher overall knowledge scores (P < 0.0001; P = 0.005) and were more likely to believe the vaccine is safe in all stages of pregnancy (P < 0.0001; P = 0.001) than those whose doctors did not discuss influenza vaccination. The 2009 H1N1 pandemic experience appeared to change attitudes and behaviours of health care providers and their pregnant patients toward influenza vaccination. PMID:25668670

  20. [Seasonal variation of cyanobacteria and its potential relationship with key environmental factors in Xiaojiang backwater area, Three Gorges Reservoir].

    PubMed

    Li, Zhe; Guo, Jing-song; Fang, Fang; Gao, Xu; Sheng, Jin-ping; Zhou, Hong; Long, Man

    2010-02-01

    Eutrophication and algal blooms occurred in the backwater areas of tributaries in Three Gorges Reservoir were the hot ecological issues in recent years. A one year field survey on cyanobacteria was put forward from May, 2007 to May, 2008 in Xiaojiang backwater area. 15 genera and 40 species of cyanophyta were detected. Mean value of cyanobacterial cell density was (23.50 +/- 10.30) x 10(5) cells x L(-1), i.e., 24.1% in the algal community, while the biomass was (768.70 +/- 287.40) microg x L(-1) which was 8.9% in the total biomass of algal community. Seasonal variation of cyanobacteria was apparent. Generally, cyanobacteria bloom occurred during late spring and early summer. Its abundance decreased after summer and reached the minimum level in winter. Anabaena, Aphanizomenon, Microcystis, Merismopedia and Phormidium were the common cynaobacterial genera. The cumulated cell density of these five genera of cyanobacteria above accounted up to 79.1% in the total cell density of cyanobacteria, while that of biomass accounted up to 77.6%. Spearman correlation analysis among the cell density, biomass as well as the key environmental factors indicated that utilization of inorganic nitrogen and phosphorus for anabolism was evident; however, nitrate would be the major nitrogen source for cyanobacteria. Moreover, increase of temperature and decrease of depth of euphotic zone had a significant effect on the abundance of cyanobacteria. According to co-analysis of hydrology and rainfall data in the whole year circle, it was found that nitrogen and phosphorus were input by the heavy rain and surface runoff with inorganic sediments, offering the enriched nutrients in water column. Meanwhile, turbidity increased by the inorganic suspended sediments decreased the depth of euphotic zone. The physiological advantage of cyanobacteria in low light and high turbidity environment might be the cause of cyanobacteria bloom in Xiaojiang backwater area. PMID:20391694

  1. The Key Sigma Factor of Transition Phase, SigH, Controls Sporulation, Metabolism, and Virulence Factor Expression in Clostridium difficile▿†

    PubMed Central

    Saujet, Laure; Monot, Marc; Dupuy, Bruno; Soutourina, Olga; Martin-Verstraete, Isabelle

    2011-01-01

    Toxin synthesis in Clostridium difficile increases as cells enter into stationary phase. We first compared the expression profiles of strain 630E during exponential growth and at the onset of stationary phase and showed that genes involved in sporulation, cellular division, and motility, as well as carbon and amino acid metabolism, were differentially expressed under these conditions. We inactivated the sigH gene, which encodes an alternative sigma factor involved in the transition to post-exponential phase in Bacillus subtilis. Then, we compared the expression profiles of strain 630E and the sigH mutant after 10 h of growth. About 60% of the genes that were differentially expressed between exponential and stationary phases, including genes involved in motility, sporulation, and metabolism, were regulated by SigH, which thus appears to be a key regulator of the transition phase in C. difficile. SigH positively controls several genes required for sporulation. Accordingly, sigH inactivation results in an asporogeneous phenotype. The spo0A and CD2492 genes, encoding the master regulator of sporulation and one of its associated kinases, and the spoIIA operon were transcribed from a SigH-dependent promoter. The expression of tcdA and tcdB, encoding the toxins, and of tcdR, encoding the sigma factor required for toxin production, increased in a sigH mutant. Finally, SigH regulates the expression of genes encoding surface-associated proteins, such as the Cwp66 adhesin, the S-layer precursor, and the flagellum components. Among the 286 genes positively regulated by SigH, about 40 transcriptional units presenting a SigH consensus in their promoter regions are good candidates for direct SigH targets. PMID:21572003

  2. A large-scale, in vivo transcription factor screen defines bivalent chromatin as a key property of regulatory factors mediating Drosophila wing development

    PubMed Central

    Schertel, Claus; Albarca, Monica; Rockel-Bauer, Claudia; Kelley, Nicholas W.; Bischof, Johannes; Hens, Korneel

    2015-01-01

    Transcription factors (TFs) are key regulators of cell fate. The estimated 755 genes that encode DNA binding domain-containing proteins comprise ∼5% of all Drosophila genes. However, the majority has remained uncharacterized so far due to the lack of proper genetic tools. We generated 594 site-directed transgenic Drosophila lines that contain integrations of individual UAS-TF constructs to facilitate spatiotemporally controlled misexpression in vivo. All transgenes were expressed in the developing wing, and two-thirds induced specific phenotypic defects. In vivo knockdown of the same genes yielded a phenotype for 50%, with both methods indicating a great potential for misexpression to characterize novel functions in wing growth, patterning, and development. Thus, our UAS-TF library provides an important addition to the genetic toolbox of Drosophila research, enabling the identification of several novel wing development-related TFs. In parallel, we established the chromatin landscape of wing imaginal discs by ChIP-seq analyses of five chromatin marks and RNA Pol II. Subsequent clustering revealed six distinct chromatin states, with two clusters showing enrichment for both active and repressive marks. TFs that carry such “bivalent” chromatin are highly enriched for causing misexpression phenotypes in the wing, and analysis of existing expression data shows that these TFs tend to be differentially expressed across the wing disc. Thus, bivalently marked chromatin can be used as a marker for spatially regulated TFs that are functionally relevant in a developing tissue. PMID:25568052

  3. Elucidating novel disease mechanisms in severe asthma.

    PubMed

    Kim, Richard Y; Rae, Brittany; Neal, Rachel; Donovan, Chantal; Pinkerton, James; Balachandran, Lohis; Starkey, Malcolm R; Knight, Darryl A; Horvat, Jay C; Hansbro, Philip M

    2016-07-01

    Corticosteroids are broadly active and potent anti-inflammatory agents that, despite the introduction of biologics, remain as the mainstay therapy for many chronic inflammatory diseases, including inflammatory bowel diseases, nephrotic syndrome, rheumatoid arthritis, chronic obstructive pulmonary disease and asthma. Significantly, there are cohorts of these patients with poor sensitivity to steroid treatment even with high doses, which can lead to many iatrogenic side effects. The dose-limiting toxicity of corticosteroids, and the lack of effective therapeutic alternatives, leads to substantial excess morbidity and healthcare expenditure. We have developed novel murine models of respiratory infection-induced, severe, steroid-resistant asthma that recapitulate the hallmark features of the human disease. These models can be used to elucidate novel disease mechanisms and identify new therapeutic targets in severe asthma. Hypothesis-driven studies can elucidate the roles of specific factors and pathways. Alternatively, 'Omics approaches can be used to rapidly generate new targets. Similar approaches can be used in other diseases. PMID:27525064

  4. Elucidating novel disease mechanisms in severe asthma

    PubMed Central

    Kim, Richard Y; Rae, Brittany; Neal, Rachel; Donovan, Chantal; Pinkerton, James; Balachandran, Lohis; Starkey, Malcolm R; Knight, Darryl A; Horvat, Jay C; Hansbro, Philip M

    2016-01-01

    Corticosteroids are broadly active and potent anti-inflammatory agents that, despite the introduction of biologics, remain as the mainstay therapy for many chronic inflammatory diseases, including inflammatory bowel diseases, nephrotic syndrome, rheumatoid arthritis, chronic obstructive pulmonary disease and asthma. Significantly, there are cohorts of these patients with poor sensitivity to steroid treatment even with high doses, which can lead to many iatrogenic side effects. The dose-limiting toxicity of corticosteroids, and the lack of effective therapeutic alternatives, leads to substantial excess morbidity and healthcare expenditure. We have developed novel murine models of respiratory infection-induced, severe, steroid-resistant asthma that recapitulate the hallmark features of the human disease. These models can be used to elucidate novel disease mechanisms and identify new therapeutic targets in severe asthma. Hypothesis-driven studies can elucidate the roles of specific factors and pathways. Alternatively, 'Omics approaches can be used to rapidly generate new targets. Similar approaches can be used in other diseases. PMID:27525064

  5. Tartaric acid in red wine as one of the key factors to induce superconductivity in FeTe0.8S0.2

    NASA Astrophysics Data System (ADS)

    Deguchi, Keita; Okuda, Tohru; Hara, Hiroshi; Demura, Satoshi; Watanabe, Tohru; Okazaki, Hiroyuki; Fujioka, Masaya; Denholme, Saleem James; Ozaki, Toshinori; Yamaguchi, Takahide; Takeya, Hiroyuki; Saito, Fumie; Hisamoto, Masashi; Takano, Yoshihiko

    2013-04-01

    We investigated the key factor of superconductivity in FeTe1-xSx induced by alcoholic beverages. To understand the reason why red wine shows larger shielding volume fraction than the other alcoholic beverages, the red wine dependence of superconductivity was performed. All the samples heated in red wine made from different grapes shows large shielding volume fraction compared with the samples heated in water and other alcoholic beverages. The shielding volume fraction of the red wine samples is proportional to the concentration of tartaric acid. We found that tartaric acid is one of the key factors to induce superconductivity in FeTe1-xSx.

  6. Key design factors affecting microbial community composition and pathogenic organism removal in horizontal subsurface flow constructed wetlands.

    PubMed

    Morató, Jordi; Codony, Francesc; Sánchez, Olga; Pérez, Leonardo Martín; García, Joan; Mas, Jordi

    2014-05-15

    Constructed wetlands constitute an interesting option for wastewater reuse since high concentrations of contaminants and pathogenic microorganisms can be removed with these natural treatment systems. In this work, the role of key design factors which could affect microbial removal and wetland performance, such as granular media, water depth and season effect was evaluated in a pilot system consisting of eight parallel horizontal subsurface flow (HSSF) constructed wetlands treating urban wastewater from Les Franqueses del Vallès (Barcelona, Spain). Gravel biofilm as well as influent and effluent water samples of these systems were taken in order to detect the presence of bacterial indicators such as total coliforms (TC), Escherichia coli, fecal enterococci (FE), Clostridium perfringens, and other microbial groups such as Pseudomonas and Aeromonas. The overall microbial inactivation ratio ranged between 1.4 and 2.9 log-units for heterotrophic plate counts (HPC), from 1.2 to 2.2 log units for total coliforms (TC) and from 1.4 to 2.3 log units for E. coli. The presence of fine granulometry strongly influenced the removal of all the bacterial groups analyzed. This effect was significant for TC (p=0.009), E. coli (p=0.004), and FE (p=0.012). Shallow HSSF constructed wetlands were more effective for removing Clostridium spores (p=0.039), and were also more efficient for removing TC (p=0.011) and E. coli (p=0.013) when fine granulometry was used. On the other hand, changes in the total bacterial community from gravel biofilm were examined by using denaturing gradient gel electrophoresis (DGGE) and sequencing of polymerase chain reaction (PCR)-amplified fragments of the 16S rRNA gene recovered from DGGE bands. Cluster analysis of the DGGE banding pattern from the different wetlands showed that microbial assemblages separated according to water depth, and sequences of different phylogenetic groups, such as Alpha, Beta and Delta-Proteobacteria, Nitrospirae, Bacteroidetes

  7. Elucidation of the Teixobactin Pharmacophore.

    PubMed

    Yang, Hyunjun; Chen, Kevin H; Nowick, James S

    2016-07-15

    This paper elucidates the teixobactin pharmacophore by comparing the arginine analogue of teixobactin Arg10-teixobactin to seven homologues with varying structure and stereochemistry. The roles of the guanidinium group at position 10, the stereochemistry of the macrolactone ring, and the "tail" comprising residues 1-5 are investigated. The guanidinium group is not necessary for activity; Lys10-teixobactin is more active than Arg10-teixobactin against Gram-positive bacteria in minimum inhibitory concentration (MIC) assays. The relative stereochemistry of the macrolactone ring is important. Diastereomer l-Thr8,Arg10-teixobactin is inactive, and diastereomer d-allo-Ile11,Arg10-teixobactin is less active. The macrolactone ring is critical; seco-Arg10-teixobactin is inactive. The absolute stereochemistry is not important; the enantiomer ent-Arg10-teixobactin is comparable in activity. The hydrophobic N-terminal tail is important. Truncation of residues 1-5 results in loss of activity, and replacement of residues 1-5 with a dodecanoyl group partially restores activity. These findings pave the way for developing simpler homologues of teixobactin with enhanced pharmacological properties. PMID:27232661

  8. Student-University Relationships and Reputation: A Study of the Links between Key Factors Fostering Students' Supportive Behavioral Intentions towards Their University

    ERIC Educational Resources Information Center

    Sung, Minjung; Yang, Sung-Un

    2009-01-01

    Focusing on academic institutions in higher education as the research context, this study examined the relations of key factors affecting students' supportive behavioral intentions toward the university (e.g., giving gifts as alumni, continuing education, and giving referrals regarding the university). Based on the literature from various…

  9. Dynamic C and N stocks - key factors controlling the C gas exchange of maize in a heterogenous peatland

    NASA Astrophysics Data System (ADS)

    Pohl, M.; Hoffmann, M.; Hagemann, U.; Giebels, M.; Albiac Borraz, E.; Sommer, M.; Augustin, J.

    2014-11-01

    Drainage and cultivation of fen peatlands creates complex small-scale mosaics of soils with extremely variable soil organic carbon (SOC) stocks and groundwater-level (GWL). To date, it remains unclear if such sites are sources or sinks for greenhouse gases like CO2 and CH4, especially if used for cropland. As individual control factors like GWL fail to account for this complexity, holistic approaches combining gas fluxes with the underlying processes are required to understand the carbon (C) gas exchange of drained fens. It can be assumed that the stocks of SOC and N located above the variable GWL - defined as dynamic C and N stocks - play a key role in the regulation of plant- and microbially mediated C gas fluxes of these soils. To test this assumption, the present study analysed the C gas exchange (gross primary production - GPP, ecosystem respiration - Reco, net ecosystem exchange - NEE, CH4) of maize using manual chambers for four years. The study sites were located near Paulinenaue, Germany. Here we selected three soils, which represent the full gradient in pedogenesis, GWL and SOC stocks (0-1 m) of the fen peatland: (a) Haplic Arenosol (AR; 8 kg C m-2); (b) Mollic Gleysol (GL; 38 kg C m-2); and (c) Hemic Histosol (HS; 87 kg C m-2). Daily GWL data was used to calculate dynamic SOC (SOCdyn) and N (Ndyn) stocks. Average annual NEE differed considerably among sites, ranging from 47 ± 30 g C m-2 a-1 at AR to -305 ± 123 g C m-2 a-1 at GL and -127 ± 212 g C m-2 a-1 at HS. While static SOC and N stocks showed no significant effect on C fluxes, SOCdyn and Ndyn and their interaction with GWL strongly influenced the C gas exchange, particularly NEE and the GPP:Reco ratio. Moreover, based on nonlinear regression analysis, 86% of NEE variability was explained by GWL and SOCdyn. The observed high relevance of dynamic SOC and N stocks in the aerobic zone for plant and soil gas exchange likely originates from the effects of GWL-dependent N availability on C formation and

  10. Dynamic C and N stocks - key factors controlling the C gas exchange of maize in heterogenous peatland

    NASA Astrophysics Data System (ADS)

    Pohl, M.; Hoffmann, M.; Hagemann, U.; Giebels, M.; Albiac Borraz, E.; Sommer, M.; Augustin, J.

    2015-05-01

    The drainage and cultivation of fen peatlands create complex small-scale mosaics of soils with extremely variable soil organic carbon (SOC) stocks and groundwater levels (GWLs). To date, the significance of such sites as sources or sinks for greenhouse gases such as CO2 and CH4 is still unclear, especially if the sites are used for cropland. As individual control factors such as GWL fail to account for this complexity, holistic approaches combining gas fluxes with the underlying processes are required to understand the carbon (C) gas exchange of drained fens. It can be assumed that the stocks of SOC and N located above the variable GWL - defined as dynamic C and N stocks - play a key role in the regulation of the plant- and microbially mediated CO2 fluxes in these soils and, inversely, for CH4. To test this assumption, the present study analysed the C gas exchange (gross primary production - GPP; ecosystem respiration - Reco; net ecosystem exchange - NEE; CH4) of maize using manual chambers for 4 years. The study sites were located near Paulinenaue, Germany, where we selected three soil types representing the full gradient of GWL and SOC stocks (0-1 m) of the landscape: (a) Haplic Arenosol (AR; 8 kg C m-2); (b) Mollic Gleysol (GL; 38 kg C m-2); and (c) Hemic Histosol (HS; 87 kg C m-2). Daily GWL data were used to calculate dynamic SOC (SOCdyn) and N (Ndyn) stocks. Average annual NEE differed considerably among sites, ranging from 47 ± 30 g C m-2 yr-1 in AR to -305 ± 123 g C m-2 yr-1 in GL and -127 ± 212 g C m-2 yr-1 in HS. While static SOC and N stocks showed no significant effect on C fluxes, SOCdyn and Ndyn and their interaction with GWL strongly influenced the C gas exchange, particularly NEE and the GPP : Reco ratio. Moreover, based on nonlinear regression analysis, 86% of NEE variability was explained by GWL and SOCdyn. The observed high relevance of dynamic SOC and N stocks in the aerobic zone for plant and soil gas exchange likely originates from the

  11. The key factor limiting plant growth in cold and humid alpine areas also plays a dominant role in plant carbon isotope discrimination

    PubMed Central

    Xu, Meng; Wang, Guoan; Li, Xiaoliang; Cai, Xiaobu; Li, Xiaolin; Christie, Peter; Zhang, Junling

    2015-01-01

    Many environmental factors affect carbon isotope discrimination in plants, yet the predominant factor influencing this process is generally assumed to be the key growth-limiting factor. However, to our knowledge this hypothesis has not been confirmed. We therefore determined the carbon isotope composition (δ13C) of plants growing in two cold and humid mountain regions where temperature is considered to be the key growth-limiting factor. Mean annual temperature (MAT) showed a significant impact on variation in carbon isotope discrimination value (Δ) irrespective of study area or plant functional type with either partial correlation or regression analysis, but the correlation between Δ and soil water content (SWC) was usually not significant. In multiple stepwise regression analysis, MAT was either the first or the only variable selected into the prediction model of Δ against MAT and SWC, indicating that the effect of temperature on carbon isotope discrimination was predominant. The results therefore provide evidence that the key growth-limiting factor is also crucial for plant carbon isotope discrimination. Changes in leaf morphology, water viscosity and carboxylation efficiency with temperature may be responsible for the observed positive correlation between Δ and temperature. PMID:26579188

  12. Decreased levels of proapoptotic factors and increased key regulators of mitochondrial biogenesis constitute new potential beneficial features of long-lived growth hormone receptor gene-disrupted mice.

    PubMed

    Gesing, Adam; Masternak, Michal M; Lewinski, Andrzej; Karbownik-Lewinska, Malgorzata; Kopchick, John J; Bartke, Andrzej

    2013-06-01

    Decreased somatotrophic signaling is among the most important mechanisms associated with extended longevity. Mice homozygous for the targeted disruption of the growth hormone (GH) receptor gene (GH receptor knockout; GHRKO) are obese and dwarf, are characterized by a reduced weight and body size, undetectable levels of GH receptor, high concentration of serum GH, and greatly reduced plasma levels of insulin and insulin-like growth factor-I, and are remarkably long lived. Recent results suggest new features of GHRKO mice that may positively affect longevity-decreased levels of proapoptotic factors and increased levels of key regulators of mitochondrial biogenesis. The alterations in levels of the proapoptotic factors and key regulators of mitochondrial biogenesis were not further improved by two other potential life-extending interventions-calorie restriction and visceral fat removal. This may attribute the primary role to GH resistance in the regulation of apoptosis and mitochondrial biogenesis in GHRKO mice in terms of increased life span. PMID:23197187

  13. A key time point for cell growth and magnetosome synthesis of Magnetospirillum gryphiswaldense based on real-time analysis of physiological factors

    PubMed Central

    Yang, Jing; Li, Shuqi; Huang, Xiuliang; Tang, Tao; Jiang, Weizhong; Zhang, Tongwei; Li, Ying

    2013-01-01

    Pure culture of magnetotactic bacteria with high magnetosome yield has been achieved for only a few strains. The major obstacles involve the nutritional requirements and culture conditions of the cells. To increase cell density and magnetosome production, it is necessary to elucidate the physiological characteristics of a particular strain during cell growth and develop an appropriate artificial control strategy. Large-scale culture of Magnetospirillum gryphiswaldense strain MSR-1 was successfully performed for 48 h in a 42-L autofermentor, and several key physiological parameters were measured in real time. Maximal values of cell density (OD565) (19.4) and cell yield (dry weight) (4.76 g/L) were attained at 40 h. The key time point for cell growth and magnetosome formation was found to be 18–20 h. At this point, cells entered the log phase of growth, the maximal values of Cmag (1.78), iron content (0.47%), and magnetosome number (26 ± 3 per cell) were observed, superoxide dismutase (SOD) activity began to decrease more rapidly, ATP content dropped to an extremely low level (0.17 fmol), and reducing power (NADH/NAD+ ratio) began to increase very rapidly. Excessive levels of dissolved oxygen (≥20 ppb) and lactic acid in the medium caused notable cytotoxic effects after 20 h. Artificial control measures for fermentation must be based on realistic cell physiological conditions. At the key time point (18–20 h), cell density is high and magnetosomes have matured. The process of magnetosome synthesis involves a high consumption of ATP and reducing power, and the cells require replenishment of nutrients prior to the 18–20 h time point. Culture conditions that effectively minimize dissolved oxygen accumulation, lactic acid content, and reducing power at this point will enhance magnetosome yield without obvious inhibition of cell growth. PMID:23898327

  14. Arginase 1 Regulation of Nitric Oxide Production Is Key to Survival of Trophic Factor-Deprived Motor Neurons

    PubMed Central

    Estévez, Alvaro G.; Sahawneh, Mary Anne; Lange, Philipp S.; Bae, Narae; Egea, Mariela; Ratan, Rajiv R.

    2008-01-01

    When deprived of trophic factors, the majority of cultured motor neurons undergo nitric oxide-dependent apoptosis. However, for reasons that have remained unclear, 30–50% of the motor neurons survive for several days without trophic factors. Here we hypothesize that the resistance of this motor neuron subpopulation to trophic factor deprivation can be attributed to diminished nitric oxide production resulting from the activity of the arginine-degrading enzyme arginase. When incubated with nor-NG-hydroxy-nor-l-arginine (NOHA), the normally resistant trophic factor-deprived motor neurons showed a drop in survival rates, whereas trophic factor-treated neurons did not. NOHA-induced motor neuron death was inhibited by blocking nitric oxide synthesis and the scavenging of superoxide and peroxynitrite, suggesting that peroxynitrite mediates NOHA toxicity. When we transfected arginase 1 into motor neurons to see whether it alone could abrogate trophic factor deprivation-induced death, we found that its forced expression did indeed do so. The protection afforded by arginase 1 expression is reversed when cells are incubated with NOHA or with low concentrations of nitric oxide. These results reveal that arginase acts as a central regulator of trophic factor-deprived motor neuron survival by suppressing nitric oxide production and the consequent peroxynitrite toxicity. They also suggest that the resistance of motor neuron subpopulations to trophic factor deprivation may result from increased arginase activity. PMID:16914676

  15. Transdiagnostic factors across fibromyalgia and mental disorders: sleep disturbances may play a key role. A clinical review.

    PubMed

    Palagini, Laura; Carmassi, Claudia; Conversano, Ciro; Gesi, Camilla; Bazzichi, Laura; Giacomelli, Camillo; Dell'Osso, Liliana

    2016-01-01

    Sleep disturbances, affective disorders, pain and fatigue are often present in individuals affected by fibromyalgia (FM). The pathophysiology of FM is not yet well understood and, to date, no treatment has been proven to be fully effective in alleviating all symptoms. Adopting a transdiagnostic perspective could thus be useful for clinicians: treatment would target a transdiagnostic process across a range of disturbances, not just a single disorder. The aim of this review is to revise the available literature about the potential role of sleep disturbances as a transdiagnostic process in FM symptomatology and mood or anxiety disorders comorbidity. We are proposing a model under which sleep disturbances can play a central role. Because conditions of sleep loss are related to the activation of the stress system, including the activation of the inflammation system, we propose this mechanism as a key one: it can be shared by mental, sleep disturbances and pain in FM and it may explain, in part, the high levels of comorbidity between them. In this frame-work sleep disturbances may play a key role and be the target of therapeutic strategies across FM symptomatology and mental disorders. PMID:27157399

  16. Hyaluronic acid regulates a key redox control factor Nrf2 via phosphorylation of Akt in bovine articular chondrocytes

    PubMed Central

    Onodera, Yuta; Teramura, Takeshi; Takehara, Toshiyuki; Fukuda, Kanji

    2015-01-01

    One important pharmacological function of hyaluronic acid (HA) in chondrocytes is reduction of cellular superoxide generation and accumulation. Here we demonstrated a relationship between HA supplementation and accumulation of Nuclear factor-erythroid-2-related factor 2 (Nrf2), which is a master transcription factor in cellular redox reactions, in cultured chondrocytes derived from bovine joint cartilage. In HA-treated chondrocytes, expression of Nrf2 and its downstream genes was upregulated. In HA-treated chondrocytes, Akt was phosphorylated, and inhibition of Akt activity or suppression of HA receptors CD44 and/or RHAMM with siRNAs prevented HA-mediated Nrf2 accumulation. Furthermore, Nrf2 siRNA inhibited the HA effect on antioxidant enzymes. These results show that HA might contribute to ROS reduction through Nrf2 regulation by activating Akt. Our study suggests a new mechanism for extracellular matrix (ECM)-mediated redox systems in chondrocytes. PMID:26106522

  17. The Four Key Factors for Commercializing Research: The Case of a Young University in a Region in Crisis.

    ERIC Educational Resources Information Center

    Laperche, Blandine

    2002-01-01

    Investigated factors in the successful commercialization of public research from higher education and then applied the ideas gleaned from a review of several case studies to the case of a young French university. Findings show the importance of close interaction between academic research and a wealthy local economy, lacking in the case of the…

  18. Factors Impacting Student Service Utilization at Ontario Colleges: Key Performance Indicators as a Measure of Success: A Niagara College View

    ERIC Educational Resources Information Center

    Veres, David

    2015-01-01

    Student success in Ontario College is significantly influenced by the utilization of student services. At Niagara College there has been a significant investment in student services as a strategy to support student success. Utilizing existing KPI data, this quantitative research project is aimed at measuring factors that influence both the use of…

  19. Life cycle assessment of lignocellulosic ethanol: a review of key factors and methods affecting calculated GHG emissions and energy use.

    PubMed

    Gerbrandt, Kelsey; Chu, Pei Lin; Simmonds, Allison; Mullins, Kimberley A; MacLean, Heather L; Griffin, W Michael; Saville, Bradley A

    2016-04-01

    Lignocellulosic ethanol has potential for lower life cycle greenhouse gas emissions compared to gasoline and conventional grain-based ethanol. Ethanol production 'pathways' need to meet economic and environmental goals. Numerous life cycle assessments of lignocellulosic ethanol have been published over the last 15 years, but gaps remain in understanding life cycle performance due to insufficient data, and model and methodological issues. We highlight key aspects of these issues, drawing on literature and a case study of corn stover ethanol. Challenges include the complexity of feedstock/ecosystems and market-mediated aspects and the short history of commercial lignocellulosic ethanol facilities, which collectively have led to uncertainty in GHG emissions estimates, and to debates on LCA methods and the role of uncertainty in decision making. PMID:26807514

  20. Aging is a primary risk factor for cardiac arrhythmias: disruption of intracellular Ca2+ regulation as a key suspect.

    PubMed

    Hatch, Fiona; Lancaster, Matthew K; Jones, Sandra A

    2011-08-01

    Aging is an inevitable time-dependent progression associated with a functional decline of the cardiovascular system even in 'healthy' individuals. Age positively correlates with an increasing risk of cardiac problems including arrhythmias. Not only the prevalence but also the severity of arrhythmias escalates with age. The reasons for this are multifactorial but dysregulation of intracellular calcium within the heart is likely to play a key role in initiating and perpetuating these life-threatening events. We now know that several aspects of cardiac calcium regulation significantly change with advancing age - changes that could produce electrical instability. Further development of knowledge of the mechanisms underlying these changes will allow us to reduce what currently is an inevitable increase in the incidence of arrhythmias in the elderly. PMID:21878050

  1. Elucidating the mysteries of wetting.

    SciTech Connect

    Webb, Edmund Blackburn, III; Bourdon, Christopher Jay; Grillet, Anne Mary; Sackinger, Philip A.; Grest, Gary Stephen; Emerson, John Allen; Ash, Benjamin Jesse; Heine, David R.; Brooks, Carlton, F.; Gorby, Allen D.

    2005-11-01

    Nearly every manufacturing and many technologies central to Sandia's business involve physical processes controlled by interfacial wetting. Interfacial forces, e.g. conjoining/disjoining pressure, electrostatics, and capillary condensation, are ubiquitous and can surpass and even dominate bulk inertial or viscous effects on a continuum level. Moreover, the statics and dynamics of three-phase contact lines exhibit a wide range of complex behavior, such as contact angle hysteresis due to surface roughness, surface reaction, or compositional heterogeneities. These thermodynamically and kinetically driven interactions are essential to the development of new materials and processes. A detailed understanding was developed for the factors controlling wettability in multicomponent systems from computational modeling tools, and experimental diagnostics for systems, and processes dominated by interfacial effects. Wettability probed by dynamic advancing and receding contact angle measurements, ellipsometry, and direct determination of the capillary and disjoining forces. Molecular scale experiments determined the relationships between the fundamental interactions between molecular species and with the substrate. Atomistic simulations studied the equilibrium concentration profiles near the solid and vapor interfaces and tested the basic assumptions used in the continuum approaches. These simulations provide guidance in developing constitutive equations, which more accurately take into account the effects of surface induced phase separation and concentration gradients near the three-phase contact line. The development of these accurate models for dynamic multicomponent wetting allows improvement in science based engineering of manufacturing processes previously developed through costly trial and error by varying material formulation and geometry modification.

  2. Where to Forage in the Absence of Sea Ice? Bathymetry As a Key Factor for an Arctic Seabird.

    PubMed

    Amélineau, Françoise; Grémillet, David; Bonnet, Delphine; Le Bot, Tangi; Fort, Jérôme

    2016-01-01

    The earth is warming at an alarming rate, especially in the Arctic, where a marked decline in sea ice cover may have far-ranging consequences for endemic species. Little auks, endemic Arctic seabirds, are key bioindicators as they forage in the marginal ice zone and feed preferentially on lipid-rich Arctic copepods and ice-associated amphipods sensitive to the consequences of global warming. We tested how little auks cope with an ice-free foraging environment during the breeding season. To this end, we took advantage of natural variation in sea ice concentration along the east coast of Greenland. We compared foraging and diving behaviour, chick diet and growth and adult body condition between two years, in the presence versus nearby absence of sea ice in the vicinity of their breeding site. Moreover, we sampled zooplankton at sea when sea ice was absent to evaluate prey location and little auk dietary preferences. Little auks foraged in the same areas both years, irrespective of sea ice presence/concentration, and targeted the shelf break and the continental shelf. We confirmed that breeding little auks showed a clear preference for larger copepod species to feed their chick, but caught smaller copepods and nearly no ice-associated amphipod when sea ice was absent. Nevertheless, these dietary changes had no impact on chick growth and adult body condition. Our findings demonstrate the importance of bathymetry for profitable little auk foraging, whatever the sea-ice conditions. Our investigations, along with recent studies, also confirm more flexibility than previously predicted for this key species in a warming Arctic. PMID:27438790

  3. Where to Forage in the Absence of Sea Ice? Bathymetry As a Key Factor for an Arctic Seabird

    PubMed Central

    Amélineau, Françoise; Grémillet, David; Bonnet, Delphine; Le Bot, Tangi; Fort, Jérôme

    2016-01-01

    The earth is warming at an alarming rate, especially in the Arctic, where a marked decline in sea ice cover may have far-ranging consequences for endemic species. Little auks, endemic Arctic seabirds, are key bioindicators as they forage in the marginal ice zone and feed preferentially on lipid-rich Arctic copepods and ice-associated amphipods sensitive to the consequences of global warming. We tested how little auks cope with an ice-free foraging environment during the breeding season. To this end, we took advantage of natural variation in sea ice concentration along the east coast of Greenland. We compared foraging and diving behaviour, chick diet and growth and adult body condition between two years, in the presence versus nearby absence of sea ice in the vicinity of their breeding site. Moreover, we sampled zooplankton at sea when sea ice was absent to evaluate prey location and little auk dietary preferences. Little auks foraged in the same areas both years, irrespective of sea ice presence/concentration, and targeted the shelf break and the continental shelf. We confirmed that breeding little auks showed a clear preference for larger copepod species to feed their chick, but caught smaller copepods and nearly no ice-associated amphipod when sea ice was absent. Nevertheless, these dietary changes had no impact on chick growth and adult body condition. Our findings demonstrate the importance of bathymetry for profitable little auk foraging, whatever the sea-ice conditions. Our investigations, along with recent studies, also confirm more flexibility than previously predicted for this key species in a warming Arctic. PMID:27438790

  4. Individual and Population Level Impact of Key HIV Risk Factors on HIV Incidence Rates in Durban, South Africa

    PubMed Central

    Ramjee, Gita; Moonsamy, Suri; Abbai, Nathlee Samantha; Wand, Handan

    2016-01-01

    We aimed to estimate the individual and joint impact of age, marital status and diagnosis with sexually transmitted infections (STIs) on HIV acquisition among young women at a population level in Durban, KwaZulu-Natal, South Africa. A total of 3,978 HIV seronegative women were recruited for four biomedical intervention trials from 2002–2009. Point and interval estimates of partial population attributable risk (PAR) were used to quantify the proportion of HIV seroconversions which can be prevented if a combination of risk factors is eliminated from a target population. More than 70% of the observed HIV acquisitions were collectively attributed to the three risk factors: younger age (<25 years old), unmarried and not cohabiting with a stable/regular partner and diagnosis with STIs. Addressing these risks requires targeted structural, behavioural, biomedical and cultural interventions in order to impact on unacceptably high HIV incidence rates among young women and the population as a whole. PMID:27104835

  5. The Postgraduate Hospital Educational Environment Measure (PHEEM) Questionnaire Identifies Quality of Instruction as a Key Factor Predicting Academic Achievement

    PubMed Central

    Vieira, Joaquim Edson

    2008-01-01

    OBJECTIVE This study analyzes the reliability of the PHEEM questionnaire translated into Portuguese. We present the results of PHEEM following distribution to doctors in three different medical residency programs at a university hospital in Brazil. INTRODUCTION Efforts to understand environmental factors that foster effective learning resulted in the development of a questionnaire to measure medical residents’ perceptions of the level of autonomy, teaching quality and social support in their programs. METHODS The questionnaire was translated using the modified Brislin back-translation technique. Cronbach’s alpha test was used to ensure good reliability and ANOVA was used to compare PHEEM results among residents from the Surgery, Anesthesiology and Internal Medicine departments. The Kappa coefficient was used as a measure of agreement, and factor analysis was employed to evaluate the construct strength of the three domains suggested by the original PHEEM questionnaire. RESULTS The PHEEM survey was completed by 306 medical residents and the resulting Cronbach’s alpha was 0.899. The weighted Kappa was showed excellent reliability. Autonomy was rated most highly by Internal Medicine residents (63.7% ± 13.6%). Teaching was rated highest in Anesthesiology (66.7% ± 15.4%). Residents across the three areas had similar perceptions of social support (59.0% ± 13.3% for Surgery; 60.5% ± 13.6% for Internal Medicine; 61.4% ± 14.4% for Anesthesiology). Factor analysis suggested that nine factors explained 58.9% of the variance. CONCLUSIONS This study indicates that PHEEM is a reliable instrument for measuring the quality of medical residency programs at a Brazilian teaching hospital. The results suggest that quality of teaching was the best indicator of overall response to the questionnaire. PMID:19060994

  6. Key Factors Controlling the Growth of Biological Soil Crusts: Towards a Protocol to Produce Biocrusts in Greenhouse Facilities

    NASA Astrophysics Data System (ADS)

    Velasco Ayuso, Sergio; María Giraldo Silva, Ana; Nelson, Corey; Barger, Nichole; Antoninka, Anita; Bowker, Matthew; Garcia-Pichel, Ferran

    2016-04-01

    Biological soil crusts (= biocrusts) are topsoil communities comprise of, but not limited to, cyanobacteria, algae, lichens, and mosses that grow intimately associated with soil particles in drylands. Biocrusts have central ecological roles in these areas as sources of carbon and nutrients, and efficiently retain water and prevent soil erosion, which improves soil structure and promotes soil fertility. However, human activities, such as cattle grazing, hiking or military training, are rapidly striking biocrusts. Although it is well known that the inoculation with cyanobacteria or lichens can enhance the recovery of biocrusts in degraded soils, little is known about the factors that control their growth rates. Using soil and inocula from four different sites located in one cold desert (Utah) and in one hot desert (New Mexico), we performed a fractional factorial experiment involving seven factors (water, light, P, N, calcium carbonate, trace metals and type of inoculum) to screen their effects on the growth of biocrusts. After four months, we measured the concentration of chlorophyll a, and we discovered that water, light and P, N or P+N were the most important factors controlling the growth of biocrusts. In the experimental treatments involving these three factors we measured a similar concentration of chlorophyll a (or even higher) to this found in the field locations. Amplification of the 16S rRNA gene segment using universal bacteria primers revealed a microbial community composition in the biocrusts grown that closely corresponds to initial measurements made on inocula. In summary, based on our success in obtaining biocrust biomass from natural communities in greenhouse facilities, without significantly changing its community composition at the phylum and cyanobacterial level, we are paving the road to propose a protocol to produce a high quality-nursed inoculum aiming to assist restoration of arid and semi-arid ecosystems affected by large-scale disturbances.

  7. Statistical key factors optimization of conditions for hydrogen production from S-TE (solubilization by thermophilic enzyme) waste sludge.

    PubMed

    Guo, Liang; Zhao, Jun; She, Zonglian; Lu, Mingmin; Zong, Yan

    2013-06-01

    Waste sludge can be solubilized after S-TE (solubilization by thermophilic enzyme) pretreatment as the cryptic growth occurs at the expense of the cell lysate. The hydrogen production from S-TE sludge is greatly influenced by many factors. In this study, factors including pH, C/N, C/P, and Fe(2+) affecting hydrogen production from S-TE sludge were optimized using uniform design. The optimum condition for maximum hydrogen yield of 68.4 ml H2/g VSS (volatile suspended solid) could be predicted from regression model, and the optimum conditions were pH of 6.4, C/N ratio of 38, C/P ratio of 265, and Fe(2+) concentration of 85 mg/L. There was interaction effect of factors on hydrogen production from S-TE sludge. Different pH, C/N, C/P and Fe(2+) conditions could influence the VSS removal rate, carbohydrate and protein utilization. When the highest compositions of acetate and ethanol and lowest propionate were observed in metabolites, effective hydrogen production was also achieved. PMID:23584408

  8. STAT5 is a key transcription factor for IL-3-mediated inhibition of RANKL-induced osteoclastogenesis

    PubMed Central

    Lee, Jongwon; Seong, Semun; Kim, Jung Ha; Kim, Kabsun; Kim, Inyoung; Jeong, Byung-chul; Nam, Kwang-Il; Kim, Kyung Keun; Hennighausen, Lothar; Kim, Nacksung

    2016-01-01

    Among the diverse cytokines involved in osteoclast differentiation, interleukin (IL)-3 inhibits RANKL-induced osteoclastogenesis. However, the mechanism underlying IL-3-mediated inhibition of osteoclast differentiation is not fully understood. Here we demonstrate that the activation of signal transducers and activators of transcription 5 (STAT5) by IL-3 inhibits RANKL-induced osteoclastogenesis through the induction of the expression of Id genes. We found that STAT5 overexpression inhibited RANKL-induced osteoclastogenesis. However, RANKL did not regulate the expression or activation of STAT5 during osteoclast differentiation. STAT5 deficiency prevented IL-3-mediated inhibition of osteoclastogenesis, suggesting a key role of STAT5 in IL-3-mediated inhibition of osteoclast differentiation. In addition, IL-3-induced STAT5 activation upregulated the expression of Id1 and Id2, which are negative regulators of osteoclastogenesis. Overexpression of ID1 or ID2 in STAT5-deficient cells reversed osteoclast development recovered from IL-3-mediated inhibition. Importantly, microcomputed tomography and histomorphometric analysis revealed that STAT5 conditional knockout mice showed reduced bone mass, with an increased number of osteoclasts. Furthermore, IL-3 inhibited RANKL-induced osteoclast differentiation less effectively in the STAT5 conditional knockout mice than in the wild-type mice after RANKL injection. Taken together, our findings indicate that STAT5 contributes to the remarkable IL-3-mediated inhibition of RANKL-induced osteoclastogenesis by activating Id genes and their associated pathways. PMID:27485735

  9. Selenium deficiency and thyroid fibrosis. A key role for macrophages and transforming growth factor beta (TGF-beta).

    PubMed

    Contempre, B; Le Moine, O; Dumont, J E; Denef, J F; Many, M C

    1996-11-29

    Free radical damage and fibrosis caused by selenium deficiency are thought to be involved in the pathogenesis of myxoedematous cretinism. So far, no pathway explains the link between selenium deficiency and tissue fibrosis. Pharmacological doses of iodine induce necrosis in iodine-deficient thyroids. Necrosis is much increased if the glands are also selenium-deficient, which then evolve to fibrosis. This rat model was reproduced to explore the role of selenium deficiency in defective tissue repair. At first, proliferation indexes of epithelial cells and fibroblasts were comparable between selenium-deficient and control groups. Then, in selenium-deficient thyroids the inflammatory reaction was more marked being mainly composed of macrophages. The proliferation index of the epithelial cells decreased, while that of the fibroblasts increased. These thyroids evolved to fibrosis. TGF-beta immunostaining was prominent in the macrophages of selenium-deficient rats. Anti TGF-beta antibodies restored the proliferation indexes, and blocked the evolution to fibrosis. In selenium deficiency, an active fibrotic process occurs in the thyroid, in which the inflammatory reaction and an excess of TGF-beta play a key role. PMID:9027319

  10. STAT5 is a key transcription factor for IL-3-mediated inhibition of RANKL-induced osteoclastogenesis.

    PubMed

    Lee, Jongwon; Seong, Semun; Kim, Jung Ha; Kim, Kabsun; Kim, Inyoung; Jeong, Byung-Chul; Nam, Kwang-Il; Kim, Kyung Keun; Hennighausen, Lothar; Kim, Nacksung

    2016-01-01

    Among the diverse cytokines involved in osteoclast differentiation, interleukin (IL)-3 inhibits RANKL-induced osteoclastogenesis. However, the mechanism underlying IL-3-mediated inhibition of osteoclast differentiation is not fully understood. Here we demonstrate that the activation of signal transducers and activators of transcription 5 (STAT5) by IL-3 inhibits RANKL-induced osteoclastogenesis through the induction of the expression of Id genes. We found that STAT5 overexpression inhibited RANKL-induced osteoclastogenesis. However, RANKL did not regulate the expression or activation of STAT5 during osteoclast differentiation. STAT5 deficiency prevented IL-3-mediated inhibition of osteoclastogenesis, suggesting a key role of STAT5 in IL-3-mediated inhibition of osteoclast differentiation. In addition, IL-3-induced STAT5 activation upregulated the expression of Id1 and Id2, which are negative regulators of osteoclastogenesis. Overexpression of ID1 or ID2 in STAT5-deficient cells reversed osteoclast development recovered from IL-3-mediated inhibition. Importantly, microcomputed tomography and histomorphometric analysis revealed that STAT5 conditional knockout mice showed reduced bone mass, with an increased number of osteoclasts. Furthermore, IL-3 inhibited RANKL-induced osteoclast differentiation less effectively in the STAT5 conditional knockout mice than in the wild-type mice after RANKL injection. Taken together, our findings indicate that STAT5 contributes to the remarkable IL-3-mediated inhibition of RANKL-induced osteoclastogenesis by activating Id genes and their associated pathways. PMID:27485735

  11. Key Factors Affecting Reproductive Success of Thoroughbred Mares and Stallions on a Commercial Stud Farm.

    PubMed

    Lane, E A; Bijnen, Mlj; Osborne, M; More, S J; Henderson, Isf; Duffy, P; Crowe, M A

    2016-04-01

    To evaluate factors contributing to fertility of thoroughbred mares, data from 3743 oestrous periods of 2385 mares were collected on a large thoroughbred farm in Ireland. Fourteen stallions (mean age 8.3 years; range 4-15 years) had bred 2385 mares (mean age 9.4 years; range 3-24 years). Maiden mares accounted for 12%, mares with a foal at foot for 64%, and barren, slipped or rested mares for 24% of the total. The mean pregnancy rate per cycle was 67.8% (68.6% in year 1 and 66.9% in year 2). Backward stepwise multivariable logistic regression analysis was utilized to develop two models to evaluate mare factors, including mare age, reproductive status, month of foaling, dystocia, month of cover, foal heat, cycle number, treatments, walk-in status and stallion factors including stallion identity, stallion age, shuttle status, time elapsed between covers and high stallion usage on the per cycle pregnancy rate and pregnancy loss. Old age (p < 0.001) and cover within 20 days post-partum (p < 0.003) were associated with lowered pregnancy rates. High mare age (p < 0.05) and barren, slipped or rested reproductive status (p = 0.05) increased the likelihood of pregnancy loss. Uterine inflammation or infection, if appropriately treated, did not affect fertility. Only high usage of stallions (used more than 21 times in previous week) was associated with lowered (p = 0.009) pregnancy rates. However, shuttle stallions were more likely to have increased (p = 0.035) pregnancy survival, perhaps reflecting a bias in stallion selection. In conclusion, mare age exerted the greatest influence on fertility; nonetheless, thoroughbreds can be effectively managed to achieve high reproductive performance in a commercial setting. PMID:26815482

  12. Early growth response transcription factors: key mediators of fibrosis and novel targets for anti-fibrotic therapy

    PubMed Central

    Bhattacharyya, Swati; Wu, Minghua; Fang, Feng; Tourtellotte, Warren; Feghali-Bostwick, Carol; Varga, John

    2011-01-01

    Fibrosis is a deregulated and ultimately defective form of tissue repair that underlies a large number of chronic human diseases, as well as obesity and aging. The pathogenesis of fibrosis involves multiple cell types and extracellular signals, of which transforming growth factor- β (TGF-β) is pre-eminent. The prevalence of fibrosis is rising worldwide, and to date no agents has shown clinical efficacy in the attenuating or reversing the process. Recent studies implicate the immediate-early response transcription factor Egr-1 in the pathogenesis of fibrosis. Egr-1 couples acute changes in the cellular environment to sustained alterations in gene expression, and mediates a broad spectrum of biological responses to injury and stress. In contrast to other ligand-activated transcription factors such as NF-κB, c-jun and Smad2/3 that undergo post-translational modification such as phosphorylation and nuclear translocation, Egr-1 activity is regulated via its biosynthesis. Aberrant Egr-1 expression or activity is implicated in cancer, inflammation, atherosclerosis, and ischemic injury and recent studies now indicate an important role for Egr-1 in TGF-β-dependent profibrotic responses. Fibrosis in various animal models and human diseases such as scleroderma (SSc) and idiopathic pulmonary fibrosis (IPF) is accompanied by aberrant Egr-1 expression. Moreover Egr-1 appears to be required for physiologic and pathological connective tissue remodeling, and Egr-1-null mice are protected from fibrosis. As a novel profibrotic mediator, Egr-1 thus appears to be a promising potential target for the development of anti-fibrotic therapies. PMID:21511034

  13. Identification of the Key Weather Factors Affecting Overwintering Success of Apolygus lucorum Eggs in Dead Host Tree Branches

    PubMed Central

    Pan, Hongsheng; Liu, Bing; Lu, Yanhui; Desneux, Nicolas

    2014-01-01

    Understanding the effects of weather on insect population dynamics is crucial to simulate and forecast pest outbreaks, which is becoming increasingly important with the effects of climate change. The mirid bug Apolygus lucorum is an important pest on cotton, fruit trees and other crops in China, and primarily lays its eggs on dead parts of tree branches in the fall for subsequent overwintering. As such, the eggs that hatch the following spring are most strongly affected by ambient weather factors, rather than by host plant biology. In this study, we investigated the effects of three major weather factors: temperature, relative humidity and rainfall, on the hatching rate of A. lucorum eggs overwintering on dead branches of Chinese date tree (Ziziphus jujuba). Under laboratory conditions, rainfall (simulated via soaking) was necessary for the hatching of overwintering A. lucorum eggs. In the absence of rainfall (unsoaked branches), very few nymphs successfully emerged under any of the tested combinations of temperature and relative humidity. In contrast, following simulated rainfall, the hatching rate of the overwintering eggs increased dramatically. Hatching rate and developmental rate were positively correlated with relative humidity and temperature, respectively. Under field conditions, the abundance of nymphs derived from overwintering eggs was positively correlated with rainfall amount during the spring seasons of 2009–2013, while the same was not true for temperature and relative humidity. Overall, our findings indicate that rainfall is the most important factor affecting the hatching rate of overwintering A. lucorum eggs on dead plant parts and nymph population levels during the spring season. It provides the basic information for precisely forecasting the emergence of A. lucorum and subsequently timely managing its population in spring, which will make it possible to regional control of this insect pest widely occurring in multiple crops in summer. PMID

  14. IGF-I: A Key Growth Factor that Regulates Neurogenesis and Synaptogenesis from Embryonic to Adult Stages of the Brain

    PubMed Central

    Nieto-Estévez, Vanesa; Defterali, Çağla; Vicario-Abejón, Carlos

    2016-01-01

    The generation of neurons in the adult mammalian brain requires the activation of quiescent neural stem cells (NSCs). This activation and the sequential steps of neuron formation from NSCs are regulated by a number of stimuli, which include growth factors. Insulin-like growth factor-I (IGF-I) exert pleiotropic effects, regulating multiple cellular processes depending on their concentration, cell type, and the developmental stage of the animal. Although IGF-I expression is relatively high in the embryonic brain its levels drop sharply in the adult brain except in neurogenic regions, i.e., the hippocampus (HP) and the subventricular zone-olfactory bulb (SVZ-OB). By contrast, the expression of IGF-IR remains relatively high in the brain irrespective of the age of the animal. Evidence indicates that IGF-I influences NSC proliferation and differentiation into neurons and glia as well as neuronal maturation including synapse formation. Furthermore, recent studies have shown that IGF-I not only promote adult neurogenesis by regulating NSC number and differentiation but also by influencing neuronal positioning and migration as described during SVZ-OB neurogenesis. In this article we will revise and discuss the actions reported for IGF-I signaling in a variety of in vitro and in vivo models, focusing on the maintenance and proliferation of NSCs/progenitors, neurogenesis, and neuron integration in synaptic circuits. PMID:26941597

  15. IGF-I: A Key Growth Factor that Regulates Neurogenesis and Synaptogenesis from Embryonic to Adult Stages of the Brain.

    PubMed

    Nieto-Estévez, Vanesa; Defterali, Çağla; Vicario-Abejón, Carlos

    2016-01-01

    The generation of neurons in the adult mammalian brain requires the activation of quiescent neural stem cells (NSCs). This activation and the sequential steps of neuron formation from NSCs are regulated by a number of stimuli, which include growth factors. Insulin-like growth factor-I (IGF-I) exert pleiotropic effects, regulating multiple cellular processes depending on their concentration, cell type, and the developmental stage of the animal. Although IGF-I expression is relatively high in the embryonic brain its levels drop sharply in the adult brain except in neurogenic regions, i.e., the hippocampus (HP) and the subventricular zone-olfactory bulb (SVZ-OB). By contrast, the expression of IGF-IR remains relatively high in the brain irrespective of the age of the animal. Evidence indicates that IGF-I influences NSC proliferation and differentiation into neurons and glia as well as neuronal maturation including synapse formation. Furthermore, recent studies have shown that IGF-I not only promote adult neurogenesis by regulating NSC number and differentiation but also by influencing neuronal positioning and migration as described during SVZ-OB neurogenesis. In this article we will revise and discuss the actions reported for IGF-I signaling in a variety of in vitro and in vivo models, focusing on the maintenance and proliferation of NSCs/progenitors, neurogenesis, and neuron integration in synaptic circuits. PMID:26941597

  16. HnRNPL as a key factor in spermatogenesis: Lesson from functional proteomic studies of azoospermia patients with sertoli cell only syndrome.

    PubMed

    Li, Jingping; Guo, Wenbin; Li, Fei; He, Jincan; Yu, Qingfeng; Wu, Xiaoqiang; Li, Jianming; Mao, Xiangming

    2012-06-01

    Sertoli cell only syndrome (SCOS) is one of the main causes leading to the abnormal spermatogenesis. However, the mechanisms for abnormal spermatogenesis in SCOS are still unclear. Here, we analyzed the clinical testis samples of SCOS patients by two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF/TOF MS) to find the key factors contributing to SCOS. Thirteen differential proteins were identified in clinical testis samples between normal spermatogenesis group and SCOS group. Interestingly, in these differential proteins, Heterogeneous nuclear ribonucleoprotein L(HnRNPL) was suggested as a key regulator involved in apoptosis, death and growth of spermatogenic cells by String and Pubgene bioinformatic programs. Down-regulated HnRNPL in testis samples of SCOS patients was further confirmed by immunohistochemical staining and western blotting. Moreover, in vitro and in vivo experiments demonstrated that knockdown of HnRNPL led to inhibited proliferation, increased apoptosis of spermatogenic cell but decreased apoptosis of sertoli cells. Expression of carcinoembryonic antigen-related cell adhesion molecule 1 in GC-1 cells or expression of inducible nitric oxide synthases in TM4 sertoli cells, was found to be regulated by HnRNPL. Our study first shows HnRNPL as a key factor involved in the spermatogenesis by functional proteomic studies of azoospermia patients with sertoli cell only syndrome. This article is part of a Special Issue entitled: Proteomics: The clinical link. PMID:22245417

  17. Widespread pain and depression are key modifiable risk factors associated with reduced social participation in older adults

    PubMed Central

    Wilkie, Ross; Blagojevic-Bucknall, Milisa; Belcher, John; Chew-Graham, Carolyn; Lacey, Rosie J.; McBeth, John

    2016-01-01

    Abstract In older adults, reduced social participation increases the risk of poor health-related quality of life, increased levels of inflammatory markers and cardiovascular disease, and increased mortality. Older adults frequently present to primary care, which offers the potential to deliver interventions at the point of care to increase social participation. The aim of this prospective study was to identify the key modifiable exposures that were associated with reduced social participation in a primary care population of older adults. The study was a population-based prospective cohort study. Participants (n = 1991) were those aged ≥65 years who had completed questionnaires at baseline, and 3 and 6-year follow-ups. Generalized linear mixed modeling framework was used to test for associations between exposures and decreasing social participation over 6 years. At baseline, 44% of participants reported reduced social participation, increasing to 49% and 55% at 3 and 6-year follow-up. Widespread pain and depression had the strongest independent association with reduced social participation over the 6-year follow-up period. The prevalence of reduced social participation for those with widespread pain was 106% (adjusted incidence rate ratio 2.06, 95% confidence interval 1.72, 2.46), higher than for those with no pain. Those with depression had an increased prevalence of 82% (adjusted incidence rate ratio 1.82, 95% confidence interval 1.62, 2.06). These associations persisted in multivariate analysis. Population ageing will be accompanied by increasing numbers of older adults with pain and depression. Future trials should assess whether screening for widespread pain and depression, and targeting appropriate treatment in primary care, increase social participation in older people. PMID:27495019

  18. The bHLH transcription factor SPATULA is a key regulator of organ size in Arabidopsis thaliana

    PubMed Central

    Makkena, Srilakshmi; Lamb, Rebecca S.

    2013-01-01

    Plant organ size and thus plant size is determined by both cell proliferation and cell expansion. The bHLH transcription factor SPATULA (SPT) was originally identified as a regulator of carpel patterning. It has subsequently been found to control growth of the organs of the shoot. It does this at least in part by controlling the size of meristematic regions of organs in parallel to gibberellic acid (GA). It also acts downstream of several environmental signals, influencing growth in response to light and temperature. We have recently demonstrated that SPT functions to repress the size of the root meristem and thus root growth and size. It appears to do this using a similar mechanism to its control of leaf size. Based on the recent work on SPT, we propose that it is a growth repressor that acts to limit the size of meristems in response to environmental signals, perhaps by regulating auxin transport. PMID:23470719

  19. Structure and dynamics of the kinase IKK-β--A key regulator of the NF-kappa B transcription factor.

    PubMed

    Kalia, Munishikha; Kukol, Andreas

    2011-11-01

    The inhibitor κB kinase-β (IKK-β) phosphorylates the NF-κB inhibitor protein IκB leading to the translocation of the transcription factor NF-κB to the nucleus. The transcription factor NF-κB and consequently IKK-β are central to signal transduction pathways of mammalian cells. The purpose of this research was to develop a 3D structural model of the IKK-β kinase domain with its ATP cofactor and investigate its dynamics and ligand binding potential. Through a combination of comparative modelling and simulated heating/annealing molecular dynamics (SAMD) simulation in explicit water the model accuracy could be substantially improved compared to comparative modelling on its own as shown by model validation measures. The structure revealed the details of ATP/Mg(2+) binding indicating hydrophobic interactions with the adenine base and a significant contribution of Mg(2+) as a bridge between ATP phosphate groups and negatively charged side chains. The molecular dynamics trajectories of the ATP-bound and free enzyme showed two conformations in each case, which contributed to the majority of the trajectory. The ATP-free enzyme revealed a novel binding site distant from the ATP binding site that was not encountered in the ATP bound enzyme. Based on the overall structural flexibility, it is suggested that a truncated version of the kinase domain from Ala14 to Leu265 should be subjected to crystallisation trials. The 3D structure of this enzyme will enable rational design of new ligands and analysis of protein-protein interactions. Furthermore, our results may provide a new impetus for wet-lab based structural investigation focussing on a truncated kinase domain. PMID:21820058

  20. Secreted frizzled related protein 2 (Sfrp2) is the key Akt-mesenchymal stem cell-released paracrine factor mediating myocardial survival and repair

    PubMed Central

    Mirotsou, Maria; Zhang, Zhongyan; Deb, Arjun; Zhang, Lunan; Gnecchi, Massimiliano; Noiseux, Nicolas; Mu, Hui; Pachori, Alok; Dzau, Victor

    2007-01-01

    Stem cell therapy has emerged as a promising tool for the treatment of a variety of diseases. Previously, we have shown that Akt-modified mesenchymal stem cells mediate tissue repair through paracrine mechanisms. Using a comprehensive functional genomic strategy, we show that secreted frizzled related protein 2 (Sfrp2) is the key stem cell paracrine factor that mediates myocardial survival and repair after ischemic injury. Sfrp2 is known to modulate Wnt signaling, and we demonstrate that cardiomyocytes treated with secreted frizzled related protein increase cellular β-catenin and up-regulate expression of antiapoptotic genes. These findings reveal the key role played by Sfrp2 in mediating the paracrine effects of Akt-mesenchymal stem cells on tissue repair and identify modulation of Wnt signaling as a therapeutic target for heart disease. PMID:17251350

  1. Key Factors for a High-Quality Peritoneal Dialysis Program — The Role of the PD Team and Continuous Quality Improvement

    PubMed Central

    Fang, Wei; Ni, Zhaohui; Qian, Jiaqi

    2014-01-01

    The proportion of end-stage renal disease (ESRD) patients on peritoneal dialysis (PD) has increased very fast in China over the last decade. Renji Hospital, affiliated with Shanghai Jiaotong University School of Medicine, is a recognized high-quality PD unit with a high PD utilization rate, excellent patient and technique survival (1-year and 5-year patient survival rate of 93% and 71%, and 1-year and 5-year technique survival of 96% and 82%, respectively), low peritonitis rate and a well-documented good quality of life of the treated patients. We believe that a dedicated and experienced PD team, a structured patient training program, continuous patient support, establishing and utilizing standardized protocols, starting PD with low dialysis dose, monitoring key performance indicators (KPIs), and continuous quality improvement (CQI) are the key factors underlying this successful PD program. PMID:24962961

  2. Low cost, small form factor, and integration as the key features for the optical component industry takeoff

    NASA Astrophysics Data System (ADS)

    Schiattone, Francesco; Bonino, Stefano; Gobbi, Luigi; Groppi, Angelamaria; Marazzi, Marco; Musio, Maurizio

    2003-04-01

    In the past the optical component market has been mainly driven by performances. Today, as the number of competitors has drastically increased, the system integrators have a wide range of possible suppliers and solutions giving them the possibility to be more focused on cost and also on footprint reduction. So, if performances are still essential, low cost and Small Form Factor issues are becoming more and more crucial in selecting components. Another evolution in the market is the current request of the optical system companies to simplify the supply chain in order to reduce the assembling and testing steps at system level. This corresponds to a growing demand in providing subassemblies, modules or hybrid integrated components: that means also Integration will be an issue in which all the optical component companies will compete to gain market shares. As we can see looking several examples offered by electronic market, to combine low cost and SFF is a very challenging task but Integration can help in achieving both features. In this work we present how these issues could be approached giving examples of some advanced solutions applied to LiNbO3 modulators. In particular we describe the progress made on automation, new materials and low cost fabrication methods for the parts. We also introduce an approach in integrating optical and electrical functionality on LiNbO3 modulators including RF driver, bias control loop, attenuator and photodiode integrated in a single device.

  3. Transcriptome Analysis of Sexually Dimorphic Chinese White Wax Scale Insects Reveals Key Differences in Developmental Programs and Transcription Factor Expression

    PubMed Central

    Yang, Pu; Chen, Xiao-Ming; Liu, Wei-Wei; Feng, Ying; Sun, Tao

    2015-01-01

    The Chinese white wax scale insect, Ericerus pela, represents one of the most dramatic examples of sexual dimorphism in any insect species. In this study, we showed that although E. pela males display complete metamorphosis similar to holometabolous insects, the species forms the sister group to Acyrthosiphon pisum and cluster with hemimetabolous insects. The gene expression profile and Gene Ontology (GO) analyses revealed that the two sexes engaged in distinct developmental programs. In particular, female development appeared to prioritize the expression of genes related to cellular, metabolic, and developmental processes and to anatomical structure formation in nymphs. By contrast, male nymphal development is characterized by the significant down-regulation of genes involved in chitin, the respiratory system, and neurons. The wing and appendage morphogenesis, anatomical and tissue structure morphogenesis programs activated after male nymphal development. Transcription factors (that convey juvenile hormone or ecdysone signals, and Hox genes) and DNA methyltransferase were also differentially expressed between females and males. These results may indicate the roles that these differentially expressed genes play in regulating sexual dimorphism through orchestrating complex genetic programs. This differential expression was particularly prominent for processes linked to female development and wing development in males. PMID:25634031

  4. Transcriptome analysis of sexually dimorphic Chinese white wax scale insects reveals key differences in developmental programs and transcription factor expression.

    PubMed

    Yang, Pu; Chen, Xiao-Ming; Liu, Wei-Wei; Feng, Ying; Sun, Tao

    2015-01-01

    The Chinese white wax scale insect, Ericerus pela, represents one of the most dramatic examples of sexual dimorphism in any insect species. In this study, we showed that although E. pela males display complete metamorphosis similar to holometabolous insects, the species forms the sister group to Acyrthosiphon pisum and cluster with hemimetabolous insects. The gene expression profile and Gene Ontology (GO) analyses revealed that the two sexes engaged in distinct developmental programs. In particular, female development appeared to prioritize the expression of genes related to cellular, metabolic, and developmental processes and to anatomical structure formation in nymphs. By contrast, male nymphal development is characterized by the significant down-regulation of genes involved in chitin, the respiratory system, and neurons. The wing and appendage morphogenesis, anatomical and tissue structure morphogenesis programs activated after male nymphal development. Transcription factors (that convey juvenile hormone or ecdysone signals, and Hox genes) and DNA methyltransferase were also differentially expressed between females and males. These results may indicate the roles that these differentially expressed genes play in regulating sexual dimorphism through orchestrating complex genetic programs. This differential expression was particularly prominent for processes linked to female development and wing development in males. PMID:25634031

  5. Searching for a Role of Nursing Personnel in Developing Landscape of Ehealth: Factors Determining Attitudes toward Key Patient Empowering Applications

    PubMed Central

    Duplaga, Mariusz

    2016-01-01

    Introduction Nurses may play an important role in the delivery of medical services based on the use of ehealth tools. Nevertheless, their taking an active role in an ehealth environment depends on their possessing the appropriate skills and mindset. The main objective of this paper was to assess nurses’ opinions and to analyze the predictors of their acceptance of ehealth features relevant to patient empowerment with a strong focus on chronic care. Methods A survey was conducted among nurses from hospital centers of south-eastern Poland based on a questionnaire designed to assess their attitudes toward the ehealth domain. The predictors of the nurses’ acceptance of ehealth usage within specific contexts were assessed with uni- and multivariate logistic regression. Results An analysis was performed on data from 648 questionnaires retained after a quality check. The duration of Internet use was consistently related to higher acceptance of ehealth applications and more certainty regarding the reliability of health-related information available on the Internet. Nurses from urban medical centers were more skeptical about the use of specific ehealth solutions. Conclusion Previous experience in using information technologies is the main factor influencing the acceptance of specific ehealth solutions relevant for care provided to patients suffering from chronic conditions. PMID:27049525

  6. Glucocorticoid-Induced Tumour Necrosis Factor Receptor-Related Protein: A Key Marker of Functional Regulatory T Cells

    PubMed Central

    Ronchetti, Simona; Ricci, Erika; Petrillo, Maria Grazia; Cari, Luigi; Migliorati, Graziella; Nocentini, Giuseppe; Riccardi, Carlo

    2015-01-01

    Glucocorticoid-induced tumour necrosis factor receptor-related protein (GITR, TNFRSF18, and CD357) is expressed at high levels in activated T cells and regulatory T cells (Tregs). In this review, we present data from mouse and human studies suggesting that GITR is a crucial player in the differentiation of thymic Tregs (tTregs), and expansion of both tTregs and peripheral Tregs (pTregs). The role of GITR in Treg expansion is confirmed by the association of GITR expression with markers of memory T cells. In this context, it is not surprising that GITR appears to be a marker of active Tregs, as suggested by the association of GITR expression with other markers of Treg activation or cytokines with suppressive activity (e.g., IL-10 and TGF-β), the presence of GITR+ cells in tissues where Tregs are active (e.g., solid tumours), or functional studies on Tregs. Furthermore, some Treg subsets including Tr1 cells express either low or no classical Treg markers (e.g., FoxP3 and CD25) and do express GITR. Therefore, when evaluating changes in the number of Tregs in human diseases, GITR expression must be evaluated. Moreover, GITR should be considered as a marker for isolating Tregs. PMID:25961057

  7. Validation of revised DNDC model for methane emissions from irrigated rice fields in Thailand and sensitivity analysis of key factors

    NASA Astrophysics Data System (ADS)

    Smakgahn, Kruamas; Fumoto, Tamon; Yagi, Kazuyuki

    2009-06-01

    The original Denitrification-Decomposition (DNDC) model and a revised version were tested against data from field observations of methane (CH4) emissions from irrigated rice fields in Thailand. The revised DNDC model, which was modified for use in Japanese rice fields by revising the crop growth and soil biogeochemical submodels, yielded better simulation results than the original model. In most cases, daily CH4 fluxes predicted by the revised DNDC model agreed well with observations. Seasonal CH4 emissions simulated by the revised model showed significantly higher correlation with observations than those obtained with the original model. Errors in the simulation appear to have resulted from uncertainties in both the input parameters and the model descriptions. Sensitivity analysis revealed that the revised DNDC model is highly sensitive to the concentration of reducible soil Fe, the rate of rice straw incorporation, and rice root biomass. Therefore, uncertainties in these factors may strongly affect the prediction of CH4 emissions. These results suggest that for reliable prediction of CH4 emissions from Thai rice fields, further work is needed to improve the estimates of reducible soil Fe, to quantify the rate of straw incorporation, and to parameterize the crop submodel for the dominant rice varieties grown in Thailand.

  8. Tannin is a key factor in the determination and prediction of energy content in sorghum grains fed to growing pigs.

    PubMed

    Pan, L; Li, P; Ma, X K; Xu, Y T; Tian, Q Y; Liu, L; Li, D F; Piao, X S

    2016-07-01

    DE and 3,973 - (262 × % tannin) - (27.24 × % ADF) for ME. Our results strongly indicate that the DE and ME content of sorghum grains are related to their chemical composition, especially their tannin content. The DE and ME content could decrease by more than 200 kcal/kg when the tannin content is increased by 1% in the sorghum grain. Overall, tannin is a key predictor for the DE and ME content as well as the ATTD of GE in sorghum grains, and the potent antinutritive properties from tannin should not be ignored when sorghum is used as an energy source for pigs. PMID:27482674

  9. Vascular endothelial growth factor-D is a key molecule that enhances lymphatic metastasis of soft tissue sarcomas

    SciTech Connect

    Yanagawa, Takashi; Shinozaki, Tetsuya; Watanabe, Hideomi; Saito, Kenichi; Raz, Avraham; Takagishi, Kenji

    2012-04-15

    Studies on lymph node metastasis of soft tissue sarcomas are insufficient because of its rarity. In this study, we examined the expressions of vascular endothelial growth factor (VEGF)-C and VEGF-D in soft tissue sarcomas metastasized to lymph nodes. In addition, the effects of the two molecules on the barrier function of a lymphatic endothelial cell monolayer against sarcoma cells were analyzed. We examined 7 patients who had soft tissue sarcomas with lymph node metastases and who had undergone neither chemotherapy nor radiotherapy before lymphadenectomy. Immunohistochemistry revealed that 2 of 7 sarcomas that metastasized to lymph nodes expressed VEGF-C both in primary and metastatic lesions. On the other hand, VEGF-D expression was detected in 4 of 7 primary and 7 of 7 metastatic lesions, respectively. Interestingly, 3 cases that showed no VEGF-D expression at primary sites expressed VEGF-D in metastatic lesions. Recombinant VEGF-C at 10{sup -8} and VEGF-D at 10{sup -7}and 10{sup -8} g/ml significantly increased the random motility of lymphatic endothelial cells compared with controls. VEGF-D significantly increased the migration of sarcoma cells through lymphatic endothelial monolayers. The fact that VEGF-D induced the migration of fibrosarcomas through the lymphatic endothelial monolayer is the probable reason for the strong relationship between VEGF-D expression and lymph node metastasis in soft tissue sarcomas. The important propensities of this molecule for the increase of lymph node metastases are not only lymphangiogenesis but also down-regulation of the barrier function of lymphatic endothelial monolayers, which facilitates sarcoma cells entering the lymphatic circulation.

  10. The Cytosolic pH of Individual Saccharomyces cerevisiae Cells Is a Key Factor in Acetic Acid Tolerance

    PubMed Central

    Fernández-Niño, Miguel; Marquina, Maribel; Swinnen, Steve; Rodríguez-Porrata, Boris

    2015-01-01

    It was shown recently that individual cells of an isogenic Saccharomyces cerevisiae population show variability in acetic acid tolerance, and this variability affects the quantitative manifestation of the trait at the population level. In the current study, we investigated whether cell-to-cell variability in acetic acid tolerance could be explained by the observed differences in the cytosolic pHs of individual cells immediately before exposure to the acid. Results obtained with cells of the strain CEN.PK113-7D in synthetic medium containing 96 mM acetic acid (pH 4.5) showed a direct correlation between the initial cytosolic pH and the cytosolic pH drop after exposure to the acid. Moreover, only cells with a low initial cytosolic pH, which experienced a less severe drop in cytosolic pH, were able to proliferate. A similar correlation between initial cytosolic pH and cytosolic pH drop was also observed in the more acid-tolerant strain MUCL 11987-9. Interestingly, a fraction of cells in the MUCL 11987-9 population showed initial cytosolic pH values below the minimal cytosolic pH detected in cells of the strain CEN.PK113-7D; consequently, these cells experienced less severe drops in cytosolic pH. Although this might explain in part the difference between the two strains with regard to the number of cells that resumed proliferation, it was observed that all cells from strain MUCL 11987-9 were able to proliferate, independently of their initial cytosolic pH. Therefore, other factors must also be involved in the greater ability of MUCL 11987-9 cells to endure strong drops in cytosolic pH. PMID:26341199

  11. Stature and jumping height are required in female volleyball, but motor coordination is a key factor for future elite success.

    PubMed

    Pion, Johan A; Fransen, Job; Deprez, Dieter N; Segers, Veerle I; Vaeyens, Roel; Philippaerts, Renaat M; Lenoir, Matthieu

    2015-06-01

    It was hypothesized that differences in anthropometry, physical performance, and motor coordination would be found between Belgian elite and sub-elite level female volleyball players using a retrospective analysis of test results gathered over a 5-year period. The test sample in this study consisted of 21 young female volleyball players (15.3 ± 1.5 years) who were selected to train at the Flemish Top Sports Academy for Volleyball in 2008. All players (elite, n = 13; sub-elite, n = 8) were included in the same talent development program, and the elite-level athletes were of a high to very high performance levels according to European competition level in 2013. Five multivariate analyses of variance were used. There was no significant effect of playing level on measures of anthropometry (F = 0.455, p = 0.718, (Equation is included in full-text article.)= 0.07), flexibility (F = 1.861, p = 0.188, (Equation is included in full-text article.)= 0.19), strength (F = 1.218, p = 0.355, (Equation is included in full-text article.)= 0.32); and speed and agility (F = 1.176, p = 0.350, (Equation is included in full-text article.)= 0.18). Multivariate analyses of variance revealed significant multivariate effects between playing levels for motor coordination (F = 3.470, p = 0.036, (Equation is included in full-text article.)= 0.59). A Mann-Whitney U test and a sequential discriminant analysis confirmed these results. Previous research revealed that stature and jump height are prerequisites for talent identification in female volleyball. In addition, the results show that motor coordination is an important factor in determining inclusion into the elite level in female volleyball. PMID:25436627

  12. The Sigma Factor AlgU Plays a Key Role in Formation of Robust Biofilms by Nonmucoid Pseudomonas aeruginosa▿

    PubMed Central

    Bazire, Alexis; Shioya, Kouki; Soum-Soutéra, Emmanuelle; Bouffartigues, Emeline; Ryder, Cynthia; Guentas-Dombrowsky, Linda; Hémery, Gaëlle; Linossier, Isabelle; Chevalier, Sylvie; Wozniak, Daniel J.; Lesouhaitier, Olivier; Dufour, Alain

    2010-01-01

    The extracytoplasmic function sigma factor AlgU of Pseudomonas aeruginosa is responsible for alginate overproduction, leading to mucoidy and chronic infections of cystic fibrosis patients. We investigated here the role of AlgU in the formation of nonmucoid biofilms. The algU mutant of P. aeruginosa PAO1 (PAOU) showed a dramatic impairment in biofilm formation under dynamic conditions. PAOU was defective both in cell attachment to glass and in development of robust, shear-resistant biofilms. This was explained by an impaired production of extracellular matrix, specifically of the exopolysaccharide Psl, as revealed by microscopy and enzyme-linked immunosorbent assay. Complementing the algU mutation with a plasmid-borne algU gene restored wild-type phenotypes. Compared with that in PAO1, expression of the psl operon was reduced in the PAOU strain, and the biofilm formation ability of this strain was partially restored by inducing the transcription of the psl operon. Furthermore, expression of the lectin-encoding lecA and lecB genes was reduced in the PAOU strain. In agreement with the requirement of LecB for type IV pilus biogenesis, PAOU displayed impaired twitching motility. Collectively, these genetic downregulation events explain the biofilm formation defect of the PAOU mutant. Promoter mapping indicated that AlgU is probably not directly responsible for transcription of the psl operon and the lec genes, but AlgU is involved in the expression of the ppyR gene, whose product was reported to positively control psl expression. Expressing the ppyR gene in PAOU partially restored the formation of robust biofilms. PMID:20348252

  13. Topography and crop management are key factors for the development of american leaf spot epidemics on coffee in costa rica.

    PubMed

    Avelino, Jacques; Cabut, Sandrine; Barboza, Bernardo; Barquero, Miguel; Alfaro, Ronny; Esquivel, César; Durand, Jean-François; Cilas, Christian

    2007-12-01

    ABSTRACT We monitored the development of American leaf spot of coffee, a disease caused by the gemmiferous fungus Mycena citricolor, in 57 plots in Costa Rica for 1 or 2 years in order to gain a clearer understanding of conditions conducive to the disease and improve its control. During the investigation, characteristics of the coffee trees, crop management, and the environment were recorded. For the analyses, we used partial least-squares regression via the spline functions (PLSS), which is a nonlinear extension to partial least-squares regression (PLS). The fungus developed well in areas located between approximately 1,100 and 1,550 m above sea level. Slopes were conducive to its development, but eastern-facing slopes were less affected than the others, probably because they were more exposed to sunlight, especially in the rainy season. The distance between planting rows, the shade percentage, coffee tree height, the type of shade, and the pruning system explained disease intensity due to their effects on coffee tree shading and, possibly, on the humidity conditions in the plot. Forest trees and fruit trees intercropped with coffee provided particularly propitious conditions. Apparently, fertilization was unfavorable for the disease, probably due to dilution phenomena associated with faster coffee tree growth. Finally, series of wet spells interspersed with dry spells, which were frequent in the middle of the rainy season, were critical for the disease, probably because they affected the production and release of gemmae and their viability. These results could be used to draw up a map of epidemic risks taking topographical factors into account. To reduce those risks and improve chemical control, our results suggested that farmers should space planting rows further apart, maintain light shading in the plantation, and prune their coffee trees. PMID:18943713

  14. Nitrous oxide emissions from intensive agricultural systems: Variations between crops and seasons, key driving variables, and mean emission factors

    NASA Astrophysics Data System (ADS)

    Dobbie, K. E.; McTaggart, I. P.; Smith, K. A.

    1999-11-01

    Emissions of nitrous oxide from intensively managed agricultural fields were measured over 3 years. Exponential increases in flux occurred with increasing soil water- filled pore space (WFPS) and temperature; increases in soil mineral N content due to fertilizer application also stimulated emissions. Fluxes were low when any of these variables was below a critical value. The largest fluxes occurred when WFPS values were very high (70-90%), indicating that denitrification was the major process responsible. The relationships with the driving variables showed strong similarities to those reported for very different environments: irrigated sugar cane crops, pastures, and forest in the tropics. Annual emissions varied widely (0.3-18.4 kg N2O-N ha-1). These variations were principally due to the degree of coincidence of fertilizer application and major rainfall events. It is concluded therefore that several years' data are required from any agricultural ecosystem in a variable climate to obtain a robust estimate of mean N2O fluxes. The emissions from small-grain cereals (winter wheat and spring barley) were consistently lower (0.2-0.7 kg N2O-N per 100 kg N applied) than from cut grassland (0.3-5.8 kg N2O- N per 100 kg N). Crops such as broccoli and potatoes gave emissions of the same order as those from the grassland. Although these differences between crop types are not apparent in general data comparisons, there may well be distinct regional differences in the relative and absolute emissions from different crops, due to local factors relating to soil type, weather patterns, and agricultural management practices. This will only be determined by more detailed comparative studies.

  15. ‘Tempos’ management in primary care: a key factor for classifying adverse events, and improving quality and safety

    PubMed Central

    Brami, J

    2012-01-01

    Background The role of time management in safe and efficient medicine is important but poorly incorporated into the taxonomies of error in primary care. This paper addresses the lack of time management, presenting a framework integrating five time scales termed ‘Tempos’ requiring parallel processing by GPs: the disease's tempo (unexpected rapid evolutions, slow reaction to treatment); the office's tempo (day-to-day agenda and interruptions); the patient's tempo (time to express symptoms, compliance, emotion); the system's tempo (time for appointments, exams, and feedback); and the time to access to knowledge. The art of medicine is to control all of these tempos in parallel and simultaneously. Method Two qualified physicians reviewed a sample of 1046 malpractice claims from one liability insurer to determine whether a medical injury had occurred and, if so, whether it was due to one or more tempo-related problems. 623 of these reports were analysed in greater detail to identify the prevalence and characteristics of claims and related time management errors. Results The percentages of contributing factors were as follows: disease tempo, 37.9%; office tempo, 13.2%; patient tempo, 13.8%; out-of-office coordination tempo, 22.6%; and GP's access to knowledge tempo, 33.2%. Conclusion Although not conceptualised in most error taxonomies, the disease and patient tempos are cornerstones in risk management in primary care. Traditional taxonomies describe events from an analytical perspective of care at the system level and offer opportunities to improve organisation, process, and evidence-based medicine. The suggested classification describes events in terms of (unsafe) dynamic control of parallel constraints from the carer's perspective, namely the GP, and offers improvement on how to self manage and coordinate different contradictory tempos and day-to-day activities. Further work is needed to test the validity and usefulness of this approach. PMID:22927486

  16. Statistical study to identify the key factors governing ground water recharge in the watersheds of the arid Central Asia.

    PubMed

    Zhu, Binq-Qi; Wang, Yue-Ling

    2016-01-01

    Understanding the source and recharge of ground waters is of great significance to our knowledge in hydrological cycles in arid environments over the world. Northern Xinjiang in northwestern China is a significant repository of information relating to the hydrological evolution and climatic changes in central Asia. In this study, two multivariate statistical techniques, hierarchical cluster analysis (HCA) and principal component analysis (PCA), were used to assess the ground water recharge and its governing factors, with the principal idea of exploring the above techniques to utilize all available hydrogeochemical variables in the quality assessment, which are not considered in the conventional techniques like Stiff and Piper diagrams. Q-mode HCA and R-mode PCA were combined to partition the water samples into seven major water clusters (C1-C7) and three principal components (PC1-PC3, PC1 salinity, PC2 hydroclimate, PC3 contaminant). The water samples C1 + C4 were classified as recharge area waters (Ca-HCO3 water), C2 + C3 as transitional zone waters (Ca-Mg-HCO3-SO4 water), and C5 + C6 + C7 as discharge area waters (Na-SO4 water). Based on the Q-mode PCA scores, three groups of geochemical processes influencing recharge regimes were identified: geogenic (i.e., caused by natural geochemical processes), geomorphoclimatic (caused by topography and climate), and anthropogenic (caused by ground water contamination). It is proposed that differences in recharge mechanism and ground water evolution, and possible bedrock composition difference, are responsible for the chemical genesis of these waters. These will continue to influence the geochemistry of the northern Xinjiang drainage system for a long time due to its steady tectonics and arid climate. This study proved that the chemistry differentiation of ground water can effectively support the identification of ground water recharge and evolution patterns. PMID:26718947

  17. The Microglial α7-Acetylcholine Nicotinic Receptor Is a Key Element in Promoting Neuroprotection by Inducing Heme Oxygenase-1 via Nuclear Factor Erythroid-2-Related Factor 2

    PubMed Central

    Parada, Esther; Egea, Javier; Buendia, Izaskun; Negredo, Pilar; Cunha, Ana C.; Cardoso, Silvia; Soares, Miguel P.

    2013-01-01

    Abstract Aims: We asked whether the neuroprotective effect of cholinergic microglial stimulation during an ischemic event acts via a mechanism involving the activation of nuclear factor erythroid-2-related factor 2 (Nrf2) and/or the expression of its target cytoprotective gene, heme oxygenase-1 (HO-1). Specifically, the protective effect of the pharmacologic alpha-7 nicotinic acetylcholine receptor (α7 nAChR) agonist PNU282987 was analyzed in organotypic hippocampal cultures (OHCs) subjected to oxygen and glucose deprivation (OGD) in vitro as well as in photothrombotic stroke in vivo. Results: OHCs exposed to OGD followed by reoxygenation elicited cell death, measured by propidium iodide and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide staining. Activation of α7 nAChR by PNU282987, after OGD, reduced cell death, reactive oxygen species production, and tumor necrosis factor release. This was associated with induction of HO-1 expression, an effect reversed by α-bungarotoxin and by tin–protoporphyrin IX. The protective effect of PNU282987 was lost in microglial-depleted OHCs as well as in OHCs from Nrf2-deficient-versus-wild-type mice, an effect associated with suppression of HO-1 expression in microglia. Administration of PNU282987 1 h after induction of photothrombotic stroke in vivo reduced the infarct size and improved motor skills in Hmox1lox/lox mice that express normal levels of HO-1, but not in LysMCreHmox1Δ/Δ in which HO-1 expression is inhibited in myeloid cells, including the microglia. Innovation: This study suggests the participation of the microglial α7 nAChR in the brain cholinergic anti-inflammatory pathway. Conclusion: Activation of the α7 nAChR/Nrf2/HO-1 axis in microglia regulates neuroinflammation and oxidative stress, affording neuroprotection under brain ischemic conditions. Antioxid. Redox Signal. 19, 1135–1148. PMID:23311871

  18. Transcription Factor ATAF1 in Arabidopsis Promotes Senescence by Direct Regulation of Key Chloroplast Maintenance and Senescence Transcriptional Cascades1[OPEN

    PubMed Central

    Garapati, Prashanth; Xue, Gang-Ping

    2015-01-01

    Senescence represents a fundamental process of late leaf development. Transcription factors (TFs) play an important role for expression reprogramming during senescence; however, the gene regulatory networks through which they exert their functions, and their physiological integration, are still largely unknown. Here, we identify the Arabidopsis (Arabidopsis thaliana) abscisic acid (ABA)- and hydrogen peroxide-activated TF Arabidopsis thaliana ACTIVATING FACTOR1 (ATAF1) as a novel upstream regulator of senescence. ATAF1 executes its physiological role by affecting both key chloroplast maintenance and senescence-promoting TFs, namely GOLDEN2-LIKE1 (GLK1) and ORESARA1 (ARABIDOPSIS NAC092), respectively. Notably, while ATAF1 activates ORESARA1, it represses GLK1 expression by directly binding to their promoters, thereby generating a transcriptional output that shifts the physiological balance toward the progression of senescence. We furthermore demonstrate a key role of ATAF1 for ABA- and hydrogen peroxide-induced senescence, in accordance with a direct regulatory effect on ABA homeostasis genes, including NINE-CIS-EPOXYCAROTENOID DIOXYGENASE3 involved in ABA biosynthesis and ABC TRANSPORTER G FAMILY MEMBER40, encoding an ABA transport protein. Thus, ATAF1 serves as a core transcriptional activator of senescence by coupling stress-related signaling with photosynthesis- and senescence-related transcriptional cascades. PMID:25953103

  19. Predicting alcohol consumption in adolescence from alcohol-specific and general externalizing genetic risk factors, key environmental exposures and their interaction

    PubMed Central

    Kendler, K. S.; Gardner, C.; Dick, D. M.

    2011-01-01

    Background Alcohol consumption is influenced by specific genetic risk factors for alcohol use disorders (AUDs), non-specific genetic risk factors for externalizing behaviors and various environmental experiences. We have limited knowledge of how these risk factors inter-relate through development. Method Retrospective assessments in 1796 adult male twins using a life history calendar of key environmental exposures and alcohol consumption from early adolescence to mid-adulthood. Analysis by linear mixed models. Results The importance of non-specific genetic risk factors on maximal alcohol consumption rose rapidly in early to mid-adolescence, peaked at ages 15–17 years and then declined slowly. Alcohol-specific genetic risk factors increased slowly in influence through mid-adulthood. We detected robust evidence for environmental moderation of genetic effects on alcohol consumption that was more pronounced in early and mid-adolescence than in later periods. Alcohol availability, peer deviance and low prosocial behaviors showing the strongest moderation effects. More interactions with environmental risk factors were seen for the non-specific externalizing disorder risk than for specific genetic risk for AUDs. Conclusions The impact of specific and non-specific genetic influences on alcohol consumption have different development trajectories. Genetic effects on alcohol use are more pronounced when social constraints are minimized (e.g. low prosocial behaviors or parental monitoring) or when the environment permits easy access to alcohol and/or encourages its use (e.g. high alcohol availability or peer deviance). Gene–environment interactions influencing alcohol intake may be more robust at younger ages, indicating greater plasticity of genetic influences early in the development of drinking patterns. PMID:20942993

  20. Understanding Mathematics: Some Key Factors

    ERIC Educational Resources Information Center

    Ali, Asma Amanat; Reid, Norman

    2012-01-01

    Mathematics is well known as a subject area where there can be problems in terms of understanding as well as retaining positive attitudes. In a large study involving 813 school students (ages approximately 10-12) drawn from two different school systems in Pakistan, the effect of limited working memory capacity on performance in mathematics was…

  1. How to identify the key factors that affect driver perception of accident risk. A comparison between Italian and Spanish driver behavior.

    PubMed

    de Oña, Juan; de Oña, Rocio; Eboli, Laura; Forciniti, Carmen; Mazzulla, Gabriella

    2014-12-01

    Road crashes can be caused by different factors, including infrastructure, vehicles, and human variables. Many research studies have focused solely on identifying the key factors that cause road crashes. From these studies, it emerged that human factors have the most relevant impact on accident severity. More specifically, accident severity depends on several factors related directly to the driver, i.e., driving experience, driver's socio-economic characteristics, and driving behavior and attitudes. In this paper, we investigate driver behaviors and attitudes while driving and specifically focus on different methods for identifying the factors that most affect the driver's perception of accident risk. To this end, we designed and conducted a survey in two different European contexts: the city of Cosenza, which is located in the south of Italy, and the city of Granada, which is located in the south of Spain. Samples of drivers were contacted for their opinions on certain aspects of driving rules and attitudes while driving, and different types of questions were addressed to the drivers to assess their judgments of these aspects. Consequently, different methods of data analysis were applied to determine the aspects that heavily influence driver perception of accident risk. An experiment based on the stated preferences (SP) was carried out with the drivers, and the SP data were analyzed using an ordered probit (OP) model. Interesting findings emerged from different analyses of the data and from the comparisons among the data collected in the two different territorial contexts. We found that both Italian and Spanish drivers consider driving in an altered psychophysical state and violating the overtaking rules to be the most risky behaviors. PMID:25247553

  2. Elucidation of wear mechanisms by ferrographic analysis

    NASA Technical Reports Server (NTRS)

    Jones, W. R., Jr.

    1981-01-01

    The use of ferrographic analysis in conjunction with light and scanning electron microscopy is described for the elucidation of wear mechanisms taking place in operating equipment. Example of adhesive wear, abrasive wear, corrosive wear, rolling element fatigue, lubricant breakdown, and other wear modes are illustrated. In addition, the use of magnetic solutions to precipitate nonmagnetic debris from aqueous and nonaqueous fluids is described.

  3. Does Pictorial Elucidation Foster Recollection of Idioms?

    ERIC Educational Resources Information Center

    Boers, Frank; Piquer Piriz, Ana Maria; Stengers, Helene; Eyckmans, June

    2009-01-01

    Experimental evidence suggests that pictorial elucidation helps learners comprehend and remember the meaning of second language (L2) idioms. In this article we address the question whether it also helps retention of the form of idioms, i.e. their precise lexical composition. In a small-scale experiment, the meaning of English idioms was clarified…

  4. Calcitonin gene-related peptide is a key factor in the homing of transplanted human MSCs to sites of spinal cord injury.

    PubMed

    Zhang, Yu; Yang, Jinhua; Zhang, Peng; Liu, Tao; Xu, Jianwei; Fan, Zhihai; Shen, Yixin; Li, Wenjie; Zhang, Huanxiang

    2016-01-01

    Mesenchymal stem cells (MSCs) can be used to treat many diseases, including spinal cord injury (SCI). Treatment relies mostly on the precise navigation of cells to the injury site for rebuilding the damaged spinal cord. However, the key factors guiding MSCs to the epicenter of SCI remain unknown. Here, we demonstrated that calcitonin gene-related peptide (CGRP), a neural peptide synthesized in spinal cord, can dramatically aid the homing of human umbilical cord mesenchymal stem cells (HUMSCs) in spinal cord-transected SCI rats. First, HUMSCs exhibited chemotactic responses in vitro to CGRP. By time-lapse video analysis, increased chemotactic index (CMI), forward migration index (FMI) and speed contributed to this observed migration. Then, through enzyme immunoassay, higher CGRP concentrations at the lesion site were observed after injury. The release of CGRP directed HUMSCs to the injury site, which was suppressed by CGRP 8-37, a CGRP antagonist. We also verified that the PI3K/Akt and p38MAPK signaling pathways played a critical role in the CGRP-induced chemotactic migration of HUMSCs. Collectively, our data reveal that CGRP is a key chemokine that helps HUMSCs migrate to the lesion site and thereby can be used as a model molecule to study MSCs homing after SCI. PMID:27296555

  5. Calcitonin gene-related peptide is a key factor in the homing of transplanted human MSCs to sites of spinal cord injury

    PubMed Central

    Zhang, Yu; Yang, Jinhua; Zhang, Peng; Liu, Tao; Xu, Jianwei; Fan, Zhihai; Shen, Yixin; Li, Wenjie; Zhang, Huanxiang

    2016-01-01

    Mesenchymal stem cells (MSCs) can be used to treat many diseases, including spinal cord injury (SCI). Treatment relies mostly on the precise navigation of cells to the injury site for rebuilding the damaged spinal cord. However, the key factors guiding MSCs to the epicenter of SCI remain unknown. Here, we demonstrated that calcitonin gene-related peptide (CGRP), a neural peptide synthesized in spinal cord, can dramatically aid the homing of human umbilical cord mesenchymal stem cells (HUMSCs) in spinal cord-transected SCI rats. First, HUMSCs exhibited chemotactic responses in vitro to CGRP. By time-lapse video analysis, increased chemotactic index (CMI), forward migration index (FMI) and speed contributed to this observed migration. Then, through enzyme immunoassay, higher CGRP concentrations at the lesion site were observed after injury. The release of CGRP directed HUMSCs to the injury site, which was suppressed by CGRP 8–37, a CGRP antagonist. We also verified that the PI3K/Akt and p38MAPK signaling pathways played a critical role in the CGRP-induced chemotactic migration of HUMSCs. Collectively, our data reveal that CGRP is a key chemokine that helps HUMSCs migrate to the lesion site and thereby can be used as a model molecule to study MSCs homing after SCI. PMID:27296555

  6. Florida Keys

    NASA Technical Reports Server (NTRS)

    2002-01-01

    The Florida Keys are a chain of islands, islets and reefs extending from Virginia Key to the Dry Tortugas for about 309 kilometers (192 miles). The keys are chiefly limestone and coral formations. The larger islands of the group are Key West (with its airport), Key Largo, Sugarloaf Key, and Boca Chica Key. A causeway extends from the mainland to Key West.

    This image was acquired on October 28, 2001, by the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) on NASA's Terra satellite. With its 14 spectral bands from the visible to the thermal infrared wavelength region, and its high spatial resolution of 15 to 90 meters (about 50 to 300 feet), ASTER images Earth to map and monitor the changing surface of our planet.

    ASTER is one of five Earth-observing instruments launched December 18, 1999, on NASA's Terra satellite. The instrument was built by Japan's Ministry of Economy, Trade and Industry. A joint U.S./Japan science team is responsible for validation and calibration of the instrument and the data products.

    The broad spectral coverage and high spectral resolution of ASTER will provide scientists in numerous disciplines with critical information for surface mapping, and monitoring of dynamic conditions and temporal change. Example applications are: monitoring glacial advances and retreats; monitoring potentially active volcanoes; identifying crop stress; determining cloud morphology and physical properties; wetlands evaluation; thermal pollution monitoring; coral reef degradation; surface temperature mapping of soils and geology; and measuring surface heat balance.

    Dr. Anne Kahle at NASA's Jet Propulsion Laboratory, Pasadena, Calif., is the U.S. Science team leader; Bjorn Eng of JPL is the project manager. The Terra mission is part of NASA's Earth Science Enterprise, a long- term research effort to understand and protect our home planet. Through the study of Earth, NASA will help to provide sound science to policy and economic

  7. Key Nutrients.

    ERIC Educational Resources Information Center

    Federal Extension Service (USDA), Washington, DC.

    Lessons written to help trainer agents prepare aides for work with families in the Food and Nutrition Program are presented in this booklet. The key nutrients discussed in the 10 lessons are protein, carbohydrates, fat, calcium, iron, iodine, and Vitamins A, B, C, and D. the format of each lesson is as follows: Purpose, Presentation, Application…

  8. Elucidating biotic factors that influence assembly of fungal endophyte communities

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Most plants harbor a diverse assemblage of non-mycorrhizal fungal endophytes. These fungi can directly influence the host plant, and can instigate trophic cascades that affect surrounding communities of herbivores, plants, and animals. Despite this, biotic mechanisms that influence assembly of funga...

  9. Transcription initiation complex structures elucidate DNA opening.

    PubMed

    Plaschka, C; Hantsche, M; Dienemann, C; Burzinski, C; Plitzko, J; Cramer, P

    2016-05-19

    Transcription of eukaryotic protein-coding genes begins with assembly of the RNA polymerase (Pol) II initiation complex and promoter DNA opening. Here we report cryo-electron microscopy (cryo-EM) structures of yeast initiation complexes containing closed and open DNA at resolutions of 8.8 Å and 3.6 Å, respectively. DNA is positioned and retained over the Pol II cleft by a network of interactions between the TATA-box-binding protein TBP and transcription factors TFIIA, TFIIB, TFIIE, and TFIIF. DNA opening occurs around the tip of the Pol II clamp and the TFIIE 'extended winged helix' domain, and can occur in the absence of TFIIH. Loading of the DNA template strand into the active centre may be facilitated by movements of obstructing protein elements triggered by allosteric binding of the TFIIE 'E-ribbon' domain. The results suggest a unified model for transcription initiation with a key event, the trapping of open promoter DNA by extended protein-protein and protein-DNA contacts. PMID:27193681

  10. Using Genomics for Natural Product Structure Elucidation.

    PubMed

    Tietz, Jonathan I; Mitchell, Douglas A

    2016-01-01

    Natural products (NPs) are the most historically bountiful source of chemical matter for drug development-especially for anti-infectives. With insights gleaned from genome mining, interest in natural product discovery has been reinvigorated. An essential stage in NP discovery is structural elucidation, which sheds light not only on the chemical composition of a molecule but also its novelty, properties, and derivatization potential. The history of structure elucidation is replete with techniquebased revolutions: combustion analysis, crystallography, UV, IR, MS, and NMR have each provided game-changing advances; the latest such advance is genomics. All natural products have a genetic basis, and the ability to obtain and interpret genomic information for structure elucidation is increasingly available at low cost to non-specialists. In this review, we describe the value of genomics as a structural elucidation technique, especially from the perspective of the natural product chemist approaching an unknown metabolite. Herein we first introduce the databases and programs of interest to the natural products chemist, with an emphasis on those currently most suited for general usability. We describe strategies for linking observed natural product-linked phenotypes to their corresponding gene clusters. We then discuss techniques for extracting structural information from genes, illustrated with numerous case examples. We also provide an analysis of the biases and limitations of the field with recommendations for future development. Our overview is not only aimed at biologically-oriented researchers already at ease with bioinformatic techniques, but also, in particular, at natural product, organic, and/or medicinal chemists not previously familiar with genomic techniques. PMID:26456468

  11. Paenibacillus larvae Chitin-Degrading Protein PlCBP49 Is a Key Virulence Factor in American Foulbrood of Honey Bees

    PubMed Central

    Garcia-Gonzalez, Eva; Poppinga, Lena; Fünfhaus, Anne; Hertlein, Gillian; Hedtke, Kati; Jakubowska, Agata; Genersch, Elke

    2014-01-01

    Paenibacillus larvae, the etiological agent of the globally occurring epizootic American Foulbrood (AFB) of honey bees, causes intestinal infections in honey bee larvae which develop into systemic infections inevitably leading to larval death. Massive brood mortality might eventually lead to collapse of the entire colony. Molecular mechanisms of host-microbe interactions in this system and of differences in virulence between P. larvae genotypes are poorly understood. Recently, it was demonstrated that the degradation of the peritrophic matrix lining the midgut epithelium is a key step in pathogenesis of P. larvae infections. Here, we present the isolation and identification of PlCBP49, a modular, chitin-degrading protein of P. larvae and demonstrate that this enzyme is crucial for the degradation of the larval peritrophic matrix during infection. PlCBP49 contains a module belonging to the auxiliary activity 10 (AA10, formerly CBM33) family of lytic polysaccharide monooxygenases (LPMOs) which are able to degrade recalcitrant polysaccharides. Using chitin-affinity purified PlCBP49, we provide evidence that PlCBP49 degrades chitin via a metal ion-dependent, oxidative mechanism, as already described for members of the AA10 family. Using P. larvae mutants lacking PlCBP49 expression, we analyzed in vivo biological functions of PlCBP49. In the absence of PlCBP49 expression, peritrophic matrix degradation was markedly reduced and P. larvae virulence was nearly abolished. This indicated that PlCBP49 is a key virulence factor for the species P. larvae. The identification of the functional role of PlCBP49 in AFB pathogenesis broadens our understanding of this important family of chitin-binding and -degrading proteins, especially in those bacteria that can also act as entomopathogens. PMID:25080221

  12. Paenibacillus larvae chitin-degrading protein PlCBP49 is a key virulence factor in American Foulbrood of honey bees.

    PubMed

    Garcia-Gonzalez, Eva; Poppinga, Lena; Fünfhaus, Anne; Hertlein, Gillian; Hedtke, Kati; Jakubowska, Agata; Genersch, Elke

    2014-07-01

    Paenibacillus larvae, the etiological agent of the globally occurring epizootic American Foulbrood (AFB) of honey bees, causes intestinal infections in honey bee larvae which develop into systemic infections inevitably leading to larval death. Massive brood mortality might eventually lead to collapse of the entire colony. Molecular mechanisms of host-microbe interactions in this system and of differences in virulence between P. larvae genotypes are poorly understood. Recently, it was demonstrated that the degradation of the peritrophic matrix lining the midgut epithelium is a key step in pathogenesis of P. larvae infections. Here, we present the isolation and identification of PlCBP49, a modular, chitin-degrading protein of P. larvae and demonstrate that this enzyme is crucial for the degradation of the larval peritrophic matrix during infection. PlCBP49 contains a module belonging to the auxiliary activity 10 (AA10, formerly CBM33) family of lytic polysaccharide monooxygenases (LPMOs) which are able to degrade recalcitrant polysaccharides. Using chitin-affinity purified PlCBP49, we provide evidence that PlCBP49 degrades chitin via a metal ion-dependent, oxidative mechanism, as already described for members of the AA10 family. Using P. larvae mutants lacking PlCBP49 expression, we analyzed in vivo biological functions of PlCBP49. In the absence of PlCBP49 expression, peritrophic matrix degradation was markedly reduced and P. larvae virulence was nearly abolished. This indicated that PlCBP49 is a key virulence factor for the species P. larvae. The identification of the functional role of PlCBP49 in AFB pathogenesis broadens our understanding of this important family of chitin-binding and -degrading proteins, especially in those bacteria that can also act as entomopathogens. PMID:25080221

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

    PubMed

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

    2016-07-01

    Cortistatin (CORT) shares high structural and functional similarities with somatostatin (SST) but displays unique sex-dependent pituitary actions. Indeed, although female CORT-knockout (CORT-KO) mice exhibit enhanced GH expression/secretion, Proopiomelanocortin expression, and circulating ACTH/corticosterone/ghrelin levels, male CORT-KO mice only display increased plasma GH/corticosterone levels. Changes in peripheral ghrelin and SST (rather than hypothalamic levels) seem to regulate GH/ACTH axes in CORT-KOs under fed conditions. Because changes in GH/ACTH axes during fasting provide important adaptive mechanisms, we sought to determine whether CORT absence influences GH/ACTH axes during fasting. Accordingly, fed and fasted male/female CORT-KO were compared with littermate controls. Fasting increased circulating GH levels in male/female controls but not in CORT-KO, suggesting that CORT can be a relevant regulator of GH secretion during fasting. However, GH levels were already higher in CORT-KO than in controls in fed state, which might preclude a further elevation in GH levels. Interestingly, although fasting-induced pituitary GH expression was elevated in both male/female controls, GH expression only increased in fasted female CORT-KOs, likely owing to specific changes observed in key factors controlling somatotrope responsiveness (ie, circulating ghrelin and IGF-1, and pituitary GHRH and ghrelin receptor expression). Fasting increased corticosterone levels in control and, most prominently, in CORT-KO mice, which might be associated with a desensitization to SST signaling and to an augmentation in CRH and ghrelin-signaling regulating corticotrope function. Altogether, these results provide compelling evidence that CORT plays a key, sex-dependent role in the regulation of the GH/ACTH axes in response to fasting. PMID:27175972

  14. Review: An urgent need for research on factors impacting adherence to and retention in care among HIV-positive youth and adolescents from key populations

    PubMed Central

    Lall, Priya; Lim, Sin How; Khairuddin, Norliana; Kamarulzaman, Adeeba

    2015-01-01

    Introduction The 50% increase in HIV-related deaths in youth and adolescents (aged 10–24) from 2005 to 2012 highlights the need to improve HIV treatment and care in this population, including treatment adherence and retention. Youth and adolescents from key populations or young key populations (YKP) in particular are highly stigmatized and may face additional barrier(s) in adhering to HIV treatment and services. We reviewed the current knowledge on treatment adherence and retention in HIV care among YKP to identify gaps in the literature and suggest future directions to improve HIV care for YKP. Methods We conducted a comprehensive literature search for YKP and their adherence to antiretroviral therapy (ART) and retention in HIV care on PsycInfo (Ovid), PubMed and Google Scholar using combinations of the keywords HIV/AIDS, ART, adolescents, young adults, adherence (or compliance), retention, men who have sex with men, transgender, injection drug users, people who inject drugs and prisoners. We included empirical studies on key populations defined by WHO; included the terms youth and adolescents and/or aged between 10 and 24; examined adherence to or retention in HIV care; and published in English-language journals. All articles were coded using NVivo. Results and discussion The systematic search yielded 10 articles on YKP and 16 articles on behaviourally infected youth and adolescents from 1999 to 2014. We found no studies reporting on youth and adolescents identified as sex workers, transgender people and prisoners. From existing literature, adherence to ART was reported to be influenced by age, access to healthcare, the burden of multiple vulnerabilities, policy involving risk behaviours and mental health. A combination of two or more of these factors negatively impacted adherence to ART among YKP. Collectively, these studies demonstrated that future programmes need to be tailored specifically to YKP to ensure adherence. Conclusions There is an urgent need for

  15. S100A13-C2A binary complex structure-a key component in the acidic fibroblast growth factor for the non-classical pathway

    SciTech Connect

    Mohan, Sepuru K.; Rani, Sandhya G.; Kumar, Sriramoju M.; Yu Chin

    2009-03-13

    Fibroblast growth factors (FGFs) are key regulators of cell proliferation, differentiation, tumor-induced angiogenesis and migration. FGFs are essential for early embryonic development, organ formation and angiogenesis. They play important roles in tumor formation, inflammation, wound healing and restenosis. The biological effects of FGFs are mediated through the activation of the four transmembrane phosphotyrosine kinase receptors (FGFRs) in the presence of heparin sulfate proteoglycans (HSPGs) and therefore require the release of FGFs into the extracellular space. However, FGF-1 lacks the signal peptide required for the releasing of these proteins through the classical endoplasmic reticulum (ER)-Golgi secretary pathway. Maciag et al. demonstrated that FGF-1 is exported through a non-classical release pathway involving the formation of a specific multiprotein complex [M. Landriscina, R. Soldi, C. Bagala, I. Micucci, S. Bellum, F. Tarantini, I. Prudovsky, T. Maciag, S100A13 participates in the release of fibroblast growth factor 1 in response to heat shock in vitro, J. Biol. Chem. 276 (2001) 22544-22552; C.M. Carreira, T.M. LaVallee, F. Tarantini, A. Jackson, J.T. Lathrop, B. Hampton, W.H. Burgess, T. Maciag, S100A13 is involved in the regulation of fibroblast growth factor-1 and p40 synaptotagmin-1 release in vitro, J. Biol. Chem. 273 (1998) 22224-22231; T.M. LaValle, F. Tarantini, S. Gamble, C.M. Carreira, A. Jackson, T. Maciag, Synaptotagmin-1 is required for fibroblast growth factor-1 release, J. Biol. Chem. 273 (1998) 22217-22223; C. Bagala, V. Kolev, A. Mandinova, R. Soldi, C. Mouta, I. Graziani, I, Prudovsky, T. Maciag, The alternative translation of synaptotagmin 1 mediates the non-classical release of FGF1, Biochem. Biophys. Res. Commun. 310 (2003) 1041-1047]. The protein constituents of this complex include FGF-1, S100A13 (a Ca{sup 2+}-binding protein), and the p40 form of synaptotagmin 1 (Syt1). To understand the molecular events in the FGF-1 releasing

  16. Projecting distribution of the overwintering population of Sogatella furcifera (Hemiptera: Delphacidae), in Yunnan, China with analysis on key influencing climatic factors.

    PubMed

    Hu, Shao-Ji; Liu, Xiao-Fei; Fu, Da-Ying; Huang, Wei; Wang, Xue-Ying; Liu, Xiao-Jun; Lü, Jian-Ping; Ye, Hui

    2015-01-01

    Sogatella furcifera (Horváth) is the most threatening migratory rice pest in Yunnan, China. S. furcifera overwinters in low- altitude basins and valleys in southern Yunnan and migrates northward in spring and summer of the following year, causing serious damage during migration. The overwintering distribution, areas, and spatial pattern of S. furcifera are relevant to the migration and outbreak of this pest. Based on a 4-yr field survey (2010-2013), this study projected areas suitable for S. furcifera to overwinter using a species distribution model, and analyzed the key influencing climatic factors using principal component analysis (PCA) and ecological niche factor analysis (ENFA). Our field survey showed that the northern latitudinal- and upper elevation limits of overwintering S. furcifera was 25.4° N and 1,608 m in western Yunnan and 24.2° N and 1,563 m in eastern Yunnan. The species distribution model produced a fragmented distribution pattern, with most of which in western Yunnan and only a few in eastern Yunnan. The PCA and ENFA analyses showed that the mean temperature of the driest quarter and the precipitation of the coldest quarter significantly influenced the distribution of S. furcifera in winter. The results suggested that the complex topography, spatial differences in winter temperatures, and host availability altogether determined the distribution of overwintering S. furcifera. Compared with previous surveys, the northern latitudinal- and upper elevation limits of overwintering S. furcifera were higher, while the population became rarer in some suitable areas due to change of farmland utilization in winter and possibly climate change. PMID:26494777

  17. Unravelling evolution of Nanog, the key transcription factor involved in self-renewal of undifferentiated embryonic stem cells, by pattern recognition in nucleotide and tandem repeats characteristics.

    PubMed

    Pashaiasl, Maryam; Khodadadi, Khodadad; Kayvanjoo, Amir Hossein; Pashaei-Asl, Roghiyeh; Ebrahimie, Esmaeil; Ebrahimi, Mansour

    2016-03-10

    Nanog, an important transcription factor in embryonic stem cells (ESC), is the key factor in maintaining pluripotency to establish ESC identity and has the ability to induce embryonic germ layers. Nanog is responsible for self-renewal and pluripotency of stem cells as well as cancer invasiveness, tumor cell proliferation, motility and drug-resistance. Understanding the underlying mechanisms of Nanog evolution and regulation can lead to future advances in treatment of cancers. Recent integration of machine learning models with genetics has provided a powerful tool for knowledge discovery and uncovering evolutionary pathways. Herein, sequences of 47 Nanog genes from various species were extracted and two datasets of features were computationally extracted from these sequences. At the first dataset, 76 nucleotide acid attributes were calculated for each Nanog sequence. The second dataset was prepared based on the 10,480 repeated nucleotide sequences (from 5 to 50bp lengths). Then, various data mining algorithms such as decision tree models were applied on these datasets to find the evolutionary pathways of Nanog diversion. Attribute weighting models were highlighted features such as the frequencies of AA and GC as the most important genomic features in Nanog gene classification and differentiation. Similar findings were obtained by tree induction algorithms. Results from the second database showed that some short sequence strings, such as ACTACT, TCCTGA, CCTGA, GAAGAC, and TATCCC can be effectively used to identify Nanog genes in various species. The outcomes of this study, for the first time, unravels the importance of particular genomic features in Nanog gene evolution paving roads toward better understanding of stem cell development and human targeted disorder therapy. PMID:26687709

  18. Increased cAMP levels modulate transforming growth factor-beta/Smad-induced expression of extracellular matrix components and other key fibroblast effector functions.

    PubMed

    Schiller, Meinhard; Dennler, Sylviane; Anderegg, Ulf; Kokot, Agatha; Simon, Jan C; Luger, Thomas A; Mauviel, Alain; Böhm, Markus

    2010-01-01

    cAMP is a key messenger of many hormones and neuropeptides, some of which modulate the composition of extracellular matrix. Treatment of human dermal fibroblasts with dibutyryl cyclic AMP and forskolin antagonized the inductive effects of transforming growth factor-beta (TGF-beta) on the expression of collagen, connective tissue growth factor, tissue inhibitor of matrix metalloproteinase-1, and plasminogen activator inhibitor type I, four prototypical TGF-beta-responsive genes. Increased intracellular cAMP prevented TGF-beta-induced Smad-specific gene transactivation, although TGF-beta-mediated Smad phosphorylation and nuclear translocation remained unaffected. However, increased cAMP levels abolished TGF-beta-induced interaction of Smad3 with its transcriptional co-activator cAMP-response element-binding protein (CREB)-binding protein (CBP)/p300. Overexpression of the transcriptional co-activator CBP/p300 rescued Smad-specific gene transcription in the presence of cAMP suggesting that sequestration of limited amounts of CBP/p300 by the activated cAMP/CREB pathway is the molecular basis of this inhibitory effect. These findings were extended by two functional assays. Increased intracellular cAMP levels suppressed the inductive activity of TGF-beta to contract mechanically unloaded collagen lattices and resulted in an attenuation of fibroblast migration of mechanically induced cell layer wounds. Of note, cAMP and TGF-beta synergistically induced hyaluronan synthase 2 (HAS2) expression and hyaluronan secretion, presumably via putative CREB-binding sites adjacent to Smad-binding sites within the HAS2 promoter. Our findings identify the cAMP pathway as a potent but differential and promoter-specific regulator of TGF-beta-mediated effects involved in extracellular matrix homeostasis. PMID:19858184

  19. Towards an effective control programme of soil-transmitted helminth infections among Orang Asli in rural Malaysia. Part 1: Prevalence and associated key factors

    PubMed Central

    2013-01-01

    Background Despite the continuous efforts to improve the quality of life of Orang Asli (Aborigines) communities, these communities are still plagued with a wide range of health problems including parasitic infections. The first part of this study aimed at determining the prevalence of soil-transmitted helminth (STH) infections and identifying their associated factors among rural Orang Asli children. Methods A cross-sectional study was carried out among 484 Orang Asli children aged ≤ 15 years (235 females and 249 males) belonging to 215 households from 13 villages in Lipis district, Pahang, Malaysia. Faecal samples were collected and examined by using formalin-ether sedimentation, Kato Katz and Harada Mori techniques. Demographic, socioeconomic, environmental and behavioural information were collected by using a pre-tested questionnaire. Results Overall, 78.1% of the children were found to be infected with one or more STH species. The prevalence of trichuriasis, ascariasis and hookworm infections were 71.7%, 37.4% and 17.6%, respectively. Almost all, three quarters and one fifth of trichuriasis, ascariasis and hookworm infections, respectively, were of moderate-to-heavy intensities. Multiple logistic regression analysis showed that age of ≥ 6 years (school-age), using unsafe water supply as a source for drinking water, absence of a toilet in the house, large family size (≥ 7 members), not washing hands before eating, and not washing hands after defecation were the key factors significantly associated with STH among these children. Conclusion This study reveals an alarmingly high prevalence of STH among Orang Asli children and clearly brings out an urgent need to implement school-based de-worming programmes and other control measures like providing a proper sanitation, as well as a treated drinking water supply and proper health education regarding good personal hygiene practices. Such an integrated control program will help significantly in

  20. Projecting Distribution of the Overwintering Population of Sogatella furcifera (Hemiptera: Delphacidae), in Yunnan, China With Analysis on Key Influencing Climatic Factors

    PubMed Central

    Hu, Shao-Ji; Liu, Xiao-Fei; Fu, Da-Ying; Huang, Wei; Wang, Xue-Ying; Liu, Xiao-Jun; Lü, Jian-Ping; Ye, Hui

    2015-01-01

    Sogatella furcifera (Horváth) is the most threatening migratory rice pest in Yunnan, China. S. furcifera overwinters in low- altitude basins and valleys in southern Yunnan and migrates northward in spring and summer of the following year, causing serious damage during migration. The overwintering distribution, areas, and spatial pattern of S. furcifera are relevant to the migration and outbreak of this pest. Based on a 4-yr field survey (2010–2013), this study projected areas suitable for S. furcifera to overwinter using a species distribution model, and analyzed the key influencing climatic factors using principal component analysis (PCA) and ecological niche factor analysis (ENFA). Our field survey showed that the northern latitudinal- and upper elevation limits of overwintering S. furcifera was 25.4° N and 1,608 m in western Yunnan and 24.2° N and 1,563 m in eastern Yunnan. The species distribution model produced a fragmented distribution pattern, with most of which in western Yunnan and only a few in eastern Yunnan. The PCA and ENFA analyses showed that the mean temperature of the driest quarter and the precipitation of the coldest quarter significantly influenced the distribution of S. furcifera in winter. The results suggested that the complex topography, spatial differences in winter temperatures, and host availability altogether determined the distribution of overwintering S. furcifera. Compared with previous surveys, the northern latitudinal- and upper elevation limits of overwintering S. furcifera were higher, while the population became rarer in some suitable areas due to change of farmland utilization in winter and possibly climate change. PMID:26494777

  1. Association, intrinsic shape, and molecular recognition: Elucidating DNA biophysics through coarse-grained simulation

    NASA Astrophysics Data System (ADS)

    Freeman, Gordon Samuel

    DNA is of central importance in biology as it is responsible for carrying, copying, and translating the genetic code into the building blocks that comprise life. In order to accomplish these tasks, the DNA molecule must be versatile and robust. Indeed, the underlying molecular interactions that allow DNA to execute these tasks are complex and their origins are only beginning to be understood. While experiments are able to elucidate many key biophysical phenomena, there remain many unanswered questions. Molecular simulation is able to shed light on phenomena at the molecular scale and provide information that is missing from experimental views of DNA behavior. In this dissertation I use state-of-the-art coarse-grained DNA models to address two key problems. In the first, metadynamics calculations are employed to uncover the free energy surface of two complimentary DNA strands. This free energy surface takes on the appearance of a hybridization funnel and reveals candidates for intermediate states in the hybridization of short DNA oligomers. Such short oligomers are important building blocks for DNA-driven self-assembly and the mechanism of hybridization in this regime is not well understood. The second problem is that of nucleosome formation. Nucleosomes are the fundamental subunit of genome compaction in the nucleus of a cell. As such, nucleosomes are a key epigenetic factor and affect gene expression and the ability of DNA-binding proteins to locate and bind to the appropriate position in the genome. However, the factors that drive nucleosome positioning are not well understood. While DNA sequence is known to affect nucleosome formation, the mechanism by which it does so has not been established and a number of hypotheses explaining this sequence-dependence exist in the literature. I demonstrate that DNA shape dominates this process with contributions arising from both intrinsic DNA curvature as well as DNA-protein interactions driven by sequence

  2. Depth keying

    NASA Astrophysics Data System (ADS)

    Gvili, Ronen; Kaplan, Amir; Ofek, Eyal; Yahav, Giora

    2003-05-01

    We present a new solution to the known problem of video keying in a natural environment. We segment foreground objects from background objects using their relative distance from the camera, which makes it possible to do away with the use of color for keying. To do so, we developed and built a novel depth video camera, capable of producing RGB and D signals, where D stands for the distance to each pixel. The new RGBD camera enables the creation of a whole new gallery of effects and applications such as multi-layer background substitutions. This new modality makes the production of real time mixed reality video possible, as well as post-production manipulation of recorded video. We address the problem of color spill -- in which the color of the foreground object is mixed, along its boundary, with the background color. This problem prevents an accurate separation of the foreground object from its background, and it is most visible when compositing the foreground objects to a new background. Most existing techniques are limited to the use of a constant background color. We offer a novel general approach to the problem with enabling the use of the natural background, based upon the D channel generated by the camera.

  3. Integrated analysis of miRNA/mRNA network in placenta identifies key factors associated with labor onset of Large White and Qingping sows.

    PubMed

    Li, Huanan; Wu, Bin; Geng, Junnan; Zhou, Jiawei; Zheng, Rong; Chai, Jin; Li, Fenge; Peng, Jian; Jiang, Siwen

    2015-01-01

    Labour onset is a very complex physiological process, and its mechanism is poorly understood. Here, we obtained the mRNA and miRNA expression profiles from the placentas of four groups of sows: Qingping sows 112 days after insemination with signs of labour onset (QS), Qingping sows 114 days after insemination with signs of labour onset (QL), Large White sows 114 days after insemination with signs of labour onset (LL) and Large White sows 112 days after insemination without signs of labour onset (LN). A set of differentially expressed genes, including 2164 mRNAs and 39 miRNAs, were found. A DAVID analysis of these differentially expressed genes revealed their critical roles in response to hormone stimulus, immune response. Cytoscape Network analysis of the functional genes found node mRNAs and that the regulatory network between the node mRNAs and miRNAs was established. A comparison of the sequencing data from the shorter gestation period (QS) and the normal gestation period (QL) indicated that these genes were responsible for the quicker and more sensitive reaction to the regulation of labour onset. This research not only detected the key factors that were involved in labour onset but also provided useful information for the research of gynaecological diseases. PMID:26272496

  4. Non-metastatic 2 (NME2)-mediated suppression of lung cancer metastasis involves transcriptional regulation of key cell adhesion factor vinculin

    PubMed Central

    Thakur, Ram Krishna; Yadav, Vinod Kumar; Kumar, Akinchan; Singh, Ankita; Pal, Krishnendu; Hoeppner, Luke; Saha, Dhurjhoti; Purohit, Gunjan; Basundra, Richa; Kar, Anirban; Halder, Rashi; Kumar, Pankaj; Baral, Aradhita; Kumar, MJ Mahesh; Baldi, Alfonso; Vincenzi, Bruno; Lorenzon, Laura; Banerjee, Rajkumar; Kumar, Praveen; Shridhar, Viji; Mukhopadhyay, Debabrata; Chowdhury, Shantanu

    2014-01-01

    Tumor metastasis refers to spread of a tumor from site of its origin to distant organs and causes majority of cancer deaths. Although >30 metastasis suppressor genes (MSGs) that negatively regulate metastasis have been identified so far, two issues are poorly understood: first, which MSGs oppose metastasis in a tumor type, and second, which molecular function of MSG controls metastasis. Herein, integrative analyses of tumor-transcriptomes (n = 382), survival data (n = 530) and lymph node metastases (n = 100) in lung cancer patients identified non-metastatic 2 (NME2) as a key MSG from a pool of >30 metastasis suppressors. Subsequently, we generated a promoter-wide binding map for NME2 using chromatin immunoprecipitation with promoter microarrays (ChIP-chip), and transcriptome profiling. We discovered novel targets of NME2 which are involved in focal adhesion signaling. Importantly, we detected binding of NME2 in promoter of focal adhesion factor, vinculin. Reduced expression of NME2 led to enhanced transcription of vinculin. In comparison, NME1, a close homolog of NME2, did not bind to vinculin promoter nor regulate its expression. In line, enhanced metastasis of NME2-depleted lung cancer cells was found in zebrafish and nude mice tumor models. The metastatic potential of NME2-depleted cells was remarkably diminished upon selective RNA-i-mediated silencing of vinculin. Together, we demonstrate that reduced NME2 levels lead to transcriptional de-repression of vinculin and regulate lung cancer metastasis. PMID:25249619

  5. Loss of striatal 90-kDa ribosomal S6 kinase (Rsk) is a key factor for motor, synaptic and transcription dysfunction in Huntington's disease.

    PubMed

    Anglada-Huguet, Marta; Giralt, Albert; Rué, Laura; Alberch, Jordi; Xifró, Xavier

    2016-07-01

    Huntington's disease (HD) is characterized by motor dysfunction due to the expression of mutant huntingtin that promotes degeneration of striatal GABAergic medium-sized spiny neurons. Here we explore the role of the 90-kDa ribosomal S6 kinase (Rsk) in the physiopathology of HD. First, we show a reduction of Rsk1 and 2 protein levels in the striatum of two HD mouse models, R6/1 and Hdh(Q7/Q111) knock-in mice, at ages when they suffer from motor disturbances. Interestingly, the analysis of post-mortem samples from HD patients revealed a significant reduction of both Rsk forms in the putamen and caudate, but not in the cortex. Rsk1 and 2 levels were also reduced in the striatum of BDNF heterozygous mice, and upon BDNF neutralization in striatal cultures, suggesting that striatal loss of BDNF could be involved in the decrease of Rsk levels. Finally, we injected recombinant adeno-associated-virus (AAV5)-Rsk in the striatum of R6/1 mice at the onset of motor symptoms. Four weeks later, we found higher Rsk levels in the striatum accompanied by improvements in motor coordination, enhanced expression of synaptic markers and increased expression of genes related to synaptic plasticity, such as cfos and egr1. Altogether, we identified Rsk as a key factor in striatal alterations associated with motor deficits in HD. PMID:27063456

  6. Identification of key factors conquering developmental arrest of somatic cell cloned embryos by combining embryo biopsy and single-cell sequencing.

    PubMed

    Liu, Wenqiang; Liu, Xiaoyu; Wang, Chenfei; Gao, Yawei; Gao, Rui; Kou, Xiaochen; Zhao, Yanhong; Li, Jingyi; Wu, You; Xiu, Wenchao; Wang, Su; Yin, Jiqing; Liu, Wei; Cai, Tao; Wang, Hong; Zhang, Yong; Gao, Shaorong

    2016-01-01

    Differentiated somatic cells can be reprogrammed into totipotent embryos through somatic cell nuclear transfer. However, most cloned embryos arrest at early stages and the underlying molecular mechanism remains largely unexplored. Here, we first developed a somatic cell nuclear transfer embryo biopsy system at two- or four-cell stage, which allows us to trace the developmental fate of the biopsied embryos precisely. Then, through single-cell transcriptome sequencing of somatic cell nuclear transfer embryos with different developmental fates, we identified that inactivation of Kdm4b, a histone H3 lysine 9 trimethylation demethylase, functions as a barrier for two-cell arrest of cloned embryos. Moreover, we discovered that inactivation of another histone demethylase Kdm5b accounts for the arrest of cloned embryos at the four-cell stage through single-cell analysis. Co-injection of Kdm4b and Kdm5b can restore transcriptional profiles of somatic cell nuclear transfer embryos and greatly improve the blastocyst development (over 95%) as well as the production of cloned mice. Our study therefore provides an effective approach to identify key factors responsible for the developmental arrest of somatic cell cloned embryos. PMID:27462457

  7. Identification of key factors conquering developmental arrest of somatic cell cloned embryos by combining embryo biopsy and single-cell sequencing

    PubMed Central

    Liu, Wenqiang; Liu, Xiaoyu; Wang, Chenfei; Gao, Yawei; Gao, Rui; Kou, Xiaochen; Zhao, Yanhong; Li, Jingyi; Wu, You; Xiu, Wenchao; Wang, Su; Yin, Jiqing; Liu, Wei; Cai, Tao; Wang, Hong; Zhang, Yong; Gao, Shaorong

    2016-01-01

    Differentiated somatic cells can be reprogrammed into totipotent embryos through somatic cell nuclear transfer. However, most cloned embryos arrest at early stages and the underlying molecular mechanism remains largely unexplored. Here, we first developed a somatic cell nuclear transfer embryo biopsy system at two- or four-cell stage, which allows us to trace the developmental fate of the biopsied embryos precisely. Then, through single-cell transcriptome sequencing of somatic cell nuclear transfer embryos with different developmental fates, we identified that inactivation of Kdm4b, a histone H3 lysine 9 trimethylation demethylase, functions as a barrier for two-cell arrest of cloned embryos. Moreover, we discovered that inactivation of another histone demethylase Kdm5b accounts for the arrest of cloned embryos at the four-cell stage through single-cell analysis. Co-injection of Kdm4b and Kdm5b can restore transcriptional profiles of somatic cell nuclear transfer embryos and greatly improve the blastocyst development (over 95%) as well as the production of cloned mice. Our study therefore provides an effective approach to identify key factors responsible for the developmental arrest of somatic cell cloned embryos. PMID:27462457

  8. Stability of the transthyretin molecule as a key factor in the interaction with a-beta peptide--relevance in Alzheimer's disease.

    PubMed

    Ribeiro, Carlos A; Saraiva, Maria João; Cardoso, Isabel

    2012-01-01

    Transthyretin (TTR) protects against A-Beta toxicity by binding the peptide thus inhibiting its aggregation. Previous work showed different TTR mutations interact differently with A-Beta, with increasing affinities correlating with decreasing amyloidogenecity of the TTR mutant; this did not impact on the levels of inhibition of A-Beta aggregation, as assessed by transmission electron microscopy. Our work aimed at probing differences in binding to A-Beta by WT, T119M and L55P TTR using quantitative assays, and at identifying factors affecting this interaction. We addressed the impact of such factors in TTR ability to degrade A-Beta. Using a dot blot approach with the anti-oligomeric antibody A11, we showed that A-Beta formed oligomers transiently, indicating aggregation and fibril formation, whereas in the presence of WT and T119M TTR the oligomers persisted longer, indicative that these variants avoided further aggregation into fibrils. In contrast, L55PTTR was not able to inhibit oligomerization or to prevent evolution to aggregates and fibrils. Furthermore, apoptosis assessment showed WT and T119M TTR were able to protect against A-Beta toxicity. Because the amyloidogenic potential of TTR is inversely correlated with its stability, the use of drugs able to stabilize TTR tetrameric fold could result in increased TTR/A-Beta binding. Here we showed that iododiflunisal, 3-dinitrophenol, resveratrol, [2-(3,5-dichlorophenyl)amino] (DCPA) and [4-(3,5-difluorophenyl)] (DFPB) were able to increase TTR binding to A-Beta; however only DCPA and DFPB improved TTR proteolytic activity. Thyroxine, a TTR ligand, did not influence TTR/A-Beta interaction and A-Beta degradation by TTR, whereas RBP, another TTR ligand, not only obstructed the interaction but also inhibited TTR proteolytic activity. Our results showed differences between WT and T119M TTR, and L55PTTR mutant regarding their interaction with A-Beta and prompt the stability of TTR as a key factor in this interaction

  9. Dose of Phenobarbital and Age of Treatment at Early Life are Two Key Factors for the Persistent Induction of Cytochrome P450 Enzymes in Adult Mouse Liver.

    PubMed

    Tien, Yun-Chen; Liu, Ke; Pope, Chad; Wang, Pengcheng; Ma, Xiaochao; Zhong, Xiao-bo

    2015-12-01

    Drug treatment of neonates and infants and its long-term consequences on drug responses have emerged in recent years as a major challenge for health care professionals. In the current study, we use phenobarbital as a model drug and mouse as an in vivo model to demonstrate that the dose of phenobarbital and age of treatment are two key factors for the persistent induction of gene expression and consequential increases of enzyme activities of Cyp2b, Cyp2c, and Cyp3a in adult livers. We show that phenobarbital treatment at early life of day 5 after birth with a low dose (<100 mg/kg) does not change expression and enzyme activities of Cyp2b, Cyp2c, and Cyp3a in adult mouse liver, whereas phenobarbital treatment with a high dose (>200 mg/kg) significantly increases expression and enzyme activities of these P450s in adult liver. We also demonstrate that phenobarbital treatment before day 10 after birth, but not at later ages, significantly increases mRNAs, proteins, and enzyme activities of the tested P450s. Such persistent induction of P450 gene expression and enzyme activities in adult livers by phenobarbital treatment only occurs within a sensitive age window early in life. The persistent induction in gene expression and enzyme activities is higher in female mice than in male mice for Cyp2b10 but not for Cyp2c29 and Cyp3a11. These results will stimulate studies to evaluate the long-term impacts of drug treatment with different doses at neonatal and infant ages on drug metabolism, therapeutic efficacy, and drug-induced toxicity throughout the rest of life. PMID:26400395

  10. Identification of a key regulatory element for the basal activity of the human insulin-like growth factor II gene promoter P3.

    PubMed Central

    Rietveld, L E; Holthuizen, P E; Sussenbach, J S

    1997-01-01

    Transcription of the human insulin-like growth factor II (IGF-II) gene is under the control of four promoters (P1-P4) that are differentially active during growth and development. Promoter 3 (P3) is the most active promoter during fetal development as well as in most adult tissues. P3 is also the most active promoter in tumour tissues and cell lines expressing IGF-II. Transient transfections of HeLa and Hep3B cells with truncated promoter constructs revealed that the region between -289 and -183 relative to the transcription start site supports basal promoter activity in both cell lines. Footprint experiments showed that the region between positions -192 and -172 (P3-4) is the only element bound by nuclear proteins. P3-4 is bound by five proteins, of which three proteins (proteins 3, 4 and 5) bind specifically and are expressed at the same levels in HeLa and Hep3B cells. Electrophoretic mobility shift assays and differential footprint experiments revealed the presence of two protein-binding regions within the P3-4 element. Proteins 4 and 5 bind box A (-193 to -188), whereas box B (-183 to -172) is bound by protein 3. From transcription experiments in vitro it can be concluded that Box A is essential for P3 activity. Box A is part of a region 11 dG residues long and is protected by proteins 4 and 5 that bind a contiguous set of six dG residues. DNA-binding of proteins 4 and 5 to box A requires the presence of Zn2+ ions. Thus structural and functional analysis reveals that the P3-4 element is a key regulatory element of P3 that contains two separate binding sites for proteins essential for the basal activity of IGF-II P3. PMID:9581544

  11. ‘Familiarity’ as a key factor influencing rural family carers’ experience of the nursing home placement of an older relative: a qualitative study

    PubMed Central

    2013-01-01

    Background Admission to a nursing home is generally regarded as a stressful time for older people and their carers. Although the choice of home is significant in facilitating a more positive transition, few studies have explored this issue in detail, particularly in the context of rural communities. With a worldwide ageing population and an increasing demand for long-term care facilities, it is important to highlight the factors that can improve the experience of entry to long-term care and the role of nursing home staff in facilitating a more positive transition for older people and their families. Methods The overall aim of this qualitative study was to explore rural family carers’ experience of the nursing home placement of an older relative. Semi structured interviews were conducted with 29 relatives of nursing home residents. Participants were selected from a large health and social care trust in the United Kingdom. Data were analysed using grounded theory principles and procedures and NVivo software. Results Rural family carers had a strong sense of familiarity with the nursing homes in their area and this appeared to permeate all aspects of their experience. Carers who reported a high degree of familiarity appeared to experience a more positive transition than others. This familiarity was influenced by the high degree of social capital that was present in the rural community where the study was conducted. This familiarity, in turn, influenced the choice of nursing home and the responses of family carers. The theory that emerged suggests that familiarity was the key factor influencing rural family carers’ experience of the nursing home placement of an older relative. Conclusions The population of the world is ageing and nursing homes are increasingly providing care to older people with multiple and complex needs. This study makes an important contribution to the ways in which the move to long term care can be managed more effectively by increasing

  12. T helper 2 and regulatory T-cell cytokine production by mast cells: a key factor in the pathogenesis of IgG4-related disease.

    PubMed

    Takeuchi, Mai; Sato, Yasuharu; Ohno, Kyotaro; Tanaka, Satoshi; Takata, Katsuyoshi; Gion, Yuka; Orita, Yorihisa; Ito, Toshihiro; Tachibana, Tomoyasu; Yoshino, Tadashi

    2014-08-01

    IgG4-related disease is a systemic disorder with unique clinicopathological features and uncertain etiological features and is frequently related to allergic disease. T helper 2 and regulatory T-cell cytokines have been reported to be upregulated in the affected tissues; thus, the production of these cytokines by T helper 2 and regulatory T cells has been suggested as an important factor in the pathogenesis of IgG4-related disease. However, it is not yet clear which cells produce these cytokines in IgG4-related disease, and some aspects of the disorder cannot be completely explained by T-cell-related processes. To address this, we analyzed paraffin-embedded sections of tissues from nine cases of IgG4-related submandibular gland disease, five cases of submandibular sialolithiasis, and six cases of normal submandibular gland in order to identify potential key players in the pathogenesis of IgG4-related disease. Real-time polymerase chain reaction analysis confirmed the significant upregulation of interleukin (IL)4, IL10, and transforming growth factor beta 1 (TGFβ1) in IgG4-related disease. Interestingly, immunohistochemical studies indicated the presence of mast cells expressing these cytokines in diseased tissues. In addition, dual immunofluorescence assays identified cells that were double-positive for each cytokine and for KIT, which is expressed by mast cells. In contrast, the distribution of T cells did not correlate with cytokine distribution in affected tissues. We also found that the mast cells were strongly positive for IgE. This observation supports the hypothesis that mast cells are involved in IgG4-related disease, as mast cells are known to be closely related to allergic reactions and are activated in the presence of elevated non-specific IgE levels. In conclusion, our results indicate that mast cells produce T helper 2 and regulatory T-cell cytokines in tissues affected by IgG4-related disease and possibly have an important role in disease

  13. Key respiratory genes elucidate bacterial community respiration in a seasonally anoxic estuary.

    PubMed

    Eggleston, Erin M; Lee, Dong Y; Owens, Michael S; Cornwell, Jeffrey C; Crump, Byron C; Hewson, Ian

    2015-07-01

    Intense annual spring phytoplankton blooms and thermohaline stratification lead to anoxia in Chesapeake Bay bottom waters. Once oxygen becomes depleted in the system, microbial communities use energetically favourable alternative electron acceptors for respiration. The extent to which changes in respiration are reflected in community gene expression have only recently been investigated. Metatranscriptomes prepared from near-bottom water plankton over a 4-month time series in central Chesapeake Bay demonstrated changes consistent with terminal electron acceptor availability. The frequency of respiration-related genes in metatranscriptomes was examined by BLASTx against curated databases of genes intimately and exclusively involved in specific electron acceptor utilization pathways. The relative expression of genes involved in denitrification and dissimilatory nitrate reduction to ammonium were coincident with changes in nitrate, nitrite and ammonium concentrations. Dissimilatory iron and manganese reduction transcript ratios increase during anoxic conditions and corresponded with the highest soluble reactive phosphate and manganese concentrations. The sulfide concentration peaked in late July and early August and also matched dissimilatory sulfate reduction transcript ratios. We show that rather than abrupt transitions between terminal electron acceptors, there is substantial overlap in time and space of these various anaerobic respiratory processes in Chesapeake Bay. PMID:25470994

  14. Elucidation of the Key Role of [Ru(bpy)3 ](2+) in Photocatalyzed RAFT Polymerization.

    PubMed

    Christmann, Julien; Ibrahim, Ahmad; Charlot, Vincent; Croutxé-Barghorn, Céline; Ley, Christian; Allonas, Xavier

    2016-08-01

    Photocatalysis reactions using [Ru(II) (bpy)3 ](2+) were studied on the example of visible-light-sensitized reversible addition-fragmentation chain transfer (RAFT) polymerization. Although both photoinduced electron- and energy-transfer mechanisms are able to describe this interaction, no definitive experimental proof has been presented so far. This paper investigates the actual mechanism governing this reaction. A set of RAFT agents was selected, their redox potentials measured by cyclic voltammetry, and relaxed triplet energies calculated by quantum mechanics. Gibbs free-energy values were calculated for both electron- and energy-transfer mechanisms. Quenching rate constants were determined by laser flash photolysis. The results undoubtedly evidence the involvement of a photoinduced energy-transfer reaction. Controlled photopolymerization experiments are discussed in the light of the primary photochemical process and photodissociation ability of RAFT agent triplet states. PMID:27124095

  15. Key factors leading to reduced recruitment and retention of health professionals in remote areas of Ghana: a qualitative study and proposed policy solutions

    PubMed Central

    2011-01-01

    Background The ability of many countries to achieve national health goals such as the Millennium Development Goals remains hindered by inadequate and poorly distributed health personnel, including doctors. The distribution of doctors in Ghana is highly skewed, with a majority serving in two major metropolitan areas (Accra and Kumasi), and inadequate numbers in remote and rural districts. Recent policies increasing health worker salaries have reduced migration of doctors out of Ghana, but made little difference to distribution within the country. This qualitative study was undertaken to understand how practicing doctors and medical leaders in Ghana describe the key factors reducing recruitment and retention of health professionals into remote areas, and to document their proposed policy solutions. Methods In-depth interviews were carried out with 84 doctors and medical leaders, including 17 regional medical directors and deputy directors from across Ghana, and 67 doctors currently practicing in 3 regions (Greater Accra, Brong Ahafo, and Upper West); these 3 regions were chosen to represent progressively more remote distances from the capital of Accra. Results and discussion All participants felt that rural postings must have special career or monetary incentives given the loss of locum (i.e. moonlighting income), the higher workload, and professional isolation of remote assignments. Career 'death' and prolonged rural appointments were a common fear, and proposed policy solutions focused considerably on career incentives, such as guaranteed promotion or a study opportunity after some fixed term of service in a remote or hardship area. There was considerable stress placed on the need for rural doctors to have periodic contact with mentors through rural rotation of specialists, or remote learning centers, and reliable terms of appointment with fixed end-points. Also raised, but given less emphasis, were concerns about the adequacy of clinical equipment in remote

  16. [Elucidating hypoglycemic mechanism of Dendrobium nobile through auxiliary elucidation system for traditional Chinese medicine mechanism].

    PubMed

    Li, Man-man; Zhang, Bai-xia; He, Shuai-bing; Zheng, Rao; Zhang, Yan-ling; Wang, Yun

    2015-10-01

    To build the Dendrobium nobile -T2DM network, and elucidate the molecular mechanism of D. nobile to type 2 diabetes (T2DM). Collect the chemical composition of D. nobile and the targets on T2DM by retrieving database and documents, build the network of D. nobile to T2DM using the entity grammar systems inference rules. The molecular mechanism of D. nobile to T2DM includes: (1) regulating lipid metabolism by lowering triglyceride; (2) reducing insulin resistance; (3) protecting islet cells; (4) promoting the glucose-dependent insulin tropic peptide (GIP) secretion; (5) inhibiting calcium channel. Under the guidance of network pharmacology, through entity grammar systems inference rules we elucidate the molecular mechanism of D. nobile to T2DM, and provide the basis for the further development of health care products based on D. nobile. PMID:26975089

  17. X-ray structure of dopamine transporter elucidates antidepressant mechanism.

    PubMed

    Penmatsa, Aravind; Wang, Kevin H; Gouaux, Eric

    2013-11-01

    Antidepressants targeting Na(+)/Cl(-)-coupled neurotransmitter uptake define a key therapeutic strategy to treat clinical depression and neuropathic pain. However, identifying the molecular interactions that underlie the pharmacological activity of these transport inhibitors, and thus the mechanism by which the inhibitors lead to increased synaptic neurotransmitter levels, has proven elusive. Here we present the crystal structure of the Drosophila melanogaster dopamine transporter at 3.0 Å resolution bound to the tricyclic antidepressant nortriptyline. The transporter is locked in an outward-open conformation with nortriptyline wedged between transmembrane helices 1, 3, 6 and 8, blocking the transporter from binding substrate and from isomerizing to an inward-facing conformation. Although the overall structure of the dopamine transporter is similar to that of its prokaryotic relative LeuT, there are multiple distinctions, including a kink in transmembrane helix 12 halfway across the membrane bilayer, a latch-like carboxy-terminal helix that caps the cytoplasmic gate, and a cholesterol molecule wedged within a groove formed by transmembrane helices 1a, 5 and 7. Taken together, the dopamine transporter structure reveals the molecular basis for antidepressant action on sodium-coupled neurotransmitter symporters and elucidates critical elements of eukaryotic transporter structure and modulation by lipids, thus expanding our understanding of the mechanism and regulation of neurotransmitter uptake at chemical synapses. PMID:24037379

  18. A systematic approach identifies FOXA1 as a key factor in the loss of epithelial traits during the epithelial-to-mesenchymal transition in lung cancer

    PubMed Central

    2013-01-01

    Background The epithelial-to-mesenchymal transition is an important mechanism in cancer metastasis. Although transcription factors including SNAIL, SLUG, and TWIST1 regulate the epithelial-to-mesenchymal transition, other unknown transcription factors could also be involved. Identification of the full complement of transcription factors is essential for a more complete understanding of gene regulation in this process. Chromatin immunoprecipitation-sequencing (ChIP-Seq) technologies have been used to detect genome-wide binding of transcription factors; here, we developed a systematic approach to integrate existing ChIP-Seq and transcriptome data. We scanned multiple transcription factors to investigate their functional impact on the epithelial-to-mesenchymal transition in the human A549 lung adenocarcinoma cell line. Results Among the transcription factors tested, impact scores identified the forkhead box protein A1 (FOXA1) as the most significant transcription factor in the epithelial-to-mesenchymal transition. FOXA1 physically associates with the promoters of its predicted target genes. Several critical epithelial-to-mesenchymal transition effectors involved in cellular adhesion and cellular communication were identified in the regulatory network of FOXA1, including FOXA2, FGA, FGB, FGG, and FGL1. The implication of FOXA1 in the epithelial-to-mesenchymal transition via its regulatory network indicates that FOXA1 may play an important role in the initiation of lung cancer metastasis. Conclusions We identified FOXA1 as a potentially important transcription factor and negative regulator in the initial stages of lung cancer metastasis. FOXA1 may modulate the epithelial-to-mesenchymal transition via its transcriptional regulatory network. Further, this study demonstrates how ChIP-Seq and expression data could be integrated to delineate the impact of transcription factors on a specific biological process. PMID:24093963

  19. Key Statistics for Thyroid Cancer

    MedlinePlus

    ... cancer? Next Topic Thyroid cancer risk factors Key statistics for thyroid cancer How common is thyroid cancer? ... remains very low compared with most other cancers. Statistics on survival rates for thyroid cancer are discussed ...

  20. Elucidating severe urban haze formation in China

    PubMed Central

    Guo, Song; Hu, Min; Zamora, Misti L.; Peng, Jianfei; Shang, Dongjie; Zheng, Jing; Du, Zhuofei; Wu, Zhijun; Shao, Min; Zeng, Limin; Molina, Mario J.; Zhang, Renyi

    2014-01-01

    As the world’s second largest economy, China has experienced severe haze pollution, with fine particulate matter (PM) recently reaching unprecedentedly high levels across many cities, and an understanding of the PM formation mechanism is critical in the development of efficient mediation policies to minimize its regional to global impacts. We demonstrate a periodic cycle of PM episodes in Beijing that is governed by meteorological conditions and characterized by two distinct aerosol formation processes of nucleation and growth, but with a small contribution from primary emissions and regional transport of particles. Nucleation consistently precedes a polluted period, producing a high number concentration of nano-sized particles under clean conditions. Accumulation of the particle mass concentration exceeding several hundred micrograms per cubic meter is accompanied by a continuous size growth from the nucleation-mode particles over multiple days to yield numerous larger particles, distinctive from the aerosol formation typically observed in other regions worldwide. The particle compositions in Beijing, on the other hand, exhibit a similarity to those commonly measured in many global areas, consistent with the chemical constituents dominated by secondary aerosol formation. Our results highlight that regulatory controls of gaseous emissions for volatile organic compounds and nitrogen oxides from local transportation and sulfur dioxide from regional industrial sources represent the key steps to reduce the urban PM level in China. PMID:25422462

  1. Elucidating severe urban haze formation in China

    NASA Astrophysics Data System (ADS)

    Guo, Song; Hu, Min; Zamora, Misti L.; Peng, Jianfei; Shang, Dongjie; Zheng, Jing; Du, Zhuofei; Wu, Zhijun; Shao, Min; Zeng, Limin; Molina, Mario J.; Zhang, Renyi

    2014-12-01

    As the world's second largest economy, China has experienced severe haze pollution, with fine particulate matter (PM) recently reaching unprecedentedly high levels across many cities, and an understanding of the PM formation mechanism is critical in the development of efficient mediation policies to minimize its regional to global impacts. We demonstrate a periodic cycle of PM episodes in Beijing that is governed by meteorological conditions and characterized by two distinct aerosol formation processes of nucleation and growth, but with a small contribution from primary emissions and regional transport of particles. Nucleation consistently precedes a polluted period, producing a high number concentration of nano-sized particles under clean conditions. Accumulation of the particle mass concentration exceeding several hundred micrograms per cubic meter is accompanied by a continuous size growth from the nucleation-mode particles over multiple days to yield numerous larger particles, distinctive from the aerosol formation typically observed in other regions worldwide. The particle compositions in Beijing, on the other hand, exhibit a similarity to those commonly measured in many global areas, consistent with the chemical constituents dominated by secondary aerosol formation. Our results highlight that regulatory controls of gaseous emissions for volatile organic compounds and nitrogen oxides from local transportation and sulfur dioxide from regional industrial sources represent the key steps to reduce the urban PM level in China.

  2. Elucidating severe urban haze formation in China.

    PubMed

    Guo, Song; Hu, Min; Zamora, Misti L; Peng, Jianfei; Shang, Dongjie; Zheng, Jing; Du, Zhuofei; Wu, Zhijun; Shao, Min; Zeng, Limin; Molina, Mario J; Zhang, Renyi

    2014-12-01

    As the world's second largest economy, China has experienced severe haze pollution, with fine particulate matter (PM) recently reaching unprecedentedly high levels across many cities, and an understanding of the PM formation mechanism is critical in the development of efficient mediation policies to minimize its regional to global impacts. We demonstrate a periodic cycle of PM episodes in Beijing that is governed by meteorological conditions and characterized by two distinct aerosol formation processes of nucleation and growth, but with a small contribution from primary emissions and regional transport of particles. Nucleation consistently precedes a polluted period, producing a high number concentration of nano-sized particles under clean conditions. Accumulation of the particle mass concentration exceeding several hundred micrograms per cubic meter is accompanied by a continuous size growth from the nucleation-mode particles over multiple days to yield numerous larger particles, distinctive from the aerosol formation typically observed in other regions worldwide. The particle compositions in Beijing, on the other hand, exhibit a similarity to those commonly measured in many global areas, consistent with the chemical constituents dominated by secondary aerosol formation. Our results highlight that regulatory controls of gaseous emissions for volatile organic compounds and nitrogen oxides from local transportation and sulfur dioxide from regional industrial sources represent the key steps to reduce the urban PM level in China. PMID:25422462

  3. Communication-oriented person-organization fit as a key factor of job-seeking behaviors: millennials' social media use and attitudes toward organizational social media policies.

    PubMed

    Cho, Jaehee; Park, Dong Jin; Ordonez, Zoa

    2013-11-01

    The main goal of this study was to assess how the millennial generation perceives companies that have different social media policies and how such perception influences key variables for job-seeking behaviors, including perceived person-organization fit (POF), organizational attraction, and job pursuit intention. Results from a univariate general linear model and path analysis supported all of the established hypotheses. In particular, the results revealed that millennials perceived higher POF for a company with organizational policies supporting employees' social media use. Further, organizational attractiveness significantly mediated the relationship between communication-oriented POF and job pursuit intention. PMID:23848961

  4. Gene Regulatory Networks Elucidating Huanglongbing Disease Mechanisms

    PubMed Central

    Martinelli, Federico; Reagan, Russell L.; Uratsu, Sandra L.; Phu, My L.; Albrecht, Ute; Zhao, Weixiang; Davis, Cristina E.; Bowman, Kim D.; Dandekar, Abhaya M.

    2013-01-01

    Next-generation sequencing was exploited to gain deeper insight into the response to infection by Candidatus liberibacter asiaticus (CaLas), especially the immune disregulation and metabolic dysfunction caused by source-sink disruption. Previous fruit transcriptome data were compared with additional RNA-Seq data in three tissues: immature fruit, and young and mature leaves. Four categories of orchard trees were studied: symptomatic, asymptomatic, apparently healthy, and healthy. Principal component analysis found distinct expression patterns between immature and mature fruits and leaf samples for all four categories of trees. A predicted protein – protein interaction network identified HLB-regulated genes for sugar transporters playing key roles in the overall plant responses. Gene set and pathway enrichment analyses highlight the role of sucrose and starch metabolism in disease symptom development in all tissues. HLB-regulated genes (glucose-phosphate-transporter, invertase, starch-related genes) would likely determine the source-sink relationship disruption. In infected leaves, transcriptomic changes were observed for light reactions genes (downregulation), sucrose metabolism (upregulation), and starch biosynthesis (upregulation). In parallel, symptomatic fruits over-expressed genes involved in photosynthesis, sucrose and raffinose metabolism, and downregulated starch biosynthesis. We visualized gene networks between tissues inducing a source-sink shift. CaLas alters the hormone crosstalk, resulting in weak and ineffective tissue-specific plant immune responses necessary for bacterial clearance. Accordingly, expression of WRKYs (including WRKY70) was higher in fruits than in leaves. Systemic acquired responses were inadequately activated in young leaves, generally considered the sites where most new infections occur. PMID:24086326

  5. Oral hygiene status in a general population of Iran, 2011: a key lifestyle marker in relation to common risk factors of non-communicable diseases

    PubMed Central

    Asgari, Fereshteh; Majidi, Azam; Koohpayehzadeh, Jalil; Etemad, Koorosh; Rafei, Ali

    2015-01-01

    Background: To estimate Oral Hygiene (OH) status in the Iranian population in 2011, and to determine the influence of socio-economic characteristics on OH, and its interrelation with common risk factors of Non-Communicable Diseases (NCDs). Methods: Data including a total of 12,105 individuals aged 6-70 years were obtained from the sixth round of the surveys of NCDs risk factors in Iran. OH was recorded through a structured questionnaire measuring daily frequencies of tooth brushing and dental flossing. Descriptive analyses were performed on demographic characteristics in the complex sample survey setting. We also employed weighted binary logistic regression to compute Odds Ratio (OR) as a measure of association between the response and explanatory factors. Furthermore, to construct an asset index, we utilized Principal Component Analysis (PCA). Results: The percentage with minimum recommended daily OH practices was 3.7% among men and 7.7% among women (OR= 2.3; P< 0.001). Urban citizens were more likely to have their teeth cleaned compared to rural people (OR= 2.8; P< 0.001). For both genders, a relatively better condition was observed in the 25–34 age group (male: 5.6%; female: 10.3%). In addition, OH status improved significantly by increase in both level of education (P< 0.001) and economic status (P< 0.001). There were also apparent associations between self-care practices and specific behavioral risk factors, though the correlation with dietary habits and tobacco use could be largely explained by socio-economic factors. Conclusion: OH situation in Iran calls for urgent need to assign proper interventions and strategies toward raising public awareness and reducing disparities in access to health facilities. PMID:26029893

  6. Spatial and seasonal factors are key determinants in the aggregation of helminths in their definitive hosts: Pseudamphistomum truncatum in otters (Lutra lutra).

    PubMed

    Sherrard-Smith, E; Perkins, S E; Chadwick, E A; Cable, J

    2015-01-01

    Parasites are typically aggregated within their host populations. The most heavily infected hosts are frequently cited as targets for optimal disease control. Yet a heavily infected individual is not necessarily highly infective and does not automatically contribute a higher proportion of infective parasitic stages than a host with fewer parasites. Here, Pseudamphistomum truncatum (Opisthorchiida) parasitic infection within the definitive otter host (Lutra lutra) is used as a model system. The hypothesis tested is that variation in parasite abundance, aggregation and egg production (fecundity, as a proxy of host infectivity) can be explained by abiotic (season and region) or biotic (host age, sex and body condition) factors. Parasite abundance was affected most strongly by the biotic factors of age and body condition, such that adults and otters with a higher condition index had heavier infections than sub-adults or those with a lower condition index, whilst there were no significant differences in parasite abundance among the seasons, regions (ecological regions defined by river catchment boundaries) or host sexes. Conversely, parasite aggregation was affected most strongly by the abiotic factors of season and region, which were supported by four different measures of parasite aggregation (the corrected moment estimate k, Taylor's Power Law, the Index of Discrepancy D, and Boulinier's J). Pseudamphistomum truncatum was highly aggregated within otters, with aggregation stronger in the Midlands (England) and Wales than in the southwestern region of the United Kingdom. Overall, more parasites were found in fewer hosts during the summer, which coincides with the summer peak in parasite fecundity. Combined, these data suggest that (i) few otters carry the majority of P. truncatum parasites and that there are more infective stages (eggs) produced during summer; and (ii) abiotic factors are most influential when describing parasite aggregation whilst biotic factors have

  7. Stratification of surface waters during the last glacial millennial climatic events: a key factor in subsurface and deep-water mass dynamics

    NASA Astrophysics Data System (ADS)

    Wary, M.; Eynaud, F.; Sabine, M.; Zaragosi, S.; Rossignol, L.; Malaizé, B.; Palis, E.; Zumaque, J.; Caulle, C.; Penaud, A.; Michel, E.; Charlier, K.

    2015-11-01

    The last glacial period was punctuated by abrupt climatic events with extrema known as Heinrich and Dansgaard-Oeschger events. These millennial events have been the subject of many paleoreconstructions and model experiments in the past decades, but yet the hydrological processes involved remain elusive. In the present work, high-resolution analyses were conducted on the 12-42 ka BP section of core MD99-2281 retrieved southwest of the Faeroe Islands, and combined with analyses conducted in two previous studies (Zumaque et al., 2012; Caulle et al., 2013). Such a multiproxy approach, coupling micropaleontological, geochemical and sedimentological analyses, allows us to track surface, subsurface, and deep hydrological processes occurring during these rapid climatic changes. Records indicate that the coldest episodes of the studied period (Greenland stadials and Heinrich stadials) were characterized by a strong stratification of surface waters. This surface stratification seems to have played a key role in the dynamics of subsurface and deep-water masses. Indeed, periods of high surface stratification are marked by a coupling of subsurface and deep circulations which sharply weaken at the beginning of stadials, while surface conditions progressively deteriorate throughout these cold episodes; conversely, periods of decreasing surface stratification (Greenland interstadials) are characterized by a coupling of surface and deep hydrological processes, with progressively milder surface conditions and gradual intensification of the deep circulation, while the vigor of the subsurface northward Atlantic flow remains constantly high. Our results also reveal different and atypical hydrological signatures during Heinrich stadials (HSs): while HS1 and HS4 exhibit a "usual" scheme with reduced overturning circulation, a relatively active North Atlantic circulation seems to have prevailed during HS2, and HS3 seems to have experienced a re-intensification of this circulation during

  8. Stratification of surface waters during the last glacial millennial climatic events: a key factor in subsurface and deep water mass dynamics

    NASA Astrophysics Data System (ADS)

    Wary, Mélanie; Eynaud, Frédérique; Sabine, Marjolaine; Zaragosi, Sébastien; Rossignol, Linda; Malaize, Bruno; Palis, Edouard; Zumaque, Jena; Caulle, Clémence; Penaud, Aurélie; Michel, Elisabeth; Charlier, Karine

    2015-04-01

    The last glacial period was punctuated by abrupt climatic events with extrema known as Heinrich events (HEs) and Dansgaard-Oeschger (DO) cycles. These millennial events have been the subject of many paleoreconstructions and model experiments in the past decades, but yet the hydrological processes involved remain elusive. In the present work, high resolution analyses were conducted on the 12-42 ka BP section of core MD99-2281 retrieved Southwest off Faeroes. Our multiproxy approach, coupling micropaleontological, geochemical and sedimentological analyses, allows us to track surface, subsurface, and deep hydrological processes occurring during these rapid climatic changes. Records indicate that the coldest episodes of the studied period (Greenland stadials and HEs) were characterized by a strong stratification of surface waters. This surface stratification seems to have played a key role in the dynamics of subsurface and deep water masses. Indeed, periods of high surface stratification are marked by a coupling of subsurface and deep circulations which sharply weaken at the beginning of stadials; simultaneously, surface conditions progressively deteriorate throughout these cold episodes. At the opposite, periods of decreasing surface stratification (Greenland interstadials) are characterized by a coupling of surface and deep hydrological processes with progressively milder surface conditions and gradual intensification of the deep circulation; at the same time, the vigor of the subsurface Atlantic inflow remains constantly high. In addition to this remarkable oceanographical scheme, our results also reveal different and atypical hydrological signatures for Heinrich events 2 and 3. Our findings thus bring valuable information to better understand hydrological processes occurring in a key area during the abrupt climatic shifts of the last glacial period.

  9. Stratification of surface waters during the last glacial millennial climatic events: a key factor in subsurface and deep water mass dynamics

    NASA Astrophysics Data System (ADS)

    Wary, M.; Eynaud, F.; Marjolaine, S.; Zaragosi, S.; Rossignol, L.; Malaizé, B.; Palis, E.; Zumaque, J.; Caulle, C.; Penaud, A.; Michel, E.; Charlier, K.

    2015-05-01

    The last glacial period was punctuated by abrupt climatic events with extrema known as Heinrich Events and Dansgaard-Oeschger cycles. These millennial events have been the subject of many paleoreconstructions and model experiments in the past decades, but yet the hydrological processes involved remain elusive. In the present work, high resolution analyses were conducted on the 12-42 ka BP section of core MD99-2281 retrieved Southwest off Faeroes. Our multiproxy approach, coupling micropaleontological, geochemical and sedimentological analyses, allows us to track surface, subsurface, and deep hydrological processes occurring during these rapid climatic changes. Records indicate that the coldest episodes of the studied period (Greenland stadials and Heinrich stadials) were characterized by a strong stratification of surface waters. This surface stratification seems to have played a key role in the dynamics of subsurface and deep water masses. Indeed, periods of high surface stratification are marked by a coupling of subsurface and deep circulations which sharply weaken at the beginning of stadials while surface conditions progressively deteriorate throughout these cold episodes; at the opposite, periods of decreasing surface stratification (Greenland interstadials) are characterized by a coupling of surface and deep hydrological processes with progressively milder surface conditions and gradual intensification of the deep circulation while the vigor of the subsurface Atlantic inflow remains constantly high. Our results also reveal different and atypical hydrological signatures during Heinrich stadials (HS): while HS1 and HS4 exhibit a "usual" scheme with reduced overturning circulation, a relatively active North Atlantic circulation seems to have prevailed during HS2, and HS3 seems to have experienced a re-intensification of this circulation at mid-event. Our findings thus bring valuable information to better understand hydrological processes occurring in a key area

  10. Substance use among Asian American adolescents: Influence of race, ethnicity, and acculturation in the context of key risk and protective factors

    PubMed Central

    Thai, Nghi D.; Connell, Christian M.; Tebes, Jacob Kraemer

    2014-01-01

    This study examines the relative influence of race/ethnicity, acculturation, peer substance use, and academic achievement on adolescent substance use among different Asian American ethnic groups and U.S. racial/ethnic groups. Data from the Wave 1 in-home sample of the National Longitudinal Study of Adolescent Health was used to examine lifetime use of alcohol, tobacco, and marijuana in a full adolescent sample of all racial/ethnic groups (N=20,745) and a subsample of Asian American adolescents (N=1,248). Path analysis examined the hypothesized relationships of peer substance use and acculturation as risk factors and academic achievement as a protective factor for racial/ethnic groups. The results indicated that when Asian American adolescents were compared to other major U.S. racial/ethnic groups, peer use and acculturation were both significant mediators of smoking, drinking, and marijuana use, and academic achievement mediated each type of use at a trend level. For Asian American ethnic groups, peer use is a risk factor and, to a lesser extent, academic achievement a protective factor for substance use. Also, although acculturation is a predictor of substance use, when peer use and academic achievement are taken into account, acculturation -- like ethnicity -- no longer predicts use. Mediation analyses indicated that: peer substance use mediates smoking, drinking, and marijuana use; academic achievement does not; and acculturation mediates substance use for some substances and some Asian American ethnic groups. The results are discussed for their implications for understanding how culturally-specific approaches can inform preventive interventions. PMID:25309680

  11. Comprehensive Profiling of Ethylene Response Factor Expression Identifies Ripening-Associated ERF Genes and Their Link to Key Regulators of Fruit Ripening in Tomato1[OPEN

    PubMed Central

    Gomes, Bruna Lima; Mila, Isabelle; Frasse, Pierre; Zouine, Mohamed; Bouzayen, Mondher

    2016-01-01

    Our knowledge of the factors mediating ethylene-dependent ripening of climacteric fruit remains limited. The transcription of ethylene-regulated genes is mediated by ethylene response factors (ERFs), but mutants providing information on the specific role of the ERFs in fruit ripening are still lacking, likely due to functional redundancy among this large multigene family of transcription factors. We present here a comprehensive expression profiling of tomato (Solanum lycopersicum) ERFs in wild-type and tomato ripening-impaired tomato mutants (Never-ripe [Nr], ripening-inhibitor [rin], and non-ripening [nor]), indicating that out of the 77 ERFs present in the tomato genome, 27 show enhanced expression at the onset of ripening while 28 display a ripening-associated decrease in expression, suggesting that different ERFs may have contrasting roles in fruit ripening. Among the 19 ERFs exhibiting the most consistent up-regulation during ripening, the expression of 11 ERFs is strongly down-regulated in rin, nor, and Nr tomato ripening mutants, while only three are consistently up-regulated. Members of subclass E, SlERF.E1, SlERF.E2, and SlERF.E4, show dramatic down-regulation in the ripening mutants, suggesting that their expression might be instrumental in fruit ripening. This study illustrates the high complexity of the regulatory network connecting RIN and ERFs and identifies subclass E members as the most active ERFs in ethylene- and RIN/NOR-dependent ripening. PMID:26739234

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

    PubMed

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

    2016-03-01

    Our knowledge of the factors mediating ethylene-dependent ripening of climacteric fruit remains limited. The transcription of ethylene-regulated genes is mediated by ethylene response factors (ERFs), but mutants providing information on the specific role of the ERFs in fruit ripening are still lacking, likely due to functional redundancy among this large multigene family of transcription factors. We present here a comprehensive expression profiling of tomato (Solanum lycopersicum) ERFs in wild-type and tomato ripening-impaired tomato mutants (Never-ripe [Nr], ripening-inhibitor [rin], and non-ripening [nor]), indicating that out of the 77 ERFs present in the tomato genome, 27 show enhanced expression at the onset of ripening while 28 display a ripening-associated decrease in expression, suggesting that different ERFs may have contrasting roles in fruit ripening. Among the 19 ERFs exhibiting the most consistent up-regulation during ripening, the expression of 11 ERFs is strongly down-regulated in rin, nor, and Nr tomato ripening mutants, while only three are consistently up-regulated. Members of subclass E, SlERF.E1, SlERF.E2, and SlERF.E4, show dramatic down-regulation in the ripening mutants, suggesting that their expression might be instrumental in fruit ripening. This study illustrates the high complexity of the regulatory network connecting RIN and ERFs and identifies subclass E members as the most active ERFs in ethylene- and RIN/NOR-dependent ripening. PMID:26739234

  13. Elucidation of the transcription network governing mammalian sex determination by exploiting strain-specific susceptibility to sex reversal

    PubMed Central

    Munger, Steven C.; Aylor, David L.; Syed, Haider Ali; Magwene, Paul M.; Threadgill, David W.; Capel, Blanche

    2009-01-01

    Despite the identification of some key genes that regulate sex determination, most cases of disorders of sexual development remain unexplained. Evidence suggests that the sexual fate decision in the developing gonad depends on a complex network of interacting factors that converge on a critical threshold. To elucidate the transcriptional network underlying sex determination, we took the first expression quantitative trait loci (eQTL) approach in a developing organ. We identified reproducible differences in the transcriptome of the embryonic day 11.5 (E11.5) XY gonad between C57BL/6J (B6) and 129S1/SvImJ (129S1), indicating that the reported sensitivity of B6 to sex reversal is consistent with a higher expression of a female-like transcriptome in B6. Gene expression is highly variable in F2 XY gonads from B6 and 129S1 intercrosses, yet strong correlations emerged. We estimated the F2 coexpression network and predicted roles for genes of unknown function based on their connectivity and position within the network. A genetic analysis of the F2 population detected autosomal regions that control the expression of many sex-related genes, including Sry (sex-determining region of the Y chromosome) and Sox9 (Sry-box containing gene 9), the key regulators of male sex determination. Our results reveal the complex transcription architecture underlying sex determination, and provide a mechanism by which individuals may be sensitized for sex reversal. PMID:19884258

  14. Activating and Elucidating Metabolism of Complex Sugars in Yarrowia lipolytica.

    PubMed

    Ryu, Seunghyun; Hipp, Julie; Trinh, Cong T

    2016-02-01

    The oleaginous yeast Yarrowia lipolytica is an industrially important host for production of organic acids, oleochemicals, lipids, and proteins with broad biotechnological applications. Albeit known for decades, the unique native metabolism of Y. lipolytica for using complex fermentable sugars, which are abundant in lignocellulosic biomass, is poorly understood. In this study, we activated and elucidated the native sugar metabolism in Y. lipolytica for cell growth on xylose and cellobiose as well as their mixtures with glucose through comprehensive metabolic and transcriptomic analyses. We identified 7 putative glucose-specific transporters, 16 putative xylose-specific transporters, and 4 putative cellobiose-specific transporters that are transcriptionally upregulated for growth on respective single sugars. Y. lipolytica is capable of using xylose as a carbon source, but xylose dehydrogenase is the key bottleneck of xylose assimilation and is transcriptionally repressed by glucose. Y. lipolytica has a set of 5 extracellular and 6 intracellular β-glucosidases and is capable of assimilating cellobiose via extra- and intracellular mechanisms, the latter being dominant for growth on cellobiose as a sole carbon source. Strikingly, Y. lipolytica exhibited enhanced sugar utilization for growth in mixed sugars, with strong carbon catabolite activation for growth on the mixture of xylose and cellobiose and with mild carbon catabolite repression of glucose on xylose and cellobiose. The results of this study shed light on fundamental understanding of the complex native sugar metabolism of Y. lipolytica and will help guide inverse metabolic engineering of Y. lipolytica for enhanced conversion of biomass-derived fermentable sugars to chemicals and fuels. PMID:26682853

  15. Activating and Elucidating Metabolism of Complex Sugars in Yarrowia lipolytica

    PubMed Central

    Ryu, Seunghyun; Hipp, Julie

    2015-01-01

    The oleaginous yeast Yarrowia lipolytica is an industrially important host for production of organic acids, oleochemicals, lipids, and proteins with broad biotechnological applications. Albeit known for decades, the unique native metabolism of Y. lipolytica for using complex fermentable sugars, which are abundant in lignocellulosic biomass, is poorly understood. In this study, we activated and elucidated the native sugar metabolism in Y. lipolytica for cell growth on xylose and cellobiose as well as their mixtures with glucose through comprehensive metabolic and transcriptomic analyses. We identified 7 putative glucose-specific transporters, 16 putative xylose-specific transporters, and 4 putative cellobiose-specific transporters that are transcriptionally upregulated for growth on respective single sugars. Y. lipolytica is capable of using xylose as a carbon source, but xylose dehydrogenase is the key bottleneck of xylose assimilation and is transcriptionally repressed by glucose. Y. lipolytica has a set of 5 extracellular and 6 intracellular β-glucosidases and is capable of assimilating cellobiose via extra- and intracellular mechanisms, the latter being dominant for growth on cellobiose as a sole carbon source. Strikingly, Y. lipolytica exhibited enhanced sugar utilization for growth in mixed sugars, with strong carbon catabolite activation for growth on the mixture of xylose and cellobiose and with mild carbon catabolite repression of glucose on xylose and cellobiose. The results of this study shed light on fundamental understanding of the complex native sugar metabolism of Y. lipolytica and will help guide inverse metabolic engineering of Y. lipolytica for enhanced conversion of biomass-derived fermentable sugars to chemicals and fuels. PMID:26682853

  16. Elucidating the role of Early Maladaptive Schemas for psychotic symptomatology.

    PubMed

    Sundag, Johanna; Ascone, Leonie; de Matos Marques, Anna; Moritz, Steffen; Lincoln, Tania M

    2016-04-30

    Although cognitive accounts postulate negative self-concepts as a causal factor in the emergence of psychotic symptoms, little is known about the role of specific self-schemas for psychotic symptomatology. Building on a differentiated and treatment-informed schema model, we aimed to elucidate the role of Early Maladaptive Schemas (EMS) for psychotic symptomatology, particularly their specificity to patients with psychosis and their association with positive versus negative symptoms. We assessed EMS with the Young Schema Questionnaire in patients with psychosis (n=81), patients with depression (n=28) as well as healthy participants (n=60). In the psychosis sample symptoms were rated using the Positive and Negative Syndrome Scale. In comparison to healthy participants, patients with either psychosis or depression showed a higher overall number and intensity of EMS whereas the psychosis and the depression sample did not significantly differ. The overall number and intensity of EMS were significantly associated with positive but not with negative symptoms. Contrary to previous findings, patients with psychosis and patients with depression did not differ in the EMS subscale Mistrust/Abuse. The results suggest that EMS are particularly relevant to positive symptoms. Our findings imply that addressing maladaptive schemas in patients with psychosis by making use of the schema-concept holds potential. PMID:27086211

  17. The nucleotide exchange factor MGE exerts a key function in the ATP-dependent cycle of mt-Hsp70-Tim44 interaction driving mitochondrial protein import.

    PubMed Central

    Schneider, H C; Westermann, B; Neupert, W; Brunner, M

    1996-01-01

    Import of preproteins into the mitochondrial matrix is driven by the ATP-dependent interaction of mt-Hsp70 with the peripheral inner membrane import protein Tim44 and the preprotein in transit. We show that Mge1p, a co-chaperone of mt-Hsp70, plays a key role in the ATP-dependent import reaction cycle in yeast. Our data suggest a cycle in which the mt-Hsp70-Tim44 complex forms with ATP: Mge1p promotes assembly of the complex in the presence of ATP. Hydrolysis of ATP by mt-Hsp70 occurs in complex with Tim44. Mge1p is then required for the dissociation of the ADP form of mt-Hsp70 from Tim44 after release of inorganic phosphate but before release of ADP. ATP hydrolysis and complex dissociation are accompanied by tight binding of mt-Hsp70 to the preprotein in transit. Subsequently, the release of mt-Hsp70 from the polypeptide chain is triggered by Mge1p which promotes release of ADP from mt-Hsp70. Rebinding of ATP to mt-Hsp70 completes the reaction cycle. Images PMID:8918457

  18. Reproductive and Obstetric Factors Are Key Predictors of Maternal Anemia during Pregnancy in Ethiopia: Evidence from Demographic and Health Survey (2011)

    PubMed Central

    Alemu, Taddese; Umeta, Melaku

    2015-01-01

    Anemia is a major public health problem worldwide. In Ethiopia, a nationally representative and consistent evidence is lacking on the prevalence and determinants during pregnancy. We conducted an in-depth analysis of demographic and health survey for the year 2011 which is a representative data collected from all regions in Ethiopia. Considering maternal anemia as an outcome variable, predicting variables from sociodemographic, household, and reproductive/obstetric characteristics were identified for analyses. Logistic regression model was applied to identify predictors at P < 0.05. The prevalence of anemia among pregnant women was 23%. Maternal age, region, pregnancy trimester, number of under five children, previous history of abortion (termination of pregnancy), breastfeeding practices, and number of antenatal care visits were key independent predictors of anemia during pregnancy. In conclusion, the level of anemia during pregnancy is a moderate public health problem in Ethiopia. Yet, special preventive measures should be undertaken for pregnant women who are older in age and having too many under five children and previous history of abortion. Further evidence is expected to be generated concerning why pregnant mothers from the eastern part of the country and those with better access to radio disproportionately develop anemia more than their counterparts. PMID:26417454

  19. Perceived Threat and Corroboration: Key Factors That Improve a Predictive Model of Trust in Internet-based Health Information and Advice

    PubMed Central

    Harris, Peter R; Briggs, Pam

    2011-01-01

    Background How do people decide which sites to use when seeking health advice online? We can assume, from related work in e-commerce, that general design factors known to affect trust in the site are important, but in this paper we also address the impact of factors specific to the health domain. Objective The current study aimed to (1) assess the factorial structure of a general measure of Web trust, (2) model how the resultant factors predicted trust in, and readiness to act on, the advice found on health-related websites, and (3) test whether adding variables from social cognition models to capture elements of the response to threatening, online health-risk information enhanced the prediction of these outcomes. Methods Participants were asked to recall a site they had used to search for health-related information and to think of that site when answering an online questionnaire. The questionnaire consisted of a general Web trust questionnaire plus items assessing appraisals of the site, including threat appraisals, information checking, and corroboration. It was promoted on the hungersite.com website. The URL was distributed via Yahoo and local print media. We assessed the factorial structure of the measures using principal components analysis and modeled how well they predicted the outcome measures using structural equation modeling (SEM) with EQS software. Results We report an analysis of the responses of participants who searched for health advice for themselves (N = 561). Analysis of the general Web trust questionnaire revealed 4 factors: information quality, personalization, impartiality, and credible design. In the final SEM model, information quality and impartiality were direct predictors of trust. However, variables specific to eHealth (perceived threat, coping, and corroboration) added substantially to the ability of the model to predict variance in trust and readiness to act on advice on the site. The final model achieved a satisfactory fit: χ2 5 = 10

  20. Quantitative Phosphoproteomics Analysis Reveals a Key Role of Insulin Growth Factor 1 Receptor (IGF1R) Tyrosine Kinase in Human Sperm Capacitation*

    PubMed Central

    Wang, Jing; Qi, Lin; Huang, Shaoping; Zhou, Tao; Guo, Yueshuai; Wang, Gaigai; Guo, Xuejiang; Zhou, Zuomin; Sha, Jiahao

    2015-01-01

    One of the most important changes during sperm capacitation is the enhancement of tyrosine phosphorylation. However, the mechanisms of protein tyrosine phosphorylation during sperm capacitation are not well studied. We used label-free quantitative phosphoproteomics to investigate the overall phosphorylation events during sperm capacitation in humans and identified 231 sites with increased phosphorylation levels. Motif analysis using the NetworKIN algorithm revealed that the activity of tyrosine phosphorylation kinases insulin growth factor 1 receptor (IGF1R)/insulin receptor is significantly enriched among the up-regulated phosphorylation substrates during capacitation. Western blotting further confirmed inhibition of IGF1R with inhibitors GSK1904529A and NVP-AEW541, which inhibited the increase in tyrosine phosphorylation levels during sperm capacitation. Additionally, sperm hyperactivated motility was also inhibited by GSK1904529A and NVP-AEW541 but could be up-regulated by insulin growth factor 1, the ligand of IGF1R. Thus, the IGF1R-mediated tyrosine phosphorylation pathway may play important roles in the regulation of sperm capacitation in humans and could be a target for improvement in sperm functions in infertile men. PMID:25693802

  1. Group 3 sigma factor gene, sigJ, a key regulator of desiccation tolerance, regulates the synthesis of extracellular polysaccharide in cyanobacterium Anabaena sp. strain PCC 7120

    PubMed Central

    Yoshimura, Hidehisa; Okamoto, Shinobu; Tsumuraya, Yoichi; Ohmori, Masayuki

    2007-01-01

    Abstract The changes in the expression of sigma factor genes during dehydration in terrestrial Nostoc HK-01 and aquatic Anabaena PCC 7120 were determined. The expression of the sigJ gene in terrestrial Nostoc HK-01, which is homologous to sigJ (alr0277) in aquatic Anabaena PCC 7120, was significantly induced in the mid-stage of dehydration. We constructed a higher-expressing transformant of the sigJ gene (HE0277) in Anabaena PCC 7120, and the transformant acquired desiccation tolerance. The results of Anabaena oligonucleotide microarray experiments showed that a comparatively large number of genes relating to polysaccharide biosynthesis were upregulated in the HE0277 cells. The extracellular polysaccharide released into the culture medium of the HE0277 cells was as much as 3.2-fold more than that released by the control cells. This strongly suggests that the group 3 sigma factor gene sigJ is fundamental and conducive to desiccation tolerance in these cyanobacteria. PMID:17376888

  2. Determination of a Comprehensive Alternative Splicing Regulatory Network and Combinatorial Regulation by Key Factors during the Epithelial-to-Mesenchymal Transition.

    PubMed

    Yang, Yueqin; Park, Juw Won; Bebee, Thomas W; Warzecha, Claude C; Guo, Yang; Shang, Xuequn; Xing, Yi; Carstens, Russ P

    2016-06-01

    The epithelial-to-mesenchymal transition (EMT) is an essential biological process during embryonic development that is also implicated in cancer metastasis. While the transcriptional regulation of EMT has been well studied, the role of alternative splicing (AS) regulation in EMT remains relatively uncharacterized. We previously showed that the epithelial cell-type-specific proteins epithelial splicing regulatory proteins 1 (ESRP1) and ESRP2 are important for the regulation of many AS events that are altered during EMT. However, the contributions of the ESRPs and other splicing regulators to the AS regulatory network in EMT require further investigation. Here, we used a robust in vitro EMT model to comprehensively characterize splicing switches during EMT in a temporal manner. These investigations revealed that the ESRPs are the major regulators of some but not all AS events during EMT. We determined that the splicing factor RBM47 is downregulated during EMT and also regulates numerous transcripts that switch splicing during EMT. We also determined that Quaking (QKI) broadly promotes mesenchymal splicing patterns. Our study highlights the broad role of posttranscriptional regulation during the EMT and the important role of combinatorial regulation by different splicing factors to fine tune gene expression programs during these physiological and developmental transitions. PMID:27044866

  3. Use of a Generalized Additive Model to Investigate Key Abiotic Factors Affecting Microcystin Cellular Quotas in Heavy Bloom Areas of Lake Taihu

    PubMed Central

    Tao, Min; Xie, Ping; Chen, Jun; Qin, Boqiang; Zhang, Dawen; Niu, Yuan; Zhang, Meng; Wang, Qing; Wu, Laiyan

    2012-01-01

    Lake Taihu is the third largest freshwater lake in China and is suffering from serious cyanobacterial blooms with the associated drinking water contamination by microcystin (MC) for millions of citizens. So far, most studies on MCs have been limited to two small bays, while systematic research on the whole lake is lacking. To explain the variations in MC concentrations during cyanobacterial bloom, a large-scale survey at 30 sites across the lake was conducted monthly in 2008. The health risks of MC exposure were high, especially in the northern area. Both Microcystis abundance and MC cellular quotas presented positive correlations with MC concentration in the bloom seasons, suggesting that the toxic risks during Microcystis proliferations were affected by variations in both Microcystis density and MC production per Microcystis cell. Use of a powerful predictive modeling tool named generalized additive model (GAM) helped visualize significant effects of abiotic factors related to carbon fixation and proliferation of Microcystis (conductivity, dissolved inorganic carbon (DIC), water temperature and pH) on MC cellular quotas from recruitment period of Microcystis to the bloom seasons, suggesting the possible use of these factors, in addition to Microcystis abundance, as warning signs to predict toxic events in the future. The interesting relationship between macrophytes and MC cellular quotas of Microcystis (i.e., high MC cellular quotas in the presence of macrophytes) needs further investigation. PMID:22384128

  4. Use of a generalized additive model to investigate key abiotic factors affecting microcystin cellular quotas in heavy bloom areas of Lake Taihu.

    PubMed

    Tao, Min; Xie, Ping; Chen, Jun; Qin, Boqiang; Zhang, Dawen; Niu, Yuan; Zhang, Meng; Wang, Qing; Wu, Laiyan

    2012-01-01

    Lake Taihu is the third largest freshwater lake in China and is suffering from serious cyanobacterial blooms with the associated drinking water contamination by microcystin (MC) for millions of citizens. So far, most studies on MCs have been limited to two small bays, while systematic research on the whole lake is lacking. To explain the variations in MC concentrations during cyanobacterial bloom, a large-scale survey at 30 sites across the lake was conducted monthly in 2008. The health risks of MC exposure were high, especially in the northern area. Both Microcystis abundance and MC cellular quotas presented positive correlations with MC concentration in the bloom seasons, suggesting that the toxic risks during Microcystis proliferations were affected by variations in both Microcystis density and MC production per Microcystis cell. Use of a powerful predictive modeling tool named generalized additive model (GAM) helped visualize significant effects of abiotic factors related to carbon fixation and proliferation of Microcystis (conductivity, dissolved inorganic carbon (DIC), water temperature and pH) on MC cellular quotas from recruitment period of Microcystis to the bloom seasons, suggesting the possible use of these factors, in addition to Microcystis abundance, as warning signs to predict toxic events in the future. The interesting relationship between macrophytes and MC cellular quotas of Microcystis (i.e., high MC cellular quotas in the presence of macrophytes) needs further investigation. PMID:22384128

  5. Enhancement by tumor necrosis factor alpha of dengue virus-induced endothelial cell production of reactive nitrogen and oxygen species is key to hemorrhage development.

    PubMed

    Yen, Yu-Ting; Chen, Hsuen-Chin; Chen, Hseun-Chin; Lin, Yang-Ding; Shieh, Chi-Chang; Wu-Hsieh, Betty A

    2008-12-01

    Hemorrhage is a severe manifestation of dengue disease. Virus strain and host immune response have been implicated as the risk factors for hemorrhage development. To delineate the complex interplay between the virus and the host, we established a dengue hemorrhage model in immune-competent mice. Mice inoculated intradermally with dengue virus develop hemorrhage within 3 days. In the present study, we showed by the presence of NS1 antigen and viral nuclei acid that dengue virus actively infects the endothelium at 12 h and 24 h after inoculation. Temporal studies showed that beginning at day 2, there was macrophage infiltration into the vicinity of the endothelium, increased tumor necrosis factor alpha (TNF-alpha) production, and endothelial cell apoptosis in the tissues. In the meantime, endothelial cells in the hemorrhage tissues expressed inducible nitric oxide synthase (iNOS) and nitrotyrosine. In vitro studies showed that primary mouse and human endothelial cells were productively infected by dengue virus. Infection by dengue virus induced endothelial cell production of reactive nitrogen and oxygen species and apoptotic cell death, which was greatly enhanced by TNF-alpha. N(G)-nitro-L-arginine methyl ester and N-acetyl cysteine reversed the effects of dengue virus and TNF-alpha on endothelial cells. Importantly, hemorrhage development and the severity of hemorrhage were greatly reduced in mice lacking iNOS or p47(phox) or treatment with oxidase inhibitor, pointing to the critical roles of reactive nitrogen and oxygen species in dengue hemorrhage. PMID:18842737

  6. NFκB2/p100 is a key factor for endotoxin tolerance in human monocytes: a demonstration using primary human monocytes from patients with sepsis.

    PubMed

    Cubillos-Zapata, Carolina; Hernández-Jiménez, Enrique; Toledano, Víctor; Esteban-Burgos, Laura; Fernández-Ruíz, Irene; Gómez-Piña, Vanesa; Del Fresno, Carlos; Siliceo, María; Prieto-Chinchiña, Patricia; Pérez de Diego, Rebeca; Boscá, Lisardo; Fresno, Manuel; Arnalich, Francisco; López-Collazo, Eduardo

    2014-10-15

    Endotoxin tolerance (ET) is a state of reduced responsiveness to endotoxin stimulation after a primary bacterial insult. This phenomenon has been described in several pathologies, including sepsis, in which an endotoxin challenge results in reduced cytokine production. In this study, we show that the NFκ L chain enhancer of activated B cells 2 (NFκB2)/p100 was overexpressed and accumulated in a well-established in vitro human monocyte model of ET. The p100 accumulation in these cells inversely correlated with the inflammatory response after LPS stimulation. Knocking down NFκB2/p100 using small interfering RNA in human monocytes further indicated that p100 expression is a crucial factor in the progression of ET. The monocytes derived from patients with sepsis had high levels of p100, and a downregulation of NFκB2/p100 in these septic monocytes reversed their ET status. PMID:25225662

  7. Fitting in or opting out: A review of key social-psychological factors influencing a sense of belonging for women in physics

    NASA Astrophysics Data System (ADS)

    Lewis, Karyn L.; Stout, Jane G.; Pollock, Steven J.; Finkelstein, Noah D.; Ito, Tiffany A.

    2016-12-01

    [This paper is part of the Focused Collection on Gender in Physics.] A number of cultural, social, environmental, and biological factors have been suggested to explain women's relatively lower representation in physics and other science, technology, engineering, and math (STEM) fields. Given its persistence, the causes of gender disparities are likely to be complex and multiply determined. In this review paper, we discuss how a sense of belonging relates to women's interest, persistence, and achievement in physics. We explore what it means to "fit in" and belong in academic contexts, the situational and interpersonal antecedents to belonging, and the consequences of a lack of belonging. We review the empirical evidence for the efficacy of interventions designed to bolster a sense of belonging. Based on these interventions we conclude the paper with a number of practical recommendations to affirm women's sense of belonging and create more welcoming and inclusive physics environments for all students.

  8. The basic helix-loop-helix differentiation factor Nex1/MATH-2 functions as a key activator of the GAP-43 gene

    PubMed Central

    Uittenbogaard, Martine; Martinka, Debra L.; Chiaramello, Anne

    2006-01-01

    Nex1/MATH-2 is a neurogenic basic Helix-Loop-Helix (bHLH) transcription factor that belongs to the NeuroD subfamily. Its expression parallels that of the GAP-43 gene and peaks during brain development, when neurite outgrowth and synaptogenesis are highly active. We previously observed a direct correlation between the levels of expression of Nex1 and GAP-43 proteins, which resulted in extensive neurite outgrowth and neuronal differentiation of PC12 cells in the absence of nerve growth factor. Since the GAP-43 gene is a target for bHLH regulation, we investigated whether Nex1 could regulate the activity of the GAP-43 promoter. We found that among the members of the NeuroD subfamily, Nex1 promoted maximal activity of the GAP-43 promoter. The Nex1-mediated activity is restricted to the conserved E1–E2 cluster located near the major transcription start sites. By electrophoretic mobility shift assay and site-directed mutagenesis, we showed that Nex1 binds as homodimers and that the E1 E-box is a high affinity binding site. We further found that Nex1 released the ME1 E-protein-mediated repression in a concentration dependent manner. Thus, the E1–E2 cluster has a dual function: it can mediate activation or repression depending on the interacting bHLH proteins. Finally, a series of N-terminal and C-terminal deletions revealed that Nex1 transcriptional activity is linked to two distinct transactivation domains, TAD1 and TAD2, with TAD1 being unique to Nex1. Together, our results suggest that Nex1 may engage in selective interactions with components of the core transcriptional machinery whose assembly is dictated by the architecture of the GAP-43 promoter and cellular environment. PMID:12562512

  9. A Major Latex-Like Protein Is a Key Factor in Crop Contamination by Persistent Organic Pollutants1[W][OA

    PubMed Central

    Inui, Hideyuki; Sawada, Mami; Goto, Junya; Yamazaki, Kiyoshi; Kodama, Noriko; Tsuruta, Hiroki; Eun, Heesoo

    2013-01-01

    This is the first report, to our knowledge, to reveal important factors by which members of the Cucurbitaceae family, such as cucumber (Cucumis sativus), watermelon (Citrullus lanatus), melon (Cucumis melo), pumpkin (Cucurbita pepo), squash (C. pepo), and zucchini (C. pepo), are selectively polluted with highly toxic hydrophobic contaminants, including organochlorine insecticides and dioxins. Xylem sap of C. pepo ssp. pepo, which is a high accumulator of hydrophobic compounds, solubilized the hydrophobic compound pyrene into the aqueous phase via some protein(s). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of xylem sap of two C. pepo subspecies revealed that the amount of 17-kD proteins in C. pepo ssp. pepo was larger than that in C. pepo ssp. ovifera, a low accumulator, suggesting that these proteins may be related to the translocation of hydrophobic compounds. The protein bands at 17 kD contained major latex-like proteins (MLPs), and the corresponding genes MLP-PG1, MLP-GR1, and MLP-GR3 were cloned from the C. pepo cultivars Patty Green and Gold Rush. Expression of the MLP-GR3 gene in C. pepo cultivars was positively correlated with the band intensity of 17-kD proteins and bioconcentration factors toward dioxins and dioxin-like compounds. Recombinant MLP-GR3 bound polychlorinated biphenyls immobilized on magnetic beads, whereas recombinant MLP-PG1 and MLP-GR1 did not. These results indicate that the high expression of MLP-GR3 in C. pepo ssp. pepo plants and the existence of MLP-GR3 in their xylem sap are related to the efficient translocation of hydrophobic contaminants. These findings should be useful for decreasing the contamination of fruit of the Cucurbitaceae family as well as the phytoremediation of hydrophobic contaminants. PMID:23404917

  10. Amyloid beta deposition and phosphorylated tau accumulation are key features in aged choroidal vessels in the complement factor H knock out model of retinal degeneration.

    PubMed

    Aboelnour, Asmaa; Kam, Jaimie Hoh; Elnasharty, M A; Sayed-Ahmed, Ahmed; Jeffery, Glen

    2016-06-01

    Extra-cellular deposition including amyloid beta (Aβ) is a feature of retinal ageing. It has been documented for Bruch's membrane (BM) where Aβ is elevated in complement factor H knockout mice (Cfh(-/-)) proposed as a model for age related macular degeneration. However, arterial deposition in choroidal vessels prior to perfusion across BM has not been examined. Aβ is associated with tau phosphorylation and these are linked in blood vessels in Alzheimers Disease where they can drive perivascular pathology. Here we ask if Aβ, tau and phosphorylated tau are features of ageing in choroidal vessels in 12 month C57 BL/6 and Cfh(-/-) mice, using immune staining and Western blot analysis. Greater levels of Aβ and phosphorylated tau are found in choroidal vessels in Cfh(-/-) mice. Western blot revealed a 40% increase in Aβ in Cfh(-/-) over C57 BL/6 mice. Aβ deposits coat around 55% of the luminal wall in Cfh(-/-) compared to only about 40% in C57 BL/6. Total tau was similar in both groups, but phosphorylated tau increased by >100% in Cfh(-/-) compared to C57 BL/6 and covered >75% of the luminal wall compared to 50% in C57 BL/6. Hence, phosphorylated tau is a marked choroidal feature in this mouse model. Aβ deposition was clumped in Cfh(-/-) mice and likely to influence blood flow dynamics. Disturbed flow is associated with atherogenesis and may be related to the accumulation of membrane attack complex recently identified between choroidal vessels in those at high risk of macular degeneration due to complement factor H polymorphisms. PMID:27181225

  11. The basic helix-loop-helix differentiation factor Nex1/MATH-2 functions as a key activator of the GAP-43 gene.

    PubMed

    Uittenbogaard, Martine; Martinka, Debra L; Chiaramello, Anne

    2003-02-01

    Nex1/MATH-2 is a neurogenic basic Helix-Loop-Helix (bHLH) transcription factor that belongs to the NeuroD subfamily. Its expression parallels that of the GAP-43 gene and peaks during brain development, when neurite outgrowth and synaptogenesis are highly active. We previously observed a direct correlation between the levels of expression of Nex1 and GAP-43 proteins, which resulted in extensive neurite outgrowth and neuronal differentiation of PC12 cells in the absence of nerve growth factor. Since the GAP-43 gene is a target for bHLH regulation, we investigated whether Nex1 could regulate the activity of the GAP-43 promoter. We found that among the members of the NeuroD subfamily, Nex1 promoted maximal activity of the GAP-43 promoter. The Nex1-mediated activity is restricted to the conserved E1-E2 cluster located near the major transcription start sites. By electrophoretic mobility shift assay and site-directed mutagenesis, we showed that Nex1 binds as homodimers and that the E1 E-box is a high affinity binding site. We further found that Nex1 released the ME1 E-protein-mediated repression in a concentration dependent manner. Thus, the E1-E2 cluster has a dual function: it can mediate activation or repression depending on the interacting bHLH proteins. Finally, a series of N-terminal and C-terminal deletions revealed that Nex1 transcriptional activity is linked to two distinct transactivation domains, TAD1 and TAD2, with TAD1 being unique to Nex1. Together, our results suggest that Nex1 may engage in selective interactions with components of the core transcriptional machinery whose assembly is dictated by the architecture of the GAP-43 promoter and cellular environment. PMID:12562512

  12. Metabolomic Elucidation of the Effects of Curcumin on Fibroblast-Like Synoviocytes in Rheumatoid Arthritis.

    PubMed

    Ahn, Joong Kyong; Kim, Sooah; Hwang, Jiwon; Kim, Jungyeon; Lee, You Sun; Koh, Eun-Mi; Kim, Kyoung Heon; Cha, Hoon-Suk

    2015-01-01

    Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by synovial inflammation and joint disability. Curcumin is known to be effective in ameliorating joint inflammation in RA. To obtain new insights into the effect of curcumin on primary fibroblast-like synoviocytes (FLS, N = 3), which are key effector cells in RA, we employed gas chromatography/time-of-flight mass spectrometry (GC/TOF-MS)-based metabolomics. Metabolomic profiling of tumor necrosis factor (TNF)-α-stimulated and curcumin-treated FLS was performed using GC/TOF-MS in conjunction with univariate and multivariate statistical analyses. A total of 119 metabolites were identified. Metabolomic analysis revealed that metabolite profiles were clearly distinct between TNF-α-stimulated vs. the control group (not stimulated by TNF-α or curcumin). Treatment of FLS with curcumin showed that the metabolic perturbation by TNF-α could be reversed to that of the control group to a considerable extent. Curcumin-treated FLS had higher restoration of amino acid and fatty acid metabolism, as indicated by the prominent metabolic restoration of intermediates of amino acid and fatty acid metabolism, compared with that observed in TNF-α-stimulated FLS. In particular, the abundance of glycine, citrulline, arachidonic acid, and saturated fatty acids in TNF-α-stimulated FLS was restored to the control level after treatment with curcumin, suggesting that the effect of curcumin on preventing joint inflammation may be elucidated with the levels of these metabolites. Our results suggest that GC/TOF-MS-based metabolomic investigation using FLS has the potential for discovering the mechanism of action of curcumin and new targets for therapeutic drugs in RA. PMID:26716989

  13. Metabolomic Elucidation of the Effects of Curcumin on Fibroblast-Like Synoviocytes in Rheumatoid Arthritis

    PubMed Central

    Hwang, Jiwon; Kim, Jungyeon; Lee, You Sun; Koh, Eun-Mi; Kim, Kyoung Heon; Cha, Hoon-Suk

    2015-01-01

    Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by synovial inflammation and joint disability. Curcumin is known to be effective in ameliorating joint inflammation in RA. To obtain new insights into the effect of curcumin on primary fibroblast-like synoviocytes (FLS, N = 3), which are key effector cells in RA, we employed gas chromatography/time-of-flight mass spectrometry (GC/TOF-MS)-based metabolomics. Metabolomic profiling of tumor necrosis factor (TNF)-α-stimulated and curcumin-treated FLS was performed using GC/TOF-MS in conjunction with univariate and multivariate statistical analyses. A total of 119 metabolites were identified. Metabolomic analysis revealed that metabolite profiles were clearly distinct between TNF-α-stimulated vs. the control group (not stimulated by TNF-α or curcumin). Treatment of FLS with curcumin showed that the metabolic perturbation by TNF-α could be reversed to that of the control group to a considerable extent. Curcumin-treated FLS had higher restoration of amino acid and fatty acid metabolism, as indicated by the prominent metabolic restoration of intermediates of amino acid and fatty acid metabolism, compared with that observed in TNF-α-stimulated FLS. In particular, the abundance of glycine, citrulline, arachidonic acid, and saturated fatty acids in TNF-α-stimulated FLS was restored to the control level after treatment with curcumin, suggesting that the effect of curcumin on preventing joint inflammation may be elucidated with the levels of these metabolites. Our results suggest that GC/TOF-MS-based metabolomic investigation using FLS has the potential for discovering the mechanism of action of curcumin and new targets for therapeutic drugs in RA. PMID:26716989

  14. Assessing the Potential Content of Ethyl Carbamate in White, Red, and Rosé Wines as a Key Factor for Pursuing Urea Degradation by Purified Acid Urease.

    PubMed

    Cerreti, Martina; Fidaleo, Marcello; Benucci, Ilaria; Liburdi, Katia; Tamborra, Pasquale; Moresi, Mauro

    2016-07-01

    The ethyl carbamate (EC) content of a wine after a given temperature-time storage was theoretically predicted from the potential concentration of ethyl carbamate (PEC), as determined via an accelerated EC formation test. Such information was used to decide whether an enzymatic treatment was needed to reduce the wine urea level before bottling/aging. To this end, 6 white, red, and rosé wines, manufactured in Italy as such or enriched with urea, were tested for their PEC content either before or after enzymatic treatment using a purified acid urease preparation derived from Lactobacillus fermentum. The treatment was severely affected by the total phenolic content (TP) of the wine, the estimated pseudo-first-order kinetic rate constant for NH3 formation reducing by a factor of approximately 2000 as the TP increased from 0 to 1.64 g L(-1) . Such a sensitivity to TP was by far greater than that pertaining to a killed cell-based enzyme preparation used previously. Urea hydrolysis was successful at reducing EC concentration in wines with low levels of TP and other EC precursors. PMID:27239804

  15. The key role of socio-demographic and socio-environmental factors in urban malaria occurrence and control - An illustration using the city of Yaoundé.

    PubMed

    Ngom, Roland; Siegmund, Alexander

    2015-05-01

    Cities in developing countries are experiencing an unprecedented population growth that illustrates a demographic transition and a shift towards modernization with consequences on their epidemiological profiles. However, this change is characterized by an important rural-to-urban social and cultural transfer that can bias the expected epidemiological transition; at the same time, this transfer renders the understanding of the occurrence of communicable diseases more complex than it appears. Urban malaria occurrence was modeled for the city of Yaoundé in Cameroon. Retrospective interviews were conducted to describe a variety of epidemiological, social and environmental variables at the household level. Various ecological variables originating from remote sensing data were also integrated. Multivariate multilevel negative binomial analyses were developed to evaluate the distinct contributions of explanatory social and ecological variables. Spatial models based on the level of urbanity were implemented to understand the intelligence of urban malaria as characterized by those variables. The results showed an overall higher statistical importance of socio-environmental variables, particularly those describing rural origin socio-cultural features in terms of non-conventional housing types and urban agriculture (UA). The spatial patterns of the urban malaria occurrences displayed a complex combination of population density gradients and socio-environmental factors, illustrating the importance of conventional urban features over rural/non-conventional features in reducing the occurrence of urban malaria. PMID:25498155

  16. Identification of a cis-acting factor modulating the transcription of FUM1, a key fumonisin-biosynthetic gene in the fungal maize pathogen Fusarium verticillioides.

    PubMed

    Montis, V; Pasquali, M; Visentin, I; Karlovsky, P; Cardinale, F

    2013-02-01

    Fumonisins, toxic secondary metabolites produced by some Fusarium spp. and Aspergillus niger, have strong agro-economic and health impacts. The genes needed for their biosynthesis, named FUM, are clustered and co-expressed in fumonisin producers. In eukaryotes, coordination of transcription can be attained through shared transcription factors, whose specificity relies on the recognition of cis-regulatory elements on target promoters. A bioinformatic analysis on FUM promoters in the maize pathogens Fusarium verticillioides and Aspergillus niger identified a degenerated, over-represented motif potentially involved in the cis-regulation of FUM genes, and of fumonisin biosynthesis. The same motif was not found in various FUM homologues of fungi that do not produce fumonisins. Comparison of the transcriptional strength of the intact FUM1 promoter with a synthetic version, where the motif had been mutated, was carried out in vivo and in planta for F. verticillioides. The results showed that the motif is important for efficient transcription of the FUM1 gene. PMID:23219667

  17. NFIL3/E4BP4 is a key transcription factor for CD8α⁺ dendritic cell development.

    PubMed

    Kashiwada, Masaki; Pham, Nhat-Long L; Pewe, Lecia L; Harty, John T; Rothman, Paul B

    2011-06-01

    Antigen presentation by mature dendritic cells (DCs) is the first step for initiating adaptive immune responses. DCs are composed of heterogeneous functional subsets; however, the molecular mechanisms that regulate differentiation of specific DC subsets are not understood. Here, we report that the basic leucine zipper transcription factor NFIL3/E4BP4 is essential for the development of CD8α(+) conventional DCs (cDCs). Nfil3(-/-) mice specifically lack CD8α(+) cDCs but not CD8α(-) cDCs or plasmacytoid DCs in lymphoid tissues. Flt3 ligand-dependent generation of CD8α(+) cDCs in lymphoid tissues and CD8α(+)-equivalent cDCs from Nfil3(-/-) bone marrow cells was also impaired. NFIL3 regulates CD8α(+) cDC development in part through Batf3 expression. Importantly, Nfil3(-/-) mice exhibited impaired cross-priming of CD8(+) T cells against cell-associated antigen, a process normally performed by CD8α(+) cDCs, and failed to produce IL-12 after TLR3 stimulation. Thus, NFIL3 plays an essential role in the development of CD8α(+) cDCs. PMID:21474667

  18. Identifying key climate and environmental factors affecting rates of post-fire big sagebrush (Artemisia tridentata) recovery in the northern Columbia Basin, USA

    USGS Publications Warehouse

    Shinneman, Douglas; McIlroy, Susan

    2016-01-01

    Sagebrush steppe of North America is considered highly imperilled, in part owing to increased fire frequency. Sagebrush ecosystems support numerous species, and it is important to understand those factors that affect rates of post-fire sagebrush recovery. We explored recovery of Wyoming big sagebrush (Artemisia tridentata ssp.wyomingensis) and basin big sagebrush (A. tridentata ssp. tridentata) communities following fire in the northern Columbia Basin (Washington, USA). We sampled plots across 16 fires that burned in big sagebrush communities from 5 to 28 years ago, and also sampled nearby unburned locations. Mixed-effects models demonstrated that density of large–mature big sagebrush plants and percentage cover of big sagebrush were higher with time since fire and in plots with more precipitation during the winter immediately following fire, but were lower when precipitation the next winter was higher than average, especially on soils with higher available water supply, and with greater post-fire mortality of mature big sagebrush plants. Bunchgrass cover 5 to 28 years after fire was predicted to be lower with higher cover of both shrubs and non-native herbaceous species, and only slightly higher with time. Post-fire recovery of big sagebrush in the northern Columbia Basin is a slow process that may require several decades on average, but faster recovery rates may occur under specific site and climate conditions.

  19. Monoclonal antibodies against all known variants of EspA: development of a simple diagnostic test for enteropathogenic Escherichia coli based on a key virulence factor

    PubMed Central

    Reissbrodt, Rolf; Kresse, Andreas; Pavankumar, Asalapuram; Sankaran, Krishnan; James, Roger; Jesudason, Mary; Anandan, Shalini; Prakasam, Agila; Balaji, Veeraraghavan; Dutta, Shanta; Dutta, Sanjucta; Ramamurthy, Thandavarayan; Fischer, Renate; Sander, Peter; Schaumann, Reiner; Navarro, Armando; Williams, Peter

    2014-01-01

    Enteropathogenic Escherichia coli (EPEC) are a major cause of infant diarrhoea in developing countries and a significant public health issue in industrialized countries. Currently there are no simple tests available for the diagnosis of EPEC. Serology of O-antigens is widely used routinely in many laboratories throughout the world, even though it has been known for many years to be an unreliable indicator of EPEC virulence. We have developed a simple, low-cost immunodiagnostic test based on the EspA filament, an essential virulence factor of EPEC and the related enterohaemorrhagic E. coli (EHEC). Using recombinant proteins of the five major variants of EspA as immunogens, we raised a panel of three monoclonal antibodies in mice that detects all variants of the native target in bacterial cultures. The antibodies proved suitable for application in sandwich-type assays, including ELISA and lateral flow immunoassays (LFI). Prototypes for both assays were specific for EPEC and EHEC strains when tested against a panel of control micro-organisms. We have also developed a simple, affordable culture medium, A/E medium, which optimizes expression of EspA allowing improved sensitivity of detection compared with standard Dulbecco’s modified Eagle’s medium. Together these reagents form the basis of robust, informative tests for EPEC for use especially in developing countries but also for routine screening in any clinical laboratory. PMID:25231626

  20. Application of Structural Equation Models for Elucidating the Ecological Drivers of Anopheles sinensis in the Three Gorges Reservoir

    PubMed Central

    Duo-quan, Wang; Lin-hua, Tang; Heng-hui, Liu; Zhen-cheng, Gu; Xiang, Zheng

    2013-01-01

    Objective To identify the major ecological drivers for malaria vector density using the structural equation model (SEM) in the Three Gorges Reservoir. Method An 11-year longitudinal surveillance of malaria vector as well as its related ecological factors was carried out in the Three Gorges Reservoir. The Delphi method was used to identify associated ecological factors. The structural equation model was repeatedly corrected and improved by the corrected index, combined with the actual situation. The final model was defined by relative simplicity, best fitting as well as the practicality. Result The final model indicated that the direct effects of temperature, livestock, humidity, and breeding on the vector were 0.015, −0.228, 0.450, 0.516 respectively, their total effects on the vector were 0.359, −0.112, 0.850, and 0.043 through different pathways. Conclusion SEM was effective and convenient in elucidating the mechanism by which malaria vector dynamics operated in this study. It identified that the breeding had the highest direct effect on vector and played a key role for mediating effect of temperature and humidity. PMID:23935887

  1. Site Selection for Mars Surveyor Landing Sites: Some Key Factors for 2001 and Relation to Long-Term Exploration of Mars

    NASA Astrophysics Data System (ADS)

    Head, James W.

    1999-01-01

    The Site Selection Process: Site selection as a process can be subdivided into several main elements and these can be represented as the corners of a tetrahedron. Successful site selection outcome requires the interactions between these elements or corners, and should also take into account several other external factors or considerations. In principle, elements should be defined in approximately the following order: (1) major scientific and programmatic goals and objectives: What are the major questions that are being asked, goals that should be achieved, and objectives that must be accomplished. Do programmatic goals (e.g., sample return) differ from mission goals (e.g., precursor to sample return)? It is most helpful if these questions can be placed in the context of site characterization and hypothesis testing (e.g., Was Mars warm and wet in the Noachian? Land at a Noachian-aged site that shows evidence of surface water and characterize it specifically to address this question). Goals and objectives, then, help define important engineering factors such as type of payload, landing regions of interest (highlands, lowlands, smooth, rough, etc.), mobility, mission duration, etc. Goals and objectives then lead to: (2) spacecraft design and engineering landing site constraints: the spacecraft is designed to optimize the areas that will meet the goals and objectives, but this in turn introduces constraints that must be met in the selection of a landing site. Scientific and programmatic goals and objectives also help to define (3), the specific lander scientific payload requirements and capabilities. For example, what observations and experiments are required to address the major questions? How do we characterize the site in reference to the specific questions? Is mobility required and if so, how much? Which experiments are on the spacecraft, which on the rover? The results of these deliberations should lead to a surface exploration strategy, in which the goals and

  2. Elucidating determinants of aerosol composition through particle-type-based receptor modeling

    NASA Astrophysics Data System (ADS)

    McGuire, M. L.; Jeong, C.-H.; Slowik, J. G.; Chang, R. Y.-W.; Corbin, J. C.; Lu, G.; Mihele, C.; Rehbein, P. J. G.; Sills, D. M. L.; Abbatt, J. P. D.; Brook, J. R.; Evans, G. J.

    2011-08-01

    An aerosol time-of-flight mass spectrometer (ATOFMS) was deployed at a semi-rural site in southern Ontario to characterize the size and chemical composition of individual particles. Particle-type-based receptor modelling of these data was used to investigate the determinants of aerosol chemical composition in this region. Individual particles were classified into particle-types and positive matrix factorization (PMF) was applied to their temporal trends to separate and cross-apportion particle-types to factors. The extent of chemical processing for each factor was assessed by evaluating the internal and external mixing state of the characteristic particle-types. The nine factors identified helped to elucidate the coupled interactions of these determinants. Nitrate-laden dust was found to be the dominant type of locally emitted particles measured by ATOFMS. Several factors associated with aerosol transported to the site from intermediate local-to-regional distances were identified: the Organic factor was associated with a combustion source to the north-west; the ECOC Day factor was characterized by nearby local-to-regional carbonaceous emissions transported from the south-west during the daytime; and the Fireworks factor consisted of pyrotechnic particles from the Detroit region following holiday fireworks displays. Regional aerosol from farther emissions sources was reflected through three factors: two Biomass Burning factors and a highly chemically processed Long Range Transport factor. The Biomass Burning factors were separated by PMF due to differences in chemical processing which were in part elucidated by the passage of two thunderstorm gust fronts with different air mass histories. The remaining two factors, ECOC Night and Nitrate Background, represented the night-time partitioning of nitrate to pre-existing particles of different origins. The distinct meteorological conditions observed during this month-long study in the summer of 2007 provided a unique

  3. C55 bacteriocin produced by ETB-plasmid positive Staphylococcus aureus strains is a key factor for competition with S. aureus strains.

    PubMed

    Kawada-Matsuo, Miki; Shammi, Fariha; Oogai, Yuichi; Nakamura, Norifumi; Sugai, Motoyuki; Komatsuzawa, Hitoshi

    2016-03-01

    Exfoliative toxin (ET) produced by Staphylococcus aureus is closely associated with the onset of bullous impetigo. To date, three ETs (ETA, ETB and ETD) have been identified. The gene encoding ETB is located in a plasmid designated pETB. Bacteriocin synthesis genes are also located in this plasmid and pETB-positive strains reportedly produce the C55 bacteriocin. In this study, the antibacterial activity against S. aureus strains of the bacteriocin produced by the pETB-positive strain TY4 was investigated. This bacteriocin demonstrated antibacterial activity against all pETB-negative but not pETB-positive strains, including TY4. Additionally, a TY4- strain from which the pETB plasmid had been deleted exhibited susceptibility to the bacteriocin. Further experiments revealed that two immunity factors (orf 46-47 and orf 48) downstream of the bacteriocin synthesis genes in the pETB plasmid are associated with immunity against the bacteriocin produced by TY4. The TY4- with orf46-47 strain exhibited complete resistance to bacteriocin, whereas the TY4- with orf48 strain exhibited partial resistance. Whether bacteriocin affects the proportion of each strain when co-cultured with S. aureus strains was also investigated. When TY4 or TY4- was co-cultured with 209P strain, which is susceptible to the bacteriocin, the proportion of 209P co-cultured with TY4 was significantly less than when 209P was co-cultured with TY4-, whereas the proportion of TY4- with orf46-48 co-cultured with TY4 was greater than with TY4-. These results suggest that the C55 bacteriocin produced by pETB-positive strains affects the proportion of each strain when pETB-positive and -negative strains co-exist. PMID:26801833

  4. Analysis of NHANES measured blood PCBs in the general US population and application of SHEDS model to identify key exposure factors.

    PubMed

    Xue, Jianping; Liu, Shi V; Zartarian, Valerie G; Geller, Andrew M; Schultz, Bradley D

    2014-11-01

    Studies have shown that the US population continues to be exposed to polychlorinated biphenyls (PCBs), despite their ban more than three decades ago, but the reasons are not fully understood. The objectives of this paper are to characterize patterns of PCBs in blood by age, gender, and ethnicity, and identify major exposure factors. EPA's Stochastic Human Exposure and Dose Simulation (SHEDS)-dietary exposure model was applied, combining fish tissue PCB levels from a NYC Asian Market survey with National Health and Nutrition Examination Survey (NHANES) dietary consumption data, and then linked with blood biomarkers for the same NHANES study subjects. Results reveal that the mean concentration of total PCBs in blood was higher with increasing age; however, for the same age, gender, and ethnicity, the blood PCB concentrations measured in the later NHANES survey were significantly lower than those in the earlier one. The decrease within an age group between the two survey periods lessened with increasing age. Blood PCBs among different ethnicities ranked differently between the older and the younger age groups within each survey. Non-Hispanic Blacks had significantly higher blood PCBs for the >30 year age group. For the 12 to ≤30 year age group, the "Asian, Pacific Islander, Native American or multiracial" group had the highest values, with patterns fairly consistent with fish consumption and modeled PCB exposure patterns. We conclude that for younger people, patterns correspond to reduced environmental contamination over time, and are strongly associated with fish consumption and dietary exposures. Higher PCB concentrations in blood of the older population may partially reflect past exposures to higher environmental PCB concentrations, particularly before the ban. PMID:24424407

  5. Key factors in the acceptability of treatment as prevention (TasP) in Scotland: a qualitative study with communities affected by HIV

    PubMed Central

    Young, I; Flowers, P; McDaid, L M

    2015-01-01

    Objectives There is a clear need to understand the factors that might prevent and/or facilitate the effective use of HIV treatment as prevention (TasP) at an individual level. This paper reports on findings from the first qualitative study in the UK exploring the acceptability of TasP among gay, bisexual and/or men who have sex with men (MSM) and migrant African communities in Scotland. Methods We conducted seven exploratory focus group discussions (FGDs) with convenience samples of MSM (five FGDs, n=22) and mixed-gender African (two FGDs, n=11) participants. Of these, three FGDs were conducted with HIV-positive MSM (n=14) and one FGD with HIV-positive Africans (n=8). We then conducted 34 in-depth interviews (IDIs) with a purposive sample of MSM (n=20) and Africans (n=14, women=10). Half were HIV-positive (MSM, n=10; African, n=7). FGD and IDI data were analysed thematically drawing on predetermined and emergent themes. Results We found that inequalities in HIV literacy could be a barrier to TasP, as could social constraints, such as criminalisation of transmission, increased risk of sexually transmitted infection and increased burden of treatment. We also identified psychological barriers such as perceptions of risk. However, relationships and shared decision making were identified as potential facilitators for TasP. Conclusions Our results suggest that potential use and management of TasP may not be straightforward. It could be contingent on reducing inequalities in HIV literacy, minimising the perceived burden of treatment and other potential risks, and addressing the dynamics of existing and socially acceptable risk management strategies, especially in relation to long-term serodiscordant relationships. PMID:25482649

  6. Comparative proteomic analysis reveals that T3SS, Tfp, and xanthan gum are key factors in initial stages of Citrus sinensis infection by Xanthomonas citri subsp. citri.

    PubMed

    Facincani, Agda P; Moreira, Leandro M; Soares, Márcia R; Ferreira, Cristiano B; Ferreira, Rafael M; Ferro, Maria I T; Ferro, Jesus A; Gozzo, Fabio C; de Oliveira, Julio C F

    2014-03-01

    The bacteria Xanthomonas citri subsp. citri (Xac) is the causal agent of citrus canker. The disease symptoms are characterized by localized host cell hyperplasia followed by tissue necrosis at the infected area. An arsenal of bacterial pathogenicity- and virulence-related proteins is expressed to ensure a successful infection process. At the post-genomic stage of Xac, we used a proteomic approach to analyze the proteins that are displayed differentially over time when the pathogen attacks the host plant. Protein extracts were prepared from infectious Xac grown in inducing medium (XAM1) for 24 h or from host citrus plants for 3 or 5 days after infection, detached times to evaluate the adaptation and virulence of the pathogen. The protein extracts were proteolyzed, and the peptides derived from tryptic digestion were investigated using liquid chromatography and tandem mass spectrometry. Changes in the protein expression profile were compared with the Xac genome and the proteome recently described under non-infectious conditions. An analysis of the proteome of Xac under infectious conditions revealed proteins directly involved in virulence such as the type III secretion system (T3SS) and effector proteins (T3SS-e), the type IV pilus (Tfp), and xanthan gum biosynthesis. Moreover, four new mutants related to proteins detected in the proteome and with different functions exhibited reduced virulence relative to the wild-type proteins. The results of the proteome analysis of infectious Xac define the processes of adaptation to the host and demonstrate the induction of the virulence factors of Xac involved in plant-pathogen interactions. PMID:24676796

  7. Key Role of the Adenylate Moiety and Integrity of the Adenylate-Binding Site for the NAD(+)/H Binding to Mitochondrial Apoptosis-Inducing Factor.

    PubMed

    Sorrentino, Luca; Calogero, Alessandra Maria; Pandini, Vittorio; Vanoni, Maria Antonietta; Sevrioukova, Irina F; Aliverti, Alessandro

    2015-12-01

    Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein with pro-life and pro-death activities, which plays critical roles in mitochondrial energy metabolism and caspase-independent apoptosis. Defects in AIF structure or expression can cause mitochondrial abnormalities leading to mitochondrial defects and neurodegeneration. The mechanism of AIF-induced apoptosis was extensively investigated, whereas the mitochondrial function of AIF is poorly understood. A unique feature of AIF is the ability to form a tight, air-stable charge-transfer (CT) complex upon reaction with NADH and to undergo a conformational switch leading to dimerization, proposed to be important for its vital and lethal functions. Although some aspects of interaction of AIF with NAD(+)/H have been analyzed, its precise mechanism is not fully understood. We investigated how the oxidized and photoreduced wild-type and G307A and -E variants of murine AIF associate with NAD(+)/H and nicotinamide mononucleotide (NMN(+)/H) to determine the role of the adenylate moiety in the binding process. Our results indicate that (i) the adenylate moiety of NAD(+)/H is crucial for the association with AIF and for the subsequent structural reorganization of the complex, but not for protein dimerization, (ii) FAD reduction rather than binding of NAD(+)/H to AIF initiates conformational rearrangement, and (iii) alteration of the adenylate-binding site by the G307E (equivalent to a pathological G308E mutation in human AIF) or G307A replacements decrease the affinity and association rate of NAD(+)/H, which, in turn, perturbs CT complex formation and protein dimerization but has no influence on the conformational switch in the regulatory peptide. PMID:26535916

  8. Why is tick-borne encephalitis increasing? A review of the key factors causing the increasing incidence of human TBE in Swedena

    PubMed Central

    2012-01-01

    to quest for hosts nearly all days of that year. These weather conditions stimulated many people to spend time outdoors in areas where they were at risk of being attacked by infective nymphs. This resulted in at least 284 human cases of overt TBE. The tick season of 2012 also started early with an exceptionally warm March. The abundance of TBEV-infective “hungry” ticks was presumably still relatively high. Precipitation during June and July was rich and will lead to a “good mushroom season”. These factors together are likely to result in a TBE incidence of 2012 similar to or higher than that of 2011. PMID:22937961

  9. Elucidation of functional consequences of signalling pathway interactions

    PubMed Central

    2009-01-01

    Background A great deal of data has accumulated on signalling pathways. These large datasets are thought to contain much implicit information on their molecular structure, interaction and activity information, which provides a picture of intricate molecular networks believed to underlie biological functions. While tremendous advances have been made in trying to understand these systems, how information is transmitted within them is still poorly understood. This ever growing amount of data demands we adopt powerful computational techniques that will play a pivotal role in the conversion of mined data to knowledge, and in elucidating the topological and functional properties of protein - protein interactions. Results A computational framework is presented which allows for the description of embedded networks, and identification of common shared components thought to assist in the transmission of information within the systems studied. By employing the graph theories of network biology - such as degree distribution, clustering coefficient, vertex betweenness and shortest path measures - topological features of protein-protein interactions for published datasets of the p53, nuclear factor kappa B (NF-κB) and G1/S phase of the cell cycle systems were ascertained. Highly ranked nodes which in some cases were identified as connecting proteins most likely responsible for propagation of transduction signals across the networks were determined. The functional consequences of these nodes in the context of their network environment were also determined. These findings highlight the usefulness of the framework in identifying possible combination or links as targets for therapeutic responses; and put forward the idea of using retrieved knowledge on the shared components in constructing better organised and structured models of signalling networks. Conclusion It is hoped that through the data mined reconstructed signal transduction networks, well developed models of the

  10. Study protocol: Transition from localized low back pain to chronic widespread pain in general practice: Identification of risk factors, preventive factors and key elements for treatment – A cohort study

    PubMed Central

    2012-01-01

    Background Chronic localized pain syndromes, especially chronic low back pain (CLBP), are common reasons for consultation in general practice. In some cases chronic localized pain syndromes can appear in combination with chronic widespread pain (CWP). Numerous studies have shown a strong association between CWP and several physical and psychological factors. These studies are population-based cross-sectional and do not allow for assessing chronology. There are very few prospective studies that explore the predictors for the onset of CWP, where the main focus is identifying risk factors for the CWP incidence. Until now there have been no studies focusing on preventive factors keeping patients from developing CWP. Our aim is to perform a cross sectional study on the epidemiology of CLBP and CWP in general practice and to look for distinctive features regarding resources like resilience, self-efficacy and coping strategies. A subsequent cohort study is designed to identify the risk and protective factors of pain generalization (development of CWP) in primary care for CLBP patients. Methods/Design Fifty-nine general practitioners recruit consecutively, during a 5 month period, all patients who are consulting their family doctor because of chronic low back pain (where the pain is lasted for 3 months). Patients are asked to fill out a questionnaire on pain anamnesis, pain-perception, co-morbidities, therapy course, medication, socio demographic data and psychosomatic symptoms. We assess resilience, coping resources, stress management and self-efficacy as potential protective factors for pain generalization. Furthermore, we raise risk factors for pain generalization like anxiety, depression, trauma and critical life events. During a twelve months follow up period a cohort of CLBP patients without CWP will be screened on a regular basis (3 monthly) for pain generalization (outcome: incident CWP). Discussion This cohort study will be the largest study which

  11. Optimizing Requirements Decisions with KEYS

    NASA Technical Reports Server (NTRS)

    Jalali, Omid; Menzies, Tim; Feather, Martin

    2008-01-01

    Recent work with NASA's Jet Propulsion Laboratory has allowed for external access to five of JPL's real-world requirements models, anonymized to conceal proprietary information, but retaining their computational nature. Experimentation with these models, reported herein, demonstrates a dramatic speedup in the computations performed on them. These models have a well defined goal: select mitigations that retire risks which, in turn, increases the number of attainable requirements. Such a non-linear optimization is a well-studied problem. However identification of not only (a) the optimal solution(s) but also (b) the key factors leading to them is less well studied. Our technique, called KEYS, shows a rapid way of simultaneously identifying the solutions and their key factors. KEYS improves on prior work by several orders of magnitude. Prior experiments with simulated annealing or treatment learning took tens of minutes to hours to terminate. KEYS runs much faster than that; e.g for one model, KEYS ran 13,000 times faster than treatment learning (40 minutes versus 0.18 seconds). Processing these JPL models is a non-linear optimization problem: the fewest mitigations must be selected while achieving the most requirements. Non-linear optimization is a well studied problem. With this paper, we challenge other members of the PROMISE community to improve on our results with other techniques.

  12. Microscale Methodology for Structure Elucidation of Natural Products

    PubMed Central

    Molinski, Tadeusz F.

    2010-01-01

    1. Summary of Recent Advances Advances in microscale spectroscopic techniques, particularly microcryoprobe NMR, allow discovery and structure elucidation of new molecules down to only a few nanomole. Newer methods for utilizing circular dichroism (CD) have pushed the limits of detection to picomole levels. NMR and CD methods are complementary to the task of elucidation of complete stereostructures of complex natural products. Together, integrated microprobe NMR spectroscopy, microscale degradation and synthesis, are synergistic tools for discovery of bioactive natural products and have opened new realm for discovery among extreme sources including compounds from uncultured microbes, rare invertebrates and environmental samples. PMID:20880694

  13. Group key management

    SciTech Connect

    Dunigan, T.; Cao, C.

    1997-08-01

    This report describes an architecture and implementation for doing group key management over a data communications network. The architecture describes a protocol for establishing a shared encryption key among an authenticated and authorized collection of network entities. Group access requires one or more authorization certificates. The implementation includes a simple public key and certificate infrastructure. Multicast is used for some of the key management messages. An application programming interface multiplexes key management and user application messages. An implementation using the new IP security protocols is postulated. The architecture is compared with other group key management proposals, and the performance and the limitations of the implementation are described.

  14. Modular Connector Keying Concept

    NASA Technical Reports Server (NTRS)

    Ishman, Scott; Dukes, Scott; Warnica, Gary; Conrad, Guy; Senigla, Steven

    2013-01-01

    For panel-mount-type connectors, keying is usually "built-in" to the connector body, necessitating different part numbers for each key arrangement. This is costly for jobs that require small quantities. This invention was driven to provide a cost savings and to reduce documentation of individual parts. The keys are removable and configurable in up to 16 combinations. Since the key parts are separate from the connector body, a common design can be used for the plug, receptacle, and key parts. The keying can then be set at the next higher assembly.

  15. Molecular characterization and mRNA expression of two key enzymes of hypoxia-sensing pathways in eastern oysters Crassostrea virginica (Gmelin): Hypoxia-inducible factor α (HIF-α) and HIF-prolyl hydroxylase (PHD)

    PubMed Central

    Piontkivska, Helen; Chung, J. Sook; Ivanina, Anna V.; Sokolov, Eugene P.; Techa, Sirinart; Sokolova, Inna M.

    2010-01-01

    Oxygen homeostasis is crucial for development, survival and normal function of all metazoans. A family of transcription factors called hypoxia-inducible factors (HIF) is critical in mediating the adaptive responses to reduced oxygen availability. The HIF transcription factor consists of a constitutively expressed β subunit and an oxygen-dependent α subunit; the abundance of the latter determines the activity of HIF and is regulated by a family of O2- and Fe2+-dependent enzymes prolyl hydroxylases (PHDs). Currently very little is known about the function of this important pathway and the molecular structure of its key players in hypoxia-tolerant intertidal mollusks including oysters, which are among the animal champions of anoxic and hypoxic tolerance and thus can serve as excellent models to study the role of HIF cascade in adaptations to oxygen deficiency. We have isolated transcripts of two key components of the oxygen sensing pathway - the oxygen-regulated HIF-α subunit and PHD - from an intertidal mollusk, the eastern oyster Crassostrea virginica, and determined the transcriptional responses of these two genes to anoxia, hypoxia and cadmium (Cd) stress. HIF-α and PHD homologs from eastern oysters C. virginica show significant sequence similarity and share key functional domains with the earlier described isoforms from vertebrates and invertebrates. Phylogenetic analysis shows that genetic diversification of HIF and PHD isoforms occurred within the vertebrate lineage indicating functional diversification and specialization of the oxygen-sensing pathways in this group, which parallels situation observed for many other important genes. HIF-α and PHD homologs are broadly expressed at the mRNA level in different oyster tissues and show transcriptional responses to prolonged hypoxia in the gills consistent with their putative role in oxygen sensing and the adaptive response to hypoxia. Similarity in amino acid sequence, domain structure and transcriptional

  16. Public Key Cryptography.

    ERIC Educational Resources Information Center

    Tapson, Frank

    1996-01-01

    Describes public key cryptography, also known as RSA, which is a system using two keys, one used to put a message into cipher and another used to decipher the message. Presents examples using small prime numbers. (MKR)

  17. A platform for actively loading cargo RNA to elucidate limiting steps in EV-mediated delivery

    PubMed Central

    Hung, Michelle E.; Leonard, Joshua N.

    2016-01-01

    Extracellular vesicles (EVs) mediate intercellular communication through transfer of RNA and protein between cells. Thus, understanding how cargo molecules are loaded and delivered by EVs is of central importance for elucidating the biological roles of EVs and developing EV-based therapeutics. While some motifs modulating the loading of biomolecular cargo into EVs have been elucidated, the general rules governing cargo loading and delivery remain poorly understood. To investigate how general biophysical properties impact loading and delivery of RNA by EVs, we developed a platform for actively loading engineered cargo RNAs into EVs. In our system, the MS2 bacteriophage coat protein was fused to EV-associated proteins, and the cognate MS2 stem loop was engineered into cargo RNAs. Using this Targeted and Modular EV Loading (TAMEL) approach, we identified a configuration that substantially enhanced cargo RNA loading (up to 6-fold) into EVs. When applied to vesicles expressing the vesicular stomatitis virus glycoprotein (VSVG) – gesicles – we observed a 40-fold enrichment in cargo RNA loading. While active loading of mRNA-length (>1.5 kb) cargo molecules was possible, active loading was much more efficient for smaller (~0.5 kb) RNA molecules. We next leveraged the TAMEL platform to elucidate the limiting steps in EV-mediated delivery of mRNA and protein to prostate cancer cells, as a model system. Overall, most cargo was rapidly degraded in recipient cells, despite high EV-loading efficiencies and substantial EV uptake by recipient cells. While gesicles were efficiently internalized via a VSVG-mediated mechanism, most cargo molecules were rapidly degraded. Thus, in this model system, inefficient endosomal fusion or escape likely represents a limiting barrier to EV-mediated transfer. Altogether, the TAMEL platform enabled a comparative analysis elucidating a key opportunity for enhancing EV-mediated delivery to prostate cancer cells, and this technology should be of

  18. Keys to Scholarship

    ERIC Educational Resources Information Center

    Hebert, Terri

    2011-01-01

    Up ahead, a foreboding wooden door showing wear from passage of earlier travelers is spotted. As the old porch light emits a pale yellow glow, a key ring emerges from deep inside the coat pocket. Searching for just the right key, the voyager settles on one that also shows age. As the key enters its receptacle and begins to turn, a clicking noise…

  19. Work Keys USA.

    ERIC Educational Resources Information Center

    Work Keys USA, 1998

    1998-01-01

    "Work Keys" is a comprehensive program for assessing and teaching workplace skills. This serial "special issue" features 18 first-hand reports on Work Keys projects in action in states across North America. They show how the Work Keys is helping businesses and educators solve the challenge of building a world-class work force. The reports are as…

  20. LIM-homeodomain transcription factor Awh is a key component activating all three fibroin genes, fibH, fibL and fhx, in the silk gland of the silkworm, Bombyx mori.

    PubMed

    Kimoto, Mai; Tsubota, Takuya; Uchino, Keiro; Sezutsu, Hideki; Takiya, Shigeharu

    2015-01-01

    In the silkworm Bombyx mori, three fibroin genes, fibroin-heavy-chain (fibH), fibroin-light-chain (fibL) and fibrohexamerin (fhx), are coexpressed only in the posterior silk gland (PSG) cells, while the sericin genes encoding silk glue proteins are expressed in the middle silk gland (MSG) cells. Silk gland factor-2 (SGF-2) is a PSG-specific activator complex of fibH, composed of a LIM-homeodomain protein, Awh, and its cofactors, Ldb and Lcaf. We investigated whether SGF-2 can activate other fibroin genes using transgenic silkworms. The genes for Ldb and Lcaf were expressed ubiquitously in various tissues, while the gene for Awh was expressed strictly specific in PSG of the wild type silkworms. Misexpression of Awh in transgenic silkworms induced ectopic expression of fibL and fhx as well as fibH in MSG. Coincidently with the induction of fibL and fhx by Awh, binding of SGF-2 to the promoter of fibL and fhx was detected in vitro, and SGF-2 binds directly to the fhx core promoter. Ectopic expression of the fibroin genes was observed at high levels in the middle part of MSG. Moreover, fibL and fhx were induced in the anterior silk gland (ASG) of the transgenic silkworms, but fibH was not. These results indicate that Awh is a key activator of all three fibroin genes, and the activity is probably regulated in conjunction with additional factors. PMID:25449130

  1. Unstructured quantum key distribution

    NASA Astrophysics Data System (ADS)

    Coles, Patrick; Metodiev, Eric; Lutkenhaus, Norbert

    Quantum key distribution (QKD) allows for communication with security guaranteed by quantum theory. The main theoretical problem in QKD is to calculate the secret key rate for a given protocol. Analytical formulas are known for protocols with a high degree of symmetry, since symmetry simplifies the analysis. However, experimental imperfections break symmetries, hence the effect of imperfections on key rates is difficult to estimate. Furthermore, it is an interesting question whether (intentionally) asymmetric protocols could outperform symmetric ones. In this work, we develop a robust numerical approach for calculating the key rate for arbitrary discrete-variable QKD protocols. Ultimately this will allow researchers to study ``unstructured'' protocols, i.e., those that lack symmetry. Our approach relies on transforming the key rate calculation to the dual optimization problem, which dramatically reduces the number of parameters and hence the calculation time. We illustrate our method by investigating some unstructured protocols for which the key rate was previously unknown.

  2. Structure Elucidation of Nigricanoside A Through Enantioselective Total Synthesis

    PubMed Central

    Chen, Jie; Koswatta, Panduka; DeBergh, J. Robb; Fu, Peng; Pan, Ende; MacMillan, John B.; Ready, Joseph M.

    2016-01-01

    Nigricanoside A was isolated from green alga, and its dimethyl ester was found to display potent cytotoxicity. Its scarcity prevented a full structure elucidation, leaving total synthesis as the only means to determine its relative and absolute stereochemistry and to explore its biological activity. Here we assign the stereochemistry of the natural product through enantioselective total synthesis and provide initial studies of its cytotoxicity. PMID:26877863

  3. Elucidation of Reaction Mechanisms Far from Thermodynamic Equilibrium.

    PubMed

    Nagao, Raphael

    2016-04-01

    Far from equilibrium: This thesis provides a deep mechanistic analysis of the electrooxidation of methanol when the system is kept far from the thermodynamic equilibrium. Under an oscillatory regime, interesting characteristics between the elementary reaction steps were observed. We were able to elucidate the effect of the intrinsic drift in a potential time-series responsible for spontaneous transition of temporal patterns and the carbon dioxide decoupling from direct and indirect pathways. PMID:27308227

  4. Isolation and Structure Elucidation of Pentahydroxyscirpene, a Trichothecene Fusarium Mycotoxin

    PubMed Central

    2013-01-01

    Pentahydroxyscirpene, a novel trichothecene-type compound, was isolated from Fusarium-inoculated rice. The structure of pentahydroxyscirpene was elucidated by 1D and 2D NMR spectroscopy and X-ray single-crystal diffraction. The conformation in solution was determined by NOESY experiments supported by quantum chemical calculations. In vitro toxicity tests showed that pentahydroxyscirpene inhibits protein synthesis as do other trichothecenes. PMID:24367932

  5. bHLH-PAS family transcription factor methoprene-tolerant plays a key role in JH action in preventing the premature development of adult structures during larval-pupal metamorphosis

    PubMed Central

    Parthasarathy, R.; Tan, Anjiang; Palli, Subba R.

    2008-01-01

    The biological actions of juvenile hormones are well studied; they regulate almost all aspects of an insect’s life. However, the molecular actions of these hormones are not well understood. Recent studies in the red flour beetle, Tribolium castaneum, demonstrated the utility of this insect as a model system to study JH action. These studies confirmed that the bHLH-PAS family transcription factor, methoprene-tolerant (TcMet,) plays a key role in JH action during larval stages. In this study, we investigated the role of TcMet in JH action during larval-pupal metamorphosis. The phenotypes of TcMet RNAi insects shared similarity with the phenotypes of some allatectomized lepidopteran larvae that were attempting to undergo precocious larval-pupal metamorphosis. Knocking-down TcMet during the final instar also disrupted larval-pupal ecdysis, resulting in the development of adultoid underneath the larval skin. However, the loss of TcMet did not completely block remodeling of internal tissues such as midgut. T. castaneum larvae injected with TcMet dsRNA demonstrated a resistance to a JH analog (JHA), hydroprene, irrespective of time and route of application. Knocking-down TcMet also caused down regulation of JH-response genes, JHE and Kr-h1 suggesting that TcMet might be involved in the expression of these genes. Based on the phenotype, gene expression, and JHA action studies in TcMet RNAi insects, this study concludes that Met plays a key role in JH action for preventing the premature development of adult structures during larval-pupal metamorphosis. PMID:18450431

  6. Elucidating the key role of the fungal mycelium on the biodegradation of n-pentane as a model hydrophobic VOC.

    PubMed

    Vergara-Fernández, Alberto; Scott, Felipe; Moreno-Casas, Patricio; Díaz-Robles, Luis; Muñoz, Raúl

    2016-08-01

    The role of the aerial mycelium of the fungus Fusarium solani in the biodegradation of n-pentane was evaluated in a continuous fungal bioreactor (FB) to determine the contribution of the aerial (hyphae) and non-aerial (monolayer) fungal biomass. The experimental results showed that although the aerial biomass fraction represented only 25.9(±3)% on a dry weight basis, it was responsible for 71.6(±4)% of n-pentane removal. The FB attained a maximum elimination capacity (ECmax) of 680(±30) g m(-3) h(-1) in the presence of fungal hyphae (which supported an interfacial area of 5.5(±1.5) × 10(6) m(2) m(-3)). In addition, a mathematical model capable of describing n-pentane biodegradation by the filamentous fungus was also developed and validated against the experimental data. This model successfully predicted the influence of the aerial biomass fraction and its partition coefficient on the n-pentane removal, with EC decreasing from 680(±30) g m(-3) h(-1) to values of 200(±14) g m(-3) h(-1) when the dimensionless partition coefficient increased from 0.21(±0.09) with aerial biomass to 0.88(±0.06) without aerial biomass. PMID:27209557

  7. Elucidating Multiscale Periosteal Mechanobiology: A Key to Unlocking the Smart Properties and Regenerative Capacity of the Periosteum?

    PubMed Central

    Evans, Sarah F.; Chang, Hana

    2013-01-01

    The periosteum, a thin, fibrous tissue layer covering most bones, resides in a dynamic, mechanically loaded environment. The periosteum also provides a niche for mesenchymal stem cells. The mechanics of periosteum vary greatly between species and anatomical locations, indicating the specialized role of periosteum as bone's bounding membrane. Furthermore, periosteum exhibits stress-state-dependent mechanical and material properties, hallmarks of a smart material. This review discusses what is known about the multiscale mechanical and material properties of the periosteum as well as their potential effect on the mechanosensitive progenitor cells within the tissue. Furthermore, this review addresses open questions and barriers to understanding periosteum's multiscale structure–function relationships. Knowledge of the smart material properties of the periosteum will maximize the translation of periosteum and substitute periosteum to regenerative medicine, facilitate the development of biomimetic tissue-engineered periosteum for use in instances where the native periosteum is lacking or damaged, and provide inspiration for a new class of smart, advanced materials. PMID:23189933

  8. Social Work Practice with Latinos: Key Issues for Social Workers

    ERIC Educational Resources Information Center

    Furman, Rich; Negi, Nalini Junko; Iwamoto, Derek Kenji; Rowan, Diana; Shukraft, Allison; Gragg, Jennifer

    2009-01-01

    The Latino population is the fastest growing group in the United States; thus, it is imperative that social workers and other mental health practitioners be knowledgeable about the current literature on how to effectively serve this population. This article elucidates key issues and knowledge, such as immigration and migration concerns; discusses…

  9. Elucidating determinants of aerosol composition through particle-type-based receptor modeling

    NASA Astrophysics Data System (ADS)

    McGuire, M. L.; Jeong, C.-H.; Slowik, J. G.; Chang, R. Y.-W.; Corbin, J. C.; Lu, G.; Mihele, C.; Rehbein, P. J. G.; Sills, D. M. L.; Abbatt, J. P. D.; Brook, J. R.; Evans, G. J.

    2011-03-01

    An aerosol time-of-flight mass spectrometer (ATOFMS) was deployed at a semi-rural site in Southern Ontario to characterize the size and chemical composition of individual particles. Particle-type-based receptor modelling of these data was used to investigate the determinants of aerosol chemical composition in this region. Individual particles were classified into particle-types and positive matrix factorization (PMF) was applied to their temporal trends to separate and cross-apportion particle-types to factors. The extent of chemical processing for each factor was assessed by evaluating the internal and external mixing state of the characteristic particle-types. The nine factors identified helped to elucidate the coupled interactions of these determinants. Nitrate-laden dust was found to be the dominant type of locally emitted particles measured by ATOFMS. Several factors associated with aerosol transported to the site from intermediate local-to-regional distances were identified: the Organic factor was associated with a combustion source to the north-west; the ECOC Day factor was characterized by nearby local-to-regional carbonaceous emissions transported from the south-west during the daytime; and the Fireworks factor consisted of pyrotechnic particles from the Detroit region following holiday fireworks displays. Regional aerosol from farther emissions sources were reflected through three factors: two biomass burning factors and a highly chemically processed long range transport factor. The biomass burning factors were separated by PMF due to differences in chemical processing which were caused in part by the passage of two thunderstorm gust fronts with different air mass histories. The remaining two factors, ECOC Night and Nitrate Background, represented the night-time partitioning of nitrate to pre-existing particles of different origins. The distinct meteorological conditions observed during this month-long study in the summer of 2007 provided a unique range

  10. Optical key system

    DOEpatents

    Hagans, Karla G.; Clough, Robert E.

    2000-01-01

    An optical key system comprises a battery-operated optical key and an isolated lock that derives both its operating power and unlock signals from the correct optical key. A light emitting diode or laser diode is included within the optical key and is connected to transmit a bit-serial password. The key user physically enters either the code-to-transmit directly, or an index to a pseudorandom number code, in the key. Such person identification numbers can be retained permanently, or ephemeral. When a send button is pressed, the key transmits a beam of light modulated with the password information. The modulated beam of light is received by a corresponding optical lock with a photovoltaic cell that produces enough power from the beam of light to operate a password-screen digital logic. In one application, an acceptable password allows a two watt power laser diode to pump ignition and timing information over a fiberoptic cable into a sealed engine compartment. The receipt of a good password allows the fuel pump, spark, and starter systems to each operate. Therefore, bypassing the lock mechanism as is now routine with automobile thieves is pointless because the engine is so thoroughly disabled.

  11. Optical key system

    SciTech Connect

    Hagans, K.G.; Clough, R.E.

    2000-04-25

    An optical key system comprises a battery-operated optical key and an isolated lock that derives both its operating power and unlock signals from the correct optical key. A light emitting diode or laser diode is included within the optical key and is connected to transmit a bit-serial password. The key user physically enters either the code-to-transmit directly, or an index to a pseudorandom number code, in the key. Such person identification numbers can be retained permanently, or ephemeral. When a send button is pressed, the key transmits a beam of light modulated with the password information. The modulated beam of light is received by a corresponding optical lock with a photovoltaic cell that produces enough power from the beam of light to operate a password-screen digital logic. In one application, an acceptable password allows a two watt power laser diode to pump ignition and timing information over a fiberoptic cable into a sealed engine compartment. The receipt of a good password allows the fuel pump, spark, and starter systems to each operate. Therefore, bypassing the lock mechanism as is now routine with automobile thieves is pointless because the engine is so thoroughly disabled.

  12. What Are the Key Statistics about Neuroblastoma?

    MedlinePlus

    ... risk factors for neuroblastoma? What are the key statistics about neuroblastoma? Neuroblastoma is by far the most ... parts of the body when it is diagnosed. Statistics related to survival are discussed in the section “ ...

  13. Elucidating the role of interfacial materials properties in microfluidic packages.

    SciTech Connect

    Edwards, Thayne L.

    2013-01-01

    The purpose of this work was to discover a method to investigate the properties of interfaces as described by a numerical physical model. The model used was adopted from literature and applied to a commercially available multiphysics software package. By doing this the internal properties of simple structures could be elucidated and then readily applied to more complex structures such as valves and pumps in laminate microfluidic structures. A numerical finite element multi-scale model of a cohesive interface comprised of heterogeneous material properties was used to elucidate irreversible damage from applied strain energy. An unknown internal state variable was applied to characterize the damage process. Using a constrained blister test, this unknown internal state variable could be determined for an adherend/adhesive/adherend body. This is particularly interesting for laminate systems with microfluidic and microstructures contained within the body. A laminate structure was designed and fabricated that could accommodate a variety of binary systems joined using nearly any technique such as adhesive, welding (solvent, laser, ultrasonic, RF, etc.), or thermal. The adhesive method was the most successful and easy to implement but also one of the more difficult to understand, especially over long periods of time. Welding methods are meant to achieve a bond that is similar to bulk properties and so are easier to predict. However, methods of welding often produce defects in the bonds.. Examples of the test structures used to elucidate the internal properties of the model were shown and demonstrated. The real life examples used this research to improve upon current designs and aided in creating complex structures for sensor and other applications.

  14. Structure elucidation of a process-related impurity of dapoxetine.

    PubMed

    Darcsi, András; Tóth, Gergő; Kökösi, József; Béni, Szabolcs

    2014-08-01

    Unknown by-product associated with the synthesis of dapoxetine was isolated. The structure elucidation of this new compound using accurate mass data and NMR spectroscopy is presented herein. The unambiguous resonance assignment concluded to the formation of a tricyclic compound 4-phenyl-2H,3H,4H-naphtho[1,2-b]pyran, a new impurity of dapoxetine which has never been reported previously. A proposed mechanism for the formation of the new carbon-carbon bond is discussed. For the separation of dapoxetine and the process-related impurities, a gradient HPLC method was developed. PMID:24793500

  15. Applications of a HOUDINI-based structure elucidation system.

    PubMed

    Schulz, K-P; Korytko, A; Munk, M E

    2003-01-01

    SESAMI, a comprehensive program for the elucidation of the structure of complex compounds of carbon, incorporates a structure reduction-based structure genearator (COCOA). Observed limitations with this program in the solution of higher molecular weight unknowns prompted the development of a structure generator (HOUDINI) which embodies a new concept, convergent structure generation. A comparison of the performance of COCOA-based and HOUDINI-based SESAMI using a set of complex, naturally occurring compounds as a test set of unknowns revealed faster execution times and more efficient processing of ambiguous structural information for the latter. PMID:14502477

  16. Toward structural elucidation of the gamma-secretase complex

    SciTech Connect

    Li, H.; Wolfe, M. S.; Selkoe, D. J.

    2009-03-11

    {gamma}-Secretase is an intramembrane protease complex that mediates the Notch signaling pathway and the production of amyloid {beta}-proteins. As such, this enzyme has emerged as an important target for development of novel therapeutics for Alzheimer disease and cancer. Great progress has been made in the identification and characterization of the membrane complex and its biological functions. One major challenge now is to illuminate the structure of this fascinating and important protease at atomic resolution. Here, we review recent progress on biochemical and biophysical probing of the structure of the four-component complex and discuss obstacles and potential pathways toward elucidating its detailed structure.

  17. Toward structural elucidation of the γ-secretase complex

    PubMed Central

    Li, Huilin; Wolfe, Michael S.; Selkoe, Dennis J.

    2009-01-01

    γ-Secretase is an intramembrane protease complex that mediates the Notch signaling pathway and the production of amyloid β-proteins. As such, this enzyme has emerged as an important target for development of novel therapeutics for Alzheimer disease and cancer. Great progress has been made in the identification and characterization of the membrane complex and its biological functions. One major challenge now is to illuminate the structure of this fascinating and important protease at atomic resolution. Here, we review recent progress on biochemical and biophysical probing of the structure of the four-component complex and discuss barriers and potential pathways toward elucidating its detailed structure. PMID:19278647

  18. Elucidation and Structural Analysis of Conserved Pools for Genome-Scale Metabolic Reconstructions

    PubMed Central

    Nikolaev, Evgeni V.; Burgard, Anthony P.; Maranas, Costas D.

    2005-01-01

    In this article, we introduce metabolite concentration coupling analysis (MCCA) to study conservation relationships for metabolite concentrations in genome-scale metabolic networks. The analysis allows the global identification of subsets of metabolites whose concentrations are always coupled within common conserved pools. Also, the minimal conserved pool identification (MCPI) procedure is developed for elucidating conserved pools for targeted metabolites without computing the entire basis conservation relationships. The approaches are demonstrated on genome-scale metabolic reconstructions of Helicobacter pylori, Escherichia coli, and Saccharomyces cerevisiae. Despite significant differences in the size and complexity of the examined organism's models, we find that the concentrations of nearly all metabolites are coupled within a relatively small number of subsets. These correspond to the overall exchange of carbon molecules into and out of the networks, interconversion of energy and redox cofactors, and the transfer of nitrogen, sulfur, phosphate, coenzyme A, and acyl carrier protein moieties among metabolites. The presence of large conserved pools can be viewed as global biophysical barriers protecting cellular systems from stresses, maintaining coordinated interconversions between key metabolites, and providing an additional mode of global metabolic regulation. The developed approaches thus provide novel and versatile tools for elucidating coupling relationships between metabolite concentrations with implications in biotechnological and medical applications. PMID:15489308

  19. An Alternative to Keys

    ERIC Educational Resources Information Center

    O'Hagan, James

    1977-01-01

    For the secondary school, the author discourages the use of dichotomous keys in favor of a punch-card system. The system is readily constructed by students for use in plant and animal classification. (CP)

  20. Secret Key Crypto Implementations

    NASA Astrophysics Data System (ADS)

    Bertoni, Guido Marco; Melzani, Filippo

    This chapter presents the algorithm selected in 2001 as the Advanced Encryption Standard. This algorithm is the base for implementing security and privacy based on symmetric key solutions in almost all new applications. Secret key algorithms are used in combination with modes of operation to provide different security properties. The most used modes of operation are presented in this chapter. Finally an overview of the different techniques of software and hardware implementations is given.

  1. Public Key FPGA Software

    Energy Science and Technology Software Center (ESTSC)

    2013-07-25

    The Public Key (PK) FPGA software performs asymmetric authentication using the 163-bit Elliptic Curve Digital Signature Algorithm (ECDSA) on an embedded FPGA platform. A digital signature is created on user-supplied data, and communication with a host system is performed via a Serial Peripheral Interface (SPI) bus. Software includes all components necessary for signing, including custom random number generator for key creation and SHA-256 for data hashing.

  2. Environmental metabolomics: Elucidating the metabolic reactions that link the "bio" and "geo" in biogeochemistry

    NASA Astrophysics Data System (ADS)

    Higgins, M. B.

    2012-12-01

    One goal of environmental microbiology is to gain a quantitative knowledge of chemical processes that occur within individual microbes and microbial ecosystems. While recent advances in techniques that combine stable isotope measurements with phylogenetic identification have been able to link key microbial players to biogeochemical processes, the precise details of metabolic pathways and their kinetics under various environmental conditions remain a challenge to measure. "Omics" approaches that focus on gene and transcript identification elucidate the biological potential for biochemical reactions but not their cellular rates. The emerging field of environmental metabolomics uses high-resolution mass spectrometry for high-throughput quantitation of large suites of cellular metabolites. Using stable-isotope labeling of microbial samples, such an approach enables both the identification of metabolites involved in biochemical pathways and an estimate of changes in cellular metabolite pool sizes under different environmental conditions, as well as kinetic measurements of biochemical fluxes.

  3. Elucidating the redox cycle of environmental phosphorus using ion chromatography.

    PubMed

    Pech, Herbe; Vazquez, Maria G; Van Buren, Jean; Shi, Lixin; Ivey, Michelle M; Salmassi, Tina M; Pasek, Matthew A; Foster, Krishna L

    2011-09-01

    Historically, it was assumed that reactive, inorganic phosphorus present in pristine environments was solely in the form of orthophosphate. However, this assumption contradicts theories of biogenesis and the observed metabolic behavior of select microorganisms. This paper discusses the role of ion chromatography (IC) in elucidating the oxidation-reduction cycle of environmental phosphorus. These methods employ suppressed-IC, coupled with tandem conductivity and electrospray mass spectrometry detectors to identify and quantify phosphorus oxyanions in natural water, synthetic cosmochemical, and biological samples. These techniques have been used to detect phosphite and orthophosphate in geothermal hot springs. Hypophosphite, phosphite, and orthophosphate have been detected in synthetic schreibersite corrosion samples, and termite extract supernatant. Synthetic schreibersite corrosion samples were also analyzed for two poly-phosphorus compounds, hypophosphate and pyrophosphate, and results show these samples did not contain concentrations above the 1.3 and 2.0 μM respective 3σ limit of detection. These methods are readily adaptable to a variety of matrices, and contribute to the elucidation of the oxidation-reduction cycle of phosphorus oxyanions in the environment. In contrast to most studies, these techniques have been used to show that phosphorus actively participates in redox processes in both the biological and geological world. PMID:21859529

  4. Key drivers of airline loyalty

    PubMed Central

    Dolnicar, Sara; Grabler, Klaus; Grün, Bettina; Kulnig, Anna

    2011-01-01

    This study investigates drivers of airline loyalty. It contributes to the body of knowledge in the area by investigating loyalty for a number of a priori market segments identified by airline management and by using a method which accounts for the multi-step nature of the airline choice process. The study is based on responses from 687 passengers. Results indicate that, at aggregate level, frequent flyer membership, price, the status of being a national carrier and the reputation of the airline as perceived by friends are the variables which best discriminate between travellers loyal to the airline and those who are not. Differences in drivers of airline loyalty for a number of segments were identified. For example, loyalty programs play a key role for business travellers whereas airline loyalty of leisure travellers is difficult to trace back to single factors. For none of the calculated models satisfaction emerged as a key driver of airline loyalty. PMID:27064618

  5. Lock and key colloids.

    PubMed

    Sacanna, S; Irvine, W T M; Chaikin, P M; Pine, D J

    2010-03-25

    New functional materials can in principle be created using colloids that self-assemble into a desired structure by means of a programmable recognition and binding scheme. This idea has been explored by attaching 'programmed' DNA strands to nanometre- and micrometre- sized particles and then using DNA hybridization to direct the placement of the particles in the final assembly. Here we demonstrate an alternative recognition mechanism for directing the assembly of composite structures, based on particles with complementary shapes. Our system, which uses Fischer's lock-and-key principle, employs colloidal spheres as keys and monodisperse colloidal particles with a spherical cavity as locks that bind spontaneously and reversibly via the depletion interaction. The lock-and-key binding is specific because it is controlled by how closely the size of a spherical colloidal key particle matches the radius of the spherical cavity of the lock particle. The strength of the binding can be further tuned by adjusting the solution composition or temperature. The composite assemblies have the unique feature of having flexible bonds, allowing us to produce flexible dimeric, trimeric and tetrameric colloidal molecules as well as more complex colloidal polymers. We expect that this lock-and-key recognition mechanism will find wider use as a means of programming and directing colloidal self-assembly. PMID:20336142

  6. Elucidating mechanisms of toxicity using phenotypic data from primary human cell systems--a chemical biology approach for thrombosis-related side effects.

    PubMed

    Berg, Ellen L; Polokoff, Mark A; O'Mahony, Alison; Nguyen, Dat; Li, Xitong

    2015-01-01

    Here we describe a chemical biology approach for elucidating potential toxicity mechanisms for thrombosis-related side effects. This work takes advantage of a large chemical biology data set comprising the effects of known, well-characterized reference agents on the cell surface levels of tissue factor (TF) in a primary human endothelial cell-based model of vascular inflammation, the BioMAP® 3C system. In previous work with the Environmental Protection Agency (EPA) for the ToxCast™ program, aryl hydrocarbon receptor (AhR) agonists and estrogen receptor (ER) antagonists were found to share an usual activity, that of increasing TF levels in this system. Since human exposure to compounds in both chemical classes is associated with increased incidence of thrombosis-related side effects, we expanded this analysis with a large number of well-characterized reference compounds in order to better understand the underlying mechanisms. As a result, mechanisms for increasing (AhR, histamine H1 receptor, histone deacetylase or HDAC, hsp90, nuclear factor kappa B or NFκB, MEK, oncostatin M receptor, Jak kinase, and p38 MAPK) and decreasing (vacuolar ATPase or V-ATPase) and mTOR) TF expression levels were uncovered. These data identify the nutrient, lipid, bacterial, and hypoxia sensing functions of autophagy as potential key regulatory points controlling cell surface TF levels in endothelial cells and support the mechanistic hypothesis that these functions are associated with thrombosis-related side effects in vivo. PMID:25569083

  7. Carnosic acid biosynthesis elucidated by a synthetic biology platform.

    PubMed

    Ignea, Codruta; Athanasakoglou, Anastasia; Ioannou, Efstathia; Georgantea, Panagiota; Trikka, Fotini A; Loupassaki, Sofia; Roussis, Vassilios; Makris, Antonios M; Kampranis, Sotirios C

    2016-03-29

    Synthetic biology approaches achieving the reconstruction of specific plant natural product biosynthetic pathways in dedicated microbial "chassis" have provided access to important industrial compounds (e.g., artemisinin, resveratrol, vanillin). However, the potential of such production systems to facilitate elucidation of plant biosynthetic pathways has been underexplored. Here we report on the application of a modular terpene production platform in the characterization of the biosynthetic pathway leading to the potent antioxidant carnosic acid and related diterpenes in Salvia pomifera and Rosmarinus officinalis.Four cytochrome P450 enzymes are identified (CYP76AH24, CYP71BE52, CYP76AK6, and CYP76AK8), the combined activities of which account for all of the oxidation events leading to the biosynthesis of the major diterpenes produced in these plants. This approach develops yeast as an efficient tool to harness the biotechnological potential of the numerous sequencing datasets that are increasingly becoming available through transcriptomic or genomic studies. PMID:26976595

  8. Elucidating the stop bands of structurally colored systems through recursion

    NASA Astrophysics Data System (ADS)

    Amir, Ariel; Vukusic, Peter

    2013-04-01

    Interference is the source of some of the spectacular colors of animals and plants in nature. In some of these systems, the physical structure consists of an ordered array of layers with alternating high and low refractive indices. This periodicity leads to an optical band structure that is analogous to the electronic band structure encountered in semiconductor physics: specific bands of wavelengths (the stop bands) are perfectly reflected. Here, we present a minimal model for optical band structure in a periodic multilayer structure and solve it using recursion relations. The stop bands emerge in the limit of an infinite number of layers by finding the fixed point of the recursion. We compare to experimental data for various beetles, whose optical structure resembles the proposed model. Thus, using only the phenomenon of interference and the idea of recursion, we are able to elucidate the concept of band structure in the context of the experimentally observed high reflectance and iridescent appearance of structurally colored beetles.

  9. Morphological elucidation of basal ganglia circuits contributing reward prediction

    PubMed Central

    Fujiyama, Fumino; Takahashi, Susumu; Karube, Fuyuki

    2015-01-01

    Electrophysiological studies in monkeys have shown that dopaminergic neurons respond to the reward prediction error. In addition, striatal neurons alter their responsiveness to cortical or thalamic inputs in response to the dopamine signal, via the mechanism of dopamine-regulated synaptic plasticity. These findings have led to the hypothesis that the striatum exhibits synaptic plasticity under the influence of the reward prediction error and conduct reinforcement learning throughout the basal ganglia circuits. The reinforcement learning model is useful; however, the mechanism by which such a process emerges in the basal ganglia needs to be anatomically explained. The actor–critic model has been previously proposed and extended by the existence of role sharing within the striatum, focusing on the striosome/matrix compartments. However, this hypothesis has been difficult to confirm morphologically, partly because of the complex structure of the striosome/matrix compartments. Here, we review recent morphological studies that elucidate the input/output organization of the striatal compartments. PMID:25698913

  10. Morphological elucidation of basal ganglia circuits contributing reward prediction.

    PubMed

    Fujiyama, Fumino; Takahashi, Susumu; Karube, Fuyuki

    2015-01-01

    Electrophysiological studies in monkeys have shown that dopaminergic neurons respond to the reward prediction error. In addition, striatal neurons alter their responsiveness to cortical or thalamic inputs in response to the dopamine signal, via the mechanism of dopamine-regulated synaptic plasticity. These findings have led to the hypothesis that the striatum exhibits synaptic plasticity under the influence of the reward prediction error and conduct reinforcement learning throughout the basal ganglia circuits. The reinforcement learning model is useful; however, the mechanism by which such a process emerges in the basal ganglia needs to be anatomically explained. The actor-critic model has been previously proposed and extended by the existence of role sharing within the striatum, focusing on the striosome/matrix compartments. However, this hypothesis has been difficult to confirm morphologically, partly because of the complex structure of the striosome/matrix compartments. Here, we review recent morphological studies that elucidate the input/output organization of the striatal compartments. PMID:25698913

  11. Tyrammonium 4-nitrophthalate dihydrate: structural and spectroscopic elucidation.

    PubMed

    Kolev, Tsonko; Koleva, Bojidarka B; Seidel, Rüdiger W; Mayer-Figge, Heike; Spiteller, Michael; Sheldrick, William S

    2009-01-01

    Tyrammonium 4-nitrophthalate has been synthesized and its structural and spectroscopic properties elucidated by single-crystal X-ray diffraction, solid-state polarized IR-spectroscopy of oriented colloids in a nematic host, HPLC with tandem mass spectrometry (HPLC ESI-MSMS), and TGV and DSC methods. The compound crystallizes in the monoclinic P2(1)/c space group and its structure consists of a 3D network of molecules joined by intermolecular interactions with the participation of cations, anions and two solvent molecules. The tyrammonium cation adopts a T trans configuration with corresponding angles of phi (1) = 76.0(4) degrees, phi (2 )= 54.8(1) degrees and phi (3) = 63.4(1) degrees, respectively. In the 4-nitrophthalate anion, the COO(-) and COOH groups are turned off the plane of the benzene ring at angles of tau (1) = 88.1(5) degrees and tau (2)= 22.1(7) degrees, respectively. PMID:18188664

  12. Transthyretin Gene (TTR) Intron One Elucidates Crocodylian Relationships

    PubMed Central

    Willis, Ray E.

    2009-01-01

    Transthyretin (TTR) is an attractive candidate for use in phylogenetic analysis because it is a short, single-copy nuclear gene with regions that are highly conserved across evolutionarily-divergent organisms from Xenopus laevis to Homo sapiens. To explore its utility as a phylogenetic marker, the complete intron one region (789–805 bp) was sequenced in 22 crocodylian species. Detailed analyses of intron 1 resolved the three expected lineages, Alligatorids, Crocodylids, and Gavialids, and offered additional evidence for the utility of synapomorphic indels in elucidating higher-level phylogenetic relationships. When used in conjunction with other genetic and morphological data sets, intron 1 should be a valuable tool in the investigation of other closely-related taxa. PMID:19751836

  13. Towards elucidation of dynamic structural changes of plant thylakoid architecture

    PubMed Central

    Anderson, Jan M.; Horton, Peter; Kim, Eun-Ha; Chow, Wah Soon

    2012-01-01

    Long-term acclimation of shade versus sun plants modulates the composition, function and structural organization of the architecture of the thylakoid membrane network. Significantly, these changes in the macroscopic structural organization of shade and sun plant chloroplasts during long-term acclimation are also mimicked following rapid transitions in irradiance: reversible ultrastructural changes in the entire thylakoid membrane network increase the number of grana per chloroplast, but decrease the number of stacked thylakoids per granum in seconds to minutes in leaves. It is proposed that these dynamic changes depend on reversible macro-reorganization of some light-harvesting complex IIb and photosystem II supracomplexes within the plant thylakoid network owing to differential phosphorylation cycles and other biochemical changes known to ensure flexibility in photosynthetic function in vivo. Some lingering grana enigmas remain: elucidation of the mechanisms involved in the dynamic architecture of the thylakoid membrane network under fluctuating irradiance and its implications for function merit extensive further studies. PMID:23148278

  14. Crystal structure and spectroscopic elucidation of 3-phenylpyridinium hydrogensquarate.

    PubMed

    Koleva, Bojidarka B; Kolev, Tsonko; Tsanev, Tsanko; Kotov, Stefan; Mayer-Figge, Heike; Spiteller, Michael; Sheldrick, William S

    2010-01-01

    The novel 3-phenylpyridinium hydrogensquarate (1) has been synthesized and its structure and properties are elucidated spectroscopically, thermally and structurally, using single crystal X-ray diffraction, linear-polarized solid-state IR-spectroscopy, UV-spectroscopy, TGA, DSC, DTA and ESI MS. Quantum chemical calculations were used to obtain the electronic structure, vibrational data and electronic spectrum. 3-Phenylpyridinium hydrogensquarate, crystallizes in the space group P-1 and the ions in the unit cell are joined into layers by intermolecular NH...O=C((Sq)) bonds with bond lengths of 2.625 and 2.626 A, respectively. Hydrogentartarates form dimers by strong O=COH...OCO interactions (2.499 A). PMID:19931483

  15. Advances in structure elucidation of small molecules using mass spectrometry

    PubMed Central

    Fiehn, Oliver

    2010-01-01

    The structural elucidation of small molecules using mass spectrometry plays an important role in modern life sciences and bioanalytical approaches. This review covers different soft and hard ionization techniques and figures of merit for modern mass spectrometers, such as mass resolving power, mass accuracy, isotopic abundance accuracy, accurate mass multiple-stage MS(n) capability, as well as hybrid mass spectrometric and orthogonal chromatographic approaches. The latter part discusses mass spectral data handling strategies, which includes background and noise subtraction, adduct formation and detection, charge state determination, accurate mass measurements, elemental composition determinations, and complex data-dependent setups with ion maps and ion trees. The importance of mass spectral library search algorithms for tandem mass spectra and multiple-stage MS(n) mass spectra as well as mass spectral tree libraries that combine multiple-stage mass spectra are outlined. The successive chapter discusses mass spectral fragmentation pathways, biotransformation reactions and drug metabolism studies, the mass spectral simulation and generation of in silico mass spectra, expert systems for mass spectral interpretation, and the use of computational chemistry to explain gas-phase phenomena. A single chapter discusses data handling for hyphenated approaches including mass spectral deconvolution for clean mass spectra, cheminformatics approaches and structure retention relationships, and retention index predictions for gas and liquid chromatography. The last section reviews the current state of electronic data sharing of mass spectra and discusses the importance of software development for the advancement of structure elucidation of small molecules. Electronic supplementary material The online version of this article (doi:10.1007/s12566-010-0015-9) contains supplementary material, which is available to authorized users. PMID:21289855

  16. Key Competencies. Second Edition.

    ERIC Educational Resources Information Center

    Haworth, David; Browne, Geoff

    Key competencies (or generic skills) have been specified in four sources: Further Education Unit (FEU), United Kingdom (1987); Finn Report (1991) and Mayer Committee (1992), Australia; U.S. Labor Secretary's Commission on Achieving Necessary Skills (SCANS) (June 1991); and Butterworth and Lovell (1983), New South Wales. A comparison of the four…

  17. Cryptographic Key Management System

    SciTech Connect

    No, author

    2014-02-21

    This report summarizes the outcome of U.S. Department of Energy (DOE) contract DE-OE0000543, requesting the design of a Cryptographic Key Management System (CKMS) for the secure management of cryptographic keys for the energy sector infrastructure. Prime contractor Sypris Electronics, in collaboration with Oak Ridge National Laboratories (ORNL), Electric Power Research Institute (EPRI), Valicore Technologies, and Purdue University's Center for Education and Research in Information Assurance and Security (CERIAS) and Smart Meter Integration Laboratory (SMIL), has designed, developed and evaluated the CKMS solution. We provide an overview of the project in Section 3, review the core contributions of all contractors in Section 4, and discuss bene ts to the DOE in Section 5. In Section 6 we describe the technical construction of the CKMS solution, and review its key contributions in Section 6.9. Section 7 describes the evaluation and demonstration of the CKMS solution in different environments. We summarize the key project objectives in Section 8, list publications resulting from the project in Section 9, and conclude with a discussion on commercialization in Section 10 and future work in Section 11.

  18. Five Keys to Success

    ERIC Educational Resources Information Center

    Peddy, Walter J.

    2009-01-01

    The first year as a principal is filled with self-doubt. As one already knows, there is no book or guide that can fully prepare someone for what the principal's position entails. All first-year principals have to learn by doing. In this article, the author discusses five keys to success that will guide and help first-year principals with the…

  19. What Are the Key Statistics about Endometrial Cancer?

    MedlinePlus

    ... cancer? Next Topic Endometrial cancer risk factors Key statistics for endometrial cancer? How common is endometrial cancer? ... endometrial cancer. Visit the American Cancer Society’s Cancer Statistics Center for more key statistics. Last Medical Review: ...

  20. What Are the Key Statistics for Childhood Leukemia?

    MedlinePlus

    ... factors for childhood leukemia? What are the key statistics for childhood leukemia? Leukemia is the most common ... about 2. Visit the American Cancer Society’s Cancer Statistics Center for more key statistics. Survival statistics for ...

  1. What Are the Key Statistics about Vulvar Cancer?

    MedlinePlus

    ... factors for vulvar cancer? What are the key statistics about vulvar cancer? In the United States, vulvar ... this cancer. Visit the American Cancer Society’s Cancer Statistics Center for more key statistics. Last Medical Review: ...

  2. What Are the Key Statistics about Uterine Sarcoma?

    MedlinePlus

    ... factors for uterine sarcoma? What are the key statistics about uterine sarcoma? The American Cancer Society's estimates ... uterine corpus. Visit the American Cancer Society’s Cancer Statistics Center for more key statistics. Last Medical Review: ...

  3. What Are the Key Statistics about Kidney Cancer?

    MedlinePlus

    ... factors for kidney cancer? What are the key statistics about kidney cancer? The American Cancer Society’s most ... by stage .” Visit the American Cancer Society’s Cancer Statistics Center for more key statistics. Last Medical Review: ...

  4. What Are the Key Statistics about Cervical Cancer?

    MedlinePlus

    ... factors for cervical cancer? What are the key statistics about cervical cancer? The American Cancer Society's estimates ... this country. Visit the American Cancer Society’s Cancer Statistics Center for more key statistics. Last Medical Review: ...

  5. What Are the Key Statistics about Multiple Myeloma?

    MedlinePlus

    ... factors for multiple myeloma? What are the key statistics about multiple myeloma? Multiple myeloma is a relatively ... in women). Visit the American Cancer Society’s Cancer Statistics Center for more key statistics. Last Medical Review: ...

  6. What Are the Key Statistics for Hodgkin Disease?

    MedlinePlus

    ... factors for Hodgkin disease? What are the key statistics about Hodgkin disease? The American Cancer Society’s estimates ... by stage .” Visit the American Cancer Society’s Cancer Statistics Center for more key statistics. Last Medical Review: ...

  7. Transthoracic Echocardiography with Doppler Tissue Imaging predicts weaning failure from mechanical ventilation: evolution of the left ventricle relaxation rate during a spontaneous breathing trial is the key factor in weaning outcome

    PubMed Central

    2012-01-01

    key factor of weaning failure. In contrast, the systolic dysfunction was not associated with weaning outcome. PMID:22583512

  8. Cryo-EM and the elucidation of new macromolecular structures: Random Conical Tilt revisited

    PubMed Central

    Sorzano, C. O. S.; Alcorlo, M.; de la Rosa-Trevín, J. M.; Melero, R.; Foche, I.; Zaldívar-Peraza, A.; del Cano, L.; Vargas, J.; Abrishami, V.; Otón, J.; Marabini, R.; Carazo, J. M.

    2015-01-01

    Cryo-Electron Microscopy (cryo-EM) of macromolecular complexes is a fundamental structural biology technique which is expanding at a very fast pace. Key to its success in elucidating the three-dimensional structure of a macromolecular complex, especially of small and non-symmetric ones, is the ability to start from a low resolution map, which is subsequently refined with the actual images collected at the microscope. There are several methods to produce this first structure. Among them, Random Conical Tilt (RCT) plays a prominent role due to its unbiased nature (it can create an initial model based on experimental measurements). In this article, we revise the fundamental mathematical expressions supporting RCT, providing new expressions handling all key geometrical parameters without the need of intermediate operations, leading to improved automation and overall reliability, essential for the success of cryo-EM when analyzing new complexes. We show that the here proposed RCT workflow based on the new formulation performs very well in practical cases, requiring very few image pairs (as low as 13 image pairs in one of our examples) to obtain relevant 3D maps. PMID:26390853

  9. Elucidations on the Reciprocal Lattice and the Ewald Sphere

    ERIC Educational Resources Information Center

    Foadi, J.; Evans, G.

    2008-01-01

    The reciprocal lattice is derived through the Fourier transform of a generic crystal lattice, as done previously in the literature. A few key derivations are this time handled in detail, and the connection with x-ray diffraction is clearly pointed out. The Ewald sphere is subsequently thoroughly explained and a few comments on its representation…

  10. Methodology for Localized and Accessible Image Formation and Elucidation

    ERIC Educational Resources Information Center

    Patil, Sandeep R.; Katiyar, Manish

    2009-01-01

    Accessibility is one of the key checkpoints in all software products, applications, and Web sites. Accessibility with digital images has always been a major challenge for the industry. Images form an integral part of certain type of documents and most Web 2.0-compliant Web sites. Individuals challenged with blindness and many dyslexics only make…

  11. Commentary: Elucidating the Neural Correlates of Early Childhood Memory

    ERIC Educational Resources Information Center

    Mullally, Sinead L.

    2015-01-01

    Both episodic memory and the key neural structure believed to support it, namely the hippocampus, are believed to undergo protracted periods of postnatal developmental. Critically however, the hippocampus is comprised of distinct subfields and circuits, and these circuits appear to mature at different rates (Lavenex and Banta Lavenex, 2013).…

  12. Elucidation of Adverse Bioactivity Profiles as Predictors of Toxicity Potential

    EPA Science Inventory

    Toxicity testing in vitro remains a formidable challenge due to lack of understanding of key molecular targets and pathways underlying many pathological events. The combination of genome sequencing and widespread application of high-throughput screening tools have provided the me...

  13. Elucidating pharmacodynamic interaction of silver nanoparticle - topical deliverable antibiotics

    NASA Astrophysics Data System (ADS)

    Thirumurugan, G.; Seshagiri Rao, J. V. L. N.; Dhanaraju, M. D.

    2016-07-01

    In order to exploit the potential benefits of antimicrobial combination therapy, we need a better understanding of the circumstances under which pharmacodynamic interactions expected. In this study, Pharmacodynamic interactions between silver nanoparticle (SNP) and topical antibiotics such as Cefazolin (CEF), Mupirocin (MUP), Gentamycin (GEN), Neomycin (NEO), Tetracycline (TET), Vancomycin (VAN) were investigated using the MIC test, Combination assay followed by Fractional Inhibitory concentration Index and Agar well diffusion method. SNP + MUP, SNP + NEO, SNP + VAN combinations showed Synergism (SN) and SNP + CEF, SNP + GEN, SNP + TET showed Partial synergism (PS) against Staphylococcus aureus. Four combinations (SNP + CEF, SNP + MUP, SNP + GEN, SNP + VAN) showed SN, SNP + TET showed PS and Indifferent effect (ID) were observed for SNP + NEO against Pseudomonas aeruginosa. SN was observed for SNP + CEF, SNP + GEN, SNP + NEO, SNP + TET and SNP + MUP showed ID, SNP + VAN showed PS against Escherichia coli. In addition, we elucidated the possible mechanism involved in the pharmacodynamic interaction between SNP-topical antibiotics by increased ROS level, membrane damage following protein release, K+ leakage and biofilm inhibition. Thus, our findings support that conjugation of the SNP with topical antibiotics have great potential in the topical formulation when treating complex resistant bacterial infections and where there is a need of more concentration to kill pathogenic bacteria.

  14. Elucidating Novel Serum Biomarkers Associated with Pulmonary Tuberculosis Treatment

    PubMed Central

    De Groote, Mary A.; Nahid, Payam; Jarlsberg, Leah; Johnson, John L.; Weiner, Marc; Muzanyi, Grace; Janjic, Nebojsa; Sterling, David G.; Ochsner, Urs A.

    2013-01-01

    In an unbiased approach to biomarker discovery, we applied a highly multiplexed proteomic technology (SOMAscan, SomaLogic, Inc, Boulder, CO) to understand changes in proteins from paired serum samples at enrollment and after 8 weeks of TB treatment from 39 patients with pulmonary TB from Kampala, Uganda enrolled in the Center for Disease Control and Prevention’s Tuberculosis Trials Consortium (TBTC) Study 29. This work represents the first large-scale proteomic analysis employing modified DNA aptamers in a study of active tuberculosis (TB). We identified multiple proteins that exhibit significant expression differences during the intensive phase of TB therapy. There was enrichment for proteins in conserved networks of biological processes and function including antimicrobial defense, tissue healing and remodeling, acute phase response, pattern recognition, protease/anti-proteases, complement and coagulation cascade, apoptosis, immunity and inflammation pathways. Members of cytokine pathways such as interferon-gamma, while present, were not as highly represented as might have been predicted. The top proteins that changed between baseline and 8 weeks of therapy were TSP4, TIMP-2, SEPR, MRC-2, Antithrombin III, SAA, CRP, NPS-PLA2, LEAP-1, and LBP. The novel proteins elucidated in this work may provide new insights for understanding TB disease, its treatment and subsequent healing processes that occur in response to effective therapy. PMID:23637781

  15. Magnetic resonance elucidation of molecule/macromolecule interaction stereochemistry

    NASA Astrophysics Data System (ADS)

    Andersen, Niels H.

    1992-07-01

    Our primary accomplishments were the development of software for the computer-aided structure elucidation of structural features of biological systems based on NOESY data: (1) simulating accurate theoretical NOESY spectra based on structural models, motional assumptions and NMR experiment parameters; and (2) the automated extraction of modeling constraints directly from raw NOESY data. The most recent software developments are the incorporation of model-free order parameters into NOESY simulations and the addition of routines for comparing computer-extracted distances (or cross-rates) with the expectation ranges based on the full spectrum of torsional freedom so as to generate precision estimates for NOE-distances from a single NOESY spectrum. These methods have been used to define the conformational states of a variety of polypeptide and drug molecule systems including: prostaglandin and steroid analogs, peptide hormones such as dynorphin-related peptides and GNRH analogs, rigid and flexible endothelin analogs, and a small protein allergen. The methods have also been applied to receptor-bound peptides.

  16. Metabolite essentiality elucidates robustness of Escherichia coli metabolism

    PubMed Central

    Kim, Pan-Jun; Lee, Dong-Yup; Kim, Tae Yong; Lee, Kwang Ho; Jeong, Hawoong; Lee, Sang Yup; Park, Sunwon

    2007-01-01

    Complex biological systems are very robust to genetic and environmental changes at all levels of organization. Many biological functions of Escherichia coli metabolism can be sustained against single-gene or even multiple-gene mutations by using redundant or alternative pathways. Thus, only a limited number of genes have been identified to be lethal to the cell. In this regard, the reaction-centric gene deletion study has a limitation in understanding the metabolic robustness. Here, we report the use of flux-sum, which is the summation of all incoming or outgoing fluxes around a particular metabolite under pseudo-steady state conditions, as a good conserved property for elucidating such robustness of E. coli from the metabolite point of view. The functional behavior, as well as the structural and evolutionary properties of metabolites essential to the cell survival, was investigated by means of a constraints-based flux analysis under perturbed conditions. The essential metabolites are capable of maintaining a steady flux-sum even against severe perturbation by actively redistributing the relevant fluxes. Disrupting the flux-sum maintenance was found to suppress cell growth. This approach of analyzing metabolite essentiality provides insight into cellular robustness and concomitant fragility, which can be used for several applications, including the development of new drugs for treating pathogens. PMID:17698812

  17. Harnessing evolution to elucidate the consequences of symbiosis.

    PubMed

    Gerardo, Nicole M

    2015-02-01

    Many organisms harbor microbial associates that have profound impacts on host traits. The phenotypic effect of symbionts on their hosts may include changes in development, reproduction, longevity, and defense against natural enemies. Determining the consequences of associating with a microbial symbiont requires experimental comparison of hosts with and without symbionts. Then, determining the mechanism by which symbionts alter these phenotypes can involve genomic, genetic, and evolutionary approaches; however, many host-associated symbionts are not amenable to genetic approaches that require cultivation of the microbe outside the host. In the current issue of PLOS Biology, Chrostek and Teixeira highlight an elegant approach to studying functional mechanisms of symbiont-conferred traits. They used directed experimental evolution to select for strains of Wolbachia wMelPop (a bacterial symbiont of fruit flies) that differed in copy number of a region of the genome suspected to underlie virulence. Copy number evolved rapidly when under selection, and wMelPop strains with more copies of the region shortened the lives of their Drosophila hosts more than symbionts with fewer copies. Interestingly, the wMelPop strains with more copies also increase host resistance to viruses compared to symbionts with fewer copies. Their study highlights the power of exploiting alternative approaches when elucidating the functional impacts of symbiotic associations. PMID:25668183

  18. Elucidating Polypharmacological Mechanisms of Polyphenols by Gene Module Profile Analysis

    PubMed Central

    Li, Bin; Xiong, Min; Zhang, Hong-Yu

    2014-01-01

    Due to the diverse medicinal effects, polyphenols are among the most intensively studied natural products. However, it is a great challenge to elucidate the polypharmacological mechanisms of polyphenols. To address this challenge, we establish a method for identifying multiple targets of chemical agents through analyzing the module profiles of gene expression upon chemical treatments. By using FABIA algorithm, we have performed a biclustering analysis of gene expression profiles derived from Connectivity Map (cMap), and clustered the profiles into 49 gene modules. This allowed us to define a 49 dimensional binary vector to characterize the gene module profiles, by which we can compare the expression profiles for each pair of chemical agents with Tanimoto coefficient. For the agent pairs with similar gene expression profiles, we can predict the target of one agent from the other. Drug target enrichment analysis indicated that this method is efficient to predict the multiple targets of chemical agents. By using this method, we identify 148 targets for 20 polyphenols derived from cMap. A large part of the targets are validated by experimental observations. The results show that the medicinal effects of polyphenols are far beyond their well-known antioxidant activities. This method is also applicable to dissect the polypharmacology of other natural products. PMID:24968267

  19. Spectroscopic elucidation of chemical structure of plasma-polymerized pyridine

    SciTech Connect

    Hozumi, K.; Kitamura, K.; Hashimoto, H.; Hamaoka, T.; Fujisawa, H.; Ishizawa, T.

    1983-05-01

    Chemical structure of the plasma-polymerized pyridine film produced on a glass reactor wall by means of the plasma technique in which the pyridine vapor was electronically excited by high-frequency power under a reduced pressure was elucidated. The polymer was highly hydrophilic and was soluble to some of the polar organic solvents so that nitrogen-containing polar functional groups were predicted to participate in the chemical structure of the polymer molecules. /sup 1/H-NMR, /sup 13/CNMR, and IR spectroscopies, high-resolution mass spectral data, and number-average molecular weight determination with some aid of microelemental analysis revealed the presence of various functional groups such as imine, nitrile, amine, pyridine ring, its N-oxide, and even amide. The oxygen atoms involved in the last two groups were supposedly introduced by contact with ambient air after the plasma process. The hydrophilic nature of the polymer which was essential for preparing reverse osmosis membrane was therefore due to the overall hydration effect of these polar functional groups.

  20. Elucidating pharmacodynamic interaction of silver nanoparticle - topical deliverable antibiotics.

    PubMed

    Thirumurugan, G; Seshagiri Rao, J V L N; Dhanaraju, M D

    2016-01-01

    In order to exploit the potential benefits of antimicrobial combination therapy, we need a better understanding of the circumstances under which pharmacodynamic interactions expected. In this study, Pharmacodynamic interactions between silver nanoparticle (SNP) and topical antibiotics such as Cefazolin (CEF), Mupirocin (MUP), Gentamycin (GEN), Neomycin (NEO), Tetracycline (TET), Vancomycin (VAN) were investigated using the MIC test, Combination assay followed by Fractional Inhibitory concentration Index and Agar well diffusion method. SNP + MUP, SNP + NEO, SNP + VAN combinations showed Synergism (SN) and SNP + CEF, SNP + GEN, SNP + TET showed Partial synergism (PS) against Staphylococcus aureus. Four combinations (SNP + CEF, SNP + MUP, SNP + GEN, SNP + VAN) showed SN, SNP + TET showed PS and Indifferent effect (ID) were observed for SNP + NEO against Pseudomonas aeruginosa. SN was observed for SNP + CEF, SNP + GEN, SNP + NEO, SNP + TET and SNP + MUP showed ID, SNP + VAN showed PS against Escherichia coli. In addition, we elucidated the possible mechanism involved in the pharmacodynamic interaction between SNP-topical antibiotics by increased ROS level, membrane damage following protein release, K(+) leakage and biofilm inhibition. Thus, our findings support that conjugation of the SNP with topical antibiotics have great potential in the topical formulation when treating complex resistant bacterial infections and where there is a need of more concentration to kill pathogenic bacteria. PMID:27427207

  1. Elucidating polypharmacological mechanisms of polyphenols by gene module profile analysis.

    PubMed

    Li, Bin; Xiong, Min; Zhang, Hong-Yu

    2014-01-01

    Due to the diverse medicinal effects, polyphenols are among the most intensively studied natural products. However, it is a great challenge to elucidate the polypharmacological mechanisms of polyphenols. To address this challenge, we establish a method for identifying multiple targets of chemical agents through analyzing the module profiles of gene expression upon chemical treatments. By using FABIA algorithm, we have performed a biclustering analysis of gene expression profiles derived from Connectivity Map (cMap), and clustered the profiles into 49 gene modules. This allowed us to define a 49 dimensional binary vector to characterize the gene module profiles, by which we can compare the expression profiles for each pair of chemical agents with Tanimoto coefficient. For the agent pairs with similar gene expression profiles, we can predict the target of one agent from the other. Drug target enrichment analysis indicated that this method is efficient to predict the multiple targets of chemical agents. By using this method, we identify 148 targets for 20 polyphenols derived from cMap. A large part of the targets are validated by experimental observations. The results show that the medicinal effects of polyphenols are far beyond their well-known antioxidant activities. This method is also applicable to dissect the polypharmacology of other natural products. PMID:24968267

  2. Elucidating pharmacodynamic interaction of silver nanoparticle - topical deliverable antibiotics

    PubMed Central

    Thirumurugan, G.; Seshagiri Rao, J. V. L. N.; Dhanaraju, M. D.

    2016-01-01

    In order to exploit the potential benefits of antimicrobial combination therapy, we need a better understanding of the circumstances under which pharmacodynamic interactions expected. In this study, Pharmacodynamic interactions between silver nanoparticle (SNP) and topical antibiotics such as Cefazolin (CEF), Mupirocin (MUP), Gentamycin (GEN), Neomycin (NEO), Tetracycline (TET), Vancomycin (VAN) were investigated using the MIC test, Combination assay followed by Fractional Inhibitory concentration Index and Agar well diffusion method. SNP + MUP, SNP + NEO, SNP + VAN combinations showed Synergism (SN) and SNP + CEF, SNP + GEN, SNP + TET showed Partial synergism (PS) against Staphylococcus aureus. Four combinations (SNP + CEF, SNP + MUP, SNP + GEN, SNP + VAN) showed SN, SNP + TET showed PS and Indifferent effect (ID) were observed for SNP + NEO against Pseudomonas aeruginosa. SN was observed for SNP + CEF, SNP + GEN, SNP + NEO, SNP + TET and SNP + MUP showed ID, SNP + VAN showed PS against Escherichia coli. In addition, we elucidated the possible mechanism involved in the pharmacodynamic interaction between SNP-topical antibiotics by increased ROS level, membrane damage following protein release, K+ leakage and biofilm inhibition. Thus, our findings support that conjugation of the SNP with topical antibiotics have great potential in the topical formulation when treating complex resistant bacterial infections and where there is a need of more concentration to kill pathogenic bacteria. PMID:27427207

  3. Elucidating the Factors that Determine the Open Circuit Voltage in Discrete Heterojunction Organic Photovoltaic Cells

    SciTech Connect

    Chauhan, V.; Hatton, R; Sullivan, P; Jones, T; Cho, S; Piper, L; DeMasi, A; Smith, K

    2010-01-01

    The operation of discrete heterojunction organic photovoltaic (OPV) cells employing chloro-aluminium phthalocyanine (ClAlPc) as the electron donor and C{sub 60} as the electron acceptor is reported and the characteristics are correlated with the energy level structure of the devices determined using X-ray photoelectron spectroscopy. The results give new insight into the origin of the open circuit voltage (V{sub oc}) in discrete heterojunction OPVs. The measured V{sub oc} in this system is found to be determined by: (i) the frontier orbital energy offsets between the donor and acceptor materials, accounting for the likely formation of an abrupt vacuum level shift at the heterojunction interface and (ii) the degree of alignment between the hole-extracting electrode Fermi level and the highest occupied molecular orbital energy of the electron donor material. The generality of the findings is demonstrated by rationalising the V{sub oc} in OPVs employing the archetypal electron donor, copper phthalocyanine.

  4. The Bremner factor for elucidation of nitrous oxide evolution from soils

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It is well established that agricultural emissions of nitrous oxide are an important source of atmospheric green house gas loading implicated in global climate change. The atmospheric concentration of nitrous oxide has increased by 17% since the 1800’s and continues to increase at an exponential r...

  5. Fungal model systems and the elucidation of pathogenicity determinants

    PubMed Central

    Perez-Nadales, Elena; Almeida Nogueira, Maria Filomena; Baldin, Clara; Castanheira, Sónia; El Ghalid, Mennat; Grund, Elisabeth; Lengeler, Klaus; Marchegiani, Elisabetta; Mehrotra, Pankaj Vinod; Moretti, Marino; Naik, Vikram; Oses-Ruiz, Miriam; Oskarsson, Therese; Schäfer, Katja; Wasserstrom, Lisa; Brakhage, Axel A.; Gow, Neil A.R.; Kahmann, Regine; Lebrun, Marc-Henri; Perez-Martin, José; Di Pietro, Antonio; Talbot, Nicholas J.; Toquin, Valerie; Walther, Andrea; Wendland, Jürgen

    2014-01-01

    Fungi have the capacity to cause devastating diseases of both plants and animals, causing significant harvest losses that threaten food security and human mycoses with high mortality rates. As a consequence, there is a critical need to promote development of new antifungal drugs, which requires a comprehensive molecular knowledge of fungal pathogenesis. In this review, we critically evaluate current knowledge of seven fungal organisms used as major research models for fungal pathogenesis. These include pathogens of both animals and plants; Ashbya gossypii, Aspergillus fumigatus, Candida albicans, Fusarium oxysporum, Magnaporthe oryzae, Ustilago maydis and Zymoseptoria tritici. We present key insights into the virulence mechanisms deployed by each species and a comparative overview of key insights obtained from genomic analysis. We then consider current trends and future challenges associated with the study of fungal pathogenicity. PMID:25011008

  6. Atomic structure of anthrax protective antigen pore elucidates toxin translocation.

    PubMed

    Jiang, Jiansen; Pentelute, Bradley L; Collier, R John; Zhou, Z Hong

    2015-05-28

    Anthrax toxin, comprising protective antigen, lethal factor, and oedema factor, is the major virulence factor of Bacillus anthracis, an agent that causes high mortality in humans and animals. Protective antigen forms oligomeric prepores that undergo conversion to membrane-spanning pores by endosomal acidification, and these pores translocate the enzymes lethal factor and oedema factor into the cytosol of target cells. Protective antigen is not only a vaccine component and therapeutic target for anthrax infections but also an excellent model system for understanding the mechanism of protein translocation. On the basis of biochemical and electrophysiological results, researchers have proposed that a phi (Φ)-clamp composed of phenylalanine (Phe)427 residues of protective antigen catalyses protein translocation via a charge-state-dependent Brownian ratchet. Although atomic structures of protective antigen prepores are available, how protective antigen senses low pH, converts to active pore, and translocates lethal factor and oedema factor are not well defined without an atomic model of its pore. Here, by cryo-electron microscopy with direct electron counting, we determine the protective antigen pore structure at 2.9-Å resolution. The structure reveals the long-sought-after catalytic Φ-clamp and the membrane-spanning translocation channel, and supports the Brownian ratchet model for protein translocation. Comparisons of four structures reveal conformational changes in prepore to pore conversion that support a multi-step mechanism by which low pH is sensed and the membrane-spanning channel is formed. PMID:25778700

  7. Key Points Concerning Amyloid Infectivity and Prion-Like Neuronal Invasion

    PubMed Central

    Espargaró, Alba; Busquets, Maria Antònia; Estelrich, Joan; Sabate, Raimon

    2016-01-01

    Amyloid aggregation has been related to an increasing number of human illnesses, from Alzheimer’s and Parkinson’s diseases (AD/PD) to Creutzfeldt-Jakob disease. Commonly, only prions have been considered as infectious agents with a high capacity of propagation. However, recent publications have shown that many amyloid proteins, including amyloid β-peptide, α-synuclein (α-syn) and tau protein, also propagate in a “prion-like” manner. Meanwhile, no link between propagation of pathological proteins and neurotoxicity has been demonstrated. The extremely low infectivity under natural conditions of most non-prion amyloids is far below the capacity to spread exhibited by prions. Nonetheless, it is important to elucidate the key factors that cause non-prion amyloids to become infectious agents. In recent years, important advances in our understanding of the amyloid processes of amyloid-like proteins and unrelated prions (i.e., yeast and fungal prions) have yielded essential information that can shed light on the prion phenomenon in mammals and humans. As shown in this review, recent evidence suggests that there are key factors that could dramatically modulate the prion capacity of proteins in the amyloid conformation. The concentration of nuclei, the presence of oligomers, and the toxicity, resistance and localization of these aggregates could all be key factors affecting their spread. In short, those factors that favor the high concentration of extracellular nuclei or oligomers, characterized by small size, with a low toxicity could dramatically increase prion propensity; whereas low concentrations of highly toxic intracellular amyloids, with a large size, would effectively prevent infectivity. PMID:27147962

  8. Key Points Concerning Amyloid Infectivity and Prion-Like Neuronal Invasion.

    PubMed

    Espargaró, Alba; Busquets, Maria Antònia; Estelrich, Joan; Sabate, Raimon

    2016-01-01

    Amyloid aggregation has been related to an increasing number of human illnesses, from Alzheimer's and Parkinson's diseases (AD/PD) to Creutzfeldt-Jakob disease. Commonly, only prions have been considered as infectious agents with a high capacity of propagation. However, recent publications have shown that many amyloid proteins, including amyloid β-peptide, α-synuclein (α-syn) and tau protein, also propagate in a "prion-like" manner. Meanwhile, no link between propagation of pathological proteins and neurotoxicity has been demonstrated. The extremely low infectivity under natural conditions of most non-prion amyloids is far below the capacity to spread exhibited by prions. Nonetheless, it is important to elucidate the key factors that cause non-prion amyloids to become infectious agents. In recent years, important advances in our understanding of the amyloid processes of amyloid-like proteins and unrelated prions (i.e., yeast and fungal prions) have yielded essential information that can shed light on the prion phenomenon in mammals and humans. As shown in this review, recent evidence suggests that there are key factors that could dramatically modulate the prion capacity of proteins in the amyloid conformation. The concentration of nuclei, the presence of oligomers, and the toxicity, resistance and localization of these aggregates could all be key factors affecting their spread. In short, those factors that favor the high concentration of extracellular nuclei or oligomers, characterized by small size, with a low toxicity could dramatically increase prion propensity; whereas low concentrations of highly toxic intracellular amyloids, with a large size, would effectively prevent infectivity. PMID:27147962

  9. Wrangling Phosphoproteomic Data to Elucidate Cancer Signaling Pathways

    PubMed Central

    Grimes, Mark L.; Lee, Wan-Jui; van der Maaten, Laurens; Shannon, Paul

    2013-01-01

    The interpretation of biological data sets is essential for generating hypotheses that guide research, yet modern methods of global analysis challenge our ability to discern meaningful patterns and then convey results in a way that can be easily appreciated. Proteomic data is especially challenging because mass spectrometry detectors often miss peptides in complex samples, resulting in sparsely populated data sets. Using the R programming language and techniques from the field of pattern recognition, we have devised methods to resolve and evaluate clusters of proteins related by their pattern of expression in different samples in proteomic data sets. We examined tyrosine phosphoproteomic data from lung cancer samples. We calculated dissimilarities between the proteins based on Pearson or Spearman correlations and on Euclidean distances, whilst dealing with large amounts of missing data. The dissimilarities were then used as feature vectors in clustering and visualization algorithms. The quality of the clusterings and visualizations were evaluated internally based on the primary data and externally based on gene ontology and protein interaction networks. The results show that t-distributed stochastic neighbor embedding (t-SNE) followed by minimum spanning tree methods groups sparse proteomic data into meaningful clusters more effectively than other methods such as k-means and classical multidimensional scaling. Furthermore, our results show that using a combination of Spearman correlation and Euclidean distance as a dissimilarity representation increases the resolution of clusters. Our analyses show that many clusters contain one or more tyrosine kinases and include known effectors as well as proteins with no known interactions. Visualizing these clusters as networks elucidated previously unknown tyrosine kinase signal transduction pathways that drive cancer. Our approach can be applied to other data types, and can be easily adopted because open source software

  10. Identification and structural elucidation of ozonation transformation products of estrone

    PubMed Central

    2013-01-01

    Background Quantitative methods for the analysis of contaminants of emerging concern (CECs) are abundant in the scientific literature. However, there are few reports on systematic methods of identification and structural identification of transformation products. For this reason, a new method based on high-resolution mass spectrometry and differential analysis was developed in order to facilitate and accelerate the process of identification and structural elucidation of transformation products CECs. This method was applied to the study of ozonation transformation products (OTPs) of the natural hormone estrone (E1). Results A control compare trend experiment consisting in the comparison of a control sample to several samples having been exposed to decreasing concentrations of O3(aq) indicated that 593 peaks could be associated with OTPs. After applying various filters to remove background noise, sample contaminants and signal spikes, this data set was reduced to 16 candidate peaks. By inspection of the shape of these peaks, only two compounds OTP-276 (m/z 275.12930) and OTP-318 (m/z 317.14008) were considered as good candidates for further study. Multi-stage tandem mass spectrometry (MSn) experiments of SPE extracts of the ozonated samples of E1 and of a deuterium-labeled analogue (E1-d4) showed that OTP-276 and OTP-318 had carboxylic acid and hydroxyl functional groups, as previously reported for OTPs of other hormones. Structures for these two compounds were proposed based on their MSn spectra. Conclusion These results indicate that the method proposed is a systematic and rapid approach to study transformation products of CECs. PMID:23618537

  11. Elucidating the Landscape of Aberrant DNA Methylation in Hepatocellular Carcinoma

    PubMed Central

    Song, Min-Ae; Tiirikainen, Maarit; Kwee, Sandi; Okimoto, Gordon; Yu, Herbert; Wong, Linda L.

    2013-01-01

    Background Hepatocellular carcinoma (HCC) is one of the most common cancers and frequently presents with an advanced disease at diagnosis. There is only limited knowledge of genome-scale methylation changes in HCC. Methods and Findings We performed genome-wide methylation profiling in a total of 47 samples including 27 HCC and 20 adjacent normal liver tissues using the Illumina HumanMethylation450 BeadChip. We focused on differential methylation patterns in the promoter CpG islands as well as in various less studied genomic regions such as those surrounding the CpG islands, i.e. shores and shelves. Of the 485,577 loci studied, significant differential methylation (DM) was observed between HCC and adjacent normal tissues at 62,692 loci or 13% (p<1.03e-07). Of them, 61,058 loci (97%) were hypomethylated and most of these loci were located in the intergenic regions (43%) or gene bodies (33%). Our analysis also identified 10,775 differentially methylated (DM) loci (17% out of 62,692 loci) located in or surrounding the gene promoters, 4% of which reside in known Differentially Methylated Regions (DMRs) including reprogramming specific DMRs and cancer specific DMRs, while the rest (10,315) involving 4,106 genes could be potential new HCC DMR loci. Interestingly, the promoter-related DM loci occurred twice as frequently in the shores than in the actual CpG islands. We further characterized 982 DM loci in the promoter CpG islands to evaluate their potential biological function and found that the methylation changes could have effect on the signaling networks of Cellular development, Gene expression and Cell death (p = 1.0e-38), with BMP4, CDKN2A, GSTP1, and NFATC1 on the top of the gene list. Conclusion Substantial changes of DNA methylation at a genome-wide level were observed in HCC. Understanding epigenetic changes in HCC will help to elucidate the pathogenesis and may eventually lead to identification of molecular markers for liver cancer diagnosis, treatment and

  12. Elucidation of denitrification mechanism in karstic Ryukyu limestone aquifer

    NASA Astrophysics Data System (ADS)

    Hijikawa, K.

    2014-12-01

    Nitrate (NO3-) concentrations in public water supplies have risen above acceptable levels in many areas of the world including Japan, largely as a result of contamination by human and animal waste and overuse of fertilizers. A previous study has characterized nitrate concentrations in groundwater in this area is a higher than the upper value (44mgL-1) of environmental quality criteria on one hands. On the other hand, there exists points where the concentration of nitric acid is not detected, which suggests the possibility of denitrification. During early 2000, a new analytical procedure for nitrate isotopic measurement, termed the "denitrifier method", was established. With the development of the nitrate isotope tracer method, much research has been reported detailing sources of groundwater nitrate and denitrification mechanisms. This study presents a pilot case study (in the southern part of Okinawa Main Island, Japan, where Ryukyu limestone is extensively distributed) using the combined stable isotope ratios of major elements (C, N and S) as net recorders of the biogeochemical reactions with the aim of elucidation of denitrification mechanism in Ryukyu limestone aquifer. As a result, significant decreases in nitrate concentrations due to denitrification were observed in groundwater at some locations, which induced increases in isotope ratios up to 59.7‰ for δ15NNO3. These points of groundwater were located above the cutoff wall of the underground dam and near the fault. It is considered that the residence time of the groundwater is longer than the other points at these denitrification points, and that reduction condition tends to be formed in the groundwater. However, the rapid rise of the groundwater level due to rainfall is likely to occur in the Ryukyu limestone aquifer, where the ground water was found to have changed dynamically from the reduction condition to the oxidation condition which a denitrification (has not occured)does not occur. Moreover, the

  13. What Are the Key Statistics about Pancreatic Cancer?

    MedlinePlus

    ... cancer? Next Topic Pancreatic cancer risk factors Key statistics for pancreatic cancer How common is pancreatic cancer? ... can be affected by certain risk factors . For statistics related to survival, see Pancreatic cancer survival rates ...

  14. A new approach to elucidating repair reactions of resveratrol.

    PubMed

    Kerzig, Christoph; Henkel, Selgar; Goez, Martin

    2015-06-01

    The repair by co-antioxidants of the phenoxy radical of resveratrol, the famous health-preserving ingredient of red wine, is a key step of radical scavenging cascades in nature. To generate that radical, we employed 355 nm photoionization as a direct and selective access that reduces the chemical complexity and is equally applicable in organized phases; to monitor it, we used its hitherto unreported absorption in the red where no other species in our systems interfere. With this novel approach, we measured rate constants and H/D kinetic isotope effects for the repairs by ascorbate, trolox (a vitamin E analogue) and 4-aminophenol, and identified the mechanisms as one-step hydrogen abstractions. Cysteine and glutathione are unreactive. In micellar solution (SDS), the repair by ascorbate is much slower and involves only the hydrophilic phenoxy moieties protruding from the micelles. The new experimental strategy also led to a reevaluation of extinction coefficients, rate constants and mechanisms. PMID:25948021

  15. Nanofluids Research: Key Issues

    PubMed Central

    2010-01-01

    Nanofluids are a new class of fluids engineered by dispersing nanometer-size structures (particles, fibers, tubes, droplets) in base fluids. The very essence of nanofluids research and development is to enhance fluid macroscopic and megascale properties such as thermal conductivity through manipulating microscopic physics (structures, properties and activities). Therefore, the success of nanofluid technology depends very much on how well we can address issues like effective means of microscale manipulation, interplays among physics at different scales and optimization of microscale physics for the optimal megascale properties. In this work, we take heat-conduction nanofluids as examples to review methodologies available to effectively tackle these key but difficult problems and identify the future research needs as well. The reviewed techniques include nanofluids synthesis through liquid-phase chemical reactions in continuous-flow microfluidic microreactors, scaling-up by the volume averaging and constructal design with the constructal theory. The identified areas of future research contain microfluidic nanofluids, thermal waves and constructal nanofluids. PMID:20676214

  16. SSME Key Operations Demonstration

    NASA Technical Reports Server (NTRS)

    Anderson, Brian; Bradley, Michael; Ives, Janet

    1997-01-01

    A Space Shuttle Main Engine (SSME) test program was conducted between August 1995 and May 1996 using the Technology Test Bed (TTB) Engine. SSTO vehicle studies have indicated that increases in the propulsion system operating range can save significant weight and cost at the vehicle level. This test program demonstrated the ability of the SSME to accommodate a wide variation in safe operating ranges and therefore its applicability to the SSTO mission. A total of eight tests were completed with four at Marshall Space Flight Center's Advanced Engine Test Facility and four at the Stennis Space Center (SSC) A-2 attitude test stand. Key demonstration objectives were: 1) Mainstage operation at 5.4 to 6.9 mixture ratio; 2) Nominal engine start with significantly reduced engine inlet pressures of 50 psia LOX and 38 psia fuel; and 3) Low power level operation at 17%, 22%, 27%, 40%, 45%, and 50% of Rated Power Level. Use of the highly instrumented TTB engine for this test series has afforded the opportunity to study in great detail engine system operation not possible with a standard SSME and has significantly contributed to a greater understanding of the capabilities of the SSME and liquid rocket engines in general.

  17. Elucidating the magnetic and superconducting phases in the alkali metal intercalated iron chalcogenides

    NASA Astrophysics Data System (ADS)

    Wang, Meng; Yi, Ming; Tian, Wei; Bourret-Courchesne, Edith; Birgeneau, Robert J.

    2016-02-01

    The complex interdigitated phases have greatly frustrated attempts to document the basic features of the superconductivity in the alkali metal intercalated iron chalcogenides. Here, using elastic neutron scattering, energy-dispersive x-ray spectroscopy, and resistivity measurements, we elucidate the relations of these phases in RbxFeySe2 -zSz . We find (i) the iron content is crucial in stabilizing the stripe antiferromagnetic (AF) phase with rhombic iron vacancy order (y ≈1.5 ) , the block AF phase with √{5 }×√{5 } iron vacancy order (y ≈1.6 ) , and the iron vacancy-free phase (y ≈2 ) ; and (ii) the iron vacancy-free superconducting phase (z =0 ) evolves into an iron vacancy-free metallic phase with sulfur substitution (z >1.5 ) due to the progressive decrease of the electronic correlation strength. Both the stripe AF phase and the block AF phase are Mott insulators. The iron-rich compounds (y >1.6 ) undergo a first order transition from an iron vacancy disordered phase at high temperatures into the √{5 }×√{5 } iron vacancy ordered phase and the iron vacancy-free phase below Ts. Our data demonstrate that there are miscibility gaps between these three phases. The existence of the miscibility gaps in the iron content is a key to understanding the relationship between these complicated phases.

  18. Elucidation of novel 13-series resolvins that increase with atorvastatin and clear infections

    PubMed Central

    Dalli, Jesmond; Chiang, Nan; Serhan, Charles N.

    2015-01-01

    Endogenous mechanisms leading to host protection and resolution of infections without immunosuppression are of wide interest1,2. Here we elucidated the structures of four new host-protective molecules produced in neutrophil-endothelial co-cultures, and present in human and mouse tissues after sterile inflammation or infection. These bioactive molecules contained conjugated triene and diene double bonds with each carrying a 13-carbon position alcohol and were derived from n-3 docosapentaenoic acid (DPA, C22:5). These compounds, termed 13-series resolvins (RvT), demonstrated potent protective actions increasing mice survival during Escherichia coli infections. RvT also regulated human and mouse phagocyte responses stimulating bacterial phagocytosis and regulating inflammasome components. Their biosynthesis during neutrophil-endothelial cell interactions was initiated by endothelial cyclooxygenase-2 (COX-2) and increased by atorvastatin via S-nitrosylation of COX-2. The actions of atorvastatin and RvT were additive in E. coli infections in mice where they accelerated resolution of inflammation and increased survival >60%. These results document novel host protective molecules in bacterial infections, namely 13-series resolvins, derived from n-3 DPA via transcellular biosynthesis and increased by atorvastatin. These novel molecules regulate key innate protective responses in the resolution of infectious-inflammation. PMID:26236990

  19. Elucidation of structure-to-property relationships of piezoresistive polymer-carbon nanotube nanocomposites

    NASA Astrophysics Data System (ADS)

    Fang, Weiqing; Leung, Siu N.

    2015-07-01

    Polymeric nanocomposites (PNC) filled with carbon nanotubes (CNTs) possess superior multifunctionality, including electrical, thermal, and mechanical properties, making them an emerging family of advanced and multifunctional materials. In recent years, flexible polymer/CNT nanocomposites are increasingly being considered as promising alternatives to conventional smart materials. Their piezoresistive behaviours have led to many potential applications in strain sensing. Despite extensive experimental and theoretical research, the underlying mechanisms for polymer/CNT nanocomposites' piezoresistive behaviours have yet been elucidated. This paper reports comprehensive investigations on the mechanisms and the structure-to-property relationships of these piezoresistive nanocomposites. Quantitative analyses revealed that piezoresistivity of polymer/CNT nanocomposites is predominantly governed by the three mechanisms related to the strain-induced morphological evolution of the CNT network embedded in the polymer matrix. Furthermore, both CNT content and CNT alignment are key structural parameters that affect the contribution of different mechanisms on PNCs' piezoresistivity and the sensitivity of flexible PNCs as strain sensors. For PNC filled with high content of randomly dispersed CNTs, the piezoresistivity was predominantly caused by the breakage of a complex conductive network into two or more simpler conductive paths. For PNC filled with low content of highly aligned CNTs, the piezoresistivity was mainly contributed by the complete disruption of originally interconnected CNTs in electrically conductive pathways.

  20. DIANA-microT web server: elucidating microRNA functions through target prediction.

    PubMed

    Maragkakis, M; Reczko, M; Simossis, V A; Alexiou, P; Papadopoulos, G L; Dalamagas, T; Giannopoulos, G; Goumas, G; Koukis, E; Kourtis, K; Vergoulis, T; Koziris, N; Sellis, T; Tsanakas, P; Hatzigeorgiou, A G

    2009-07-01

    Computational microRNA (miRNA) target prediction is one of the key means for deciphering the role of miRNAs in development and disease. Here, we present the DIANA-microT web server as the user interface to the DIANA-microT 3.0 miRNA target prediction algorithm. The web server provides extensive information for predicted miRNA:target gene interactions with a user-friendly interface, providing extensive connectivity to online biological resources. Target gene and miRNA functions may be elucidated through automated bibliographic searches and functional information is accessible through Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The web server offers links to nomenclature, sequence and protein databases, and users are facilitated by being able to search for targeted genes using different nomenclatures or functional features, such as the genes possible involvement in biological pathways. The target prediction algorithm supports parameters calculated individually for each miRNA:target gene interaction and provides a signal-to-noise ratio and a precision score that helps in the evaluation of the significance of the predicted results. Using a set of miRNA targets recently identified through the pSILAC method, the performance of several computational target prediction programs was assessed. DIANA-microT 3.0 achieved there with 66% the highest ratio of correctly predicted targets over all predicted targets. The DIANA-microT web server is freely available at www.microrna.gr/microT. PMID:19406924

  1. Elucidation of novel 13-series resolvins that increase with atorvastatin and clear infections.

    PubMed

    Dalli, Jesmond; Chiang, Nan; Serhan, Charles N

    2015-09-01

    Endogenous mechanisms leading to host protection and resolution of infections without immunosuppression are of wide interest. Here we elucidate the structures of four new host-protective molecules produced in neutrophil-endothelial cocultures and present in human and mouse tissues after sterile inflammation or infection. The bioactive molecules contain conjugated triene and diene double bonds, carry an alcohol at C13 and are derived from n-3 docosapentaenoic acid (DPA, C22:5). These compounds, termed 13-series resolvins (RvTs), demonstrated potent protective actions increasing mice survival during Escherichia coli infections. RvTs also regulated human and mouse phagocyte responses stimulating bacterial phagocytosis and regulating inflammasome components. Their biosynthesis during neutrophil-endothelial cell interactions was initiated by endothelial cyclooxygenase-2 (COX-2), increased by atorvastatin via S-nitrosylation of COX-2 and reduced by COX-2 inhibitors. The actions of atorvastatin and RvTs were additive in E. coli infections in mice, where they accelerated resolution of inflammation and increased survival >60%. Taken together, these results document host-protective molecules in bacterial infections, namely RvTs, derived from n-3 DPA via transcellular biosynthesis and increased by atorvastatin. These molecules regulate key innate protective responses in the resolution of infectious inflammation. PMID:26236990

  2. Elucidating Microbial Adaptation Dynamics via Autonomous Exposure and Sampling

    NASA Astrophysics Data System (ADS)

    Grace, J. M.; Verseux, C.; Gentry, D.; Moffet, A.; Thayabaran, R.; Wong, N.; Rothschild, L.

    2013-12-01

    The adaptation of micro-organisms to their environments is a complex process of interaction between the pressures of the environment and of competition. Reducing this multifactorial process to environmental exposure in the laboratory is a common tool for elucidating individual mechanisms of evolution, such as mutation rates[Wielgoss et al., 2013]. Although such studies inform fundamental questions about the way adaptation and even speciation occur, they are often limited by labor-intensive manual techniques[Wassmann et al., 2010]. Current methods for controlled study of microbial adaptation limit the length of time, the depth of collected data, and the breadth of applied environmental conditions. Small idiosyncrasies in manual techniques can have large effects on outcomes; for example, there are significant variations in induced radiation resistances following similar repeated exposure protocols[Alcántara-Díaz et al., 2004; Goldman and Travisano, 2011]. We describe here a project under development to allow rapid cycling of multiple types of microbial environmental exposure. The system allows continuous autonomous monitoring and data collection of both single species and sampled communities, independently and concurrently providing multiple types of controlled environmental pressure (temperature, radiation, chemical presence or absence, and so on) to a microbial community in dynamic response to the ecosystem's current status. When combined with DNA sequencing and extraction, such a controlled environment can cast light on microbial functional development, population dynamics, inter- and intra-species competition, and microbe-environment interaction. The project's goal is to allow rapid, repeatable iteration of studies of both natural and artificial microbial adaptation. As an example, the same system can be used both to increase the pH of a wet soil aliquot over time while periodically sampling it for genetic activity analysis, or to repeatedly expose a culture of

  3. Atomic structure of anthrax PA pore elucidates toxin translocation

    PubMed Central

    Jiang, Jiansen; Pentelute, Bradley L.; Collier, R. John; Zhou, Z. Hong

    2015-01-01

    Summary Anthrax toxin, comprising protective antigen (PA), lethal factor (LF) and edema factor (EF), is the major virulence factor of Bacillus anthracis, an agent that causes high mortality in human and animals. PA forms oligomeric prepores that undergo conversion to membrane-spanning pores by endosomal acidification, and these pores translocate the enzymes LF and EF into the cytosol of target cells1. PA is not only a vaccine component and therapeutic target for anthrax infections but also an excellent model system for understanding the mechanism of protein translocation. Based on biochemical and electrophysiological results, researchers have proposed that a Φ-clamp composed of Phe427 residues of PA catalyzes protein translocation via a charge-state dependent Brownian ratchet2–9. Although atomic structures of PA prepores are available10–14, how PA senses low pH, converts to active pore and translocates LF and EF are not well defined without an atomic model of the PA pore. Here, by cryo electron microscopy (cryoEM) with direct electron counting, we have determined the PA pore structure at 2.9-Å resolution. The structure reveals the long-sought-after catalytic Φ-clamp and the membrane-spanning translocation channel, and supports the Brownian ratchet model for protein translocation. Comparisons of four structures reveal conformational changes in prepore to pore conversion that support a multi-step mechanism by which low-pH is sensed and the membrane-spanning channel is formed. PMID:25778700

  4. Reaction products in mass spectrometry elucidated with infrared spectroscopy.

    PubMed

    Polfer, Nick C; Oomens, Jos

    2007-08-01

    Determining the structure and dynamics of large biologically relevant molecules is one of the key challenges facing biology. Although X-ray crystallography (XRD) and nuclear magnetic resonance (NMR) yield accurate structural information, they are of limited use when sample quantities are low. Mass spectrometry (MS) on the other hand has been very successful in analyzing biological molecules down to atto-mole quantities and has hence begun to challenge XRD and NMR as the key technology in the life sciences. This trend has been further assisted by the development of MS techniques that yield structural information on biomolecules. Of these techniques, collision-induced dissociation (CID) and hydrogen/deuterium exchange (HDX) are among the most popular. Despite advances in applying these techniques, little direct experimental evidence had been available until recently to verify their proposed underlying reaction mechanisms. The possibility to record infrared spectra of mass-selected molecular ions has opened up a novel avenue in the structural characterization of ions and their reaction products. On account of its high pulse energies and wide wavelength tunability, the free electron laser for infrared experiments (FELIX) at FOM Rijnhuizen has been shown to be ideally suited to study trapped molecular ions with infrared photo-dissociation spectroscopy. In this paper, we review recent experiments in our laboratory on the infrared spectroscopic characterization of reaction products from CID and HDX, thereby corroborating some of the reaction mechanisms that have been proposed. In particular, it is shown that CID gives rise to linear fragment ion structures which have been proposed for some time, but also yields fully cyclical ring structures. These latter structures present a possible challenge for using tandem MS in the sequencing of peptides/proteins, as they can lead to a scrambling of the amino acid sequence information. In gas-phase HDX of an amino acid it is shown

  5. Transposon mouse models to elucidate the genetic mechanisms of hepatitis B viral induced hepatocellular carcinoma.

    PubMed

    Chiu, Amy P; Tschida, Barbara R; Lo, Lilian H; Moriarity, Branden S; Rowlands, Dewi K; Largaespada, David A; Keng, Vincent W

    2015-11-14

    The major type of human liver cancer is hepatocellular carcinoma (HCC), and there are currently many risk factors that contribute to this deadly disease. The majority of HCC occurrences are associated with chronic hepatitis viral infection, and hepatitis B viral (HBV) infection is currently a major health problem in Eastern Asia. Elucidating the genetic mechanisms associated with HBV-induced HCC has been difficult due to the heterogeneity and genetic complexity associated with this disease. A repertoire of animal models has been broadly used to study the pathophysiology and to develop potential treatment regimens for HBV-associated HCC. The use of these animal models has provided valuable genetic information and has been an important contributor to uncovering the factors involved in liver malignant transformation, invasion and metastasis. Recently, transposon-based mouse models are becoming more widely used in liver cancer research to interrogate the genome by forward genetics and also used to validate genes rapidly in a reverse genetic manner. Importantly, these transposon-based rapid reverse genetic mouse models could become crucial in testing potential therapeutic agents before proceeding to clinical trials in human. Therefore, this review will cover the use of transposon-based mouse models to address the problems of liver cancer, especially HBV-associated HCC occurrences in Asia. PMID:26576100

  6. A single cell bioengineering approach to elucidate mechanisms of adult stem cell self-renewal.

    PubMed

    Gilbert, Penney M; Corbel, Stephane; Doyonnas, Regis; Havenstrite, Karen; Magnusson, Klas E G; Blau, Helen M

    2012-04-01

    The goal of regenerative medicine is to restore form and function to damaged and aging tissues. Adult stem cells, present in tissues such as skeletal muscle, comprise a reservoir of cells with a remarkable capacity to proliferate and repair tissue damage. Muscle stem cells, known as satellite cells, reside in a quiescent state in an anatomically distinct compartment, or niche, ensheathed between the membrane of the myofiber and the basal lamina. Recently, procedures for isolating satellite cells were developed and experiments testing their function upon transplantation into muscles revealed an extraordinary potential to contribute to muscle fibers and access and replenish the satellite cell compartment. However, these properties are rapidly lost once satellite cells are plated in culture. Accordingly, elucidating the role of extrinsic factors in controlling muscle stem cell fate, in particular self-renewal, is critical. Through careful design of bioengineered culture platforms, analysis of specific proteins presented to stem cells is possible. Critical to the success of the approach is single cell analysis, as more rapidly proliferating progenitors may mask the behavior of stem cells that proliferate slowly. Bioengineering approaches provide a potent means of gaining insight into the role of extrinsic factors in the stem cell microenvironment on stem cell function and the mechanisms that control their diverse fates. Ultimately, the multidisciplinary approach presented here will lead to novel therapeutic strategies for degenerative diseases. PMID:22327505

  7. Transposon mouse models to elucidate the genetic mechanisms of hepatitis B viral induced hepatocellular carcinoma

    PubMed Central

    Chiu, Amy P; Tschida, Barbara R; Lo, Lilian H; Moriarity, Branden S; Rowlands, Dewi K; Largaespada, David A; Keng, Vincent W

    2015-01-01

    The major type of human liver cancer is hepatocellular carcinoma (HCC), and there are currently many risk factors that contribute to this deadly disease. The majority of HCC occurrences are associated with chronic hepatitis viral infection, and hepatitis B viral (HBV) infection is currently a major health problem in Eastern Asia. Elucidating the genetic mechanisms associated with HBV-induced HCC has been difficult due to the heterogeneity and genetic complexity associated with this disease. A repertoire of animal models has been broadly used to study the pathophysiology and to develop potential treatment regimens for HBV-associated HCC. The use of these animal models has provided valuable genetic information and has been an important contributor to uncovering the factors involved in liver malignant transformation, invasion and metastasis. Recently, transposon-based mouse models are becoming more widely used in liver cancer research to interrogate the genome by forward genetics and also used to validate genes rapidly in a reverse genetic manner. Importantly, these transposon-based rapid reverse genetic mouse models could become crucial in testing potential therapeutic agents before proceeding to clinical trials in human. Therefore, this review will cover the use of transposon-based mouse models to address the problems of liver cancer, especially HBV-associated HCC occurrences in Asia. PMID:26576100

  8. Elucidating the role of transport processes in leaf glucosinolate distribution.

    PubMed

    Madsen, Svend Roesen; Olsen, Carl Erik; Nour-Eldin, Hussam Hassan; Halkier, Barbara Ann

    2014-11-01

    In Arabidopsis (Arabidopsis thaliana), a strategy to defend its leaves against herbivores is to accumulate glucosinolates along the midrib and at the margin. Although it is generally assumed that glucosinolates are synthesized along the vasculature in an Arabidopsis leaf, thereby suggesting that the margin accumulation is established through transport, little is known about these transport processes. Here, we show through leaf apoplastic fluid analysis and glucosinolate feeding experiments that two glucosinolate transporters, GTR1 and GTR2, essential for long-distance transport of glucosinolates in Arabidopsis, also play key roles in glucosinolate allocation within a mature leaf by effectively importing apoplastically localized glucosinolates into appropriate cells. Detection of glucosinolates in root xylem sap unambiguously shows that this transport route is involved in root-to-shoot glucosinolate allocation. Detailed leaf dissections show that in the absence of GTR1 and GTR2 transport activity, glucosinolates accumulate predominantly in leaf margins and leaf tips. Furthermore, we show that glucosinolates accumulate in the leaf abaxial epidermis in a GTR-independent manner. Based on our results, we propose a model for how glucosinolates accumulate in the leaf margin and epidermis, which includes symplasmic movement through plasmodesmata, coupled with the activity of putative vacuolar glucosinolate importers in these peripheral cell layers. PMID:25209984

  9. Thermal control of virulence factors in bacteria: A hot topic

    PubMed Central

    Lam, Oliver; Wheeler, Jun; Tang, Christoph M

    2014-01-01

    Pathogenic bacteria sense environmental cues, including the local temperature, to control the production of key virulence factors. Thermal regulation can be achieved at the level of DNA, RNA or protein and although many virulence factors are subject to thermal regulation, the exact mechanisms of control are yet to be elucidated in many instances. Understanding how virulence factors are regulated by temperature presents a significant challenge, as gene expression and protein production are often influenced by complex regulatory networks involving multiple transcription factors in bacteria. Here we highlight some recent insights into thermal regulation of virulence in pathogenic bacteria. We focus on bacteria which cause disease in mammalian hosts, which are at a significantly higher temperature than the outside environment. We outline the mechanisms of thermal regulation and how understanding this fundamental aspect of the biology of bacteria has implications for pathogenesis and human health. PMID:25494856

  10. Elucidating the Composition and Distribution of Trace Metals in Corals

    NASA Astrophysics Data System (ADS)

    Farfan, G.; Webb, S. M.; Apprill, A.; Hansel, C. M.

    2014-12-01

    Coral reefs host a plethora of marine life and thereby provide a wealth of aesthetic and economic benefits to coastal countries. Anthropogenic influences, including local coastal water contamination, however threaten the health of these delicate ecosystems. Metal incorporation into carbonate minerals, the backbone of coral reefs, is known to have a large yet variable impact on carbonate structure and solubility. Yet, trace metal influences on the structure, porosity, composition, and solubility of coral skeletons is largely unknown. Here, we coupled synchrotron-based micro-X-ray fluorescence (u-XRF) mapping and X-ray absorption near edge structure (XANES) spectroscopy with micro-X-ray diffraction (XRD) to explore the distribution and speciation of trace metals associated with corals and their impact on the carbonate structure of corals obtained from reefs varying in anthropogenic influence - Florida Keys, FL USA and the Federated States of Micronesia. Iron and copper were the most abundant metals in the biological tissue, while in some areas zinc was observed in the tissue, overlapping with the skeleton. Trace metals were not detectable in the aragonite skeletons; in fact, the distributions of Ca and Fe were anti-correlated. XANES spectra show that the iron is primarily Fe(III), likely as the poorly crystalline iron oxide ferrihydrite structure or trapped within ferretin proteins. The same trace metals were observed in corals of different species and from different environments. This in situ investigation corroborates previous studies that corals tend to incorporate iron into the biological components but not into the aragonite skeleton. Given the dominant partitioning of metals within the biological tissue rather than the coral skeleton, the specific carbon molecules responsible for metal attenuation and their fate under changing geochemical conditions and following coral death require exploration.

  11. The Keys to Election 2000.

    ERIC Educational Resources Information Center

    Lichtman, Allan J.

    1999-01-01

    Describes the role of the "Keys to the White House" in predicting future U.S. presidents during political campaigns for office. Explains that the "Keys to the White House" consist of 13 statements favoring the reelection of the incumbent party. Provides a table demonstrating the status of the keys for Election 2000. (CMK)

  12. Key Concepts in Informatics: Algorithm

    ERIC Educational Resources Information Center

    Szlávi, Péter; Zsakó, László

    2014-01-01

    "The system of key concepts contains the most important key concepts related to the development tasks of knowledge areas and their vertical hierarchy as well as the links of basic key concepts of different knowledge areas." (Vass 2011) One of the most important of these concepts is the algorithm. In everyday life, when learning or…

  13. Pharmacogenetics of paraoxonase activity: elucidating the role of high-density lipoprotein in disease

    PubMed Central

    Kim, Daniel Seung; Marsillach, Judit; Furlong, Clement E; Jarvik, Gail P

    2014-01-01

    PON1 is a key component of high-density lipoproteins (HDLs) and is at least partially responsible for HDL's antioxidant/atheroprotective properties. PON1 is also associated with numerous human diseases, including cardiovascular disease, Parkinson's disease and cancer. In addition, PON1 metabolizes a broad variety of substrates, including toxic organophosphorous compounds, statin adducts, glucocorticoids, the likely atherogenic l-homocysteine thiolactone and the quorum-sensing factor of Pseudomonas aeruginosa. Numerous cardiovascular and antidiabetic pharmacologic agents, dietary macronutrients, lifestyle factors and antioxidant supplements affect PON1 expression and enzyme activity levels. Owing to the importance of PON1 to HDL function and its individual association with diverse human diseases, pharmacogenomic interactions between PON1 and the various factors that alter its expression and activity may represent an important therapeutic target for future investigation. PMID:24024900

  14. Elucidating the links between endocrine disruptors and neurodevelopment.

    PubMed

    Schug, Thaddeus T; Blawas, Ashley M; Gray, Kimberly; Heindel, Jerrold J; Lawler, Cindy P

    2015-06-01

    Recent data indicate that approximately 12% of children in the United States are affected by neurodevelopmental disorders, including attention deficit hyperactivity disorder, learning disorders, intellectual disabilities, and autism spectrum disorders. Accumulating evidence indicates a multifactorial etiology for these disorders, with social, physical, genetic susceptibility, nutritional factors, and chemical toxicants acting together to influence risk. Exposure to endocrine-disrupting chemicals during the early stages of life can disrupt normal patterns of development and thus alter brain function and disease susceptibility later in life. This article highlights research efforts and pinpoints approaches that could shed light on the possible associations between environmental chemicals that act on the endocrine system and compromised neurodevelopmental outcomes. PMID:25714811

  15. Discovery of Rare Mutations in Autism: Elucidating Neurodevelopmental Mechanisms.

    PubMed

    Gamsiz, Ece D; Sciarra, Laura N; Maguire, Abbie M; Pescosolido, Matthew F; van Dyck, Laura I; Morrow, Eric M

    2015-07-01

    Autism spectrum disorder (ASD) is a group of highly genetic neurodevelopmental disorders characterized by language, social, cognitive, and behavioral abnormalities. ASD is a complex disorder with a heterogeneous etiology. The genetic architecture of autism is such that a variety of different rare mutations have been discovered, including rare monogenic conditions that involve autistic symptoms. Also, de novo copy number variants and single nucleotide variants contribute to disease susceptibility. Finally, autosomal recessive loci are contributing to our understanding of inherited factors. We will review the progress that the field has made in the discovery of these rare genetic variants in autism. We argue that mutation discovery of this sort offers an important opportunity to identify neurodevelopmental mechanisms in disease. The hope is that these mechanisms will show some degree of convergence that may be amenable to treatment intervention. PMID:26105128

  16. Key management for large scale end-to-end encryption

    SciTech Connect

    Witzke, E.L.

    1994-07-01

    Symmetric end-to-end encryption requires separate keys for each pair of communicating confidants. This is a problem of Order N{sup 2}. Other factors, such as multiple sessions per pair of confidants and multiple encryption points in the ISO Reference Model complicate key management by linear factors. Public-key encryption can reduce the number of keys managed to a linear problem which is good for scaleability of key management, but comes with complicating issues and performance penalties. Authenticity is the primary ingredient of key management. If each potential pair of communicating confidants can authenticate data from each other, then any number of public encryption keys of any type can be communicated with requisite integrity. These public encryption keys can be used with the corresponding private keys to exchange symmetric cryptovariables for high data rate privacy protection. The Digital Signature Standard (DSS), which has been adopted by the United States Government, has both public and private components, similar to a public-key cryptosystem. The Digital Signature Algorithm of the DSS is intended for authenticity but not for secrecy. In this paper, the authors will show how the use of the Digital Signature Algorithm combined with both symmetric and asymmetric (public-key) encryption techniques can provide a practical solution to key management scaleability problems, by reducing the key management complexity to a problem of order N, without sacrificing the encryption speed necessary to operate in high performance networks.

  17. New models for considering the role of medication in the treatment and elucidation of the etiology of autism.

    PubMed

    Smile, Sharon; Anagnostou, Evdokia

    2012-12-01

    Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder. Over the past decades, much research has been conducted to elucidate a single etiological factor and effective pharmacotherapuetics to address the core symptom domains of ASD with limited success. Research has changed focus from behavioral observations of ASD to translating findings from animal models, genomic manipulation studies and basic science studies to pharmacological agents with the aim to lessen or reverse core symptoms of ASD. This paper evaluates potential models for translating information from the biology of ASD to pharmacological treatments. PMID:22986996

  18. Key management approach of multicast

    NASA Astrophysics Data System (ADS)

    Jiang, Zhen; Wang, Xi-lian; Zhang, Hong-ke; Zhang, Li-yong

    2002-09-01

    A key management approach of multicast is provided in this paper. It is based on the approach of assignment key to every group member through key center. In view of some management schemes where members join, leave or are deleted, key service center must distribute new key through unicast another time. The bigger amount of members the greater expenses will be spent. In this paper with member varying their upper key service center still distribute the new keythrough multicast and an ID is assigned to every member to identify their transmission message so as to implement data origin authentication. The essential principle of this approach is distributing a key generator for each member. For example a random number generator depending on certain algorithm can be distributed. And every member needs store a seed table. In this project key can automatically be renewed as time goes by or immediately renewed. Replace unicast by multicast to renew key decrease the spending. It is not only suitable for the key centralized management scheme with fewer members but also for the key separated management scheme with large group members and member frequently changed.

  19. Elucidating glycosaminoglycan–protein–protein interactions using carbohydrate microarray and computational approaches

    PubMed Central

    Rogers, Claude J.; Clark, Peter M.; Tully, Sarah E.; Abrol, Ravinder; Garcia, K. Christopher; Goddard, William A.; Hsieh-Wilson, Linda C.

    2011-01-01

    Glycosaminoglycan polysaccharides play critical roles in many cellular processes, ranging from viral invasion and angiogenesis to spinal cord injury. Their diverse biological activities are derived from an ability to regulate a remarkable number of proteins. However, few methods exist for the rapid identification of glycosaminoglycan–protein interactions and for studying the potential of glycosaminoglycans to assemble multimeric protein complexes. Here, we report a multidisciplinary approach that combines new carbohydrate microarray and computational modeling methodologies to elucidate glycosaminoglycan–protein interactions. The approach was validated through the study of known protein partners for heparan and chondroitin sulfate, including fibroblast growth factor 2 (FGF2) and its receptor FGFR1, the malarial protein VAR2CSA, and tumor necrosis factor-α (TNF-α). We also applied the approach to identify previously undescribed interactions between a specific sulfated epitope on chondroitin sulfate, CS-E, and the neurotrophins, a critical family of growth factors involved in the development, maintenance, and survival of the vertebrate nervous system. Our studies show for the first time that CS is capable of assembling multimeric signaling complexes and modulating neurotrophin signaling pathways. In addition, we identify a contiguous CS-E-binding site by computational modeling that suggests a potential mechanism to explain how CS may promote neurotrophin-tyrosine receptor kinase (Trk) complex formation and neurotrophin signaling. Together, our combined microarray and computational modeling methodologies provide a general, facile means to identify new glycosaminoglycan–protein–protein interactions, as well as a molecular-level understanding of those complexes. PMID:21628576

  20. Elucidating dimensions of posttraumatic stress symptoms and their functional correlates in disaster-exposed adolescents.

    PubMed

    Sumner, Jennifer A; Pietrzak, Robert H; Danielson, Carla Kmett; Adams, Zachary W; Ruggiero, Kenneth J

    2014-12-01

    The aim of this study was to elucidate the dimensional structure of posttraumatic stress disorder (PTSD) and potential moderators and functional correlates of this structure in disaster-affected adolescents. A population-based sample of 2000 adolescents aged 12-17 years (M = 14.5 years; 51% female) completed interviews on post-tornado PTSD symptoms, substance use, and parent-adolescent conflict between 4 and 13 months (M = 8.8, SD = 2.6) after tornado exposure. Confirmatory factor analyses revealed that all models fit well but a 5-factor dysphoric arousal model provided a statistically significantly better representation of adolescent PTSD symptoms compared to 4-factor dysphoria and emotional numbing models. There was evidence of measurement invariance of the dysphoric arousal model across gender and age, although girls and older adolescents aged 15-17 years had higher mean scores than boys and younger adolescents aged 12-14 years, respectively, on some PTSD dimensions. Differential magnitudes of association between PTSD symptom dimensions and functional correlates were observed, with emotional numbing symptoms most strongly positively associated with problematic substance use since the tornado, and dysphoric arousal symptoms most strongly positively associated with parent-adolescent conflict; both correlations were significantly larger than the corresponding correlations with anxious arousal. Taken together, these results suggest that the dimensional structure of tornado-related PTSD symptomatology in adolescents is optimally characterized by five separate clusters of re-experiencing, avoidance, numbing, dysphoric arousal, and anxious arousal symptoms, which showed unique associations with functional correlates. Findings emphasize that PTSD in disaster-exposed adolescents is not best conceptualized as a homogenous construct and highlight potential differential targets for post-disaster assessment and intervention. PMID:25248557

  1. Elucidating Dimensions of Posttraumatic Stress Symptoms and their Functional Correlates in Disaster-Exposed Adolescents

    PubMed Central

    Sumner, Jennifer A.; Pietrzak, Robert H.; Danielson, Carla Kmett; Adams, Zachary W.; Ruggiero, Kenneth J.

    2014-01-01

    The aim of this study was to elucidate the dimensional structure of posttraumatic stress disorder (PTSD) and potential moderators and functional correlates of this structure in disaster-affected adolescents. A population-based sample of 2,000 adolescents aged 12–17 years (M=14.5 years; 51% female) completed interviews on post-tornado PTSD symptoms, substance use, and parent-adolescent conflict between 4 and 13 months (M=8.8, SD=2.6) after tornado exposure. Confirmatory factor analyses revealed that all models fit well but a 5-factor dysphoric arousal model provided a statistically significantly better representation of adolescent PTSD symptoms compared to 4-factor dysphoria and emotional numbing models. There was evidence of measurement invariance of the dysphoric arousal model across gender and age, although girls and older adolescents aged 15–17 years had higher mean scores than boys and younger adolescents aged 12–14 years, respectively, on some PTSD dimensions. Differential magnitudes of association between PTSD symptom dimensions and functional correlates were observed, with emotional numbing symptoms most strongly positively associated with problematic substance use since the tornado, and dysphoric arousal symptoms most strongly positively associated with parent-adolescent conflict; both correlations were significantly larger than the corresponding correlations with anxious arousal. Taken together, these results suggest that the dimensional structure of tornado-related PTSD symptomatology in adolescents is optimally characterized by five separate clusters of re-experiencing, avoidance, numbing, dysphoric arousal, and anxious arousal symptoms, which showed unique associations with functional correlates. Findings emphasize that PTSD in disaster-exposed adolescents is not best conceptualized as a homogeneous construct and highlight potential differential targets for post-disaster assessment and intervention. PMID:25248557

  2. Secure key storage and distribution

    DOEpatents

    Agrawal, Punit

    2015-06-02

    This disclosure describes a distributed, fault-tolerant security system that enables the secure storage and distribution of private keys. In one implementation, the security system includes a plurality of computing resources that independently store private keys provided by publishers and encrypted using a single security system public key. To protect against malicious activity, the security system private key necessary to decrypt the publication private keys is not stored at any of the computing resources. Rather portions, or shares of the security system private key are stored at each of the computing resources within the security system and multiple security systems must communicate and share partial decryptions in order to decrypt the stored private key.

  3. Limitations on quantum key repeaters.

    PubMed

    Bäuml, Stefan; Christandl, Matthias; Horodecki, Karol; Winter, Andreas

    2015-01-01

    A major application of quantum communication is the distribution of entangled particles for use in quantum key distribution. Owing to noise in the communication line, quantum key distribution is, in practice, limited to a distance of a few hundred kilometres, and can only be extended to longer distances by use of a quantum repeater, a device that performs entanglement distillation and quantum teleportation. The existence of noisy entangled states that are undistillable but nevertheless useful for quantum key distribution raises the question of the feasibility of a quantum key repeater, which would work beyond the limits of entanglement distillation, hence possibly tolerating higher noise levels than existing protocols. Here we exhibit fundamental limits on such a device in the form of bounds on the rate at which it may extract secure key. As a consequence, we give examples of states suitable for quantum key distribution but unsuitable for the most general quantum key repeater protocol. PMID:25903096

  4. Elucidating transient macromolecular interactions using paramagnetic relaxation enhancement

    PubMed Central

    Clore, G. Marius; Tang, Chun; Iwahara, Junji

    2007-01-01

    Recent advances in the use of paramagnetic relaxation enhancement (PRE) in structure refinement and in the analysis of transient dynamic processes involved in macromolecular complex formation are presented. In the slow exchange regime, we show, using the SRY/DNA complex as an example, that the PRE provides a powerful tool that can lead to significant increases in the reliability and accuracy of NMR structure determinations. Refinement necessitates the use of an ensemble representation of the paramagnetic center and a model free extension of the Solomon-Bloembergen equations. In the fast exchange regime, the PRE provides insight into dynamic processes and the existence of transient, low population intermediate species. The PRE allows one to characterize dynamic non-specific binding of a protein to DNA; to directly demonstrate that the search process whereby a transcription factor locates its specific DNA target site involves both intramolecular (sliding) and intermolecular (hopping and intersegment transfer) translocation; and to detect and visualize the distribution of an ensemble of transient encounter complexes in protein-protein association. PMID:17913493

  5. The elucidation of stress memory inheritance in Brassica rapa plants

    PubMed Central

    Bilichak, Andriy; Ilnytskyy, Yaroslav; Wóycicki, Rafal; Kepeshchuk, Nina; Fogen, Dawson; Kovalchuk, Igor

    2015-01-01

    Plants are able to maintain the memory of stress exposure throughout their ontogenesis and faithfully propagate it into the next generation. Recent evidence argues for the epigenetic nature of this phenomenon. Small RNAs (smRNAs) are one of the vital epigenetic factors because they can both affect gene expression at the place of their generation and maintain non-cell-autonomous gene regulation. Here, we have made an attempt to decipher the contribution of smRNAs to the heat-shock-induced transgenerational inheritance in Brassica rapa plants using sequencing technology. To do this, we have generated comprehensive profiles of a transcriptome and a small RNAome (smRNAome) from somatic and reproductive tissues of stressed plants and their untreated progeny. We have demonstrated that the highest tissue-specific alterations in the transcriptome and smRNAome profile are detected in tissues that were not directly exposed to stress, namely, in the endosperm and pollen. Importantly, we have revealed that the progeny of stressed plants exhibit the highest fluctuations at the smRNAome level but not at the transcriptome level. Additionally, we have uncovered the existence of heat-inducible and transgenerationally transmitted tRNA-derived small RNA fragments in plants. Finally, we suggest that miR168 and braAGO1 are involved in the stress-induced transgenerational inheritance in plants. PMID:25653665

  6. SUCROSE SYNTHASE: ELUCIDATION OF COMPLEX POST-TRANSLATIONAL REGULATORY MECHANISMS

    SciTech Connect

    Steven C. Huber

    2009-05-12

    Studies have focused on the enzyme sucrose synthase, which plays an important role in the metabolism of sucrose in seeds and tubers. There are three isoforms of SUS in maize, referred to as SUS1, SUS-SH1, and SUS2. SUS is generally considered to be tetrameric protein but recent evidence suggests that SUS can also occur as a dimeric protein. The formation of tetrameric SUS is regulated by sucrose concentration in vitro and this could also be an important factor in the cellular localization of the protein. We found that high sucrose concentrations, which promote tetramer formation, also inhibit the binding of SUS1 to actin filaments in vitro. Previously, high sucrose concentrations were shown to promote SUS association with the plasma membrane. The specific regions of the SUS molecule involved in oligomerization are not known, but we identified a region of the SUS1 moelcule by bioinformatic analysis that was predicted to form a coiled coil. We demonstrated that this sequence could, in fact, self-associate as predicted for a coiled coil, but truncation analysis with the full-length recombinant protein suggested that it was not responsible for formation of dimers or tetramers. However, the coiled coil may function in binding of other proteins to SUS1. Overall, sugar availability may differentially influence the binding of SUS to cellular structures, and these effects may be mediated by changes in the oligomeric nature of the enzyme.

  7. Walking along the Fibroblast Growth Factor 10 Route: A Key Pathway to Understand the Control and Regulation of Epithelial and Mesenchymal Cell-Lineage Formation during Lung Development and Repair after Injury

    PubMed Central

    Bellusci, Saverio

    2014-01-01

    Basic research on embryonic lung development offers unique opportunities to make important discoveries that will impact human health. Developmental biologists interested in the molecular control of branching morphogenesis have intensively studied the developing lung, with its complex and seemingly stereotyped ramified structure. However, it is also an organ that is linked to a vast array of clinical problems in humans such as bronchopulmonary dysplasia in premature babies and emphysema, chronic obstructive pulmonary disease, fibrosis, and cancer in adults. Epithelial stem/progenitor cells reside in niches where they interact with specific extracellular matrices as well as with mesenchymal cells; the latter are still poorly characterized. Interactions of epithelial stem/progenitor cells with their microenvironments are usually instructive, controlling quiescence versus activation, proliferation, differentiation, and migration. During the past 18 years, Fgf10 has emerged not only as a marker for the distal lung mesenchyme during early lung development, but also as a key player in branching morphogenesis and a critical component of the niche for epithelial stem cells. In this paper, we will present the current knowledge regarding the lineage tree in the lung, with special emphasis on cell-lineage decisions in the lung mesenchyme and the role of Fgf10 in this context. PMID:25298902

  8. Walking along the Fibroblast Growth Factor 10 Route: A Key Pathway to Understand the Control and Regulation of Epithelial and Mesenchymal Cell-Lineage Formation during Lung Development and Repair after Injury.

    PubMed

    El Agha, Elie; Bellusci, Saverio

    2014-01-01

    Basic research on embryonic lung development offers unique opportunities to make important discoveries that will impact human health. Developmental biologists interested in the molecular control of branching morphogenesis have intensively studied the developing lung, with its complex and seemingly stereotyped ramified structure. However, it is also an organ that is linked to a vast array of clinical problems in humans such as bronchopulmonary dysplasia in premature babies and emphysema, chronic obstructive pulmonary disease, fibrosis, and cancer in adults. Epithelial stem/progenitor cells reside in niches where they interact with specific extracellular matrices as well as with mesenchymal cells; the latter are still poorly characterized. Interactions of epithelial stem/progenitor cells with their microenvironments are usually instructive, controlling quiescence versus activation, proliferation, differentiation, and migration. During the past 18 years, Fgf10 has emerged not only as a marker for the distal lung mesenchyme during early lung development, but also as a key player in branching morphogenesis and a critical component of the niche for epithelial stem cells. In this paper, we will present the current knowledge regarding the lineage tree in the lung, with special emphasis on cell-lineage decisions in the lung mesenchyme and the role of Fgf10 in this context. PMID:25298902

  9. Elucidating spatially explicit behavioral landscapes in the Willow Flycatcher

    USGS Publications Warehouse

    Bakian, Amanda V.; Sullivan, Kimberly A.; Paxton, Eben H.

    2012-01-01

    Animal resource selection is a complex, hierarchical decision-making process, yet resource selection studies often focus on the presence and absence of an animal rather than the animal's behavior at resource use locations. In this study, we investigate foraging and vocalization resource selection in a population of Willow Flycatchers, Empidonax traillii adastus, using Bayesian spatial generalized linear models. These models produce “behavioral landscapes” in which space use and resource selection is linked through behavior. Radio telemetry locations were collected from 35 adult Willow Flycatchers (n = 14 males, n = 13 females, and n = 8 unknown sex) over the 2003 and 2004 breeding seasons at Fish Creek, Utah. Results from the 2-stage modeling approach showed that habitat type, perch position, and distance from the arithmetic mean of the home range (in males) or nest site (in females) were important factors influencing foraging and vocalization resource selection. Parameter estimates from the individual-level models indicated high intraspecific variation in the use of the various habitat types and perch heights for foraging and vocalization. On the population level, Willow Flycatchers selected riparian habitat over other habitat types for vocalizing but used multiple habitat types for foraging including mountain shrub, young riparian, and upland forest. Mapping of observed and predicted foraging and vocalization resource selection indicated that the behavior often occurred in disparate areas of the home range. This suggests that multiple core areas may exist in the home ranges of individual flycatchers, and demonstrates that the behavioral landscape modeling approach can be applied to identify spatially and behaviorally distinct core areas. The behavioral landscape approach is applicable to a wide range of animal taxa and can be used to improve our understanding of the spatial context of behavior and resource selection.

  10. Homology modeling, molecular docking, and molecular dynamics simulations elucidated α-fetoprotein binding modes

    PubMed Central

    2013-01-01

    Background An important mechanism of endocrine activity is chemicals entering target cells via transport proteins and then interacting with hormone receptors such as the estrogen receptor (ER). α-Fetoprotein (AFP) is a major transport protein in rodent serum that can bind and sequester estrogens, thus preventing entry to the target cell and where they could otherwise induce ER-mediated endocrine activity. Recently, we reported rat AFP binding affinities for a large set of structurally diverse chemicals, including 53 binders and 72 non-binders. However, the lack of three-dimensional (3D) structures of rat AFP hinders further understanding of the structural dependence for binding. Therefore, a 3D structure of rat AFP was built using homology modeling in order to elucidate rat AFP-ligand binding modes through docking analyses and molecular dynamics (MD) simulations. Methods Homology modeling was first applied to build a 3D structure of rat AFP. Molecular docking and Molecular Mechanics-Generalized Born Surface Area (MM-GBSA) scoring were then used to examine potential rat AFP ligand binding modes. MD simulations and free energy calculations were performed to refine models of binding modes. Results A rat AFP tertiary structure was first obtained using homology modeling and MD simulations. The rat AFP-ligand binding modes of 13 structurally diverse, representative binders were calculated using molecular docking, (MM-GBSA) ranking and MD simulations. The key residues for rat AFP-ligand binding were postulated through analyzing the binding modes. Conclusion The optimized 3D rat AFP structure and associated ligand binding modes shed light on rat AFP-ligand binding interactions that, in turn, provide a means to estimate binding affinity of unknown chemicals. Our results will assist in the evaluation of the endocrine disruption potential of chemicals. PMID:24266910

  11. Comparative transcriptome analysis of different chemotypes elucidates withanolide biosynthesis pathway from medicinal plant Withania somnifera.

    PubMed

    Gupta, Parul; Goel, Ridhi; Agarwal, Aditya Vikram; Asif, Mehar Hasan; Sangwan, Neelam Singh; Sangwan, Rajender Singh; Trivedi, Prabodh Kumar

    2015-01-01

    Withania somnifera is one of the most valuable medicinal plants synthesizing secondary metabolites known as withanolides. Despite pharmaceutical importance, limited information is available about the biosynthesis of withanolides. Chemo-profiling of leaf and root tissues of Withania suggest differences in the content and/or nature of withanolides in different chemotypes. To identify genes involved in chemotype and/or tissue-specific withanolide biosynthesis, we established transcriptomes of leaf and root tissues of distinct chemotypes. Genes encoding enzymes for intermediate steps of terpenoid backbone biosynthesis with their alternatively spliced forms and paralogous have been identified. Analysis suggests differential expression of large number genes among leaf and root tissues of different chemotypes. Study also identified differentially expressing transcripts encoding cytochrome P450s, glycosyltransferases, methyltransferases and transcription factors which might be involved in chemodiversity in Withania. Virus induced gene silencing of the sterol ∆7-reductase (WsDWF5) involved in the synthesis of 24-methylene cholesterol, withanolide backbone, suggests role of this enzyme in biosynthesis of withanolides. Information generated, in this study, provides a rich resource for functional analysis of withanolide-specific genes to elucidate chemotype- as well as tissue-specific withanolide biosynthesis. This genomic resource will also help in development of new tools for functional genomics and breeding in Withania. PMID:26688389

  12. Host gene targets for novel influenza therapies elucidated by high-throughput RNA interference screens

    PubMed Central

    Meliopoulos, Victoria A.; Andersen, Lauren E.; Birrer, Katherine F.; Simpson, Kaylene J.; Lowenthal, John W.; Bean, Andrew G. D.; Stambas, John; Stewart, Cameron R.; Tompkins, S. Mark; van Beusechem, Victor W.; Fraser, Iain; Mhlanga, Musa; Barichievy, Samantha; Smith, Queta; Leake, Devin; Karpilow, Jon; Buck, Amy; Jona, Ghil; Tripp, Ralph A.

    2012-01-01

    Influenza virus encodes only 11 viral proteins but replicates in a broad range of avian and mammalian species by exploiting host cell functions. Genome-wide RNA interference (RNAi) has proven to be a powerful tool for identifying the host molecules that participate in each step of virus replication. Meta-analysis of findings from genome-wide RNAi screens has shown influenza virus to be dependent on functional nodes in host cell pathways, requiring a wide variety of molecules and cellular proteins for replication. Because rapid evolution of the influenza A viruses persistently complicates the effectiveness of vaccines and therapeutics, a further understanding of the complex host cell pathways coopted by influenza virus for replication may provide new targets and strategies for antiviral therapy. RNAi genome screening technologies together with bioinformatics can provide the ability to rapidly identify specific host factors involved in resistance and susceptibility to influenza virus, allowing for novel disease intervention strategies.—Meliopoulos, V. A., Andersen, L. E., Birrer, K. F., Simpson, K.