Science.gov

Sample records for elucidating key factors

  1. [Elucidation of key genes in sex determination in genetics teaching].

    PubMed

    Li, Meng; He, Zhumei

    2014-06-01

    Sex is an important and complex feature of organisms, which is controlled by the genetic and environmental factors. The genetic factors, i.e., genes, are vital in sex determination. However, not all the related genes play the same roles, and some key genes play a vital role in the sex determination and differentiation. With the development of the modern genetics, a great progress on the key genes has been made in sex determination. In this review, we summarize the mechanism of sex determination and the strategy of how to study the key genes in sex determination. It will help us to understand the mechanism of sex determination better in the teaching of genetics.

  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

    2014-10-10

    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.

  3. 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

  4. 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.

  5. Extended key-factor/key-stage analysis for longitudinal data.

    PubMed

    Yamamura, Kohji

    2012-01-01

    Key-factor/key-stage analysis was originally a descriptive approach to analyze life tables. However, this method can be extended to analyze longitudinal data in pharmaceutical experiments. By dividing the variance into components, the extended key-factor/key-stage analysis indicates which factor is influential, and through which stage the factor generates its influence in determining the outcome of treatments. Such knowledge helps us in constructing a class of nonlinear longitudinal models that can be interpretable than linear models. Example SAS programs and R programs are provided for the calculation. Supplemental materials are available for this article. Go to the publisher's online edition of Journal of Biopharmaceutical Statistics to view the supplemental files.

  6. ELUCIDATION OF THE FACTORS TO BE CONSIDERED IN AYURVEDIC CLINICAL

    PubMed Central

    Kumar, D. Suresh

    1992-01-01

    The theory and practice of Ayurveda are based on the doctrine of tridosa, according to which disease states spring from the disturbance of the three factors vata, pitta and kapha. Being a wholistic medical system Ayurveda considers several variables in the diagnosis and treatment of diseases. This report identifies these variables in detail and highlights their clinical significance. PMID:22556606

  7. Overcoming drug crystallization in electrospun fibers--Elucidating key parameters and developing strategies for drug delivery.

    PubMed

    Seif, Salem; Franzen, Lutz; Windbergs, Maike

    2015-01-15

    For the development of novel therapeutics, uncontrolled crystallization of drugs within delivery systems represents a major challenge. Especially for thin and flexible polymeric systems such as oral films or dermal wound dressings, the formation and growth of drug crystals can significantly affect drug distribution and release kinetics as well as physical storage stability. In this context, electrospinning was introduced as a fabrication technique with the potential to encapsulate drugs within ultrafine fibers by rapid solvent evaporation overcoming drug crystallization during fabrication and storage. However, these effects could so far only be shown for specific drug-polymer combinations and an in-depth understanding of the underlying processes of drug-loaded fiber formation and influencing key parameters is still missing. In this study, we systematically investigated crystal formation of caffeine as a model drug in electrospun fibers comparing different polymers. The solvent polarity was found to have a major impact on the drug crystal formation, whereas only a minor effect was attributed to the electrospinning process parameters. Based on an in-depth understanding of the underlying processes determining drug crystallization processes in electrospun fibers, key parameters could be identified which allow for the rational development of drug-loaded electrospun fibers overcoming drug crystallization.

  8. Elucidating a Key Component of Cancer Metastasis: CXCL12 (SDF-1α) Binding to CXCR4

    PubMed Central

    2015-01-01

    The chemotactic signaling induced by the binding of chemokine CXCL12 (SDF-1α) to chemokine receptor CXCR4 is of significant biological importance and is a potential therapeutic axis against HIV-1. However, as CXCR4 is overexpressed in certain cancer cells, the CXCL12:CXCR4 signaling is involved in tumor metastasis, progression, angiogenesis, and survival. Motivated by the pivotal role of the CXCL12:CXCR4 axis in cancer, we employed a comprehensive set of computational tools, predominantly based on free energy calculations and molecular dynamics simulations, to obtain insights into the molecular recognition of CXCR4 by CXCL12. We report, what is to our knowledge, the first computationally derived CXCL12:CXCR4 complex structure which is in remarkable agreement with experimental findings and sheds light into the functional role of CXCL12 and CXCR4 residues which are associated with binding and signaling. Our results reveal that the CXCL12 N-terminal domain is firmly bound within the CXCR4 transmembrane domain, and the central 24–50 residue domain of CXCL12 interacts with the upper N-terminal domain of CXCR4. The stability of the CXCL12:CXCR4 complex structure is attributed to an abundance of nonpolar and polar intermolecular interactions, including salt bridges formed between positively charged CXCL12 residues and negatively charged CXCR4 residues. The success of the computational protocol can mainly be attributed to the nearly exhaustive docking conformational search, as well as the heterogeneous dielectric implicit water-membrane-water model used to simulate and select the optimum conformations. We also recently utilized this protocol to elucidate the binding of an HIV-1 gp120 V3 loop in complex with CXCR4, and a comparison between the molecular recognition of CXCR4 by CXCL12 and the HIV-1 gp120 V3 loop shows that both CXCL12 and the HIV-1 gp120 V3 loop share the same CXCR4 binding pocket, as they mostly interact with the same CXCR4 residues. PMID:24660779

  9. Key Impact Factors on Dam Break Fatalities

    NASA Astrophysics Data System (ADS)

    Huang, D.; Yu, Z.; Song, Y.; Han, D.; Li, Y.

    2016-12-01

    Dam failures can lead to catastrophes on human society. However, there is a lack of research about dam break fatalities, especially on the key factors that affect fatalities. Based on the analysis of historical dam break cases, most studies have used the regression analysis to explore the correlation between those factors and fatalities, but without implementing optimization to find the dominating factors. In order to understand and reduce the risk of fatalities, this study has proposed a new method to select the impact factors on the fatality. It employs an improved ANN (Artificial Neural Network) combined with LOOCV (Leave-one-out cross-validation) and SFS (Stepwise Forward Selection) approach to explore the nonlinear relationship between impact factors and life losses. It not only considers the factors that have been widely used in the literature but also introduces new factors closely involved with fatalities. Dam break cases occurred in China from 1954 to 2013 are summarized, within which twenty-five cases are selected with a comprehensive coverage of geographic position and temporal variation. Twelve impact factors are taken into account as the inputs, i.e., severity of dam break flood (SF), population at risk (PR), public understanding of dam break (UB), warning time (TW), evacuation condition (EC), weather condition during dam break (WB), dam break mode (MB), water storage (SW), building vulnerability (VB), dam break time (TB), average distance from the affected area to the dam (DD) and preventive measures by government (PG).From those, three key factors of SF, MB and TB are chosen. The proposed method is able to extract the key factors, and the derived fatality model performs well in various types of dam break conditions.

  10. SARS: Key factors in crisis management.

    PubMed

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

    2005-03-01

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

  11. Elucidating Key Motifs Required for Arp2/3-Dependent and Independent Actin Nucleation by Las17/WASP

    PubMed Central

    Urbanek, Agnieszka N.; Smaczynska-de Rooij, Iwona I.

    2016-01-01

    Actin nucleation is the key rate limiting step in the process of actin polymerization, and tight regulation of this process is critical to ensure actin filaments form only at specific times and at defined regions of the cell. Arp2/3 is a well-characterised protein complex that can promote nucleation of new filaments, though its activity requires additional nucleation promotion factors (NPFs). The best recognized of these factors are the WASP family of proteins that contain binding motifs for both monomeric actin and for Arp2/3. Previously we demonstrated that the yeast WASP homologue, Las17, in addition to activating Arp2/3 can also nucleate actin filaments de novo, independently of Arp2/3. This activity is dependent on its polyproline rich region. Through biochemical and in vivo analysis we have now identified key motifs within the polyproline region that are required for nucleation and elongation of actin filaments, and have addressed the role of the WH2 domain in the context of actin nucleation without Arp2/3. We have also demonstrated that full length Las17 is able to bind liposomes giving rise to the possibility of direct linkage of nascent actin filaments to specific membrane sites to which Las17 has been recruited. Overall, we propose that Las17 functions as the key initiator of de novo actin filament formation at endocytic sites by nucleating, elongating and tethering nascent filaments which then serve as a platform for Arp2/3 recruitment and function. PMID:27637067

  12. Student Success Factors: Identifying Key Predictors

    ERIC Educational Resources Information Center

    Sulaiman, Ainin; Mohezar, Suhana

    2006-01-01

    The authors' main aim in this study was to identify key predictors of Master of Business Administration (MBA) students' academic performance. The authors measured performance by the students' cumulative grade point average achieved, using data from the Students Information Systems and Application database. The authors found that a student's…

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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.

  18. 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.

  19. Elucidating biological risk factors in suicide: role of protein kinase A.

    PubMed

    Dwivedi, Yogesh; Pandey, Ghanshyam N

    2011-06-01

    Suicide is a major public health concern. Although there have been several studies of suicidal behavior that focused on the roles of psychosocial and sociocultural factors, these factors are of too little predictive value to be clinically useful. Therefore, research on the biological perspective of suicide has gained a stronghold and appears to provide a promising approach to identify biological risk factors associated with suicidal behavior. Recent studies demonstrate that an alteration in synaptic and structural plasticity is key to affective illnesses and suicide. Signal transduction molecules play an important role in such plastic events. Protein kinase A (PKA) is a crucial enzyme in the adenylyl cyclase signal transduction pathway and is involved in regulating gene transcription, cell survival, and plasticity. In this review, we critically and comprehensively discuss the role of PKA in suicidal behavior. Because stress is an important component of suicide, we also discuss whether stress affects PKA and how this may be associated with suicidal behavior. In addition, we also discuss the functional significance of the findings regarding PKA by describing the role of important PKA substrates (i.e., Rap1, cyclic adenosine monophosphate response element binding protein, and target gene brain-derived neurotrophic factor). These studies suggest the interesting possibility that PKA and related signaling molecules may serve as important neurobiological factors in suicide and may be relevant in target-specific therapeutic interventions for these disorders.

  20. Elucidating biological risk factors in suicide: role of protein kinase A

    PubMed Central

    Dwivedi, Yogesh; Pandey, Ghanshyam N.

    2010-01-01

    Suicide is a major public health concern. Although there have been several studies of suicidal behavior that focused on the roles of psychosocial and sociocultural factors, these factors are of too little predictive value to be clinically useful. Therefore, research on the biological perspective of suicide has gained a stronghold and appears to provide a promising approach to identify biological risk factors associated with suicidal behavior. Recent studies demonstrate that an alteration in synaptic and structural plasticity is key to affective illnesses and suicide. Signal transduction molecules play an important role in such plastic events. Protein kinase A (PKA) is a crucial enzyme in the adenylyl cyclase signal transduction pathway and is involved in regulating gene transcription, cell survival, and plasticity. In this review, we critically and comprehensively discuss the role of PKA in suicidal behavior. Because stress is an important component of suicide, we also discuss whether stress affects PKA and how this may be associated with suicidal behavior. In addition, we also discuss the functional significance of the findings regarding PKA by describing the role of important PKA substrates (i.e., Rap1, cyclic adenosine monophosphate–response element binding protein, and target gene brain-derived neurotrophic factor). These studies suggest the interesting possibility that PKA and related signaling molecules may serve as important neurobiological factors in suicide and may be relevant in target-specific therapeutic interventions for these disorders. PMID:20817068

  1. Elucidating the transcriptome of Fasciola hepatica - a key to fundamental and biotechnological discoveries for a neglected parasite.

    PubMed

    Young, Neil D; Hall, Ross S; Jex, Aaron R; Cantacessi, Cinzia; Gasser, Robin B

    2010-01-01

    Liver flukes of animals are parasitic flatworms (Platyhelminthes: Digenea) of major socioeconomic importance in many countries. Key representatives, such as Fasciola hepatica and F. gigantica, cause "liver fluke disease" (= fascioliasis), which is of major animal health significance worldwide. In particular, F. hepatica is a leading cause of production losses to the livestock (mainly sheep and cattle) and meat industries due to clinical disease, reduced weight gain and milk production, and deaths. This parasite is also a major food-borne pathogen of humans throughout parts of the Middle East, Asia and South America. Currently, there is a significant focus on the development of new approaches for the prevention and control of fascioliasis in livestock. Recent technological advances in genomics and bioinformatics provide unique opportunities for the identification and prevalidation of drug targets and vaccines through a better understanding of the biology of F. hepatica and related species as well as their relationship with their hosts at the molecular level. Surprisingly, despite the widespread socioeconomic impact of fascioliasis, genomic datasets for F. hepatica are scant, limiting the molecular biological research of this parasite. The present article explores specifically the transcriptome of the adult stage of F. hepatica using an integrated genomic-bioinformatic platform. The analysis of the current data reveals numerous molecules of biological relevance, some of which are inferred to be involved in key biological processes or pathways that could serve as targets for new trematocidal drugs or vaccines. Improved insights into the transcriptome of F. hepatica should pave the way for future, comparative analysis of the transcriptomes of other developmental stages of this and related parasites, such as F. gigantica, cancer-causing flatworms (Clonorchis sinensis and Opisthorchis viverrini) and blood flukes (Schistosoma mansoni and S. japonicum). Prediction of the

  2. Aerobic oxidation of β-isophorone catalyzed by N-hydroxyphthalimide: the key features and mechanism elucidated.

    PubMed

    Chen, Kexian; Sun, Yong; Wang, Congmin; Yao, Jia; Chen, Zhirong; Li, Haoran

    2012-09-21

    Due to the insufficient understanding of the selective oxidation mechanism of α/β-isophorones (α/β-IP) to ketoisophorone (KIP), the key features in the β-IP oxidation catalyzed by N-hydroxyphthalimide (NHPI) have been explored via theoretical calculations. β-IP is more favourable to being activated by phthalimide-N-oxyl radical (PINO˙) and peroxyl radical (ROO˙) than α-IP owing to the different C-H strengths at their reactive sites, thereby exhibiting selective product distributions. It was found that NHPI accelerates β-IP activation due to the higher reactivity of PINO˙ than ROO˙ and the equilibrium reaction between them, yielding considerable hydroperoxide (ROOH) and ROO˙. In addition, the ROOH decomposition is more favourable viaα-H abstraction by radicals than its self-dehydration and thermal dissociation. The strong exothermicity of this α-H abstraction, along with that from H-abstraction by co-yielded hot HO˙, is in favor of the straightforward formation of KIP, simultaneously leading to the isomerization of a few β-IP to α-IP and production of 4-hydroxyisophorone (HIP) and water. The proposed mechanisms, consistent with the experimental observations, allow for the deeper understanding and effective design of oxidation systems involving similar substrates or NHPI analogues that are of industrial importance.

  3. The life of the freshwater bryozoan Stephanella hina (Bryozoa, Phylactolaemata)-a crucial key to elucidating bryozoan evolution.

    PubMed

    Schwaha, Thomas; Hirose, Masato; Wanninger, Andreas

    2016-01-01

    Phylactolaemata is the earliest branch and the sister group to all extant bryozoans. It is considered a small relict group that, perhaps due to the invasion of freshwater, has retained ancestral features. Reconstruction of the ground pattern of Phylactolaemata is thus essential for reconstructing the ground pattern of all Bryozoa, and for inferring phylogenetic relationships to possible sister taxa. It is well known that Stephanella hina, the sole member of the family Stephanelllidae, is probably one of the earliest offshoots among the Phylactolaemata and shows some morphological peculiarities. However, key aspects of its biology are largely unknown. The aim of the present study was to analyze live specimens of this species, in order to both document its behavior and describe its colony morphology. The colony morphology of Stephanella hina consists of zooidal arrangements with lateral budding sites reminiscent of other bryozoan taxa, i.e., Steno- and Gymnolaemata. Zooids protrude vertically from the substrate and are covered in a non-rigid jelly-like ectocyst. The latter is a transparent, sticky hull that for the most part shows no distinct connection to the endocyst. Interestingly, individual zooids can be readily separated from the rest of the colony. The loose tube-like ectocyst can be removed from the animals that produces individuals that are unable to retract their lophophore, but merely shorten their trunk by contraction of the retractor muscles. These observations indicate that S. hina is unique among Phylactolaemata and support the notion that bryozoans evolved from worm-like ancestors. In addition, we raise several arguments for its placement into a separate family, Stephanellidae, rather than among the Plumatellidae, as previously suggested.

  4. 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.

  5. 3 Key Lifestyle Factors Can Lower Breast Cancer Odds

    MedlinePlus

    ... 165873.html 3 Key Lifestyle Factors Can Lower Breast Cancer Odds Stay trim, exercise and cut back on ... appear to help lower a woman's risk of breast cancer, a new review says. The review found that ...

  6. Key factors influencing management decisions concerning safety equipment selection.

    PubMed

    Chinda, Thanwadee; Ammarapala, Veeris; Suanmali, Suthathip

    2017-08-31

    The construction industry involves many hazardous activities that may expose workers to a wide variety of health hazards. Selection of construction safety equipment is crucial in ensuring workers' safety. This article aims to examine key factors influencing management decisions concerning safety equipment selection, utilizing exploratory factor analysis (EFA) and the analytic hierarchy process (AHP). A questionnaire survey is conducted in the construction companies in Bangkok, Thailand. The factor analysis extracts 103 sets of data into six key factors - namely supplier agreements, supplier support, personal, equipment design, safety-related policies and cost value factors - with a total of 20 associated items. The AHP results conclude that the safety-related policies, equipment design and personal factors are the most important factors when selecting construction safety equipment. A construction company can use the study results as a checklist to help assess different safety equipment, and to select the best equipment.

  7. Desire: A Key Factor for Successful Online GED Adult Learners

    ERIC Educational Resources Information Center

    Shaw, Donita; Tham, Yuen San Sarah; Hogle, Julie; Koch, Jody

    2015-01-01

    The purpose of this study was to analyze the experiences of 12 adult online General Educational Development (GED) students to determine the role of program and personal factors that influenced their successful passing of the GED or their dropping-out of the program. Through surveys and interviews, we discovered that desire was the key factor for…

  8. Desire: A Key Factor for Successful Online GED Adult Learners

    ERIC Educational Resources Information Center

    Shaw, Donita; Tham, Yuen San Sarah; Hogle, Julie; Koch, Jody

    2015-01-01

    The purpose of this study was to analyze the experiences of 12 adult online General Educational Development (GED) students to determine the role of program and personal factors that influenced their successful passing of the GED or their dropping-out of the program. Through surveys and interviews, we discovered that desire was the key factor for…

  9. Elucidation of laser welding phenomena and factors affecting weld penetration and welding defects

    NASA Astrophysics Data System (ADS)

    Katayama, Seiji; Kawahito, Yousuke; Mizutani, Masami

    The behavior and effect of a plasma plume on the weld penetration are greatly different between CO2 laser welding and YAG, disk or fiber laser welding. The effects of the power and the power density on the weld penetration are elucidated. Spattering leading to the formation of underfilled weld beads is controlled by inclining the laser beam. Porosity is formed from bubbles generated from the tip of the keyhole at low welding speed or from the middle part of the keyhole at high laser power density. Cracking easily occurs in pulsed spot welding of aluminum alloys.

  10. A systems biology approach for elucidating the interaction of curcumin with Fanconi anemia FANC G protein and the key disease targets of leukemia.

    PubMed

    Mahato, David; Samanta, Dipayan; Mukhopadhyay, Sudit S; Krishnaraj, R Navanietha

    2017-06-01

    Fanconi anemia (FA) is an autosomal recessive disorder with a high risk of malignancies including acute myeloid leukemia and squamous cell carcinoma. There is a constant search out of new potential therapeutic molecule to combat this disorder. In most cases, patients with FA develop haematological malignancies with acute myeloid leukemia and acute lymphoblastic leukemia. Identifying drugs which can efficiently block the pathways of both these disorders can be an ideal and novel strategy to treat FA. The curcumin, a natural compound obtained from turmeric is an interesting therapeutic molecule as it has been reported in the literature to combat both FA as well as leukemia. However, its complete mechanism is not elucidated. Herein, a systems biology approach for elucidating the therapeutic potential of curcumin against FA and leukemia is investigated by analyzing the computational molecular interactions of curcumin ligand with FANC G of FA and seven other key disease targets of leukemia. The proteins namely DOT1L, farnesyl transferase (FDPS), histone decetylase (EP3000), Polo-like kinase (PLK-2), aurora-like kinase (AUKRB), tyrosine kinase (ABL1), and retinoic acid receptor alpha (RARA) were chosen as disease targets for leukemia and modeled structure of FANC G protein as the disease target for FA. The docking investigations showed that curcumin had a very high binding affinity of -8.1 kcal/mol with FANC G protein. The key disease targets of leukemia namely tyrosine kinase (ABL1), aurora-like kinase (AUKRB), and polo-like kinase (PLK-2) showed that they had the comparable binding affinities of -9.7 k cal/mol, -8.7 k cal/mol, and -8.6 k cal/mol, respectively with curcumin. Further, the percentage similarity scores obtained from PAM50 using EMBOSS MATCHER was shown to provide a clue to understand the structural relationships to an extent and to predict the binding affinity. This investigation shows that curcumin effectively interacts with the disease targets of both

  11. 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…

  12. 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)…

  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. Elucidation of a four-site allosteric network in fibroblast growth factor receptor tyrosine kinases

    PubMed Central

    Chen, Huaibin; Marsiglia, William M; Cho, Min-Kyu; Huang, Zhifeng; Deng, Jingjing; Blais, Steven P; Gai, Weiming; Bhattacharya, Shibani; Neubert, Thomas A; Traaseth, Nathaniel J; Mohammadi, Moosa

    2017-01-01

    Receptor tyrosine kinase (RTK) signaling is tightly regulated by protein allostery within the intracellular tyrosine kinase domains. Yet the molecular determinants of allosteric connectivity in tyrosine kinase domain are incompletely understood. By means of structural (X-ray and NMR) and functional characterization of pathogenic gain-of-function mutations affecting the FGF receptor (FGFR) tyrosine kinase domain, we elucidated a long-distance allosteric network composed of four interconnected sites termed the ‘molecular brake’, ‘DFG latch’, ‘A-loop plug’, and ‘αC tether’. The first three sites repress the kinase from adopting an active conformation, whereas the αC tether promotes the active conformation. The skewed design of this four-site allosteric network imposes tight autoinhibition and accounts for the incomplete mimicry of the activated conformation by pathogenic mutations targeting a single site. Based on the structural similarity shared among RTKs, we propose that this allosteric model for FGFR kinases is applicable to other RTKs. DOI: http://dx.doi.org/10.7554/eLife.21137.001 PMID:28166054

  15. Structural insights into dynamics of RecU-HJ complex formation elucidates key role of NTR and stalk region toward formation of reactive state.

    PubMed

    Khavnekar, Sagar; Dantu, Sarath Chandra; Sedelnikova, Svetlana; Ayora, Sylvia; Rafferty, John; Kale, Avinash

    2017-01-25

    Holliday junction (HJ) resolving enzyme RecU is involved in DNA repair and recombination. We have determined the crystal structure of inactive mutant (D88N) of RecU from Bacillus subtilis in complex with a 12 base palindromic DNA fragment at a resolution of 3.2 Å. This structure shows the stalk region and the essential N-terminal region (NTR) previously unseen in our DNA unbound structure. The flexible nature of the NTR in solution was confirmed using SAXS. Thermofluor studies performed to assess the stability of RecU in complex with the arms of an HJ indicate that it confers stability. Further, we performed molecular dynamics (MD) simulations of wild type and an NTR deletion variant of RecU, with and without HJ. The NTR is observed to be highly flexible in simulations of the unbound RecU, in agreement with SAXS observations. These simulations revealed domain dynamics of RecU and their role in the formation of complex with HJ. The MD simulations also elucidate key roles of the NTR, stalk region, and breathing motion of RecU in the formation of the reactive state.

  16. Structural insights into dynamics of RecU–HJ complex formation elucidates key role of NTR and stalk region toward formation of reactive state

    PubMed Central

    Khavnekar, Sagar; Dantu, Sarath Chandra; Sedelnikova, Svetlana; Ayora, Sylvia; Rafferty, John; Kale, Avinash

    2017-01-01

    Holliday junction (HJ) resolving enzyme RecU is involved in DNA repair and recombination. We have determined the crystal structure of inactive mutant (D88N) of RecU from Bacillus subtilis in complex with a 12 base palindromic DNA fragment at a resolution of 3.2 Å. This structure shows the stalk region and the essential N-terminal region (NTR) previously unseen in our DNA unbound structure. The flexible nature of the NTR in solution was confirmed using SAXS. Thermofluor studies performed to assess the stability of RecU in complex with the arms of an HJ indicate that it confers stability. Further, we performed molecular dynamics (MD) simulations of wild type and an NTR deletion variant of RecU, with and without HJ. The NTR is observed to be highly flexible in simulations of the unbound RecU, in agreement with SAXS observations. These simulations revealed domain dynamics of RecU and their role in the formation of complex with HJ. The MD simulations also elucidate key roles of the NTR, stalk region, and breathing motion of RecU in the formation of the reactive state. PMID:27903910

  17. 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.

  18. 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.

  19. From shared care to disease management: key-influencing factors

    PubMed Central

    Eijkelberg, Irmgard M.J.G.; Spreeuwenberg, Cor; Mur-Veeman, Ingrid M.; Wolffenbuttel, Bruce H.R.

    2001-01-01

    Abstract Background In order to improve the quality of care of chronically ill patients the traditional boundaries between primary and secondary care are questioned. To demolish these boundaries so-called ‘shared care’ projects have been initiated in which different ways of substitution of care are applied. When these projects end, disease management may offer a solution to expand the achieved co-operation between primary and secondary care. Objective Answering the question: What key factors influence the development and implementation of shared care projects from a management perspective and how are they linked? Theory The theoretical framework is based on the concept of the learning organisation. Design Reference point is a multiple case study that finally becomes a single case study. Data are collected by means of triangulation. The studied cases concern two interrelated Dutch shared care projects for type 2 diabetic patients, that in the end proceed as one disease management project. Results In these cases the predominant key-influencing factors appear to be the project management, commitment and local context, respectively. The factor project management directly links the latter two, albeit managing both appear prerequisites to its success. In practice this implies managing the factors' interdependency by the application of change strategies and tactics in a committed and skilful way. Conclusion Project management, as the most important and active key factor, is advised to cope with the interrelationships of the influencing factors in a gradually more fundamental way by using strategies and tactics that enable learning processes. Then small-scale shared care projects may change into a disease management network at a large scale, which may yield the future blueprint to proceed. PMID:16896415

  20. From shared care to disease management: key-influencing factors.

    PubMed

    Eijkelberg, I M; Spreeuwenberg, C; Mur-Veeman, I M; Wolffenbuttel, B H

    2001-01-01

    In order to improve the quality of care of chronically ill patients the traditional boundaries between primary and secondary care are questioned. To demolish these boundaries so-called 'shared care' projects have been initiated in which different ways of substitution of care are applied. When these projects end, disease management may offer a solution to expand the achieved co-operation between primary and secondary care. Answering the question: What key factors influence the development and implementation of shared care projects from a management perspective and how are they linked? The theoretical framework is based on the concept of the learning organisation. Reference point is a multiple case study that finally becomes a single case study. Data are collected by means of triangulation. The studied cases concern two interrelated Dutch shared care projects for type 2 diabetic patients, that in the end proceed as one disease management project. In these cases the predominant key-influencing factors appear to be the project management, commitment and local context, respectively. The factor project management directly links the latter two, albeit managing both appear prerequisites to its success. In practice this implies managing the factors' interdependency by the application of change strategies and tactics in a committed and skillful way. Project management, as the most important and active key factor, is advised to cope with the interrelationships of the influencing factors in a gradually more fundamental way by using strategies and tactics that enable learning processes. Then small-scale shared care projects may change into a disease management network at a large scale, which may yield the future blueprint to proceed.

  1. 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.

  2. Key factors affecting dying children and their families.

    PubMed

    Hinds, Pamela S; Schum, Lisa; Baker, Justin N; Wolfe, Joanne

    2005-01-01

    The death of a child alters the life and health of others immediately and for the rest of their lives. How a child dies influences parents' abilities to continue their role functions as well as siblings' abilities to make and maintain friendships, and may be the basis for health care providers' decisions to exit direct care roles. Thus, facilitating a "good death"-an obvious care priority for all involved with the dying child-ought also to be a priority for the health of bereaved families and affected health care providers. Making this a care priority is complicated by a serious lack of data, as details of the last hours or weeks of a dying child or adolescent's life are largely unknown. The purpose of this paper is to identify key factors that affect the course of dying children and adolescents and that of their bereaved survivors, and to link those key factors to needed research that could produce clinically relevant findings to improve the care of these patients. Key factors described here include suffering (physical, psychological, and spiritual), communication, decision making, prognostic ambiguities, ability of the seriously ill child to give assent to research participation, and educational preparation of health care providers to give competent end-of-life care.

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

    PubMed

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

    2016-01-01

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

  4. Elucidating the factors influencing the biodegradation of cylindrospermopsin in drinking water sources.

    PubMed

    Smith, Maree J; Shaw, Glen R; Eaglesham, Geoff K; Ho, Lionel; Brookes, Justin D

    2008-06-01

    The cyanotoxin cylindrospermopsin (CYN) is produced by several species of cyanobacteria and can be persistent in drinking waters supplies, which is of major concern to water authorities because of its potential to severely compromise human health. Consequently, there is a need to fully understand the persistence of CYN in water supplies, in particular, to determine whether this toxin is readily degraded by endemic aquatic organisms. This study provides insights into the environmental factors that can influence the biodegradation of this toxin in Australian drinking water supplies. Biodegradation of CYN was only evident in water supplies that had a history of toxic Cylindrospermopsis raciborskii blooms. In addition, lag periods were evident prior to the onset of biodegradation; however, repeated exposure of the endemic organisms to CYN resulted in substantial decreases in the lag periods. Furthermore, the concentration of CYN was shown to influence biodegradation with a near linear relationship (R(2) of 0.9549) existing between the biodegradation rate and the initial CYN concentration. Temperature was also shown to affect the biodegradation of CYN, which is important since CYN is now being detected in more temperate climates. The presence of copper-based algicides inhibited CYN degradation, which has significant implications since copper-based algicides are commonly used to control cyanobacterial growth in water bodies. The results from this study indicate that the biodegradation of CYN in natural water bodies is a complex process that can be influenced by many environmental factors, some of which include CYN concentration, temperature, and the presence of copper-based algicides.

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

    PubMed

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

    2015-11-30

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

  6. 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

  7. 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

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

    PubMed

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

    2015-04-07

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

  9. 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

  10. 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.

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

    PubMed

    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.

  12. Elucidation of Thermally Induced Changes in Key Odorants of White Mustard Seeds (Sinapis alba L.) and Rapeseeds (Brassica napus L.) Using Molecular Sensory Science.

    PubMed

    Ortner, Eva; Granvogl, Michael; Schieberle, Peter

    2016-11-02

    Heat-processing of Brassica seeds led to the formation of a characteristic pleasant popcorn-like and coffee-like aroma impression compared to the mainly pea-like aroma of the corresponding raw seeds. To analyze this phenomenon on a molecular basis, raw and roasted white mustard seeds and rapeseeds were analyzed using the sensomics approach. Application of comparative aroma extract dilution analysis (cAEDA) and identification experiments to raw and roasted (140 °C, 30 min) mustard seeds revealed 36 odorants (all identified for the first time) and 47 odorants (41 newly identified), respectively. Twenty-seven odorants in raw and 43 odorants in roasted (140 °C, 60 min) rapeseeds were found, which were all described for the first time. Among the set of volatiles, 2-isopropyl-3-methoxypyrazine (earthy, pea-like) and 4-ethenyl-2-methoxyphenol (clove-like, smoky) showed high FD factors in both raw seeds. 4-Hydroxy-2,5-dimethylfuran-3(2H)-one (caramel-like), 2,3-diethyl-5-methylpyrazine (earthy), dimethyl trisulfide (cabbage-like), and 2-acetyl-1-pyrroline (popcorn-like) were present at high flavor dilution (FD) factors in both roasted Brassica seeds. Odorants, differing in cAEDA or showing high FD factors in at least one of the seeds, were quantitated by stable isotope dilution analysis (SIDA), followed by the calculation of odor activity values (OAVs) using odor thresholds determined in refined sunflower oil. Eighteen aroma compounds in raw and 28 in roasted mustard seeds as well as 14 in raw and 25 in roasted rapeseeds revealed OAVs ≥1. All four aroma recombinates, prepared by mixing the odorants showing OAVs ≥1 in their naturally occurring concentrations, showed a very good similarity with the original seeds and, thus, proved the successful characterization of the respective key odorants.

  13. 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

  14. Identification of Key Transcription Factors Associated with Lung Squamous Cell Carcinoma

    PubMed Central

    Zhang, Feng; Chen, Xia; Wei, Ke; Liu, Daoming; Xu, Xiaodong; Zhang, Xing; Shi, Hong

    2017-01-01

    Background Lung squamous cell carcinoma (lung SCC) is a common type of lung cancer, but its mechanism of pathogenesis is unclear. The aim of this study was to identify key transcription factors in lung SCC and elucidate its mechanism. Material/Methods Six published microarray datasets of lung SCC were downloaded from Gene Expression Omnibus (GEO) for integrated bioinformatics analysis. Significance analysis of microarrays was used to identify differentially expressed genes (DEGs) between lung SCC and normal controls. The biological functions and signaling pathways of DEGs were mapped in the Gene Otology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database, respectively. A transcription factor gene regulatory network was used to obtain insights into the functions of DEGs. Results A total of 1,011 genes, including 539 upregulated genes and 462 downregulated genes, were filtered as DEGs between lung SCC and normal controls. DEGs were significantly enriched in cell cycle, DNA replication, p53 signaling pathway, pathways in cancer, adherens junction, and cell adhesion molecules signaling pathways. There were 57 transcription factors identified, which were used to construct a regulatory network. The network consisted of 736 interactions between 49 transcription factors and 486 DEGs. NFIC, BRCA1, and NFATC2 were the top 3 transcription factors that had the highest connectivity with DEGs and that regulated 83, 82, and 75 DEGs in the network, respectively. Conclusions NFIC, BRCA1, and NFATC2 might be the key transcription factors in the development of lung SCC by regulating the genes involved in cell cycle and DNA replication pathways. PMID:28081052

  15. Key factors affecting mechanical behavior of metallic glass nanowires

    NASA Astrophysics Data System (ADS)

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

    2017-01-01

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

  16. Key factors affecting mechanical behavior of metallic glass nanowires.

    PubMed

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

    2017-01-30

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

  17. Key factors affecting mechanical behavior of metallic glass nanowires

    PubMed Central

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

    2017-01-01

    Both strengthening and weakening trends with decreasing diameter have been observed for metallic glass nanowires, sometimes even in the samples with the same chemical composition. How to reconcile the results has reminded a puzzle. Since the detailed stress state and microstructure of metallic glass nanowires may differ from each other significantly depending on preparation, to discover the intrinsic size effect it is necessary to study metallic glass nanowires fabricated differently. Here we show the complex size effects from one such class of metallic glass nanowires prepared by casting using molecular dynamics simulations. As compared with the nanowires of the same composition prepared by other methods, the cast nanowires deform nearly homogeneously with much lower strength but better ductility; and also show strengthening in tension but weakening in compression with decreasing wire diameter. The subtle size dependence is shown to be related to the key factors including internal and surface stress state, atomic structure variation, and presence of various gradients. The complex interplay of these factors at decreasing size leads to the different deformation behaviors. PMID:28134292

  18. 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

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

    PubMed

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

    2011-12-01

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

  20. Inflammatory risk factors and pathologies promoting Alzheimer's disease progression: is RAGE the key?

    PubMed

    Matrone, Carmela; Djelloul, Mehdi; Taglialatela, Giulio; Perrone, Lorena

    2015-02-01

    Epidemiological studies reveal growing evidence that most cases of Alzheimer`s Disease (AD) likely involve a combination of genetic and environmental risk factors. Identifying and validating these risk factors remains one of the most critical scientific challenges. Several diseases appear to have strong implications for neurodegeneration leading to dementia. This risk encompasses different forms of cardiovascular disease, carotid atherosclerosis, history of hypertension or high cholesterol, Type II diabetes, stroke or transient ischemic attack and brain trauma. However, the molecular pathways that are common and central in the progression of these diseases and AD are not yet elucidated. Unveiling these critical mechanisms at the molecular level is necessary for the development of therapeutic strategies aimed at preventing AD progression. The Receptor for Advanced Glycation Endproducts (RAGE) plays a key role in all the diseases that represent a risk for AD. RAGE-mediated signaling also contributes to neurodegeneration in AD, suggesting that it may mediate the effect of risk factors in promoting AD. We will summarize the current knowledge on the role of RAGE in pathologies promoting AD and in AD progression. We will also provide evidence showing the relevance of RAGE-induced inflammation as a risk pathway that is implicated in AD pathophysiology.

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

    USDA-ARS?s Scientific Manuscript database

    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...

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

    NASA Astrophysics Data System (ADS)

    Sato, Takehiko; Yokoyama, Mayo; Johkura, Kohei

    2011-09-01

    Recently, a plasma flow has been applied to medical treatment using effects of various kinds of stimuli such as chemical species, charged particles, heat, light, shock wave and electric fields. Among them, the chemical species are known to cause an inactivation of cell viability. However, the mechanisms and key factors of this event are not yet clear. In this study, we focused on the effect of H2O2 in plasma-treated culture medium because it is generated in the culture medium and it is also chemically stable compared with free radicals generated by the plasma flow. To elucidate the significance of H2O2, we assessed the differences in the effects of plasma-treated medium and H2O2-added medium against inactivation of HeLa cell viability. These two media showed comparable effects on HeLa cells in terms of the survival ratios, morphological features of damage processes, permeations of H2O2 into the cells, response to H2O2 decomposition by catalase and comprehensive gene expression. The results supported that among chemical species generated in a plasma-treated culture medium, H2O2 is one of the main factors responsible for inactivation of HeLa cell viability.

  3. 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

    2015-10-02

    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.

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

    PubMed

    Lingafelter, Steven W; Nearns, Eugenio H

    2013-01-01

    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 facilitates this determination and as a preferable method, given the convoluted and subordinate discussion, exceptions, and qualifications laid out in ICZN (1999: 49-50). Examples and citations are provided for each case one can encounter while making this assessment of availability status of names following the binomen.

  5. Elucidating the Key Role of a Lewis Base Solvent in the Formation of Perovskite Films Fabricated from the Lewis Adduct Approach.

    PubMed

    Cao, Xiaobing; Zhi, Lili; Li, Yahui; Fang, Fei; Cui, Xian; Yao, Youwei; Ci, Lijie; Ding, Kongxian; Wei, Jinquan

    2017-09-27

    High-quality perovskite films can be fabricated from Lewis acid-base adducts through molecule exchange. Substantial work is needed to fully understand the formation mechanism of the perovskite films, which helps to further improve their quality. Here, we study the formation of CH3NH3PbI3 perovskite films by introducing some dimethylacetamide into the PbI2/N,N-dimethylformamide solution. We reveal that there are three key processes during the formation of perovskite films through the Lewis acid-base adduct approach: molecule intercalation of solvent into the PbI2 lattice, molecule exchange between the solvent and CH3NH3I, and dissolution-recrystallization of the perovskite grains during annealing. The Lewis base solvents play multiple functions in the above processes. The properties of the solvent, including Lewis basicity and boiling point, play key roles in forming smooth perovskite films with large grains. We also provide some rules for choosing Lewis base additives to prepare high-quality perovskite films through the Lewis adduct approach.

  6. Profiling conserved biological pathways in Autosomal Dominant Polycystic Kidney Disorder (ADPKD) to elucidate key transcriptomic alterations regulating cystogenesis: A cross-species meta-analysis approach.

    PubMed

    Chatterjee, Shatakshee; Verma, Srikant Prasad; Pandey, Priyanka

    2017-09-05

    Initiation and progression of fluid filled cysts mark Autosomal Dominant Polycystic Kidney Disease (ADPKD). Thus, improved therapeutics targeting cystogenesis remains a constant challenge. Microarray studies in single ADPKD animal models species with limited sample sizes tend to provide scattered views on underlying ADPKD pathogenesis. Thus we aim to perform a cross species meta-analysis to profile conserved biological pathways that might be key targets for therapy. Nine ADPKD microarray datasets on rat, mice and human fulfilled our study criteria and were chosen. Intra-species combined analysis was performed after considering removal of batch effect. Significantly enriched GO biological processes and KEGG pathways were computed and their overlap was observed. For the conserved pathways, biological modules and gene regulatory networks were observed. Additionally, Gene Set Enrichment Analysis (GSEA) using Molecular Signature Database (MSigDB) was performed for genes found in conserved pathways. We obtained 28 modules of significantly enriched GO processes and 5 major functional categories from significantly enriched KEGG pathways conserved in human, mice and rats that in turn suggest a global transcriptomic perturbation affecting cyst - formation, growth and progression. Significantly enriched pathways obtained from up-regulated genes such as Genomic instability, Protein localization in ER and Insulin Resistance were found to regulate cyst formation and growth whereas cyst progression due to increased cell adhesion and inflammation was suggested by perturbations in Angiogenesis, TGF-beta, CAMs, and Infection related pathways. Additionally, networks revealed shared genes among pathways e.g. SMAD2 and SMAD7 in Endocytosis and TGF-beta. Our study suggests cyst formation and progression to be an outcome of interplay between a set of several key deregulated pathways. Thus, further translational research is warranted focusing on developing a combinatorial therapeutic

  7. 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 the…

  8. 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 the…

  9. Elucidating the thermal decomposition of dimethyl methylphosphonate by vacuum ultraviolet (VUV) photoionization: pathways to the PO radical, a key species in flame-retardant mechanisms.

    PubMed

    Liang, Shuyu; Hemberger, Patrick; Neisius, N Matthias; Bodi, Andras; Grützmacher, Hansjörg; Levalois-Grützmacher, Joelle; Gaan, Sabyasachi

    2015-01-12

    The production of phosphoryl species (PO, PO2, HOPO) is believed to be of great importance for efficient flame-retardant action in the gas phase. We present a detailed investigation of the thermal decomposition of dimethyl methylphosphonate (DMMP) probed by vacuum ultraviolet (VUV) synchrotron radiation and imaging photoelectron photoion coincidence (iPEPICO) spectroscopy. This technique provides a snapshot of the thermolysis process and direct evidence of how the reactive phosphoryl species are generated during heat exposure. One of the key findings of this work is that only PO is formed in high concentration upon DMMP decomposition, whereas PO2 is absent. It can be concluded that the formation of PO2 needs an oxidative environment, which is typically the case in a real flame. Based on the identification of products such as methanol, formaldehyde, and PO, as well as the intermediates O=P-CH3, H2C=P-OH, and H2C=P(=O)H, supported by quantum chemical calculations, we were able to describe the predominant pathways that lead to active phosphoryl species during the thermal decomposition of DMMP. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Experimental Infections with Mycoplasma agalactiae Identify Key Factors Involved in Host-Colonization

    PubMed Central

    Baranowski, Eric; Bergonier, Dominique; Sagné, Eveline; Hygonenq, Marie-Claude; Ronsin, Patricia; Berthelot, Xavier; Citti, Christine

    2014-01-01

    Mechanisms underlying pathogenic processes in mycoplasma infections are poorly understood, mainly because of limited sequence similarities with classical, bacterial virulence factors. Recently, large-scale transposon mutagenesis in the ruminant pathogen Mycoplasma agalactiae identified the NIF locus, including nifS and nifU, as essential for mycoplasma growth in cell culture, while dispensable in axenic media. To evaluate the importance of this locus in vivo, the infectivity of two knock-out mutants was tested upon experimental infection in the natural host. In this model, the parental PG2 strain was able to establish a systemic infection in lactating ewes, colonizing various body sites such as lymph nodes and the mammary gland, even when inoculated at low doses. In these PG2-infected ewes, we observed over the course of infection (i) the development of a specific antibody response and (ii) dynamic changes in expression of M. agalactiae surface variable proteins (Vpma), with multiple Vpma profiles co-existing in the same animal. In contrast and despite a sensitive model, none of the knock-out mutants were able to survive and colonize the host. The extreme avirulent phenotype of the two mutants was further supported by the absence of an IgG response in inoculated animals. The exact role of the NIF locus remains to be elucidated but these data demonstrate that it plays a key role in the infectious process of M. agalactiae and most likely of other pathogenic mycoplasma species as many carry closely related homologs. PMID:24699671

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

    PubMed

    Baranowski, Eric; Bergonier, Dominique; Sagné, Eveline; Hygonenq, Marie-Claude; Ronsin, Patricia; Berthelot, Xavier; Citti, Christine

    2014-01-01

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

  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. Elucidation of Softening Mechanism in Rinse-Cycle Fabric Softeners. Part 2: Uneven Adsorption-The Key Phenomenon to the Effect of Fabric Softeners.

    PubMed

    Igarashi, Takako; Nakamura, Koichi; Hoshi, Masato; Hara, Teruyuki; Kojima, Hironori; Itou, Masatsugu; Ikeda, Reiko; Okamoto, Yoshimasa

    We investigated the actual factor determining the softening effect of a fabric softener. The adsorption area of the softener on model cotton cloths and yarns was identified using bromophenol blue. There was almost no softener at the cross-points of the yarns in the cloth samples or in the inner part of the yarns. The softening performance was better when there was less softener at the cross-points of the yarns than when the yarns were evenly covered by the softener. Thus we conclude that the presence of softener at the cross-points of yarns is not a vital factor in the softening effect. In addition, more softener was found on the outer part of the yarn than the inner part, indicating gradation in the adsorption pattern of the softener. Thus, we propose that more softener is adsorbed on the exposed part of the yarn in a cloth, and the formation of a hydrogen-bonding network containing bound water is inhibited, thus softening the outer part of the yarn. However, the presence of a small amount of softener in the inner part of the yarn preserves the hydrogen-bonding network. Favorable elasticity, or bounce, of the yarns and cloth is realized when an appropriate amount of softener is used. Excess softener would reach the inner part of the yarn, reducing the diameter of the core part of the yarn, making the cloth appear wilted.

  14. 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

  15. Genome-Wide Transcriptional Profiling to Elucidate Key Candidates Involved in Bud Burst and Rattling Growth in a Subtropical Bamboo (Dendrocalamus hamiltonii)

    PubMed Central

    Bhandawat, Abhishek; Singh, Gagandeep; Seth, Romit; Singh, Pradeep; Sharma, Ram K.

    2017-01-01

    Bamboo, one of the fastest growing plants, can be a promising model system to understand growth. The study provides an insight into the complex interplay between environmental signaling and cellular machineries governing initiation and persistence of growth in a subtropical bamboo (Dendrocalamus hamiltonii). Phenological and spatio-temporal transcriptome analysis of rhizome and shoot during the major vegetative developmental transitions of D. hamiltonii was performed to dissect factors governing growth. Our work signifies the role of environmental cues, predominantly rainfall, decreasing day length, and high humidity for activating dormant bud to produce new shoot, possibly through complex molecular interactions among phosphatidylinositol, calcium signaling pathways, phytohormones, circadian rhythm, and humidity responses. We found the coordinated regulation of auxin, cytokinin, brassinosteroid signaling and cell cycle modulators; facilitating cell proliferation, cell expansion, and cell wall biogenesis supporting persistent growth of emerging shoot. Putative master regulators among these candidates were identified using predetermined Arabidopsis thaliana protein-protein interaction network. We got clues that the growth signaling begins far back in rhizome even before it emerges out as new shoot. Putative growth candidates identified in our study can serve in devising strategies to engineer bamboos and timber trees with enhanced growth and biomass potentials. PMID:28123391

  16. Leadership and management quality: key factors in effective health systems.

    PubMed

    Pfeffermann, Guy

    2012-01-01

    The effectiveness of health care systems in the developing world is related to the quality of their leadership and management, yet that factor has been neglected by academics and funders. Based on replicable existing models, the article proposes an approach to strengthening local management training institutions.

  17. 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…

  18. Particle size distribution: a key factor in estimating powder dustiness.

    PubMed

    López-Lilao, Ana; Sanfélix, Forner Vicenta; Mallol, Gasch Gustavo; Monfort, Gimeno Eliseo

    2017-08-01

    ASTRACT A wide variety of raw materials, involving more than twenty samples of quartzes, feldspars, nephelines, carbonates, dolomites, sands, zircons, and alumina, were selected and characterised. Dustiness, i.e. a materials' tendency to generate dust on handling, was determined using the continuous drop method. These raw materials were selected to encompass a wide range of particle sizes (1.6-294 µm) and true densities (2650-4680 kg/m(3)). The dustiness of the raw materials, i.e. their tendency to generate dust on handling, was determined using the continuous drop method. The influence of some key material parameters (particle size distribution, flowability and specific surface area) on dustiness was assessed. In this regard, dustiness was found to be significantly affected by particle size distribution. Data analysis enabled development of a model for predicting the dustiness of the studied materials, assuming that dustiness depended on the particle fraction susceptible to emission and on the bulk material's susceptibility to release these particles. On the one hand, the developed model allows the dustiness mechanisms to be better understood. In this regard, it may be noted that relative emission increased with mean particle size. However, this did not necessarily imply that dustiness did, because dustiness also depended on the fraction of particles susceptible to be emitted. On the other hand, the developed model enables dustiness to be estimated using just the particle size distribution data. The quality of the fits was quite good and the fact that only particle size distribution data are needed facilitates industrial application, since these data are usually known by raw materials managers, thus making additional tests unnecessary. This model may therefore be deemed a key tool in drawing up efficient preventive and/or corrective measures to reduce dust emissions during bulk powder processing, both inside and outside industrial facilities. It is recommended

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

    PubMed

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

    2016-09-19

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

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

    PubMed

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

    2010-11-01

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

  1. 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.

  2. Detection of key factors affecting lycopene in vitro accessibility.

    PubMed

    Periago, M J; Bravo, S; García-Alonso, F J; Rincón, F

    2013-04-24

    On the basis of a Plackett-Burman experimental design for a resolution IV level obtained via a foldover strategy, the effect of 11 factors on lycopene in vitro accessibility was investigated. The selected factors were thermal treatment (X1), olive oil addition (X2), gastric pH (X3), gastric digestion time (X4), pepsin concentration (X5), intestinal pH (X6), pancreatin concentration (X7), bile salts concentration (X8), colipase addition (X9), intestinal digestion time (X10), and intestinal digestion speed (X11). Tomato passata was used as a natural source of lycopene. Samples were collected after gastric and intestinal digestion, and from the micellar phase, to quantify the (all-E)-lycopene and its (Z)-isomers by HPLC. Except for X3, X6, X7, and X11, the other factors studied explained lycopene in vitro accessibility, mainly regarding intestinal digestion, with R(2) values ≥ 0.60. Our results showed that the accessibility of lycopene is influenced by the conditions applied during in vitro intestinal digestion.

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

    PubMed

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

    2016-06-15

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

  4. 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.

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

    PubMed

    Serra-Majem, Lluis; Bautista-Castaño, Inmaculada

    2013-09-01

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

  6. Circulation a key factor in Mediterranean algal growth

    NASA Astrophysics Data System (ADS)

    Orwig, Jessica

    2014-12-01

    The early appearance of nitrate in December appears to have been the driving force for favorable conditions for algal blooms in the Mediterranean, a new study indicates. To better understand the role of nutrients' availability to enable the growth of phytoplankton in temperate seas, D'Ortenzio et al. installed nitrate concentration sensors on two profiling floats in the northwestern Mediterranean basin in summer 2011. Each spring, the phytoplankton in this basin rapidly grow to form a bloom that blankets the surface and contributes to the transport of carbon from the atmosphere to the deep ocean. Scientists are still unsure exactly what produces the conditions for these blooms, but they know that the availability of nutrients, induced by large-scale circulation in the oceans, during the winter is a factor.

  7. 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

  8. Fire fatality and alcohol intake: analysis of key risk factors.

    PubMed

    Bruck, Dorothy; Ball, Michelle; Thomas, Ian R

    2011-09-01

    After a brief review of the literature on the role of alcohol in residential fire deaths, a comparison of different risk factors for residential fire fatality was undertaken by closely analyzing the circumstances of fire victims as a function of alcohol intake. Analyses were based on Australian coroners' fire fatality records for the state of Victoria (1998-2006) and considered demographic, behavioral, and environmental factors for the 95 adult fire victims who were tested for alcohol (64 male, 31 female). Most (58%) had a positive blood alcohol concentration (BAC) test, with 31% of the total sample having a BAC of more than 0.20 gm per 100 ml. Odds ratio analyses showed that four variables were significantly more associated with victims who had consumed alcohol compared with sober victims. In descending odds ratio order, these variables were as follows: (a) being aged 18-60 years, (b) involving smoking materials (e.g. cigarettes, pipes), (c) having no conditions preventing escape, and (d) being male. An important new finding is that fire fatalities with positive BAC levels were more than three times less likely to have their clothing alight or exits blocked than sober fire victims. The risk of dying in a fire for alcohol-affected people who are capable of being alerted and escaping may be reduced if they can be alerted more quickly and effectively. Suitable measures for improving smoke alarms via interlinking and the use of an alarm signal demonstrated to be more effective at waking sleepers, including those who are alcohol affected, are discussed.

  9. Risk factor control is key in diabetic nephropathy.

    PubMed

    Lewis, Gareth; Maxwell, Alexander P

    2014-02-01

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

  10. The Future of Government Funding for Persons with Disabilities: Some Key Factors.

    ERIC Educational Resources Information Center

    Ross, E. Clarke

    1980-01-01

    The paper identifies and discusses key factors associated with government funding for disabled individuals. An introductory section traces the growth of public expenditures in recent years. Five key factors affecting government funding are examined (sample subtopics in parentheses): state government tax and spending limits (Proposition 13 and the…

  11. Identification of key factors regulating self-renewal and differentiation in EML hematopoietic precursor cells by RNA-sequencing analysis.

    PubMed

    Zong, Shan; Deng, Shuyun; Chen, Kenian; Wu, Jia Qian

    2014-11-11

    Hematopoietic stem cells (HSCs) are used clinically for transplantation treatment to rebuild a patient's hematopoietic system in many diseases such as leukemia and lymphoma. Elucidating the mechanisms controlling HSCs self-renewal and differentiation is important for application of HSCs for research and clinical uses. However, it is not possible to obtain large quantity of HSCs due to their inability to proliferate in vitro. To overcome this hurdle, we used a mouse bone marrow derived cell line, the EML (Erythroid, Myeloid, and Lymphocytic) cell line, as a model system for this study. RNA-sequencing (RNA-Seq) has been increasingly used to replace microarray for gene expression studies. We report here a detailed method of using RNA-Seq technology to investigate the potential key factors in regulation of EML cell self-renewal and differentiation. The protocol provided in this paper is divided into three parts. The first part explains how to culture EML cells and separate Lin-CD34+ and Lin-CD34- cells. The second part of the protocol offers detailed procedures for total RNA preparation and the subsequent library construction for high-throughput sequencing. The last part describes the method for RNA-Seq data analysis and explains how to use the data to identify differentially expressed transcription factors between Lin-CD34+ and Lin-CD34- cells. The most significantly differentially expressed transcription factors were identified to be the potential key regulators controlling EML cell self-renewal and differentiation. In the discussion section of this paper, we highlight the key steps for successful performance of this experiment. In summary, this paper offers a method of using RNA-Seq technology to identify potential regulators of self-renewal and differentiation in EML cells. The key factors identified are subjected to downstream functional analysis in vitro and in vivo.

  12. Interactions between environmental factors and maternal-fetal genetic variations: strategies to elucidate risks of preterm birth.

    PubMed

    Pereyra, Silvana; Bertoni, Bernardo; Sapiro, Rossana

    2016-07-01

    Preterm birth (PTB) is a complex disease in which medical, social, cultural, and hereditary factors contribute to the pathogenesis of this adverse event. Interactions between genes and environmental factors may complicate our understanding of the relative influence of both effects on PTB. To overcome this, we combined data obtained from a cohort of newborns and their mothers with multiplex analysis of inflammatory-related genes and several environmental risk factors of PTB to describe the environmental-genetic influence on PTB. The study aimed to investigate the association between maternal and fetal genetic variations in genes related to the inflammation pathway with PTB and to assess the interaction between environmental factors with these variations. We conducted a case-control study at the Pereira Rossell Hospital Center, Montevideo, Uruguay. The study included 143 mother-offspring dyads who delivered at preterm (gestational age<37 weeks) and 108 mother-offspring dyads who delivered at term. We used real-time PCR followed by a high-resolution melting analysis to simultaneously identify gene variations involved in inflammatory pathways in the context of environmental variables. The genes analyzed were: Toll-like receptor 4 (TLR4), Interleukin 6 (IL6), Interleukin 1 beta (IL1B) and Interleukin 12 receptor beta (IL12RB). We detected a significant interaction between IL1B rs16944 polymorphism in maternal samples and IL6 rs1800795 polymorphism in newborns, emphasizing the role of the interaction of maternal and fetal genomes in PTB. In addition, smoke exposure and premature rupture of membranes (PROM) were significantly different between the premature group and controls. IL1B and IL6 polymorphisms in mothers were significantly associated with PTB when controlling for smoke exposure. TLR4 polymorphism and PROM were significantly associated with PTB when controlling for PROM, but only in the case of severe PTB. Interactions between maternal and fetal genomes may

  13. Pharmacokinetics of Exosomes-an Important Factor for Elucidating the Biological Roles of Exosomes and for the Development of Exosome-Based Therapeutics.

    PubMed

    Morishita, Masaki; Takahashi, Yuki; Nishikawa, Makiya; Takakura, Yoshinobu

    2017-03-07

    Exosomes are small membrane vesicles containing lipids, proteins, and nucleic acids. Recently, researchers have uncovered that exosomes are involved in various biological events, such as tumor growth, metastasis, and the immune response, by delivering their cargos to exosome-receiving cells. Moreover, exosomes are expected to be employed in therapeutic treatments, such as tissue regeneration therapy and antitumor immunotherapy, since exosomes are effective delivery vehicles for proteins, nucleic acids, and other bioactive compounds. To elucidate the biological functions of exosomes, and for the development of exosome-based therapeutics, the pharmacokinetics of exosomes is important. In this review, we aim to summarize current knowledge about the pharmacokinetics and biodistribution of exosomes. The pharmacokinetics of exogenously administered exosomes is discussed based on the tissue distribution, types of cells taking up exosomes, and key molecules in the pharmacokinetics of exosomes. In addition, recent progress in the methods to control the pharmacokinetics of exosomes is reviewed.

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

    PubMed

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

    2016-03-01

    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. 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. 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. 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 high level of clinical alertness regarding the diagnosis, early pulmonary referral, and cessation of gemcitabine on suspicion of GRP. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. 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

  16. 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.

  17. Elucidation of the regulation of an adult cuticle gene Acp65A by the transcription factor Broad.

    PubMed

    Cui, H-Y; Lestradet, M; Bruey-Sedano, N; Charles, J-P; Riddiford, L M

    2009-08-01

    Broad (BR), an ecdysone-inducible transcription factor, is a major determinant of the pupal stage. The misexpression of BR-Z1 isoform (BR-Z1) during adult development of Drosophila melanogaster prevents the expression of the adult cuticle protein 65A gene (Acp65A). We found that the proximal 237 bp of the 5' flanking region of Acp65A were sufficient to mediate this suppression. A targeted point mutation of a putative BR-Z1 response element (BRE) within this region showed that it was not involved. Drosophila hormone receptor-like 38 (DHR38) is required for Acp65A expression. We found that BR-Z1 repressed DHR38 expression and that BR's inhibition of Acp65A expression was rescued by exogenous expression of DHR38. Thus, BR-Z1 suppresses Acp65A expression by preventing the normal up-regulation of DHR38 at the time of adult cuticle formation.

  18. Combining risk assessment and epidemiological risk factors to elucidate the sources of human E. coli O157 infection.

    PubMed

    Rotariu, O; Ogden, I D; MacRitchie, L; Forbes, K J; Williams, A P; Cross, P; Hunter, C J; Teunis, P F M; Strachan, N J C

    2012-08-01

    E. coli O157 can be transmitted to humans by three primary (foodborne, environmental, waterborne) and one secondary (person-to-person transmission) pathways. A regression model and quantitative microbiological risk assessments (QMRAs) were applied to determine the relative importance of the primary transmission pathways in NE Scotland. Both approaches indicated that waterborne infection was the least important but it was unclear whether food or the environment was the main source of infection. The QMRAs over-predicted the number of cases by a factor of 30 and this could be because all E. coli O157 strains may not be equally infective and/or the level of infectivity in the dose-response model was too high. The efficacy of potential risk mitigation strategies to reduce human exposure to E. coli O157 using QMRAs was simulated. Risk mitigation strategies focusing on food and environment are likely to have the biggest impact on infection figures.

  19. Elucidation of potentially virulent factors of Candida albicans during serum adaptation by using quantitative time-course proteomics.

    PubMed

    Aoki, Wataru; Tatsukami, Yohei; Kitahara, Nao; Matsui, Kazuma; Morisaka, Hironobu; Kuroda, Kouichi; Ueda, Mitsuyoshi

    2013-10-08

    Candida albicans is an opportunistic pathogen that causes fatal disease if the host immunity is compromised. The mortality rate of systemic candidiasis is very high; hence, there is a ceaseless demand for novel pharmaceuticals. In this study, quantitative time-course proteomics of C. albicans during adaptation to fetal bovine serum (FBS) is described. Survival in blood is essential for virulence of C. albicans, and a detailed analysis is required. We cultivated C. albicans in FBS for 0-180min, and determined quantitative time-course variations of 1024 proteins in the cultured cells by using a LC-MS/MS system with a long monolithic silica capillary column. Clustering analysis identified FBS-induced proteins associated with detoxification of oxidative species, high-affinity glucose transport, citrate cycle, oxidative phosphorylation, and iron acquisition. Furthermore, we identified possible virulence factors such as orf19.4914.1 (named Blood-induced peptide 1, Blp1). Heterologous expression of BLP1 in Saccharomyces cerevisiae shortened the lag phase and resulted in a pleiotropic stress-tolerance phenotype, indicating a possible role for quick adaptation to a stressful environment. While further experiments are necessary to prove virulence of the identified factors, systematic identification of candidate virulence proteins in this study will lead to profound understanding of virulence of C. albicans. This paper describes time-course proteomics of C. albicans during adaptation to serum, which is an essential process for fatal systemic candidiasis. Using a LC-MS/MS system with a monolithic silica capillary column, we have successfully characterized time-course variations of 1024 proteins. Among them, orf19.4914.1 (Blp1) was identified as a novel pleiotropic stress-tolerance peptide, which could have an important role for virulence of C. albicans. © 2013.

  20. Elucidation of eukaryotic elongation factor-2 contact sites within the catalytic domain of Pseudomonas aeruginosa exotoxin A.

    PubMed Central

    Yates, Susan P; Merrill, Allan R

    2004-01-01

    Pseudomonas aeruginosa produces the virulence factor, ETA (exotoxin A), which catalyses an ADP-ribosyltransferase reaction of its target protein, eEF2 (eukaryotic elongation factor-2). Currently, this protein-protein interaction is poorly characterized and this study was aimed at identifying the contact sites between eEF2 and the catalytic domain of ETA (PE24H, an ETA from P. aeruginosa, a 24 kDa C-terminal fragment containing a His6 tag). Single-cysteine residues were introduced into the toxin at 21 defined surface-exposed sites and labelled with the fluorophore, IAEDANS [5-(2-iodoacetylaminoethylamino)-1-napthalenesulphonic acid]. Fluorescence quenching studies using acrylamide, and fluorescence lifetime and wavelength emission maxima analyses were conducted in the presence and absence of eEF2. Large changes in the microenvironment of the AEDANS [5-(2-aminoethylamino)-1-naphthalenesulphonic acid] probe after eEF2 binding were not observed as dictated by both fluorescence lifetime and wavelength emission maxima values. This supported the proposed minimal contact model, which suggests that only small, discrete contacts occur between these proteins. As dictated by the bimolecular quenching constant (k(q)) for acrylamide, binding of eEF2 with toxin caused the greatest change in acrylamide accessibility (>50%) when the fluorescence label was near the active site or was located within a known catalytic loop. All mutant proteins showed a decrease in accessibility to acrylamide once eEF2 bound, although the relative change varied for each labelled protein. From these data, a low-resolution model of the toxin-eEF2 complex was constructed based on the minimal contact model with the intention of enhancing our knowledge on the mode of inactivation of the ribosome translocase by the Pseudomonas toxin. PMID:14733615

  1. MicroRNA and Transcription Factor Gene Regulatory Network Analysis Reveals Key Regulatory Elements Associated with Prostate Cancer Progression

    PubMed Central

    Sadeghi, Mehdi; Ranjbar, Bijan; Ganjalikhany, Mohamad Reza; M. Khan, Faiz; Schmitz, Ulf; Wolkenhauer, Olaf; Gupta, Shailendra K.

    2016-01-01

    Technological and methodological advances in multi-omics data generation and integration approaches help elucidate genetic features of complex biological traits and diseases such as prostate cancer. Due to its heterogeneity, the identification of key functional components involved in the regulation and progression of prostate cancer is a methodological challenge. In this study, we identified key regulatory interactions responsible for primary to metastasis transitions in prostate cancer using network inference approaches by integrating patient derived transcriptomic and miRomics data into gene/miRNA/transcription factor regulatory networks. One such network was derived for each of the clinical states of prostate cancer based on differentially expressed and significantly correlated gene, miRNA and TF pairs from the patient data. We identified key elements of each network using a network analysis approach and validated our results using patient survival analysis. We observed that HOXD10, BCL2 and PGR are the most important factors affected in primary prostate samples, whereas, in the metastatic state, STAT3, JUN and JUNB are playing a central role. Benefiting integrative networks our analysis suggests that some of these molecules were targeted by several overexpressed miRNAs which may have a major effect on the dysregulation of these molecules. For example, in the metastatic tumors five miRNAs (miR-671-5p, miR-665, miR-663, miR-512-3p and miR-371-5p) are mainly responsible for the dysregulation of STAT3 and hence can provide an opportunity for early detection of metastasis and development of alternative therapeutic approaches. Our findings deliver new details on key functional components in prostate cancer progression and provide opportunities for the development of alternative therapeutic approaches. PMID:28005952

  2. MicroRNA and Transcription Factor Gene Regulatory Network Analysis Reveals Key Regulatory Elements Associated with Prostate Cancer Progression.

    PubMed

    Sadeghi, Mehdi; Ranjbar, Bijan; Ganjalikhany, Mohamad Reza; M Khan, Faiz; Schmitz, Ulf; Wolkenhauer, Olaf; Gupta, Shailendra K

    2016-01-01

    Technological and methodological advances in multi-omics data generation and integration approaches help elucidate genetic features of complex biological traits and diseases such as prostate cancer. Due to its heterogeneity, the identification of key functional components involved in the regulation and progression of prostate cancer is a methodological challenge. In this study, we identified key regulatory interactions responsible for primary to metastasis transitions in prostate cancer using network inference approaches by integrating patient derived transcriptomic and miRomics data into gene/miRNA/transcription factor regulatory networks. One such network was derived for each of the clinical states of prostate cancer based on differentially expressed and significantly correlated gene, miRNA and TF pairs from the patient data. We identified key elements of each network using a network analysis approach and validated our results using patient survival analysis. We observed that HOXD10, BCL2 and PGR are the most important factors affected in primary prostate samples, whereas, in the metastatic state, STAT3, JUN and JUNB are playing a central role. Benefiting integrative networks our analysis suggests that some of these molecules were targeted by several overexpressed miRNAs which may have a major effect on the dysregulation of these molecules. For example, in the metastatic tumors five miRNAs (miR-671-5p, miR-665, miR-663, miR-512-3p and miR-371-5p) are mainly responsible for the dysregulation of STAT3 and hence can provide an opportunity for early detection of metastasis and development of alternative therapeutic approaches. Our findings deliver new details on key functional components in prostate cancer progression and provide opportunities for the development of alternative therapeutic approaches.

  3. 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

  4. 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

  5. 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

  6. 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

    2015-11-30

    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.

  7. Genome-wide analysis of the distribution of AP2/ERF transcription factors reveals duplication and CBFs genes elucidate their potential function in Brassica oleracea

    PubMed Central

    2014-01-01

    Background Cabbage (Brassica oleracea) is one of the most important leaf vegetables grown worldwide. The entire cabbage genome sequence and more than fifty thousand proteins have been obtained to date. However a high degree of sequence similarity and conserved genome structure remain between cabbage and Arabidopsis; therefore, Arabidopsis is a viable reference species for comparative genomics studies. Transcription factors (TFs) are important regulators involved in plant development and physiological processes and the AP2/ERF protein family contains transcriptional factors that play a crucial role in plant growth and development, as well as response to biotic and abiotic stress conditions in plants. However, no detailed expression profile of AP2/ERF-like genes is available for B. oleracea. Results In the present study, 226 AP2/ERF TFs were identified from B. oleracea based on the available genome sequence. Based on sequence similarity, the AP2/ERF superfamily was classified into five groups (DREB, ERF, AP2, RAV and Soloist) and 15 subgroups. The identification, classification, phylogenetic construction, conserved motifs, chromosome distribution, functional annotation, expression patterns and interaction network were then predicted and analyzed. AP2/ERF transcription factor expression levels exhibited differences in response to varying abiotic stresses based on expressed sequence tags (ESTs). BoCBF1a, 1b, 2, 3 and 4, which were highly conserved in Arabidopsis and B. rapa CBF/DREB genes families were well characterized. Expression analysis enabled elucidation of the molecular and genetic level expression patterns of cold tolerance (CT) and susceptible lines (CS) of cabbage and indicated that all BoCBF genes responded to abiotic stresses. Conclusions Comprehensive analysis of the physiological functions and biological roles of AP2/ERF superfamily genes and BoCBF family genes in B. oleracea is required to fully elucidate AP2/ERF, which will provide rich resources and

  8. 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…

  9. 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…

  10. Key factors, Soil N Processes, and nitrite accumulation affecting nitrous oxide emissions

    USDA-ARS?s Scientific Manuscript database

    A better understanding of the key factors affecting nitrous oxide (N2O) emission and potential mitigation strategies is essential for sustainable agriculture. The objective of this study was to examine the important factors affecting N2O emissions, soil processes involved, and potential mitigation s...

  11. 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.

  12. 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…

  13. Key Educational Factors in the Education of Students with a Medical Condition

    ERIC Educational Resources Information Center

    Capurso, Michele; Dennis, John L.

    2017-01-01

    The education of children with a medical condition represents a unique educational context. The key educational factors that can help these children continue their education despite the burdens associated with their illness were discussed and analysed by a pool of experts for an EU funded project. In this context, "relationships,"…

  14. 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…

  15. 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…

  16. 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…

  17. 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…

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

    DTIC Science & Technology

    2012-07-01

    Environmental Response / Health and Safety, Housing, Restoration & Revitalization of Infrastructure Systems, Natural and Cultural Resources, Public and...revitalization of infrastructure; implementation of long-term housing solutions; a sustainable economy; and strengthening of the health, social, cultural ...Services  Housing  Infrastructure Systems  Natural and Cultural Resources Key Planning Factors For a wide-area CBR incident, each RSF will have

  19. Identifying the key factors that affect the formation of humic substance during different materials composting.

    PubMed

    Wu, Junqiu; Zhao, Yue; Qi, Haishi; Zhao, Xinyu; Yang, Tianxue; Du, Yingqiu; Zhang, Hui; Wei, Zimin

    2017-11-01

    The aim of this work was to identify the factors which can affect humic substance (HS) formation. Composting periods, HS precursors, bacteria communities and environment factors were recognized as the key factors and few studies explored the potential relationships among them. During composting, HS precursors were mainly formed in the heating and thermophilic phases, but HS were polymerized in the cooling and mature phases. Moreover, bacterial species showed similar classification of community structure in the same composting period of different materials. Furthermore, structural equation model showed that NH4(-)-N and NO3(-)-N were the indirect environmental factors for regulating HS formation by the bacteria and precursors as the indirect and direct driver, respectively. Therefore, both environmental factors and HS precursors can be the regulating factors to promote HS formation. Given that, a new staging regulating method had been proposed to improve the amount of HS during different materials composting. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. 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.

  1. Identifying Key Drivers of Return Reversal with Dynamical Bayesian Factor Graph.

    PubMed

    Zhao, Shuai; Tong, Yunhai; Wang, Zitian; Tan, Shaohua

    2016-01-01

    In the stock market, return reversal occurs when investors sell overbought stocks and buy oversold stocks, reversing the stocks' price trends. In this paper, we develop a new method to identify key drivers of return reversal by incorporating a comprehensive set of factors derived from different economic theories into one unified dynamical Bayesian factor graph. We then use the model to depict factor relationships and their dynamics, from which we make some interesting discoveries about the mechanism behind return reversals. Through extensive experiments on the US stock market, we conclude that among the various factors, the liquidity factors consistently emerge as key drivers of return reversal, which is in support of the theory of liquidity effect. Specifically, we find that stocks with high turnover rates or high Amihud illiquidity measures have a greater probability of experiencing return reversals. Apart from the consistent drivers, we find other drivers of return reversal that generally change from year to year, and they serve as important characteristics for evaluating the trends of stock returns. Besides, we also identify some seldom discussed yet enlightening inter-factor relationships, one of which shows that stocks in Finance and Insurance industry are more likely to have high Amihud illiquidity measures in comparison with those in other industries. These conclusions are robust for return reversals under different thresholds.

  2. Identifying Key Drivers of Return Reversal with Dynamical Bayesian Factor Graph

    PubMed Central

    Zhao, Shuai; Tong, Yunhai; Wang, Zitian; Tan, Shaohua

    2016-01-01

    In the stock market, return reversal occurs when investors sell overbought stocks and buy oversold stocks, reversing the stocks’ price trends. In this paper, we develop a new method to identify key drivers of return reversal by incorporating a comprehensive set of factors derived from different economic theories into one unified dynamical Bayesian factor graph. We then use the model to depict factor relationships and their dynamics, from which we make some interesting discoveries about the mechanism behind return reversals. Through extensive experiments on the US stock market, we conclude that among the various factors, the liquidity factors consistently emerge as key drivers of return reversal, which is in support of the theory of liquidity effect. Specifically, we find that stocks with high turnover rates or high Amihud illiquidity measures have a greater probability of experiencing return reversals. Apart from the consistent drivers, we find other drivers of return reversal that generally change from year to year, and they serve as important characteristics for evaluating the trends of stock returns. Besides, we also identify some seldom discussed yet enlightening inter-factor relationships, one of which shows that stocks in Finance and Insurance industry are more likely to have high Amihud illiquidity measures in comparison with those in other industries. These conclusions are robust for return reversals under different thresholds. PMID:27893780

  3. [Sensitivity evaluation and key sensitive factors identification of soil erosion around Hangzhou Bay based on RUSLE].

    PubMed

    Li, Cheng; Li, Jun-Xiang; Zhu, Fei-Ge; Cao, Lu; Chen, Zhu; Wu, Tong; Wu, Ming; Sun, Hai-Jing

    2009-07-01

    By using GIS and RS techniques and RUSLE, the rainfall erosivity (R), soil erodibility (K), vegetation and management factor (C), and slope length and steepness factor (LS) around Hangzhou Bay of Zhejiang Province, China were calculated to make a comprehensive sensitivity evaluation of soil erosion in the study area. In the meantime, the contribution of each natural factor, i. e., rainfall, soil texture, slope, and elevation, was analyzed, and a new approach, overlapping and ordering method, was developed to identify the key affecting factors in the given sensitive areas. In the study area, soil erosion was mainly at non-sensitive and low sensitive levels. The percentages of the areas with different soil erosion sensitivity varied with the strength of the affecting factors. Soil erosion sensitivity increased with increasing rainfall and slope, and the percentage of the area with high soil erosion sensitivity was the largest at elevation 200-500 meters. The overlapping and ordering method was a practicable approach in identifying the key affecting factors in given sensitive areas, being helpful to understand the mechanisms causing soil erosion.

  4. ION COMPOSITION ELUCIDATION (ICE)

    EPA Science Inventory



    Ion Composition Elucidation (ICE) utilizes selected ion recording with a double focusing mass spectrometer to simultaneously determine exact masses and relative isotopic abundances from mass peak profiles. These can be determined more accurately and at higher sensitivity ...

  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.

  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.

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

    PubMed Central

    Tofighi, Shahram; Teymourzadeh, Ehsan; Heydari, Majid

    2017-01-01

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

  8. Plant NF-Y transcription factors: Key players in plant-microbe interactions, root development and adaptation to stress.

    PubMed

    Zanetti, María Eugenia; Rípodas, Carolina; Niebel, Andreas

    2017-05-01

    NF-Ys are heterotrimeric transcription factors composed by the NF-YA, NF-YB and NF-YC subunits. In plants, NF-Y subunits are encoded by multigene families whose members show structural and functional diversifications. An increasing number of NF-Y genes has been shown to play key roles during different stages of root nodule and arbuscular mycorrhizal symbiosis, as well as during the interaction of plants with pathogenic microorganisms. Individual members of the NF-YA and NF-YB families have also been implicated in the development of primary and lateral roots. In addition, different members of the NF-YA and NF-YB gene families from mono- and di-cotyledonous plants have been involved in plant responses to water and nutrient scarcity. This review presents the most relevant and striking results concerning these NF-Y subunits. A phylogenetic analysis of the functionally characterized NF-Y genes revealed that, across plant species, NF-Y proteins functioning in the same biological process tend to belong to common phylogenetic groups. Finally, we discuss the forthcoming challenges of plant NF-Y research, including the detailed dissection of expression patterns, the elucidation of functional specificities as well as the characterization of the potential NF-Y-mediated epigenetic mechanisms by which they control the expression of their target genes. This article is part of a Special Issue entitled: Nuclear Factor Y in Development and Disease, edited by Prof. Roberto Mantovani. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Elucidating the role of the FoxO3a transcription factor in the IGF-1-induced migration and invasion of uveal melanoma cancer cells.

    PubMed

    Yan, Fengxia; Liao, Rifang; Farhan, Mohd; Wang, Tinghuai; Chen, Jiashu; Wang, Zhong; Little, Peter J; Zheng, Wenhua

    2016-12-01

    Uveal melanoma (UM) is the most common primary intraocular malignant tumor of adults. It has high mortality rate due to liver metastasis. However, the epidemiology and pathogenesis of liver metastasis in UM are not elucidated and there is no effective therapy available for preventing the development of this disease. IGF-1 is a growth factor involved in cell proliferation, malignant transformation and inhibition of apoptosis. In previous report, IGF-1 receptor was found to be highly expressed in UM and this was related to tumor prognosis. FoxO3a is a Forkhead box O (FOXO) transcription factor and a downstream target of the IGF-1R/PI3K/Akt pathway involved in a number of physiological and pathological processes including cancer. However, the role of FoxO3a in UM is unknown. In the present study, we investigated fundamental mechanisms in the growth, migration and invasion of UM and the involvement of FoxO3a. IGF-1 increased the cell viability, invasion, migration and S-G2/M cell cycle phase accumulation of UM cells. Western blot analysis showed that IGF-1 led to activation of Akt and concomitant phosphorylation of FoxO3a. FoxO3a phosphorylation was associated with its translocation into the cytoplasm from the nucleus and its functional inhibition led to the inhibition of expression of Bim and p27, but an increase in the expression of Cyclin D1. The effects of IGF-1 on UM cells were reversed by LY294002 (a PI3K inhibitor) or Akt siRNA, and the overexpression of FoxO3a also attenuated basal invasion and migration of UM. Taken all together, these results suggest that inhibition of FoxO3a by IGF-1 via the PI3K/Akt pathway has an important role in IGF-1 induced proliferation and invasion of UM cells. These findings also support FoxO3a and IGF signaling may represent a valid target for investigating the development of new strategies for the treatment and prevention of the pathology of UM. Copyright © 2016. Published by Elsevier Masson SAS.

  10. 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

    2013-04-19

    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.

  11. 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.

  12. 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

  13. Lifestyle of Chinese centenarians and their key beneficial factors in Chongqing, China.

    PubMed

    Li, Yu; Bai, Yang; Tao, Qing-liu; Zeng, Huan; Han, Ling-li; Luo, Ming-yu; Zhang, Na; Zhong, Xiao-ni; Xie, Yao-jie; Zhao, Yong

    2014-01-01

    This study aims to describe the lifestyle of Chinese centenarians and to identify the beneficial factors that are correlated to their longevity. A census-based survey was conducted among centenarians in Chongqing, Southwest China, to identify the lifestyle factors affecting their health. From screening identification cards, 878 centenarians (age range 100-117, mean 102) were identified and interviewed. The survey indicated that 64% centenarians were able to take care of themselves. The majority of centenarians were nonsmokers (92%) and non-drinkers (83%). No significant difference was observed between urban and rural distributions (Χ2=0.939, p=0.625). Moreover, 43% centenarians maintained a regular diet, and only 33% had a sedentary lifestyle. A nutritious diet, adequate physical exercise, and a harmonious family environment may be the key lifestyle factors for their longevity of centenarians in Chongqing. These observations might be helpful in designing health promotion and welfare strategies for the elderly.

  14. 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

  15. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Growth differentiation factor 5 is a key physiological regulator of dendrite growth during development.

    PubMed

    Osório, Catarina; Chacón, Pedro J; Kisiswa, Lilian; White, Matthew; Wyatt, Sean; Rodríguez-Tébar, Alfredo; Davies, Alun M

    2013-12-01

    Dendrite size and morphology are key determinants of the functional properties of neurons. Here, we show that growth differentiation factor 5 (GDF5), a member of the bone morphogenetic protein (BMP) subclass of the transforming growth factor β superfamily with a well-characterised role in limb morphogenesis, is a key regulator of the growth and elaboration of pyramidal cell dendrites in the developing hippocampus. Pyramidal cells co-express GDF5 and its preferred receptors, BMP receptor 1B and BMP receptor 2, during development. In culture, GDF5 substantially increased dendrite, but not axon, elongation from these neurons by a mechanism that depends on activation of SMADs 1/5/8 and upregulation of the transcription factor HES5. In vivo, the apical and basal dendritic arbours of pyramidal cells throughout the hippocampus were markedly stunted in both homozygous and heterozygous Gdf5 null mutants, indicating that dendrite size and complexity are exquisitely sensitive to the level of endogenous GDF5 synthesis.

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

    PubMed

    Ylipää, Antti; Yli-Harja, Olli; Zhang, Wei; Nykter, Matti

    2011-01-01

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

  18. 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.

  19. 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.

  20. 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

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

    PubMed

    Park, YoHan; Park, YoungHo

    2016-12-14

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

  2. Astragaloside IV ameliorates allergic inflammation by inhibiting key initiating factors in the initial stage of sensitization

    PubMed Central

    Bao, Kai-fan; Yu, Xi; Wei, Xiao; Gui, Li-li; Liu, Hai-liang; Wang, Xiao-yu; Tao, Yu; Jiang, Guo-rong; Hong, Min

    2016-01-01

    To illuminate the anti-allergy mechanism of astragaloside IV (AS-IV), we assessed its effects in a murine model of allergic contact dermatitis (ACD). AS-IV administered in the sensitization phase, rather than in the elicitation phase, dramatically alleviated the symptoms of allergic inflammation. We hypothesized that AS-IV exerts its anti-allergy effects by regulating the production of key pro-allergic cytokines based on the fact that interleukin (IL)-33 and thymic stromal lymphopoietin (TSLP) levels increase significantly in the initial stage of the sensitization phase. AS-IV administered in the initial stage of ACD inhibited TSLP and IL-33 expression and reduced the proportion of type-2 innate lymphoid cells (ILC2s). An in vitro study showed that the production of pro-allergic cytokines was significantly inhibited in AS-IV presenting HaCaT cells. We also verified that AS-IV administered only in the initial stage markedly alleviated inflammation, including ear swelling, Th2 cytokine expression, and histological changes. Taken together, these results suggest that AS-IV effectively ameliorates the progression of allergic inflammation by inhibiting key initiating factors, including TSLP and IL-33, and can be used to prevent and/or treat patients with ACD. Our data also suggest that these key pro-allergic cytokines are potential therapeutic targets for allergic diseases. PMID:27917896

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

    PubMed Central

    Park, YoHan; Park, YoungHo

    2016-01-01

    Secure communication is a significant issue in wireless sensor networks. User authentication and key agreement are essential for providing a secure system, especially in user-oriented mobile services. It is also necessary to protect the identity of each individual in wireless environments to avoid personal privacy concerns. Many authentication and key agreement schemes utilize a smart card in addition to a password to support security functionalities. However, these schemes often fail to provide security along with privacy. In 2015, Chang et al. analyzed the security vulnerabilities of previous schemes and presented the two-factor authentication scheme that provided user privacy by using dynamic identities. However, when we cryptanalyzed Chang et al.’s scheme, we found that it does not provide sufficient security for wireless sensor networks and fails to provide accurate password updates. This paper proposes a security-enhanced authentication and key agreement scheme to overcome these security weaknesses using biometric information and an elliptic curve cryptosystem. We analyze the security of the proposed scheme against various attacks and check its viability in the mobile environment. PMID:27983616

  4. Available nitrogen is the key factor influencing soil microbial functional gene diversity in tropical rainforest.

    PubMed

    Cong, Jing; Liu, Xueduan; Lu, Hui; Xu, Han; Li, Yide; Deng, Ye; Li, Diqiang; Zhang, Yuguang

    2015-08-20

    Tropical rainforests cover over 50% of all known plant and animal species and provide a variety of key resources and ecosystem services to humans, largely mediated by metabolic activities of soil microbial communities. A deep analysis of soil microbial communities and their roles in ecological processes would improve our understanding on biogeochemical elemental cycles. However, soil microbial functional gene diversity in tropical rainforests and causative factors remain unclear. GeoChip, contained almost all of the key functional genes related to biogeochemical cycles, could be used as a specific and sensitive tool for studying microbial gene diversity and metabolic potential. In this study, soil microbial functional gene diversity in tropical rainforest was analyzed by using GeoChip technology. Gene categories detected in the tropical rainforest soils were related to different biogeochemical processes, such as carbon (C), nitrogen (N) and phosphorus (P) cycling. The relative abundance of genes related to C and P cycling detected mostly derived from the cultured bacteria. C degradation gene categories for substrates ranging from labile C to recalcitrant C were all detected, and gene abundances involved in many recalcitrant C degradation gene categories were significantly (P < 0.05) different among three sampling sites. The relative abundance of genes related to N cycling detected was significantly (P < 0.05) different, mostly derived from the uncultured bacteria. The gene categories related to ammonification had a high relative abundance. Both canonical correspondence analysis and multivariate regression tree analysis showed that soil available N was the most correlated with soil microbial functional gene structure. Overall high microbial functional gene diversity and different soil microbial metabolic potential for different biogeochemical processes were considered to exist in tropical rainforest. Soil available N could be the key factor in shaping the

  5. 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. Copyright © 2013 Elsevier Inc. All rights reserved.

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

    NASA Astrophysics Data System (ADS)

    Sanchez-Campos, Teodoro

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

  7. Fibroblast growth factor 2 is a key determinant of vascular sprouting during bovine luteal angiogenesis.

    PubMed

    Woad, Kathryn J; Hunter, Morag G; Mann, George E; Laird, Mhairi; Hammond, Amanda J; Robinson, Robert S

    2012-01-01

    Fibroblast growth factor (FGF) 2 and vascular endothelial growth factor (VEGF) A are thought to be key controllers of luteal angiogenesis; however, their precise roles in the regulation and coordination of this complex process remain unknown. Thus, the temporal and spatial patterns of endothelial network formation were determined by culturing mixed cell types from early bovine corpora lutea on fibronectin in the presence of FGF2 and VEGFA (6 h to 9 days). Endothelial cells, as determined by von Willebrand factor immunohistochemistry, initially grew in cell islands (days 0-3), before undergoing a period of vascular sprouting to display a more tubule-like appearance (days 3-6), and after 9 days in culture had formed extensive intricate networks. Mixed populations of luteal cells were treated with SU1498 (VEGF receptor 2 inhibitor) or SU5402 (FGF receptor 1 inhibitor) or control on days 0-3, 3-6 or 6-9 to determine the role of FGF2 and VEGFA during these specific windows. The total area of endothelial cells was unaffected by SU1498 treatment during any window. In contrast, SU5402 treatment caused maximal reduction in the total area of endothelial cell networks on days 3-6 vs controls (mean reduction 81%; P<0.001) during the period of tubule initiation. Moreover, SU5402 treatment on days 3-6 dramatically reduced the total number of branch points (P<0.001) and degree of branching per endothelial cell island (P<0.05) in the absence of changes in mean island area. This suggests that FGF2 is a key determinant of vascular sprouting and hence critical to luteal development.

  8. Effect of demographics on excretion of key urinary factors related to kidney stone risk

    PubMed Central

    Perinpam, Majuran; Ware, Erin B.; Smith, Jennifer A.; Turner, Stephen T.; Kardia, Sharon L.R.; Lieske, John C.

    2015-01-01

    Objective To investigate the effect of demographics including age and sex on excretion of four key urinary factors (calcium (Ca), magnesium (Mg), oxalate (Ox) and uric acid (UA)) related to kidney stone risk. Methods Twenty-four hour urine samples were collected from non-Hispanic white sibships in Rochester, MN. Height, weight, blood pressure, serum creatinine and cystatin C (CC) were measured. Diet was assessed using the Viocare food frequency questionnaire. Effects of demographics and dietary elements on urinary excretions were evaluated in univariate, multivariate, and interaction models that included age, sex, and body mass index (BMI). Results Samples were available from 709 individuals. In multivariate models, sex was a significant predictor of all four urinary factors, age was significant for all but UA excretion, and serum creatinine was significant only for Ca and Mg excretion (p<0.05). BMI or weight positively correlated with Mg, Ox and UA excretion (p<0.05). Use of a thiazide diuretic (lower) and dietary protein (higher) were associated with Ca excretion, while dietary Ca was associated with higher Mg excretion. Urinary UA excretion increased with animal protein intake and CC estimated glomerular filtration rate (eGFR), and was lower with concurrent loop diuretic use. Significant interaction effects on urinary UA excretion were observed for loop diuretic use and sex, eGFR and sex, age and animal protein intake, and BMI and eGFR (p<0.05). Conclusions Age and sex influence excretion of key urinary factors related to kidney stone risk, and should be taken into account when evaluating kidney stone patients. PMID:26206452

  9. Key factor in rice husk ash/CaO sorbent for high flue gas desulfurization activity

    SciTech Connect

    Irvan Dahlan; Keat Teong Lee; Azlina Harun Kamaruddin; Abdul Rahman Mohamed

    2006-10-01

    Siliceous materials such as rice husk ash (RHA) have potential to be utilized as high performance sorbents for the flue gas desulfurization process in small-scale industrial boilers. This study presents findings on identifying the key factor for high desulfurization activity in sorbents prepared from RHA. Initially, a systematic approach using central composite rotatable design was used to develop a mathematical model that correlates the sorbent preparation variables to the desulfurization activity of the sorbent. The sorbent preparation variables studied are hydration period, x{sub 1} (6-16 h), amount of RHA, x{sub 2} (5-15 g), amount of CaO, x{sub 3} (2-6 g), amount of water, x{sub 4} (90-110 mL), and hydration temperature, x{sub 5} (150-250{sup o}C). The mathematical model developed was subjected to statistical tests and the model is adequate for predicting the SO{sub 2} desulfurization activity of the sorbent within the range of the sorbent preparation variables studied. Based on the model, the amount of RHA, amount of CaO, and hydration period used in the preparation step significantly influenced the desulfurization activity of the sorbent. The ratio of RHA and CaO used in the preparation mixture was also a significant factor that influenced the desulfurization activity of the sorbent. A RHA to CaO ratio of 2.5 leads to the formation of specific reactive species in the sorbent that are believed to be the key factor responsible for high desulfurization activity in the sorbent. Other physical properties of the sorbent such as pore size distribution and surface morphology were found to have insignificant influence on the desulfurization activity of the sorbent. 31 refs., 5 figs., 3 tabs.

  10. 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

  11. Identification of guanine exchange factor key residues involved in exchange activity and Ras interaction.

    PubMed

    Camus, C; Hermann-Le Denmat, S; Jacquet, M

    1995-09-07

    We have carried out a functional analysis of the human HGRF55 exchange factor in the yeast Saccharomyces cerevisiae. Twelve residues conserved among most of all known guanine exchange factors (GEFs) have been independently changed to alanine. Taking advantage of the ability of Hgrf55p to replace the yeast Cdc25p exchange factor, and using the two-hybrid system with RAS2ala22 allele, we have identified key residues for the interaction with Ras and/or its activation. Substitution of arginine 392 to alanine leads to a complete loss of interaction with Ras, though the protein remains stable. Substitution of Asp266 or Arg359 to alanine results in inactive proteins at 39 degrees C, still able however to interact with Ras. The other charged-to-alanine substitutions led to no detectable phenotype when present alone but most of them dramatically increased the temperature sensitive phenotype observed with [Asp266Ala] substitution. Surprisingly, the cysteine to alanine substitution in the highly conserved PCVPF/Y motif proved to be without effect, suggesting that the sulfhydryl group is not essential for stability or interaction with Ras.

  12. The plant RWP-RK transcription factors: key regulators of nitrogen responses and of gametophyte development.

    PubMed

    Chardin, Camille; Girin, Thomas; Roudier, François; Meyer, Christian; Krapp, Anne

    2014-10-01

    The plant specific RWP-RK family of transcription factors, initially identified in legumes and Chlamydomonas, are found in all vascular plants, green algae, and slime molds. These proteins possess a characteristic RWP-RK motif, which mediates DNA binding. Based on phylogenetic and domain analyses, we classified the RWP-RK proteins of six different species in two subfamilies: the NIN-like proteins (NLPs), which carry an additional PB1 domain at their C-terminus, and the RWP-RK domain proteins (RKDs), which are divided into three subgroups. Although, the functional analysis of this family is still in its infancy, several RWP-RK proteins have a key role in regulating responses to nitrogen availability. The nodulation-specific NIN proteins are involved in nodule organogenesis and rhizobial infection under nitrogen starvation conditions. Arabidopsis NLP7 in particular is a major player in the primary nitrate response. Several RKDs act as transcription factors involved in egg cell specification and differentiation or gametogenesis in algae, the latter modulated by nitrogen availability. Further studies are required to extend the general picture of the functional role of these exciting transcription factors.

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

    PubMed

    Via, Laura E; Tsytsykova, Alla V; Rajsbaum, Ricardo; Falvo, James V; Goldfeld, Anne E

    2012-01-01

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

  14. 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

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

    PubMed Central

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

    2013-01-01

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

  16. 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.

  17. Vascular endothelial growth factor and other angioglioneurins: key molecules in brain development and restoration.

    PubMed

    Lafuente, José Vicente; Ortuzar, Naiara; Bengoetxea, Harkaitz; Bulnes, Susana; Argandoña, Enrike G

    2012-01-01

    Angioneurines are a family of molecules that include vascular growth factors such as VEGF, neurotrophins such as BDNF, IGF-I, and Erythropoietin, among others. They affect both neural and vascular processes. Due to the fact that all of them act over glia, we propose the term angioglioneurins to name them. They play a key role in the neurogliovascular unit that represents the functional core maintaining BBB. Although delivery to CNS is still an unsolved problem nowadays, exogenous angioglioneurin administration represents a promising therapeutic strategy for many neurological pathologies due to their neurotrophic and neurogenic role. In brains, VEGF is produced by neurons and astrocytes in different stages and situation, binding to tyrosine kinase receptors and also to neuropilin family. This fact reinforces its key role in the cross talk between neural and vascular development and activity. Angioglioneurins described in this report might become an important therapeutic resource in CNS restoration, especially in pathologies as stroke or traumatic brain injury. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. 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.

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

    PubMed

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

    2013-12-02

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

  20. 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.

  1. Key factor in rice husk Ash/CaO sorbent for high flue gas desulfurization activity.

    PubMed

    Dahlan, Irvan; Lee, Keat Teong; Kamaruddin, Azlina Harun; Mohamed, Abdul Rahman

    2006-10-01

    Siliceous materials such as rice husk ash (RHA) have potential to be utilized as high performance sorbents for the flue gas desulfurization process in small-scale industrial boilers. This study presents findings on identifying the key factorfor high desulfurization activity in sorbents prepared from RHA. Initially, a systematic approach using central composite rotatable design was used to develop a mathematical model that correlates the sorbent preparation variables to the desulfurization activity of the sorbent. The sorbent preparation variables studied are hydration period, x1 (6-16 h), amount of RHA, x2 (5-15 g), amount of CaO, x3 (2-6 g), amount of water, x4 (90-110 mL), and hydration temperature, x5 (150-250 degrees C). The mathematical model developed was subjected to statistical tests and the model is adequate for predicting the SO2 desulfurization activity of the sorbent within the range of the sorbent preparation variables studied. Based on the model, the amount of RHA, amount of CaO, and hydration period used in the preparation step significantly influenced the desulfurization activity of the sorbent. The ratio of RHA and CaO used in the preparation mixture was also a significant factor that influenced the desulfurization activity of the sorbent. A RHA to CaO ratio of 2.5 leads to the formation of specific reactive species in the sorbent that are believed to be the key factor responsible for high desulfurization activity in the sorbent. Other physical properties of the sorbent such as pore size distribution and surface morphology were found to have insignificant influence on the desulfurization activity of the sorbent.

  2. Expression profiles of key transcription factors involved in lipid metabolism in Beijing-You chickens.

    PubMed

    Fu, R Q; Liu, R R; Zhao, G P; Zheng, M Q; Chen, J L; Wen, J

    2014-03-01

    Intramuscular fat (IMF) is a crucial factor for the meat quality of chickens. With the aim of studying the molecular mechanisms underlying IMF deposition in chickens, the expression profiles of five candidate transcription factors involved in lipid metabolism in several tissues were examined in Beijing-You (BJY) chickens at five ages (0, 4, 8, 14 and 20 wk). Results showed that accumulation of IMF in breast (IMFbr), thigh (IMFth) and abdominal fat weight increased significantly (P<0.01) after 8 wk. Accumulation of both IMFbr and IMFth from 8 to 14 wk exceeded that from 14 to 20 wk; IMFth was 4-7 times of IMFbr. As for the expression profiles of key transcription factors: 1) expression of C/EBPα and PPARγ in abdominal fat was significantly higher than that in breast and thigh muscles at all ages. The expression of C/EBPα was positively correlated with PPARγ in both breast and thigh muscles, which indicated that both C/EBPα and PPARγ promoted fat deposition and might act through a unified pathway; 2) the expression of SREBP-1 in 0, 4, and 8 wk in thigh muscle was significantly higher than that in breast; 3) expression of C/EBPβ at 4 and 8 wk was significantly higher than that at 14 and 20 wk; and it was positively correlated with IMFth and IMFbr from 0 to 8 wk; 4) expression of PPARα in breast and thigh muscles was significantly higher than that in abdominal fat. Taken together, all five transcription factors studied play roles in lipid metabolism in chickens with C/EBPα and PPARγ being important effectors.

  3. Hepatocyte growth factor plays a key role in insulin resistance-associated compensatory mechanisms.

    PubMed

    Araújo, Tiago G; Oliveira, Alexandre G; Carvalho, Bruno M; Guadagnini, Dioze; Protzek, André O P; Carvalheira, Jose B C; Boschero, Antonio C; Saad, Mario J A

    2012-12-01

    Insulin resistance is present in obesity and in type 2 diabetes and is associated with islet cell hyperplasia and hyperinsulinemia, but the driving forces behind this compensatory mechanism are incompletely understood. Previous data have suggested the involvement of an unknown circulating insulin resistance-related β-cell growth factor. In this context, looking for candidates to be a circulating factor, we realized that hepatocyte growth factor (HGF) is a strong candidate as a link between insulin resistance and increased mass of islets/hyperinsulinemia. Our approach aimed to show a possible cause-effect relationship between increase in circulating HGF levels and compensatory islet hyperplasia/hyperinsulinemia by showing the strength of the association, whether or not is a dose-dependent response, the temporality, consistency, plausibility, and reversibility of the association. In this regard, our data showed: 1) a strong and consistent correlation between HGF and the compensatory mechanism in three animal models of insulin resistance; 2) HGF increases β-cell mass in a dose-dependent manner; 3) blocking HGF shuts down the compensatory mechanisms; and 4) an increase in HGF levels seems to precede the compensatory response associated with insulin resistance, indicating that these events occur in a sequential mode. Additionally, blockages of HGF receptor (Met) worsen the impaired insulin-induced insulin signaling in liver of diet-induced obesity rats. Overall, our data indicate that HGF is a growth factor playing a key role in islet mass increase and hyperinsulinemia in diet-induced obesity rats and suggest that the HGF-Met axis may have a role on insulin signaling in the liver.

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

    SciTech Connect

    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. - Highlights: • One-week selective reduction of gluco- and lipo-toxicity in db/db mice was performed. • Selective glucotoxicity reduction increases key pancreatic β-cell factors expression. • Selective glucotoxicity reduction improves β-cell factors over pretreatment levels. • Selective glucotoxicity reduction turns β-cell mass toward increase. • Lipotoxicity reduction has additive effects on glucotoxicity reduction.

  5. Public/private partners. Key factors in creating a strategic alliance for community health.

    PubMed

    Nelson, J C; Rashid, H; Galvin, V G; Essien, J D; Levine, L M

    1999-04-01

    The rapidly evolving American health system creates economic and societal incentives for public and private health organizations to collaborate. Despite the apparent benefits of collaboration, there is a paucity of information available to help local agencies develop partnerships. This study, itself a collaboration between a school of public health (SPH) and a Georgia health district, was undertaken to identify critical factors necessary to successfully initiate and sustain a public/private community health collaboration. Professional staff at the SPH conducted 26 standardized interviews involving participants from Cobb and Douglas counties Boards of Health; Promina Northwest (now known as Wellstar), a not-for-profit health system; and community stakeholders. Content analysis of each interview question was performed and comparisons were made both within each group and across groups. Trends were identified in the following key areas: vision of health care for Cobb and Douglas counties, forces driving collaboration, strengths of each organization, critical negotiating issues, and potential community gain resulting from the partnership. A shared vision between potential collaborators facilitates communication regarding strategies to achieve common goals. A previous history of working together in limited capacities allowed the partners to develop trust and respect for one another prior to entering negotiations. These factors, when taken in conjunction with each organization's strong leadership and knowledge of the community, build a strong foundation for a successful partnership.

  6. Tissue Factor–Factor VII Complex As a Key Regulator of Ovarian Cancer Phenotypes

    PubMed Central

    Koizume, Shiro; Miyagi, Yohei

    2015-01-01

    Tissue factor (TF) is an integral membrane protein widely expressed in normal human cells. Blood coagulation factor VII (fVII) is a key enzyme in the extrinsic coagulation cascade that is predominantly secreted by hepatocytes and released into the bloodstream. The TF–fVII complex is aberrantly expressed on the surface of cancer cells, including ovarian cancer cells. This procoagulant complex can initiate intracellular signaling mechanisms, resulting in malignant phenotypes. Cancer tissues are chronically exposed to hypoxia. TF and fVII can be induced in response to hypoxia in ovarian cancer cells at the gene expression level, leading to the autonomous production of the TF–fVII complex. Here, we discuss the roles of the TF–fVII complex in the induction of malignant phenotypes in ovarian cancer cells. The hypoxic nature of ovarian cancer tissues and the roles of TF expression in endometriosis are discussed. Arguments will be extended to potential strategies to treat ovarian cancers based on our current knowledge of TF–fVII function. PMID:26396550

  7. Successful collaboration between occupational health service providers and client companies: Key factors.

    PubMed

    Schmidt, Lisa; Sjöström, John; Antonsson, Ann-Beth

    2015-06-05

    Occupational health services (OHS) are often described as an important resource to reduce work-related diseases and improve the workplace. This paper identifies key factors for successful collaboration between Swedish OHS providers and their client companies. Interviews were carried out with representatives of 15 companies and their OHS providers. The interviews were transcribed and their content analyzed. The results revealed that successful collaboration was highly correlated with six factors. First, the collaboration depends on both parties; ``it takes two to tango''. Second, the company and the OHS provider have a joint commitment to a long-term collaboration. Third, the collaboration is built on frequent contact at different organizational levels. Fourth, the company has a well-structured work environment for occupational health and safety management. Fifth, the OHS provider uses a consultative approach in its prevention and promotion activities. Finally, OHS providers seek to treat the company, not the individual. Our research indicates that a successful collaboration requires both occupational health and safety management (OHSM) within the company and the assistance of a competent OHS provider. A change toward more promotion and prevention services benefits the company, since the occupational health services are better tailored to the company's needs.

  8. Uncertainty about effects is a key factor influencing institutional review boards' approval of clinical studies.

    PubMed

    Wao, Hesborn; Mhaskar, Rahul; Kumar, Ambuj; Miladinovic, Branko; Guterbock, Thomas; Hozo, Iztok; Djulbegovic, Benjamin

    2014-10-01

    To investigate factors, which influence institutional review boards' (IRBs') decision to approve or not approve clinical studies, a nationwide vignette-based online survey of IRB members was conducted. A factorial design was used, whereby seven aspects of each hypothetical study were randomly varied in 15 phrases in each vignette to produce unique vignettes. Participants indicated the degree of study approval and described factors influencing approval decision. Qualitative responses were thematically content analyzed. Sixteen themes were obtained from 208 participants from 42 institutions. Uncertainty, adherence, study design, and harms were frequently and intensely cited to influence study approval. Analysis of two extreme subgroups (approvers vs. nonapprovers) showed that uncertainty influenced approval decisions, odds ratios (OR) = 3.5 (95% confidence interval [CI], 1.3-9.8) and OR = 3.2 (95% CI, 1.1-8.9), respectively, based on theme frequency and theme intensity, ignoring multiple observations per person. Taking into consideration multiple observations per person, similar results were obtained for uncertainty: OR = 8.9 (95% CI, 0.93-85.4). Perceived uncertainty about benefits and harms of a proposed intervention is a key driver in IRB members' approval of clinical trials. This, in turn, calls for improved standardization in the communications of information on benefits and harms in the research protocols considered by the IRBs. Published by Elsevier Inc.

  9. SOX9 modulates the expression of key transcription factors required for heart valve development.

    PubMed

    Garside, Victoria C; Cullum, Rebecca; Alder, Olivia; Lu, Daphne Y; Vander Werff, Ryan; Bilenky, Mikhail; Zhao, Yongjun; Jones, Steven J M; Marra, Marco A; Underhill, T Michael; Hoodless, Pamela A

    2015-12-15

    Heart valve formation initiates when endothelial cells of the heart transform into mesenchyme and populate the cardiac cushions. The transcription factor SOX9 is highly expressed in the cardiac cushion mesenchyme, and is essential for heart valve development. Loss of Sox9 in mouse cardiac cushion mesenchyme alters cell proliferation, embryonic survival, and valve formation. Despite this important role, little is known about how SOX9 regulates heart valve formation or its transcriptional targets. Therefore, we mapped putative SOX9 binding sites by ChIP-Seq in E12.5 heart valves, a stage at which the valve mesenchyme is actively proliferating and initiating differentiation. Embryonic heart valves have been shown to express a high number of genes that are associated with chondrogenesis, including several extracellular matrix proteins and transcription factors that regulate chondrogenesis. Therefore, we compared regions of putative SOX9 DNA binding between E12.5 heart valves and E12.5 limb buds. We identified context-dependent and context-independent SOX9-interacting regions throughout the genome. Analysis of context-independent SOX9 binding suggests an extensive role for SOX9 across tissues in regulating proliferation-associated genes including key components of the AP-1 complex. Integrative analysis of tissue-specific SOX9-interacting regions and gene expression profiles on Sox9-deficient heart valves demonstrated that SOX9 controls the expression of several transcription factors with previously identified roles in heart valve development, including Twist1, Sox4, Mecom and Pitx2. Together, our data identify SOX9-coordinated transcriptional hierarchies that control cell proliferation and differentiation during valve formation. © 2015. Published by The Company of Biologists Ltd.

  10. 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.

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

    PubMed

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

    2017-02-01

    Recovery of e-waste in China had caused serious pollutions. Eddy current separation is an environment-friendly technology of separating nonferrous metallic particles from crushed e-waste. However, due to complex particle characters, separation efficiency of traditional eddy current separator was low. In production, controllable operation factors of eddy current separation are feeding speed, (ωR-v), and Sp. There is little special information about influencing mechanism and critical parameters of these factors in eddy current separation. This paper provided the special information of these key factors in eddy current separation of recovering aluminum particles from crushed waste refrigerator cabinets. Detachment angles increased as the increase of (ωR-v). Separation efficiency increased with the growing of detachment angles. Aluminum particles were completely separated from plastic particles in critical parameters of feeding speed 0.5m/s and detachment angles greater than 6.61deg. Sp/Sm of aluminum particles in crushed waste refrigerators ranged from 0.08 to 0.51. Separation efficiency increased as the increase of Sp/Sm. This enlightened us to develop new separator to separate smaller nonferrous metallic particles in e-waste recovery. High feeding speed destroyed separation efficiency. However, greater Sp of aluminum particles brought positive impact on separation efficiency. Greater Sp could increase critical feeding speed to offer greater throughput of eddy current separation. This paper will guide eddy current separation in production of recovering nonferrous metals from crushed e-waste. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Myocardial ischemia is a key factor in the management of stable coronary artery disease

    PubMed Central

    Iwasaki, Kohichiro

    2014-01-01

    Previous studies demonstrated that coronary revascularization, especially percutaneous coronary intervention (PCI), does not significantly decrease the incidence of cardiac death or myocardial infarction in patients with stable coronary artery disease. Many studies using myocardial perfusion imaging (MPI) showed that, for patients with moderate to severe ischemia, revascularization is the preferred therapy for survival benefit, whereas for patients with no to mild ischemia, medical therapy is the main choice, and revascularization is associated with increased mortality. There is some evidence that revascularization in patients with no or mild ischemia is likely to result in worsened ischemia, which is associated with increased mortality. Studies using fractional flow reserve (FFR) demonstrate that ischemia-guided PCI is superior to angiography-guided PCI, and the presence of ischemia is the key to decision-making for PCI. Complementary use of noninvasive MPI and invasive FFR would be important to compensate for each method’s limitations. Recent studies of appropriateness criteria showed that, although PCI in the acute setting and coronary bypass surgery are properly performed in most patients, PCI in the non-acute setting is often inappropriate, and stress testing to identify myocardial ischemia is performed in less than half of patients. Also, some studies suggested that revascularization in an inappropriate setting is not associated with improved prognosis. Taken together, the presence and the extent of myocardial ischemia is a key factor in the management of patients with stable coronary artery disease, and coronary revascularization in the absence of myocardial ischemia is associated with worsened prognosis. PMID:24772253

  13. 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.

  14. Gremlin is a Key Pro-fibrogenic Factor in Chronic Pancreatitis

    PubMed Central

    Xu, Meihua; Feng, Xueping; Aronson, Judith F.; Falzon, Miriam; Greeley, George H.; Rastellini, Cristiana; Chao, Celia; Hellmich, Mark R.; Cao, Yanna; Ko, Tien C.

    2016-01-01

    The current study aims to identify the pro-fibrogenic role of Gremlin, an endogenous antagonist of bone morphogenetic proteins (BMPs) in chronic pancreatitis (CP). CP is a highly debilitating disease characterized by progressive pancreatic inflammation and fibrosis that ultimately leads to exocrine and endocrine dysfunction. While transforming growth factor (TGF)-β is a known key pro-fibrogenic factor in CP, the TGF-β superfamily members BMPs exert an anti-fibrogenic function in CP reported by our group recently. To investigate how BMP signaling is regulated in CP by BMP antagonists, the mouse CP model induced by cerulein was used. During CP induction, TGF-β1 mRNA increased 156-fold in two weeks, a BMP antagonist Gremlin 1 (Grem1) mRNA levels increased 145-fold at three weeks, and increases in Grem1 protein levels correlated with increases in collagen deposition. Increased Grem1 was also observed in human CP pancreata compared to normal. Grem1 knockout in Grem1+/− mice revealed a 33.2% reduction in pancreatic fibrosis in CP compared to wild-type littermates. In vitro in isolated pancreatic stellate cells, TGF-β induced Grem1 expression. Addition of the recombinant mouse Grem1 protein blocked BMP2-induced Smad1/5 phosphorylation and abolished BMP2's suppression effects on TGF-β-induced collagen expression. Evidences presented herein demonstrate that Grem1, induced by TGF-β, is pro-fibrogenic by antagonizing BMP activity in CP. PMID:26141517

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

    PubMed

    Strzalka, Wojciech; Ziemienowicz, Alicja

    2011-05-01

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

  16. Key factors in the design of a LED volumetric 3D display system

    NASA Astrophysics Data System (ADS)

    Lin, Yuanfang; Liu, Xu; Yao, Yi; Zhang, Xiaojie; Liu, Xiangdong; Lin, Fengchun

    2005-01-01

    Through careful consideration of key factors that impact upon voxel attributes and image quality, a volumetric three-dimensional (3D) display system employing the rotation of a two-dimensional (2D) thin active panel was developed. It was designed as a lower-cost 3D visualization platform for experimentation and demonstration. Light emitting diodes (LEDs) were arranged into a 256x64 dot matrix on a single surface of the panel, which was positioned symmetrically about the axis of rotation. The motor and necessary supporting structures were located below the panel. LEDs individually of 500 ns response time, 1.6 mm×0.8 mm×0.6 mm external dimensions, 0.38 mm×0.43 mm horizontal and vertical spacing were adopted. The system is functional, providing 512×256×64, i.e. over 8 million addressable voxels within a 292 mm×165 mm cylindrical volume at a refresh frequency in excess of 16 Hz. Due to persistence of vision, momentarily addressed voxels will be perceived and fused into a 3D image. Many static or dynamic 3D scenes were displayed, which can be directly viewed from any position with few occlusion zones and dead zones. Important depth cues like binocular disparity and motion parallax are satisfied naturally.

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

    PubMed

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

    2014-07-01

    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. © International & American Associations for Dental Research.

  18. Quartz dustiness: A key factor in controlling exposure to crystalline silica in the workplace.

    PubMed

    López-Lilao, A; Escrig, A; Orts, M J; Mallol, Gustavo; Monfort, E

    2016-11-01

    The classification of Respirable Crystalline Silica (RCS) as carcinogenic for humans has drawn greater attention to crystalline silica exposure in the workplace in recent years, leading to recommendations by safety and health bodies in Europe and the U.S. for lower occupational exposure limits. In view of this new scenario, the present study examined quartz dustiness, as quartz handling is a major source of crystalline silica in the workplace. The study was conducted on test samples with different mean particle sizes, prepared from several commercial quartzes. The quartz particle samples were characterised and the influence of certain quartz particle parameters on quartz dustiness was determined. The results indicate that quartz dustiness may be significantly affected by mean particle size, specific surface area, the Hausner ratio, and fine particle content. The study shows that, in order to minimise the adverse health effects associated with the inhalation of crystalline silica, quartz dustiness may be deemed a key factor in controlling the generation of fugitive quartz emissions during quartz processing, both into the outside atmosphere (air pollution) and inside the facilities (occupational health).

  19. Key factors determining the efficacy of gene therapy for continuous DOPA delivery in the Parkinsonian brain.

    PubMed

    Cederfjäll, Erik; Sahin, Gurdal; Kirik, Deniz

    2012-11-01

    L-DOPA is currently the standard treatment for alleviating the motor symptoms in Parkinson's disease. The therapeutic efficacy, however, diminishes as the disease progresses. It has been suggested that the beneficial effect of L-DOPA could be reestablished by changing the mode of administration. Indeed, continuous delivery of l-DOPA has been shown to be an effective way to circumvent many of the side effects seen with traditional oral administration, which results in an intermittent supply of the dopamine precursor to the brain. However, all currently tested continuous dopaminergic stimulation approaches rely on peripheral administration. This is not ideal since it gives rise to off target effects and is difficult to maintain long-term. Thus, there is an unmet need for an effective continuous administration method with an acceptable side effect profile. Viral-mediated gene therapy is a promising alternative paradigm that can meet this demand. Encouraging preclinical studies in animal models of Parkinson's disease showed therapeutic efficacy after expression of the genes encoding the enzymes required for biosynthesis of dopamine. Although the first phase I clinical trials using these approaches have been conducted, clear positive data in placebo controlled efficacy studies is still lacking. We are now at a critical junction and need to carefully review the preclinical data from the clinical translation perspective and identify the key factors that will determine the potential for success in gene therapy for Parkinson's disease.

  20. Components of breeding productivity in a marine bird community: key factors and concordance

    USGS Publications Warehouse

    Hatch, Scott A.; Hatch, Martha A.

    1990-01-01

    We estimated components of annual breeding productivity for eight species of marine birds on the Semidi Islands in the western Gulf of Alaska. Mortality of eggs and young, caused primarily by avian predators, accounted for most of the annual variation in productivity. Failure to produce eggs, clutch size variation, and the hatchability of eggs were generally less important. The stage of breeding at which annual productivity was most strongly regulated differed among species. In murres, chick-rearing success accounted for the largest share of annual variation in overall productivity, whereas incubation success was the key factor in fulmars, kittiwakes, and puffins. Although avian predators were the dominant proximate cause of egg and chick losses in some species, food supply seemed ultimately responsible for variation in all the major components of productivity. Concordance of productivity among species was low for the marine bird community as a whole, but selected pairs of species exhibited a greater tendency for high and low productivities to occur in the same years. Compared with the same or similar species outside Alaska, Semidi Islands birds were in one of three categories: (i) species whose productivity was about the same as reported from other areas (fulmars and gulls), (ii) species with comparatively low productivity (murres, puffins, kittiwakes), and (iii) species with similar mean productivity but greater annual variation (cormorants). These patterns suggest that specialized consumers of forage fish experienced food shortages at the Semidi Islands and that surface feeders were more severely affected than divers.

  1. Inactivation of key factors of the plasma proteinase cascade systems by Bacteroides gingivalis.

    PubMed Central

    Nilsson, T; Carlsson, J; Sundqvist, G

    1985-01-01

    The effect of Bacteroides gingivalis W83 on various key components of the human plasma proteinase cascade systems was studied. When purified C1-inhibitor was incubated with the bacterium, the inhibitor was rapidly inactivated by limited proteolytic cleavage. In citrated whole plasma, C1-inhibitor, antithrombin, plasminogen, prekallikrein, prothrombinase complex, the clotting factor X, and most of the alpha 2-antiplasmin were functionally eliminated after 30 min of incubation with the bacterium. Fibrinogen disappeared from the plasma almost immediately upon mixing with the bacterial suspension. In contrast, there was no appreciable decrease in the bulk of other plasma proteins, such as various transport proteins (albumin, prealbumin, transferrin) and immunoglobulins, during 4 h of incubation with the bacterium. Most of the observed effects can be assigned to the proteolytic activity of the bacterium itself, since there was little evidence for generation of intrinsic plasma proteinase activity, despite the loss of proteinase inhibitory activities. B. gingivalis W83 thus seems to be equipped with proteolytic enzyme systems which selectively recognize and rapidly inactivate the most important proteinase inhibitors and proenzymes present in human plasma. This bacterium therefore seems to be able to efficiently paralyze the host's various defenses against invading microorganisms. Images PMID:3902645

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

    PubMed

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

    2017-08-05

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

  3. 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.

  4. Small molecule modulators of eukaryotic initiation factor 2α kinases, the key regulators of protein synthesis.

    PubMed

    Joshi, Manali; Kulkarni, Abhijeet; Pal, Jayanta K

    2013-11-01

    Eukaryotic initiation factor 2 alpha kinases (eIF-2α kinases) are key mediators of stress response in cells. In mammalian cells, there are four eIF-2α kinases, namely HRI (Heme-Regulated Inhibitor), PKR (RNA-dependent Protein Kinase), PERK (PKR-like ER Kinase) and GCN2 (General Control Non-derepressible 2). These kinases get activated during diverse cytoplasmic stress conditions and phosphorylate the alpha-subunit of eIF2, leading to global protein synthesis inhibition. Therefore, eIF-2α kinases play a vital role in various cellular processes such as proliferation, differentiation, apoptosis and cell signaling. Deregulation of eIF-2α kinases and protein synthesis has been linked to numerous pathological conditions such as certain cancers, anemia and neurodegenerative disorders. Thus, modulation of these kinases by small molecules holds a great therapeutic promise. In this review we have compiled the available information on inhibitors and activators of these four eIF-2α kinases. The review concludes with a note on the selectivity issue of currently available modulators and future perspectives for the design of specific small molecule probes.

  5. 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.

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

    PubMed

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

    2008-10-15

    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 BRE(u) 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.

  7. The gut microbiota: A key factor in the therapeutic effects of (poly)phenols.

    PubMed

    Espín, Juan Carlos; González-Sarrías, Antonio; Tomás-Barberán, Francisco A

    2017-09-01

    (Poly)phenols (PPs) constitute a large family of phytochemicals with high chemical diversity that are known to be active principles of plant-derived nutraceuticals and herbal medicinal products. Their pharmacological activity, however, is difficult to demonstrate due to their mild physiological effects, and to the large inter-individual variability observed. Many PPs have little bioavailability and reach the colon almost unaltered. There they encounter the gut microbes resulting in a two-way interaction in which PPs modulate the gut microbiota composition, and the intestinal microbes catabolize the ingested PPs to release metabolites that are often more active and better absorbed than the native phenolic compounds. The type and quantity of the PP metabolites produced in humans depend on the gut microbiota composition and function, and different metabotypes have been identified. However, not all the metabolites have the same biological activity, and therefore the final health effects of dietary PPs depend on the gut microbiota composition. Stratification in clinical trials according to individuals' metabotypes is necessary to fully understand the health effects of PPs. In this review, we present and discuss the most significant and updated knowledge regarding the reciprocal interrelation of the gut microbiota with dietary PPs as a key factor that modulates the health effects of these compounds. The review will focus in those PPs that are known to be metabolized by gut microbiota resulting in bioactive metabolites. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Mechanisms of fertilization elucidated by gene-manipulated animals.

    PubMed

    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.

  9. 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…

  10. 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…

  11. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    NASA Astrophysics Data System (ADS)

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

    2008-01-01

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

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

    PubMed Central

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

    2017-01-01

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

  14. 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

  15. Phytochrome C is a key factor controlling long-day flowering in barley.

    PubMed

    Nishida, Hidetaka; Ishihara, Daisuke; Ishii, Makoto; Kaneko, Takuma; Kawahigashi, Hiroyuki; Akashi, Yukari; Saisho, Daisuke; Tanaka, Katsunori; Handa, Hirokazu; Takeda, Kazuyoshi; Kato, Kenji

    2013-10-01

    The spring-type near isogenic line (NIL) of the winter-type barley (Hordeum vulgare ssp. vulgare) var. Hayakiso 2 (HK2) was developed by introducing VERNALIZATION-H1 (Vrn-H1) for spring growth habit from the spring-type var. Indo Omugi. Contrary to expectations, the spring-type NIL flowered later than winter-type HK2. This phenotypic difference was controlled by a single gene, which cosegregated only with phytochrome C (HvPhyC) among three candidates around the Vrn-H1 region (Vrn-H1, HvPhyC, and CASEIN KINASE IIα), indicating that HvPhyC was the most likely candidate gene. Compared with the late-flowering allele HvPhyC-l from the NIL, the early-flowering allele HvPhyC-e from HK2 had a single nucleotide polymorphism T1139C in exon 1, which caused a nonsynonymous amino acid substitution of phenylalanine at position 380 by serine in the functionally essential GAF (3', 5'-cyclic-GMP phosphodiesterase, adenylate cyclase, formate hydrogen lyase activator protein) domain. Functional assay using a rice (Oryza sativa) phyA phyC double mutant line showed that both of the HvPhyC alleles are functional, but HvPhyC-e may have a hyperfunction. Expression analysis using NILs carrying HvPhyC-e and HvPhyC-l (NIL [HvPhyC-e] and NIL [HvPhyC-l], respectively) showed that HvPhyC-e up-regulated only the flowering promoter FLOWERING LOCUS T1 by bypassing the circadian clock genes and flowering integrator CONSTANS1 under a long photoperiod. Consistent with the up-regulation, NIL (HvPhyC-e) flowered earlier than NIL (HvPhyC-l) under long photoperiods. These results implied that HvPhyC is a key factor to control long-day flowering directly.

  16. 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

  17. Lipid shape is a key factor for membrane interactions of amphipathic helical peptides.

    PubMed

    Strandberg, Erik; Tiltak, Deniz; Ehni, Sebastian; Wadhwani, Parvesh; Ulrich, Anne S

    2012-07-01

    The membrane alignment of the amphiphilic alpha-helical model peptide MSI-103 (sequence [KIAGKIA]3-NH2) was examined by solid state 2H-NMR in different lipid systems by systematically varying the acyl chain length and degree of saturation, the lipid head group type, and the peptide-to-lipid molar ratio. In liquid crystalline phosphatidylcholine (PC) lipids with saturated chains, the amphiphilic helix changes its orientation from a surface-bound "S-state" to a tilted "T-state" with increasing peptide concentration. In PC lipids with unsaturated chains, on the other hand, the S-state is found throughout all concentrations. Using phosphatidylethanolamine lipids with a small head group or by addition of lyso-lipids with only one acyl chain, the spontaneous curvature of the bilayer was purposefully changed. In the first case with a negative curvature only the S-state was found, whereas in systems with a positive curvature the peptide preferred the obliquely immersed T-state at high concentration. The orientation of MSI-103 thus correlates very well with the shape of the lipid molecules constituting the membrane. Lipid charge, on the other hand, was found to affect only the initial electrostatic attraction to the membrane surface but not the alignment preferences. In bilayers that are "sealed" with 20% cholesterol, MSI-103 cannot bind in a well-oriented manner and forms immobilized aggregates instead. We conclude that the curvature properties of a membrane are a key factor in the interactions of amphiphilic helical peptides in general, whose re-alignment and immersion preferences may thus be inferred in a straightforward manner from the lipid-shape concept.

  18. Interlocking of chelae is a key factor for dominance hierarchy formation in crayfish.

    PubMed

    Ueno, Ryusuke; Nagayama, Toshiki

    2012-08-15

    We characterized the role of chelae during agonistic encounters of the crayfish Procambarus clarkii. Physical asymmetries in body length, body mass and chelae size were directly related to dominance hierarchy formation. More than 80% of winning crayfish had longer body and chelae lengths, and winners were usually heavier in body mass, even if their differences were less than 3% compared with losing opponents. In mismatched pairings, large crayfish with short chelae were beaten by small crayfish with large chelae. Three physical elements of body length, body mass and chelae length equally affected the outcome of agonistic bouts. Chelae restriction, in which chelae were tightly closed using rubber bands, affected the outcome of agonistic bouts between large and small crayfish. Before chelae restriction, large crayfish won in all pairings. Following chelae restriction for at least 30 days from the first encounters, the winning rate of large crayfish that were previous winners decreased significantly in the second encounters against the same opponents that were previous losers. The handicap of chelae restriction significantly prolonged the time to formation of the winner-loser relationship. Individual fights escalated during agonistic bouts between large crayfish with one chela restricted and small crayfish with intact chelae, whereas the number of fights increased but the duration of individual fights did not increase in large crayfish with both chelae restricted. Furthermore, when the chelae of both large and small crayfish were disabled, the dominance order was frequently not formed during 30 min of agonistic bouts. Preventing chelae from interlocking prevented escalation of agonistic bouts. We show that interlocking of chelae acted as a key factor for the formation of dominance hierarchy.

  19. 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

  20. Gremlin is a key pro-fibrogenic factor in chronic pancreatitis.

    PubMed

    Staloch, Dustin; Gao, Xuxia; Liu, Ka; Xu, Meihua; Feng, Xueping; Aronson, Judith F; Falzon, Miriam; Greeley, George H; Rastellini, Cristiana; Chao, Celia; Hellmich, Mark R; Cao, Yanna; Ko, Tien C

    2015-10-01

    The current study aims to identify the pro-fibrogenic role of Gremlin, an endogenous antagonist of bone morphogenetic proteins (BMPs) in chronic pancreatitis (CP). CP is a highly debilitating disease characterized by progressive pancreatic inflammation and fibrosis that ultimately leads to exocrine and endocrine dysfunction. While transforming growth factor (TGF)-β is a known key pro-fibrogenic factor in CP, the TGF-β superfamily member BMPs exert an anti-fibrogenic function in CP as reported by our group recently. To investigate how BMP signaling is regulated in CP by BMP antagonists, the mouse CP model induced by cerulein was used. During CP induction, TGF-β1 messenger RNA (mRNA) increased 156-fold in 2 weeks, a BMP antagonist Gremlin 1 (Grem1) mRNA levels increased 145-fold at 3 weeks, and increases in Grem1 protein levels correlated with increases in collagen deposition. Increased Grem1 was also observed in human CP pancreata compared to normal. Grem1 knockout in Grem1 (+/-) mice revealed a 33.2 % reduction in pancreatic fibrosis in CP compared to wild-type littermates. In vitro in isolated pancreatic stellate cells, TGF-β induced Grem1 expression. Addition of the recombinant mouse Grem1 protein blocked BMP2-induced Smad1/5 phosphorylation and abolished BMP2's suppression effects on TGF-β-induced collagen expression. Evidences presented herein demonstrate that Grem1, induced by TGF-β, is pro-fibrogenic by antagonizing BMP activity in CP. • Gremlin is upregulated in human chronic pancreatitis and a mouse CP model in vivo. • Deficiency of Grem1 in mice attenuates pancreatic fibrosis under CP induction in vivo. • TGF-β induces Gremlin mRNA and protein expression in pancreatic stellate cells in vitro. • Gremlin blocks BMP2 signaling and function in pancreatic stellate cells in vitro. • This study discloses a pro-fibrogenic role of Gremlin by antagonizing BMP activity in chronic pancreatitis.

  1. Regulation and Function of Cdt1; A Key Factor in Cell Proliferation and Genome Stability

    PubMed Central

    Pozo, Pedro N.; Cook, Jeanette Gowen

    2016-01-01

    Successful cell proliferation requires efficient and precise genome duplication followed by accurate chromosome segregation. The Cdc10-dependent transcript 1 protein (Cdt1) is required for the first step in DNA replication, and in human cells Cdt1 is also required during mitosis. Tight cell cycle controls over Cdt1 abundance and activity are critical to normal development and genome stability. We review here recent advances in elucidating Cdt1 molecular functions in both origin licensing and kinetochore–microtubule attachment, and we describe the current understanding of human Cdt1 regulation. PMID:28025526

  2. Distributed Factorization Computation on Multiple Volunteered Mobile Resource to Break RSA Key

    NASA Astrophysics Data System (ADS)

    Jaya, I.; Hardi, S. M.; Tarigan, J. T.; Zamzami, E. M.; Sihombing, P.

    2017-01-01

    Similar to common asymmeric encryption, RSA can be cracked by usmg a series mathematical calculation. The private key used to decrypt the massage can be computed using the public key. However, finding the private key may require a massive amount of calculation. In this paper, we propose a method to perform a distributed computing to calculate RSA’s private key. The proposed method uses multiple volunteered mobile devices to contribute during the calculation process. Our objective is to demonstrate how the use of volunteered computing on mobile devices may be a feasible option to reduce the time required to break a weak RSA encryption and observe the behavior and running time of the application on mobile devices.

  3. The Polyadenylation Factor Subunit CLEAVAGE AND POLYADENYLATION SPECIFICITY FACTOR30: A Key Factor of Programmed Cell Death and a Regulator of Immunity in Arabidopsis1[W

    PubMed Central

    Bruggeman, Quentin; Garmier, Marie; de Bont, Linda; Soubigou-Taconnat, Ludivine; Mazubert, Christelle; Benhamed, Moussa; Raynaud, Cécile; Bergounioux, Catherine; Delarue, Marianne

    2014-01-01

    Programmed cell death (PCD) is essential for several aspects of plant life, including development and stress responses. Indeed, incompatible plant-pathogen interactions are well known to induce the hypersensitive response, a localized cell death. Mutational analyses have identified several key PCD components, and we recently identified the mips1 mutant of Arabidopsis (Arabidopsis thaliana), which is deficient for the key enzyme catalyzing the limiting step of myoinositol synthesis. One of the most striking features of mips1 is the light-dependent formation of lesions on leaves due to salicylic acid (SA)-dependent PCD, revealing roles for myoinositol or inositol derivatives in the regulation of PCD. Here, we identified a regulator of plant PCD by screening for mutants that display transcriptomic profiles opposing that of the mips1 mutant. Our screen identified the oxt6 mutant, which has been described previously as being tolerant to oxidative stress. In the oxt6 mutant, a transfer DNA is inserted in the CLEAVAGE AND POLYADENYLATION SPECIFICITY FACTOR30 (CPSF30) gene, which encodes a polyadenylation factor subunit homolog. We show that CPSF30 is required for lesion formation in mips1 via SA-dependent signaling, that the prodeath function of CPSF30 is not mediated by changes in the glutathione status, and that CPSF30 activity is required for Pseudomonas syringae resistance. We also show that the oxt6 mutation suppresses cell death in other lesion-mimic mutants, including lesion-simulating disease1, mitogen-activated protein kinase4, constitutive expressor of pathogenesis-related genes5, and catalase2, suggesting that CPSF30 and, thus, the control of messenger RNA 3′ end processing, through the regulation of SA production, is a key component of plant immune responses. PMID:24706550

  4. 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.

  5. Phytochrome C Is A Key Factor Controlling Long-Day Flowering in Barley1[W

    PubMed Central

    Nishida, Hidetaka; Ishihara, Daisuke; Ishii, Makoto; Kaneko, Takuma; Kawahigashi, Hiroyuki; Akashi, Yukari; Saisho, Daisuke; Tanaka, Katsunori; Handa, Hirokazu; Takeda, Kazuyoshi; Kato, Kenji

    2013-01-01

    The spring-type near isogenic line (NIL) of the winter-type barley (Hordeum vulgare ssp. vulgare) var. Hayakiso 2 (HK2) was developed by introducing VERNALIZATION-H1 (Vrn-H1) for spring growth habit from the spring-type var. Indo Omugi. Contrary to expectations, the spring-type NIL flowered later than winter-type HK2. This phenotypic difference was controlled by a single gene, which cosegregated only with phytochrome C (HvPhyC) among three candidates around the Vrn-H1 region (Vrn-H1, HvPhyC, and CASEIN KINASE IIα), indicating that HvPhyC was the most likely candidate gene. Compared with the late-flowering allele HvPhyC-l from the NIL, the early-flowering allele HvPhyC-e from HK2 had a single nucleotide polymorphism T1139C in exon 1, which caused a nonsynonymous amino acid substitution of phenylalanine at position 380 by serine in the functionally essential GAF (3′, 5′-cyclic-GMP phosphodiesterase, adenylate cyclase, formate hydrogen lyase activator protein) domain. Functional assay using a rice (Oryza sativa) phyA phyC double mutant line showed that both of the HvPhyC alleles are functional, but HvPhyC-e may have a hyperfunction. Expression analysis using NILs carrying HvPhyC-e and HvPhyC-l (NIL [HvPhyC-e] and NIL [HvPhyC-l], respectively) showed that HvPhyC-e up-regulated only the flowering promoter FLOWERING LOCUS T1 by bypassing the circadian clock genes and flowering integrator CONSTANS1 under a long photoperiod. Consistent with the up-regulation, NIL (HvPhyC-e) flowered earlier than NIL (HvPhyC-l) under long photoperiods. These results implied that HvPhyC is a key factor to control long-day flowering directly. PMID:24014575

  6. 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.

  7. Real-time imaging elucidates the role of H2O2 in regulating kinetics of epidermal growth factor-induced and Src-mediated tyrosine phosphorylation signaling

    NASA Astrophysics Data System (ADS)

    Su, Ting; Li, Xiangyong; Liu, Nisha; Pan, Shaotao; Lu, Jinling; Yang, Jie; Zhang, Zhihong

    2012-07-01

    Reversible oxidation is emerging as an important regulatory mechanism in protein tyrosine phosphorylation. Generation of hydrogen peroxide (H2O2), upon growth factor stimulation, is hypothesized to inhibit activity of protein tyrosine phosphatases (PTPs). This ensures that protein tyrosine kinases can elevate the steady-state level of protein tyrosine phosphorylation, which then allows propagation of the tyrosine phosphorylation signal. However, the effects of H2O2 on the kinetics of tyrosine phosphorylation signaling remain poorly understood, especially in living cells. Therefore, we used a genetically encoded Src kinase-specific biosensor based on fluorescence resonance energy transfer (FRET) to image the kinetics of the Src-mediated tyrosine phosphorylation signaling (Src signaling) induced by epidermal growth factor (EGF). We examined the kinetics under increased and decreased H2O2 levels. Through a straightforward, quantitative analysis method which characterized the signaling kinetics, we demonstrated that H2O2 modulated the amplitude and duration of the signal by inhibiting PTPs' activity. Our evidence also suggested the effect of H2O2 on Src activation is mediated by H2O2-dependent inhibition of PTPs. Furthermore, we provide evidence showing global elevation of intracellular H2O2 level attenuates EGF-induced Src signaling.

  8. 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,…

  9. 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…

  10. 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,…

  11. 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…

  12. Role of Education in Rural Development: A Key Factor for Developing Countries.

    ERIC Educational Resources Information Center

    Navaratnam, Kathiravelu K.

    Relevent, locally-controlled educational programs play key roles in rural development in developing nations. Education has a desirable controlling influence over development of the rural individual, family, community, and society, leading to reduced poverty, income equity, and controlled unemployment. The failure of trickle-down development and…

  13. 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…

  14. Drug packaging. A key factor to be taken into account when choosing a treatment.

    PubMed

    2011-10-01

    A drug's packaging contributes to its harm-benefit balance. Highlighting the key practical information and identifying potential sources of error or mix-ups is part and parcel of the correct use of medicines. Select labelling that clearly and prominently displays the important information, including the international nonproprietary name (INN).

  15. 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…

  16. A comparison study on detection of key geochemical variables and factors through three different types of factor analysis

    NASA Astrophysics Data System (ADS)

    Hoseinzade, Zohre; Mokhtari, Ahmad Reza

    2017-10-01

    Large numbers of variables have been measured to explain different phenomena. Factor analysis has widely been used in order to reduce the dimension of datasets. Additionally, the technique has been employed to highlight underlying factors hidden in a complex system. As geochemical studies benefit from multivariate assays, application of this method is widespread in geochemistry. However, the conventional protocols in implementing factor analysis have some drawbacks in spite of their advantages. In the present study, a geochemical dataset including 804 soil samples collected from a mining area in central Iran in order to search for MVT type Pb-Zn deposits was considered to outline geochemical analysis through various fractal methods. Routine factor analysis, sequential factor analysis, and staged factor analysis were applied to the dataset after opening the data with (additive logratio) alr-transformation to extract mineralization factor in the dataset. A comparison between these methods indicated that sequential factor analysis has more clearly revealed MVT paragenesis elements in surface samples with nearly 50% variation in F1. In addition, staged factor analysis has given acceptable results while it is easy to practice. It could detect mineralization related elements while larger factor loadings are given to these elements resulting in better pronunciation of mineralization.

  17. Polycythaemia-inducing mutations in the erythropoietin receptor (EPOR): mechanism and function as elucidated by epidermal growth factor receptor-EPOR chimeras.

    PubMed

    Gross, Mor; Ben-Califa, Nathalie; McMullin, Mary F; Percy, Melanie J; Bento, Celeste; Cario, Holger; Minkov, Milen; Neumann, Drorit

    2014-05-01

    Primary familial and congenital polycythaemia (PFCP) is a disease characterized by increased red blood cell mass, and can be associated with mutations in the intracellular region of the erythropoietin (EPO) receptor (EPOR). Here we explore the mechanisms by which EPOR mutations induce PFCP, using an experimental system based on chimeric receptors between epidermal growth factor receptor (EGFR) and EPOR. The design of the chimeras enabled EPOR signalling to be triggered by EGF binding. Using this system we analysed three novel EPOR mutations discovered in PFCP patients: a deletion mutation (Del1377-1411), a nonsense mutation (C1370A) and a missense mutation (G1445A). Three different chimeras, bearing these mutations in the cytosolic, EPOR region were generated; Hence, the differences in the chimera-related effects are specifically attributed to the mutations. The results show that the different mutations affect various aspects related to the signalling and metabolism of the chimeric receptors. These include slower degradation rate, higher levels of glycan-mature chimeric receptors, increased sensitivity to low levels of EGF (replacing EPO in this system) and extended signalling cascades. This study provides a novel experimental system to study polycythaemia-inducing mutations in the EPOR, and sheds new light on underlying mechanisms of EPOR over-activation in PFCP patients.

  18. Elucidation of the time course of adenosine deaminase APOBEC3G and viral infectivity factor vif in HIV-2287-infected infant macaques

    PubMed Central

    Endsley, Aaron N.; Ho, Rodney J.Y.

    2012-01-01

    Background Although the interactions of cellular cytidine deaminase A3G and viral infection factor (vif) of human immunodeficiency virus (HIV) were reported, regulation of A3G after in vivo HIV infection and disease progression is not known. Methods Time courses of plasma virus, CD4+ T lymphocyte Macaca levels, and concentrations of A3G and vif transcripts were determined in infant macaques infected with HIV-2287. These in vivo results were compared with those collected in vitro in HIV-2-infected T cells. Results Human immunodeficiency virus-infected macaques exhibited plasma viremia (≥108 copies/ml) followed by a precipitous CD4+ T-cell (from 40–70 to ≤5%) decline. An initial increase in A3G transcripts coincides with early increases in virus and vif RNA. As virus load continues to increase, A3G RNA decreases but recovers at a later phase as virus level stabilizes. Pearson correlation analysis revealed strong interactions of A3G–CD4, vif–CD4, and A3G–vif. Conclusions There is a time-dependent A3G and vif RNA interaction throughout the course of HIV infection. PMID:22017399

  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. Selenoproteins: the key factor in selenium essentiality. State of the art analytical techniques for selenoprotein studies.

    PubMed

    Lopez Heras, Isabel; Palomo, Maria; Madrid, Yolanda

    2011-06-01

    Selenium is an essential element for human health. The benefits of selenium are many including protection against cancer, heart diseases and other cardiovascular and muscle disorders. Selenium is also helpful in controlling gastrointestinal disorders, enhancing immunity of the human body and reducing age-related diseases. The health-promoting properties of Se are due to vital functions of selenoproteins in which selenium is present as selenocysteine, the 21st amino acid. To date, dozens of selenoprotein families have been described though many have roles that have not been fully elucidated. Selenoproteins research has attracted tremendous interest from different scientific areas. Analytical chemists have not remained indifferent to the attractive features of these unique proteins. Different analytical techniques, such as multidimensional chromatography-inductively coupled plasma mass spectrometry (ICPMS), electrospray (tandem) mass spectrometry (ESI-MS/MS), matrix-assisted laser desorption ionization time-of flight (MALDI-TOF) and sodium dodecyl sulphate polyacrylamide gel electrophoresis-laser ablation inductively coupled plasma mass spectrometry (SDS-PAGE-LA-ICPMS), have been applied to the determination of selenoproteins and selenium-containing proteins. This review describes the best-characterized selenoproteins to date in addition to the major contributions of analytical chemistry to the field of selenoproteins. The article also highlights the challenges of combining elemental and molecular mass spectrometry for the determination of selenoproteins and selenium-containing proteins.

  1. Perceived key injury risk factors in World Cup alpine ski racing—an explorative qualitative study with expert stakeholders

    PubMed Central

    Spörri, Jörg; Kröll, Josef; Amesberger, Günter; Blake, Ollie M; Müller, Erich

    2012-01-01

    Background There is limited knowledge about key injury risk factors in alpine ski racing, particularly for World Cup (WC) athletes. Objective This study was undertaken to compile and explore perceived intrinsic and extrinsic risk factors for severe injuries in WC alpine ski racing. Methods Qualitative study. Interviews were conducted with 61 expert stakeholders of the WC ski racing community. Experts’ statements were collected, paraphrased and loaded into a database with inductively derived risk factor categories (Risk Factor Analysis). At the end of the interviews, experts were asked to name those risk factors they believed to have a high potential impact on injury risk and to rank them according to their priority of impact (Risk Factor Rating). Results In total, 32 perceived risk factors categories were derived from the interviews within the basic categories Athlete, Course, Equipment and Snow. Regarding their perceived impact on injury risk, the experts’ top five categories were: system ski, binding, plate and boot; changing snow conditions; physical aspects of the athletes; speed and course setting aspects and speed in general. Conclusions Severe injuries in WC alpine ski racing can have various causes. This study compiled a list of perceived intrinsic and extrinsic risk factors and explored those factors with the highest believed impact on injury risk. Hence, by using more detailed hypotheses derived from this explorative study, further studies should verify the plausibility of these factors as true risk factors for severe injuries in WC alpine ski racing. PMID:22872684

  2. 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.…

  3. 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:…

  4. 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:…

  5. Pan-Genomic Analysis Permits Differentiation of Virulent and Non-virulent Strains of Xanthomonas arboricola That Cohabit Prunus spp. and Elucidate Bacterial Virulence Factors.

    PubMed

    Garita-Cambronero, Jerson; Palacio-Bielsa, Ana; López, María M; Cubero, Jaime

    2017-01-01

    Xanthomonas arboricola is a plant-associated bacterial species that causes diseases on several plant hosts. One of the most virulent pathovars within this species is X. arboricola pv. pruni (Xap), the causal agent of bacterial spot disease of stone fruit trees and almond. Recently, a non-virulent Xap-look-a-like strain isolated from Prunus was characterized and its genome compared to pathogenic strains of Xap, revealing differences in the profile of virulence factors, such as the genes related to the type III secretion system (T3SS) and type III effectors (T3Es). The existence of this atypical strain arouses several questions associated with the abundance, the pathogenicity, and the evolutionary context of X. arboricola on Prunus hosts. After an initial characterization of a collection of Xanthomonas strains isolated from Prunus bacterial spot outbreaks in Spain during the past decade, six Xap-look-a-like strains, that did not clustered with the pathogenic strains of Xap according to a multi locus sequence analysis, were identified. Pathogenicity of these strains was analyzed and the genome sequences of two Xap-look-a-like strains, CITA 14 and CITA 124, non-virulent to Prunus spp., were obtained and compared to those available genomes of X. arboricola associated with this host plant. Differences were found among the genomes of the virulent and the Prunus non-virulent strains in several characters related to the pathogenesis process. Additionally, a pan-genomic analysis that included the available genomes of X. arboricola, revealed that the atypical strains associated with Prunus were related to a group of non-virulent or low virulent strains isolated from a wide host range. The repertoire of the genes related to T3SS and T3Es varied among the strains of this cluster and those strains related to the most virulent pathovars of the species, corylina, juglandis, and pruni. This variability provides information about the potential evolutionary process associated to the

  6. Pan-Genomic Analysis Permits Differentiation of Virulent and Non-virulent Strains of Xanthomonas arboricola That Cohabit Prunus spp. and Elucidate Bacterial Virulence Factors

    PubMed Central

    Garita-Cambronero, Jerson; Palacio-Bielsa, Ana; López, María M.; Cubero, Jaime

    2017-01-01

    Xanthomonas arboricola is a plant-associated bacterial species that causes diseases on several plant hosts. One of the most virulent pathovars within this species is X. arboricola pv. pruni (Xap), the causal agent of bacterial spot disease of stone fruit trees and almond. Recently, a non-virulent Xap-look-a-like strain isolated from Prunus was characterized and its genome compared to pathogenic strains of Xap, revealing differences in the profile of virulence factors, such as the genes related to the type III secretion system (T3SS) and type III effectors (T3Es). The existence of this atypical strain arouses several questions associated with the abundance, the pathogenicity, and the evolutionary context of X. arboricola on Prunus hosts. After an initial characterization of a collection of Xanthomonas strains isolated from Prunus bacterial spot outbreaks in Spain during the past decade, six Xap-look-a-like strains, that did not clustered with the pathogenic strains of Xap according to a multi locus sequence analysis, were identified. Pathogenicity of these strains was analyzed and the genome sequences of two Xap-look-a-like strains, CITA 14 and CITA 124, non-virulent to Prunus spp., were obtained and compared to those available genomes of X. arboricola associated with this host plant. Differences were found among the genomes of the virulent and the Prunus non-virulent strains in several characters related to the pathogenesis process. Additionally, a pan-genomic analysis that included the available genomes of X. arboricola, revealed that the atypical strains associated with Prunus were related to a group of non-virulent or low virulent strains isolated from a wide host range. The repertoire of the genes related to T3SS and T3Es varied among the strains of this cluster and those strains related to the most virulent pathovars of the species, corylina, juglandis, and pruni. This variability provides information about the potential evolutionary process associated to the

  7. 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.

  8. A sensitivity analysis of key natural factors in the modeled global acetone budget

    NASA Astrophysics Data System (ADS)

    Brewer, J. F.; Bishop, M.; Kelp, M.; Keller, C. A.; Ravishankara, A. R.; Fischer, E. V.

    2017-02-01

    Acetone is one of the most abundant carbonyl compounds in the atmosphere, and it serves as an important source of HOx (OH + HO2) radicals in the upper troposphere and a precursor for peroxyacetyl nitrate. We present a global sensitivity analysis targeted at several major natural source and sink terms in the global acetone budget to find the input factor or factors to which the simulated acetone mixing ratio was most sensitive. The ranges of input factors were taken from literature. We calculated the influence of these factors in terms of their elementary effects on model output. Of the six factors tested here, the four factors with the highest contribution to total global annual model sensitivity are direct emissions of acetone from the terrestrial biosphere, acetone loss to photolysis, the concentration of acetone in the ocean mixed layer, and the dry deposition of acetone to ice-free land. The direct emissions of acetone from the terrestrial biosphere are globally important in determining acetone mixing ratios, but their importance varies seasonally outside the tropics. Photolysis is most influential in the upper troposphere. Additionally, the influence of the oceanic mixed layer concentrations are relatively invariant between seasons, compared to the other factors tested. Monoterpene oxidation in the troposphere, despite the significant uncertainties in acetone yield in this process, is responsible for only a small amount of model uncertainty in the budget analysis.

  9. 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

  10. 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.

  11. [Key influencing factors on essential oil components of Atractylodes lancea and study on its division of climate adaptability].

    PubMed

    Guo, Lan-Ping; Huang, Lu-Qi; Jiang, You-Xu; Liu, Xu-Long; Pan, Yao-Zhong; Lu, Dong-Mei; Zhang, Qing

    2007-05-01

    To find the key factors that influence the content of the essential oil components of Atractylodes lancea and classify the habitat of A. lancea based the essential oil components, as well as explore a new method to conduct division of Chinese natural medicin through geographic information system (GIS) ultimately. The key factors were obtained by canonical correlation and stepwise regressive analysis. Then the interpolation of climatic data for 30 years (1971-2000) was done by Sufer 7.0, and the habitat division was done by ARCGIS 9. 0. There were 6 correlation models between climate factors and 6 main essential oil componets were obtained, and a division map about essential oil components content of A. lancea base on clamate adaptability were drawn. It was found that the climate condition in Octobers played a key role on forming the essential oil components and the interaction of tempreture and precipitation was the most important factor on forming the essential oil components of A. lancea. The adaptive habitat for forming the essential oil components of A. lancea was different from growing A. lancea ones. And GIS can be used perspective for division of Chinese natural medicine.

  12. 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.

  13. An acoustic key to eight languages/dialects: Factor analyses of critical-band-filtered speech

    PubMed Central

    Ueda, Kazuo; Nakajima, Yoshitaka

    2017-01-01

    The peripheral auditory system functions like a frequency analyser, often modelled as a bank of non-overlapping band-pass filters called critical bands; 20 bands are necessary for simulating frequency resolution of the ear within an ordinary frequency range of speech (up to 7,000 Hz). A far smaller number of filters seemed sufficient, however, to re-synthesise intelligible speech sentences with power fluctuations of the speech signals passing through them; nevertheless, the number and frequency ranges of the frequency bands for efficient speech communication are yet unknown. We derived four common frequency bands—covering approximately 50–540, 540–1,700, 1,700–3,300, and above 3,300 Hz—from factor analyses of spectral fluctuations in eight different spoken languages/dialects. The analyses robustly led to three factors common to all languages investigated—the low & mid-high factor related to the two separate frequency ranges of 50–540 and 1,700–3,300 Hz, the mid-low factor the range of 540–1,700 Hz, and the high factor the range above 3,300 Hz—in these different languages/dialects, suggesting a language universal. PMID:28198405

  14. Binding Mode Analysis of Zerumbone to Key Signal Proteins in the Tumor Necrosis Factor Pathway

    PubMed Central

    Fatima, Ayesha; Abdul, Ahmad Bustamam Hj.; Abdullah, Rasedee; Karjiban, Roghayeh Abedi; Lee, Vannajan Sanghiran

    2015-01-01

    Breast cancer is the second most common cancer among women worldwide. Several signaling pathways have been implicated as causative and progression agents. The tumor necrosis factor (TNF) α protein plays a dual role in promoting and inhibiting cancer depending largely on the pathway initiated by the binding of the protein to its receptor. Zerumbone, an active constituent of Zingiber zerumbet, Smith, is known to act on the tumor necrosis factor pathway upregulating tumour necrosis factor related apoptosis inducing ligand (TRAIL) death receptors and inducing apoptosis in cancer cells. Zerumbone is a sesquiterpene that is able to penetrate into the hydrophobic pockets of proteins to exert its inhibiting activity with several proteins. We found a good binding with the tumor necrosis factor, kinase κB (IKKβ) and the Nuclear factor κB (NF-κB) component proteins along the TNF pathway. Our results suggest that zerumbone can exert its apoptotic activities by inhibiting the cytoplasmic proteins. It inhibits the IKKβ kinase that activates the NF-κB and also binds to the NF-κB complex in the TNF pathway. Blocking both proteins can lead to inhibition of cell proliferating proteins to be downregulated and possibly ultimate induction of apoptosis. PMID:25629232

  15. 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.

  16. An acoustic key to eight languages/dialects: Factor analyses of critical-band-filtered speech.

    PubMed

    Ueda, Kazuo; Nakajima, Yoshitaka

    2017-02-15

    The peripheral auditory system functions like a frequency analyser, often modelled as a bank of non-overlapping band-pass filters called critical bands; 20 bands are necessary for simulating frequency resolution of the ear within an ordinary frequency range of speech (up to 7,000 Hz). A far smaller number of filters seemed sufficient, however, to re-synthesise intelligible speech sentences with power fluctuations of the speech signals passing through them; nevertheless, the number and frequency ranges of the frequency bands for efficient speech communication are yet unknown. We derived four common frequency bands-covering approximately 50-540, 540-1,700, 1,700-3,300, and above 3,300 Hz-from factor analyses of spectral fluctuations in eight different spoken languages/dialects. The analyses robustly led to three factors common to all languages investigated-the low &mid-high factor related to the two separate frequency ranges of 50-540 and 1,700-3,300 Hz, the mid-low factor the range of 540-1,700 Hz, and the high factor the range above 3,300 Hz-in these different languages/dialects, suggesting a language universal.

  17. 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

  18. 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

  19. Initiation and maintenance of a hospital-based parent group for parents of premature infants: key factors for success.

    PubMed

    Bracht, M; Ardal, F; Bot, A; Cheng, C M

    1998-04-01

    The impact of a premature birth can be very traumatic for parents. They are usually not prepared for this event, and their sense of grief and loss is so intense that they often have difficulty coping with the situation. A parent group can help parents adapt to the crisis of prematurity by providing information and family support. This article describes the development of a parent group at a regional perinatal center in Ontario and identifies key factors for its successful initiation and maintenance.

  20. Vitamin D Receptor Deficiency and Low Vitamin D Diet Stimulate Aortic Calcification and Osteogenic Key Factor Expression in Mice

    PubMed Central

    Schmidt, Nadine; Brandsch, Corinna; Kühne, Hagen; Thiele, Alexandra; Hirche, Frank; Stangl, Gabriele I.

    2012-01-01

    Low levels of 25-hydroxy vitamin D (25(OH)D) are associated with cardiovascular diseases. Herein, we tested the hypothesis that vitamin D deficiency could be a causal factor in atherosclerotic vascular changes and vascular calcification. Aortic root sections of vitamin D receptor knockout (VDR−/−) mice that were stained for vascular calcification and immunostained for osteoblastic differentiation factors showed more calcified areas and a higher expression of the osteogenic key factors Msx2, Bmp2, and Runx2 than the wild-type mice (P<0.01). Data from LDL receptor knockout (LDLR−/−) mice that were fed western diet with either low (50 IU/kg), recommended (1,000 IU/kg), or high (10,000 IU/kg) amounts of vitamin D3 over 16 weeks revealed increasing plasma concentrations of 25(OH)D (P<0.001) with increasing intake of vitamin D, whereas levels of calcium and phosphorus in plasma and femur were not influenced by the dietary treatment. Mice treated with the low vitamin D diet had more calcified lesions and a higher expression of Msx2, Bmp2, and Runx2 in aortic roots than mice fed recommended or high amounts of vitamin D (P<0.001). Taken together, these findings indicate vitamin D deficiency as a risk factor for aortic valve and aortic vessel calcification and a stimulator of osteogenic key factor expression in these vascular areas. PMID:22536373

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

    PubMed Central

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

    2014-01-01

    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

  2. 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

    2014-12-09

    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.

  3. Environmental Factors as Key Determinants for Visceral Leishmaniasis in Solid Organ Transplant Recipients, Madrid, Spain

    PubMed Central

    López-Medrano, Francisco; Fernández-Ruiz, Mario; Carrillo, Eugenia; Moreno, Javier; García-Reyne, Ana; Pérez-Ayala, Ana; Rodríguez-Ferrero, María Luisa; Lumbreras, Carlos; San-Juan, Rafael; Alvar, Jorge; Aguado, José María

    2017-01-01

    During a visceral leishmaniasis outbreak in an area of Madrid, Spain, the incidence of disease among solid organ transplant recipients was 10.3% (7/68). Being a black person from sub-Saharan Africa, undergoing transplantation during the outbreak, and residing <1,000 m from the epidemic focus were risk factors for posttransplant visceral leishmaniasis. PMID:28628447

  4. Key factors influencing canine heartworm, Dirofilaria immitis, in the United States

    PubMed Central

    2012-01-01

    An examination of the Companion Animal Parasite Council’s (CAPC) canine heartworm data to clarify the spatial prevalence of heartworm in the United States. Factors thought to influence the spatial risk of disease, as identified in a recent CAPC workshop, are discussed. PMID:23111089

  5. 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…

  6. 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…

  7. 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…

  8. 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…

  9. 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…

  10. Identifying the Key Factors Affecting the Chance of Passing Vocational Education and Training Subjects

    ERIC Educational Resources Information Center

    John, David

    2004-01-01

    This report identifies student characteristics--demographic and life-stage factors--which influence successful completion of vocational education and training (VET) subjects. It finds the likelihood of passing is significantly reduced for people who are Indigenous, have a disability, are of non-English speaking background, are unemployed or are…

  11. 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.; Murray, Jessica R.; Pollitz, Fred F.; Langbein, John O.; Svarc, Jerry L.; Schwartz, David P.; Ponti, Daniel J.; Hecker, Suzanne; DeLong, Stephen B.; Rosa, Carla M.; Jones, Brenda; Lamb, Rynn M.; Rosinski, Anne M.; McCrink, Timothy P.; Dawson, Timothy E.; Seitz, Gordon G.; 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.

  12. 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.

  13. KU80, a key factor for non-homologous end-joining, retards geminivirus multiplication.

    PubMed

    Richter, Kathrin S; Jeske, Holger

    2015-09-01

    KU80 is well-known as a key component of the non-homologous end-joining pathway used to repair DNA double-strand breaks. In addition, the KU80-containing DNA-dependent protein kinase complex in mammals can act as a cytoplasmic sensor for viral DNA to activate innate immune response. We have now, to our knowledge for the first time, demonstrated that the speed of a systemic infection with a plant DNA geminivirus in Arabidopsis thaliana is KU80-dependent. The early emergence of Euphorbia yellow mosaic virus DNA was significantly increased in ku80 knockout mutants compared with wild-type sibling controls. The possible impact of KU80 on geminivirus multiplication by generating non-productive viral DNAs or its role as a pattern-recognition receptor against DNA virus infection is discussed.

  14. Transcriptome analyses identify key cellular factors associated with HIV-1 associated neuropathogenesis in infected men

    PubMed Central

    Venkatachari, Narasimhan J.; Jain, Siddhartha; Walker, Leah; Bivalkar-Mehla, Shalmali; Chattopadhyay, Ansuman; Bar-Joseph, Ziv; Rinaldo, Charles; Ragin, Ann; Seaberg, Eric; Levine, Andrew; Becker, James; Martin, Eileen; Sacktor, Ned; Ayyavoo, Velpandi

    2017-01-01

    Objective HIV-1 viral proteins and host inflammatory factors have a direct role in neuronal toxicity in in vitro, however, the contribution of these factors in vivo in HIV-1 associated neurocognitive disorder (HAND) is not fully understood. We applied novel Systems Biology approaches to identify specific cellular and viral factors and their related pathways that are associated with different stages of HAND. Design A cross-sectional study of individuals enrolled in the Multicenter AIDS Cohort Study (MACS) including HIV-1 seronegative (N=36) and HIV-1 seropositive individuals without neurocognitive symptoms (N=16), or with mild neurocognitive disorder (MND) (N=8) or HIV-associated dementia (HAD) (N=16). Methods A systematic evaluation of global transcriptome of peripheral blood mononuclear cells (PBMCs) obtained from HIV-1 seronegative individuals and from HIV-1 positive men without neurocognitive symptoms, or MND or HAD was performed. Results MND and HAD were associated with specific changes in mRNA transcripts and miRNAs in PBMCs. Comparison of upstream regulators and TimePath analyses identified specific cellular factors associated with MND and HAD, while HIV-1 viral proteins played a greater role in HAD. Additionally, expression of specific microRNAs – miR-let-7a, miR-124, miR-15a and others were found to correlate with mRNA gene expression and may have a potential protective role in asymptomatic HIV-1 seropositive individuals by regulating cellular signal transduction pathways downstream of chemokines and cytokines. Conclusions These results identify signature transcriptome changes in PBMCs associated with stages of HAND and shed light on the potential contribution of host cellular factors and viral proteins in HAND development. PMID:28005686

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. Patients' support for health information exchange: a literature review and classification of key factors.

    PubMed

    Esmaeilzadeh, Pouyan; Sambasivan, Murali

    2017-04-04

    Literature indicates that one of the most important factors affecting the widespread adoption of Health Information Exchange (HIE) is patient support and endorsement. In order to reap all the expected benefits of HIE, patients' acceptance of technology is a challenge that is not fully studied. There are a few studies which have focused on requirements of electronic medical information exchange from consumers' views and expectations. This study is aimed at reviewing the literature to articulate factors that affect patients to support HIE efforts. A literature review of current studies addressing patients' views on HIE from 2005 was undertaken. Five electronic research databases (Science Direct, PubMed, Web of Science, CINAHL, and Academic Search Premiere) were searched to retrieve articles reporting pros and cons of HIE from patients' opinion. One hundred and ninety six articles were initially retrieved from the databases. Out of 196, 36 studies met the inclusion criteria and were fully reviewed. Our findings indicate that patient's attitude toward HIE is affected by seven main factors: perceived benefits, perceived concerns, patient characteristics, patient participation level in HIE, type of health information, identity of recipients, and patient preferences regarding consent and features. The findings provide useful theoretical implications for research by developing a classification of significant factors and a framework based on the lessons learned from the literature to help guide HIE efforts. Our results also have fundamental practical implications for policy makers, current and potential organizers of HIEs by highlighting the role of patients in the widespread implementation of HIE. The study indicates that new approaches should be applied to completely underline HIE benefits for patients and also address their concerns.

  2. Tissue factor and tissue factor pathway inhibitor as key regulators of global hemostasis: measurement of their levels in coagulation assays.

    PubMed

    Kasthuri, Raj S; Glover, Sam L; Boles, Jeremiah; Mackman, Nigel

    2010-10-01

    The tissue factor (TF)/factor (F)VIIa complex is the primary initiator of coagulation in vivo. Tissue factor pathway inhibitor (TFPI) is the physiological inhibitor of the TF/FVIIa complex. Deficiencies of either TF or TFPI have not been reported in humans, and a complete absence of either of these two proteins in mice is embryonically lethal. To maintain normal hemostasis, levels of TF and TFPI need to be balanced. Increased levels of TF can overwhelm the inhibitory capacity of TFPI, resulting in thrombosis. Decreased levels of TF are associated with bleeding. Global assays of coagulation are defined as tests capable of evaluating all components of the clotting cascade that are present in plasma. In these tests the thrombogenic surface is either provided by platelets or exogenous phospholipids. Clotting assays currently used in clinical practice are not designed to measure endogenous levels of TF and TFPI. Therefore, there is a need to develop sensitive and specific assays for measuring levels of functional TF and TFPI in whole blood and plasma. These assays could be useful in patient management in many scenarios.

  3. Tissue Factor and Tissue Factor Pathway Inhibitor as Key Regulators of Global Hemostasis: Measurement of Their Levels in Coagulation Assays

    PubMed Central

    Kasthuri, Raj S.; Glover, Sam L.; Boles, Jeremiah; Mackman, Nigel

    2011-01-01

    The tissue factor (TF)/factor (F)VIIa complex is the primary initiator of coagulation in vivo. Tissue factor pathway inhibitor (TFPI) is the physiological inhibitor of the TF/FVIIa complex. Deficiencies of either TF or TFPI have not been reported in humans, and a complete absence of either of these two proteins in mice is embryonically lethal. To maintain normal hemostasis, levels of TF and TFPI need to be balanced. Increased levels of TF can overwhelm the inhibitory capacity of TFPI, resulting in thrombosis. Decreased levels of TF are associated with bleeding. Global assays of coagulation are defined as tests capable of evaluating all components of the clotting cascade that are present in plasma. In these tests the thrombogenic surface is either provided by platelets or exogenous phospholipids. Clotting assays currently used in clinical practice are not designed to measure endogenous levels of TF and TFPI. Therefore, there is a need to develop sensitive and specific assays for measuring levels of functional TF and TFPI in whole blood and plasma. These assays could be useful in patient management in many scenarios. PMID:20978997

  4. Patterns of justice involvement among adults with schizophrenia and bipolar disorder: key risk factors.

    PubMed

    Robertson, Allison G; Swanson, Jeffrey W; Frisman, Linda K; Lin, Hsiuju; Swartz, Marvin S

    2014-07-01

    Adults with serious mental illness have a relatively high risk of criminal justice involvement. Some risk factors for justice involvement are known, but the specific interaction of these risk factors has not been examined. This study explored the interaction of gender, substance use disorder, and psychiatric diagnosis among patients with schizophrenia or bipolar disorder to identify subgroups at higher risk of justice involvement. Administrative service records of 25,133 adults with schizophrenia or bipolar disorder who were clients of Connecticut's public behavioral health system during 2005-2007 were merged with state records of criminal convictions, incarceration, and other measures of justice involvement. The main effects and the effects of interactions of gender, substance use disorder, and psychiatric diagnosis on risk of justice involvement ("offending") were estimated by using multivariable logistic regression. Men with bipolar disorder and co-occurring substance use disorder had the highest absolute risk of offending in every category of justice involvement. For both men and women, bipolar disorder was associated with an increased risk of offending versus schizophrenia, but the increase was significantly greater for women. Substance use disorder also increased risk of offending more among women than men, especially among those with schizophrenia. Men and women with bipolar disorder and substance use disorders have much higher risk of justice involvement than those with schizophrenia, especially those without a substance use disorder. Research is needed to validate these effects in other populations and specify risk factors for justice involvement among adults with mental illness.

  5. 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.

  6. 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.

  7. 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

  8. Ikaros could be a key factor in the maintenance of "B-side" of B-1 cells.

    PubMed

    Oliveira, Vivian Cristina; Moretti, Nilmar Silvo; Augusto, Leonardo da Silva; Schenkman, Sergio; Mariano, Mario; Popi, Ana Flavia

    2015-11-01

    Ikaros, a zinc finger transcription factor, is an important regulator of the hematopoietic system. Several studies have suggested the role of Ikaros in the development, maturation, activation and differentiation of lymphocytes. To elucidate this mechanism, it is important to understand how this transcription factor works in the dichotomy of the hematopoietic system, a topic that remains uncertain. Herein, we investigated the role of Ikaros in the control of the lymphomyeloid phenotype of B-1 lymphocytes. We found that Ikaros, as well as its target genes, are expressed in B-1 cells,. Moreover, Ikaros positively regulates the expression of Flt3, Gfi and Il7r, while it down-regulates PU.1. During the induction of differentiation of B-1 cells toward phagocytes, Ikaros transcription was reduced. Taken together, these data pointed to the relevance of Ikaros in the maintenance of the promiscuous gene profile of B-1 cells. It could be suggested that Ikaros functions as a guardian of B-1 lymphoid pattern, and that its absence directs the differentiation of B-1 cells into phagocytes.

  9. Identification of key factors in deep O2 cell perfusion for vascular tissue engineering.

    PubMed

    Cheema, Umber; Hadjipanayi, Ektoras; Tammi, Noor; Alp, Burcak; Mudera, Vivek; Brown, Robert A

    2009-06-01

    Blood vessel engineering requires an understanding of the parameters governing the survival of resident vascular smooth muscle cells. We have developed an in vitro, collagen-based 3D model of vascular media to examine the correlation of cell density, O2 requirements, and viability. Dense collagen sheets (100 micron) seeded with porcine pulmonary artery smooth muscle cells (PASMCs) at low or high (11.6 or 23.2x10(6) cells/mL) densities were spiraled around a mandrel to create tubular constructs and cultured for up to 6 days in vitro, under both static and dynamic perfusion conditions. Real-time in situ monitoring showed that within 24 hours core O2 tension dropped from 140 mmHg to 20 mmHg and 80 mmHg for high and low cell density static cultures, respectively, with no significant cell death associated with the lowest O2 tension. A significant reduction in core O2 tension to 60 mmHg was achieved by increasing the O2 diffusion distance of low cell density constructs by 33% (p<0.05). After 6 days of static, high cell density culture, viability significantly decreased in the core (55%), with little effect at the surface (75%), whereas dynamic perfusion in a re-circulating bioreactor (1 ml/min) significantly improved core viability (70%, p<0.05), largely eliminating the problem. This study has identified key parameters dictating vascular smooth muscle cell behavior in 3D engineered tissue culture.

  10. Use of simulink to address key factors for radon mitigation in a Fairbanks home.

    PubMed

    Marsik, Tom; Johnson, Ron

    2008-05-01

    Hilly areas around Fairbanks, Alaska, are known to have elevated soil radon concentrations. Due to geological conditions, cold winters, and the resulting stack effect, houses in these areas are prone to higher indoor radon concentrations. Key variables with respect to radon mitigation were addressed in this paper by using a dynamic model implemented in MATLAB Simulink. These variables included the ventilation rate; the foundation flow resistance, which can be affected by sealing the foundation during the construction of a house; and the differential pressure between the subslab and the house interior, which can be affected by using a subslab depressurization system. The model was used for the scenario of a varying differential pressure and then for the scenario of a varying ventilation rate at a Fairbanks home where real-time radon concentrations were measured. The correlation coefficients between the model-predicted and measured radon concentrations were 0.96 and 0.94, for both scenarios respectively, which verified the feasibility of the model for predicting indoor radon concentrations.

  11. Mechanisms of surgical control of type 2 diabetes: GLP-1 is key factor.

    PubMed

    Holst, Jens Juul; Madsbad, Sten

    2016-07-01

    GLP-1 secretion in response to meals is dramatically increased after gastric bypass operations. GLP-1 is a powerful insulinotropic and anorectic hormone, and analogs of GLP-1 are widely used for the treatment of diabetes and recently approved also for obesity treatment. It is, therefore, reasonable to assume that the exaggerated GLP-1 secretion contributes to the antidiabetic and anorectic effects of gastric bypass. Indeed, human experiments with the GLP-1 receptor antagonist, Exendin 9-39, have shown that the improved insulin secretion, which is responsible for part of the antidiabetic effect of the operation, is reduced and or abolished after GLP-1 receptor blockade. Also the postoperative improvement of glucose tolerance is eliminated and or reduced by the antagonist, pointing to a key role for the exaggerated GLP-1 secretion. Indeed, there is evidence that the exaggerated GLP-1 secretion is also responsible for postprandial hypoglycemia sometimes observed after bypass. Other operations (biliopancreatic-diversion and or sleeve gastrectomy) appear to involve different and/or additional mechanisms, and so does experimental bariatric surgery in rodents. However, unlike bypass surgery in humans, the rodent operations are generally associated with increased energy metabolism pointing to an entirely different mechanism of action in the animals.

  12. Key factors in imprecision in radiological emergency response assessments using the NAME model.

    PubMed

    Haywood, S M; Bedwell, P; Hort, M C

    2010-03-01

    In the very early stages of response to an accidental release of radioactivity leading to environmental contamination, it is likely that only limited measurements of radioactivity in the local environment will be available on which to base decisions concerning protection measures and radiation monitoring activities. Model predictions will be used to aid understanding of the radiological situation and to form a basis for emergency health protection decisions. This paper presents an analysis of the relative importance of contributors to the imprecision associated with emergency response calculations based on a few off-site measurements, using predictions from the UK Met Office's NAME III (Numerical Atmospheric dispersion Modelling Environment version 5.2) dispersion model. The results presented extend those from a previous study in which a simple Gaussian plume model was used and confirm the key parameters contributing to imprecision. The potential extent of the sheltering countermeasure resulting from a hypothetical release in real weather conditions occurring in 2007 and 2008 is also presented.

  13. Evaluation of thermal steam-explosion key operation factors to optimize biogas production from biological sludge.

    PubMed

    Pérez-Elvira, S I; Sapkaite, I; Fdz-Polanco, F

    2015-01-01

    Thermal steam-explosion is the most extended hydrolysis pretreatment to enhance anaerobic digestion of sludge. Thermal hydrolysis key parameters are temperature (T) and time (t), and the generally accepted values reported from full-scale information are: 150-230 °C and 20-60 min. This study assesses the influence of different temperature-time-flash combinations (110-180 °C, 5-60 min, 1-3 re-flashing) on the anaerobic degradation of secondary sludge through biochemical methane potential (BMP) tests. All the conditions tested presented higher methane production compared to the untreated sludge, and both solubilization (after the hydrolysis) and degradation (by anaerobic digestion) increased linearly when increasing the severity (T-t) of the pretreatment, reaching 40% solubilization and degradation of the particulate matter at 180° C-60 min. However, for the 180 °C temperature, the treatment time impacted negatively on the lag phase. No influence of re-flashing the pretreated matter was observed. In conclusion, thermal steam-explosion at short operation times (5 min) and moderate temperatures (145 °C) seems to be very attractive from a degradation point of view thus presenting a methane production enhancement similar to the one obtained at 180°C and without negative influence of the lag phase.

  14. 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.

  15. 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.

  16. Functional Characterization of the GATA Transcription Factors GNC and CGA1 Reveals Their Key Role in Chloroplast Development, Growth, and Division in Arabidopsis1[W][OA

    PubMed Central

    Chiang, Yi-Hsuan; Zubo, Yan O.; Tapken, Wiebke; Kim, Hyo Jung; Lavanway, Ann M.; Howard, Louisa; Pilon, Marinus; Kieber, Joseph J.; Schaller, G. Eric

    2012-01-01

    Chloroplasts develop from proplastids in a process that requires the interplay of nuclear and chloroplast genomes, but key steps in this developmental process have yet to be elucidated. Here, we show that the nucleus-localized transcription factors GATA NITRATE-INDUCIBLE CARBON-METABOLISM-INVOLVED (GNC) and CYTOKININ-RESPONSIVE GATA1 (CGA1) regulate chloroplast development, growth, and division in Arabidopsis (Arabidopsis thaliana). GNC and CGA1 are highly expressed in green tissues, and the phytohormone cytokinin regulates their expression. A gnc cga1 mutant exhibits a reduction in overall chlorophyll levels as well as in chloroplast size in the hypocotyl. Ectopic overexpression of either GNC or CGA1 promotes chloroplast biogenesis in hypocotyl cortex and root pericycle cells, based on increases in the number and size of the chloroplasts, and also results in expanded zones of chloroplast production into the epidermis of hypocotyls and cotyledons and into the cortex of roots. Ectopic overexpression also promotes the development of etioplasts from proplastids in dark-grown seedlings, subsequently enhancing the deetiolation process. Inducible expression of GNC demonstrates that GNC-mediated chloroplast biogenesis can be regulated postembryonically, notably so for chloroplast production in cotyledon epidermal cells. Analysis of the gnc cga1 loss-of-function and overexpression lines supports a role for these transcription factors in regulating the effects of cytokinin on chloroplast division. These data support a model in which GNC and CGA1 serve as two of the master transcriptional regulators of chloroplast biogenesis, acting downstream of cytokinin and mediating the development of chloroplasts from proplastids and enhancing chloroplast growth and division in specific tissues. PMID:22811435

  17. Functional characterization of the GATA transcription factors GNC and CGA1 reveals their key role in chloroplast development, growth, and division in Arabidopsis.

    PubMed

    Chiang, Yi-Hsuan; Zubo, Yan O; Tapken, Wiebke; Kim, Hyo Jung; Lavanway, Ann M; Howard, Louisa; Pilon, Marinus; Kieber, Joseph J; Schaller, G Eric

    2012-09-01

    Chloroplasts develop from proplastids in a process that requires the interplay of nuclear and chloroplast genomes, but key steps in this developmental process have yet to be elucidated. Here, we show that the nucleus-localized transcription factors GATA NITRATE-INDUCIBLE CARBON-METABOLISM-INVOLVED (GNC) and CYTOKININ-RESPONSIVE GATA1 (CGA1) regulate chloroplast development, growth, and division in Arabidopsis (Arabidopsis thaliana). GNC and CGA1 are highly expressed in green tissues, and the phytohormone cytokinin regulates their expression. A gnc cga1 mutant exhibits a reduction in overall chlorophyll levels as well as in chloroplast size in the hypocotyl. Ectopic overexpression of either GNC or CGA1 promotes chloroplast biogenesis in hypocotyl cortex and root pericycle cells, based on increases in the number and size of the chloroplasts, and also results in expanded zones of chloroplast production into the epidermis of hypocotyls and cotyledons and into the cortex of roots. Ectopic overexpression also promotes the development of etioplasts from proplastids in dark-grown seedlings, subsequently enhancing the deetiolation process. Inducible expression of GNC demonstrates that GNC-mediated chloroplast biogenesis can be regulated postembryonically, notably so for chloroplast production in cotyledon epidermal cells. Analysis of the gnc cga1 loss-of-function and overexpression lines supports a role for these transcription factors in regulating the effects of cytokinin on chloroplast division. These data support a model in which GNC and CGA1 serve as two of the master transcriptional regulators of chloroplast biogenesis, acting downstream of cytokinin and mediating the development of chloroplasts from proplastids and enhancing chloroplast growth and division in specific tissues.

  18. The growth factor myostatin, a key regulator in skeletal muscle growth and homeostasis.

    PubMed

    Matsakas, A; Diel, P

    2005-03-01

    Skeletal muscle possesses the ability to both respond and adapt to changing environmental stimuli, leading to a set of metabolic and morphological adaptations, which allow it to better meet the energy demands of sustained physical activity. Great progress has been achieved over the past years by means of innovative molecular techniques, which has led to the discovery of new growth factors and the identification of molecular mechanisms involved in the regulation of muscle development. These findings provide new starting points to understand the molecular mechanisms involved in the adaptation of skeletal muscle to exercise training. One of these new identified growth factors is myostatin, a member of the transforming growth factor-beta family of proteins that has been demonstrated to play a fundamental role in the regulation of skeletal muscle growth during embryogenesis. Blocking of the myostatin signalling transduction pathway by specific inhibitors and genetic manipulations has been shown to result in a dramatic increase of skeletal muscle mass. This review focuses on the importance of myostatin in mediating skeletal muscle homeostasis in response to training as well as during the progress of myogenic disease, like atrophy or dystrophy. Manipulations of myostatin signalling may be useful for agriculture applications, treatment of muscle diseases, inhibition of muscle atrophy and last but not least as life style drugs in antiaging therapies or manipulations of the muscle to fat ratio. Drugs with the ability to modulate myostatin signalling may have the potential to enhance physical performance in athletes and therefore they probably represent a new class of doping substances.

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

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

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

  20. Hydrology and human behavior: two key factors of diarrhea incidence in montane tropical humid areas

    NASA Astrophysics Data System (ADS)

    Boithias, Laurie; Choisy, Marc; Souliyaseng, Noy; Jourdren, Marine; Quet, Fabrice; Buisson, Yves; Thammahacksa, Chanthamousone; Silvera, Norbert; Latsachack, Keooudone; Sengtaheuanghoung, Oloth; Pierret, Alain; Rochelle-Newall, Emma; Becerra, Sylvia; Ribolzi, Olivier

    2017-04-01

    The global burden of diarrhea is a leading cause of morbidity and mortality worldwide. In montane areas of South-East Asia such as northern Laos, recent changes in land use have induced increased runoff, soil erosion and in-stream suspended sediment loads, and potential pathogen dissemination. In this study we hypothesized that climate factors combined with human behavior control diarrhea incidence, either because higher rainfall, leading to higher stream discharges, suspended sediment loads and Fecal Indicator Bacteria (FIB) counts, are associated with higher numbers of reported diarrhea cases during the rainy season, or because water shortage leads to the use of less safe water sources during the dry season. For this mixed methods approach, we conducted a retrospective time series analysis of meteorological variables (rainfall, air temperature), hydrological variables (discharge, suspended sediments, FIB counts, water temperature) at the outlet of 2 catchments in Northern Lao PDR, and the number of diarrheal disease cases reported in 6 health centers located in the Luang Prabang Province. We also examined the socio-behavioral factors potentially affecting vulnerability to the effect of the climate factors, such as drinking water sources and hygiene habits. We found the FIB Escherichia coli to be present all year long (100-1,000 MPN 100 mL-1) indicating that fecal contamination is ubiquitous and constant. We found that populations switch their water supply from wells to surface water during drought periods, the latter of which appear to be at higher risk of bacterial contamination than municipal water fountains. We thus found that water shortage in the Luang Prabang area triggers diarrhea peaks during the dry and hot season and that rainfall and aquifer refill ends the epidemic during the wet season. We thus found that anthropogenic drivers, such as hygiene practices, were at least as important as environmental drivers in determining the seasonal pattern of a

  1. Youth-Adult Connectedness:: A Key Protective Factor for Adolescent Health.

    PubMed

    Sieving, Renee E; McRee, Annie-Laurie; McMorris, Barbara J; Shlafer, Rebecca J; Gower, Amy L; Kapa, Hillary M; Beckman, Kara J; Doty, Jennifer L; Plowman, Shari L; Resnick, Michael D

    2017-03-01

    Over the past 30 years, prevention science in the adolescent health field has moved from interventions focused on preventing single problem behaviors to efforts employing a dual approach, addressing risk factors that predict problems while simultaneously nurturing protective factors and promoting positive development. Through an examination of previous research and empirical case examples with vulnerable youth, this article considers the hypothesis that adolescents' sense of connectedness to caring adults acts as a protective factor against a range of risk behaviors. Multivariate analyses with existing data examined indicators of youth-adult connectedness among two groups at high risk for poor health outcomes: (1) mentor-youth relationship quality in an urban, ethnically diverse sample of students in a school-based mentoring program (2014 survey, N=239); and (2) parent-youth connectedness in a statewide sample of high school students who reported homelessness in the past year (2013 survey, N=3,627). For youth in the mentoring program, a high-quality youth-mentor relationship was significantly associated with positive social, academic, and health-related behaviors. Among students who experienced homelessness, all measures of parent connectedness were significantly associated with lower sexual risk levels. Collectively, findings from these analyses and previously published studies by this research group provide evidence that strong, positive relationships with parents and other caring adults protect adolescents from a range of poor health-related outcomes and promote positive development. Youth-adult connectedness appears to be foundational for adolescent health and well-being. Program, practice, and policy decisions should consider what strengthens or hinders caring, connected youth-adult relationships.

  2. 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

  3. 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

  4. Investigation of Key Factors for Accident Severity at Railroad Grade Crossings by Using a Logit Model

    PubMed Central

    Hu, Shou-Ren; Li, Chin-Shang; Lee, Chi-Kang

    2009-01-01

    Although several studies have used logit or probit models and their variants to fit data of accident severity on roadway segments, few have investigated accident severity at a railroad grade crossing (RGC). Compared to accident risk analysis in terms of accident frequency and severity of a highway system, investigation of the factors contributing to traffic accidents at an RGC may be more complicated because of additional highway–railway interactions. Because the proportional odds assumption was violated while fitting cumulative logit modeled by the proportional odds models with stepwise variable selection to ordinal accident severity data collected at 592 RGCs in Taiwan, as suggested by Strokes et al. (2000, p. 249) a generalized logit model with stepwise variable selection was used instead to identify explanatory variables (factors or covariates) that were significantly associated with the severity of collisions. Hence, the fitted model was used to predict the level of accident severity, given a set of values in the explanatory variables. Number of daily trains, highway separation, number of daily trucks, obstacle detection device, and approaching crossing markings significantly affected levels of accident severity at an RGC (p-value = 0.0009, 0.0008, 0.0112, 0.0017, and 0.0003, respectively). Finally, marginal effect analysis on the number of daily trains and law enforcement camera was conducted to evaluate the effect of the number of daily trains and presence of a law enforcement camera on the potential accident severity. PMID:20161414

  5. On the key factors of angular correlations in complex-forming elementary reactions

    NASA Astrophysics Data System (ADS)

    Bonnet, L.; Rayez, J. C.

    2006-04-01

    In the mid-seventies, Case and Herschbach argued that for complex-forming three-atom reactions governed by long-range forces and performed in supersonic molecular beam experiments, vectorial properties are determined by a single parameter Λ' = , L' and j' being respectively the moduli of the orbital and rotational angular momenta of the products. A simple mathematical relation between vectorial properties and Λ' was then proposed. However, Λ' must be determined beforehand by phase space theory calculations. Besides, we have recently shown that scalar properties are mainly controled by two factors ρ'1 and ρ'2 respectively called angular excitation and diatomic inertial contribution. We show here that these factors control also vectorial properties. Moreover, the way they control them is summarized in a set of four figures. The advantage of our method is that ρ'1 and ρ'2 are related to the mechanical parameters of the reaction by very simple formulas, contrary to Λ'. Last by not least, our parameters appear to be mostly independent, so that vectorial properties cannot be said to strictly depend on Λ'. Nevertheless, it turns out that the rule proposed by Case and Herschbach is reasonable in many realistic situations.

  6. Developing Talented Soccer Players: An Analysis of Socio-Spatial Factors as Possible Key Constraints

    PubMed Central

    Pastor-Vicedo, Juan C.; González-Víllora, Sixto; Teoldo da Costa, Israel

    2016-01-01

    Abstract Most studies on the identification and development of soccer talent have been one-dimensional in nature. Although some multi-dimensional analyses have been conducted, few research studies have assessed in any depth the socio-spatial factors influencing talent development. The aim of this particular study was to analyse variations in the international representation of clubs (n = 821) and countries (n = 59) in the development of players who took part in the 2014 FIFA Soccer World Cup. Clubs and countries were ranked and divided into quartiles according to the number of players developed between the ages of 15 and 21 (clubs and countries that developed players for at least three years between these ages) and the number of official league matches played by these players up to the age of 23. Significant variations were observed between clubs in terms of the number of developed players who took part in the World Cup and the number of official league matches played by these players up to the age of 23 (p < .05), and also between countries (p < .05). The findings reveal the need to carry out more in-depth studies into the type of training and competition engaged in by elite players in the period of development between the ages of 15 and 21. It may be the case that these factors are potentially decisive socio-spatial constraints in the development of soccer talent. PMID:28031773

  7. Identifying key factors in homeowner's adoption of water quality best management practices.

    PubMed

    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.

  8. The HIV/AIDS Epidemic in the Dominican Republic: Key Contributing Factors.

    PubMed

    Rojas, Patria; Malow, Robert; Ruffin, Beverly; Rothe, Eugenio M; Rosenberg, Rhonda

    2011-01-01

    This article reviews HIV/AIDS epidemiological data and recent research conducted in the Dominican Republic, with a focus on explaining the variability in estimated seroincidence and prevalence within the country. HIV seroprevalence estimates range from 1.0% (in the general population) to 11.0% among men who have sex with men (MSM). Some have indicated that the highest HIV seroprevalence occurs in Haitian enclaves called bateyes (US Agency for International Development [USAID], 2008), which are migrant worker shantytowns primarily serving the sugar industry in the Dominican Republic. Others report higher or comparable rates to the bateyes in areas related to the tourism and sex industries. As in other Caribbean and Latin American countries, reported HIV transmission in the Dominican Republic is predominantly due to unprotected heterosexual sex and the infection rate has been increasing disproportionally among women. The Dominican Republic represents two thirds of the Hispaniola island; the western one third is occupied by Haiti, the nation with the highest HIV prevalence in the western hemisphere. Although data is limited, it shows important differences in seroprevalence and incidence between these two countries, but commonalities such as poverty, gender inequalities, and stigma appear to be pivotal factors driving the epidemic. This article will discuss these and other factors that may contribute to the HIV epidemic in the Dominican Republic, as well as highlight the gaps in the literature and provide recommendations to guide further work in this area, particularly in the role of governance in sustainable HIV prevention.

  9. Developing Talented Soccer Players: An Analysis of Socio-Spatial Factors as Possible Key Constraints.

    PubMed

    Serra-Olivares, Jaime; Pastor-Vicedo, Juan C; González-Víllora, Sixto; Teoldo da Costa, Israel

    2016-12-01

    Most studies on the identification and development of soccer talent have been one-dimensional in nature. Although some multi-dimensional analyses have been conducted, few research studies have assessed in any depth the socio-spatial factors influencing talent development. The aim of this particular study was to analyse variations in the international representation of clubs (n = 821) and countries (n = 59) in the development of players who took part in the 2014 FIFA Soccer World Cup. Clubs and countries were ranked and divided into quartiles according to the number of players developed between the ages of 15 and 21 (clubs and countries that developed players for at least three years between these ages) and the number of official league matches played by these players up to the age of 23. Significant variations were observed between clubs in terms of the number of developed players who took part in the World Cup and the number of official league matches played by these players up to the age of 23 (p < .05), and also between countries (p < .05). The findings reveal the need to carry out more in-depth studies into the type of training and competition engaged in by elite players in the period of development between the ages of 15 and 21. It may be the case that these factors are potentially decisive socio-spatial constraints in the development of soccer talent.

  10. 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.

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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.

  18. Pertussis toxin and adenylate cyclase toxin: key virulence factors of Bordetella pertussis and cell biology tools

    PubMed Central

    Carbonetti, Nicholas H

    2010-01-01

    Pertussis toxin and adenylate cyclase toxin are two important virulence factors of Bordetella pertussis, the bacterial cause of the respiratory disease pertussis or whooping cough. In addition to studies on the structure, function and role in pathogenesis of these two toxins, they are both used as cell biology tools for a variety of applications owing to their ability to enter mammalian cells, perform enzymatic activities and modify cell signaling events. In this article, recent data from the research literature that enhance our understanding of the nature of these two toxins, their role in the pathogenesis of B. pertussis infection and disease, particularly in modulating host immune responses, and their use as tools for other areas of research will be outlined. PMID:20210554

  19. 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.

  20. Leadership, Knowledge Sharing, and Creativity: The Key Factors in Nurses' Innovative Behaviors.

    PubMed

    Kim, Sung-Jin; Park, Myonghwa

    2015-12-01

    This study identified the factors that affect the innovative behaviors of nurses at general hospitals based on their individual and organizational characteristics. The predictors of innovative nursing behaviors, such as self-leadership, individual knowledge sharing, creative self-efficacy, organizational knowledge sharing, and innovative organizational cultures, should be explored at individual and organizational level. This study administered a cross-sectional survey to 347 registered nurses working at 6 general hospitals (with >300 beds) in central South Korea. Data were collected using a self-report questionnaire and analyzed using structural equation modeling. Self-leadership, creative self-efficacy, and individual knowledge sharing directly affected individual innovative behaviors. Organizational knowledge sharing indirectly affected individual innovative behaviors, and this effect was mediated by an innovative organizational culture. This study contributes to the knowledge base regarding the effective management of individuals and organizations through innovative behavior; furthermore, it provides future directions for nursing interventions.

  1. Merkel Cell Carcinoma: An Update of Key Imaging Techniques, Prognostic Factors, Treatment, and Follow-up.

    PubMed

    Llombart, B; Kindem, S; Chust, M

    2017-03-01

    Merkel cell carcinoma, though rare, is one of the most aggressive tumors a dermatologist faces. More than a third of patients with this diagnosis die from the disease. Numerous researchers have attempted to identify clinical and pathologic predictors to guide prognosis, but their studies have produced inconsistent results. Because the incidence of Merkel cell carcinoma is low and it appears in patients of advanced age, prospective studies have not been done and no clear treatment algorithm has been developed. This review aims to provide an exhaustive, up-to-date account of Merkel cell carcinoma for the dermatologist. We describe prognostic factors and the imaging techniques that are most appropriate for evaluating disease spread. We also discuss current debates on treating Merkel cell carcinoma.

  2. Key factors for providing appropriate medical care in secondary school athletics: athletic training services and budget.

    PubMed

    Wham, George S; Saunders, Ruth; Mensch, James

    2010-01-01

    Research suggests that appropriate medical care for interscholastic athletes is frequently lacking. However, few investigators have examined factors related to care. To examine medical care provided by interscholastic athletics programs and to identify factors associated with variations in provision of care. Cross-sectional study. Mailed and e-mailed survey. One hundred sixty-six South Carolina high schools. The 132-item Appropriate Medical Care Assessment Tool (AMCAT) was developed and pilot tested. It included 119 items assessing medical care based on the Appropriate Medical Care for Secondary School-Age Athletes (AMCSSAA) Consensus Statement and Monograph (test-retest reliability: r = 0.89). Also included were items assessing potential influences on medical care. Presence, source, and number of athletic trainers; school size; distance to nearest medical center; public or private status; sports medicine supply budget; and varsity football regional championships served as explanatory variables, whereas the school setting, region of state, and rate of free or reduced lunch qualifiers served as control variables. The Appropriate Care Index (ACI) score from the AMCAT provided a quantitative measure of medical care and served as the response variable. The ACI score was determined based on a school's response to items relating to AMCSSAA guidelines. Regression analysis revealed associations with ACI score for athletic training services and sports medicine supply budget (both P < .001) when controlling for the setting, region, and rate of free or reduced lunch qualifiers. These 2 variables accounted for 30% of the variance in ACI score (R(2) = 0.302). Post hoc analysis showed differences between ACI score based on the source of the athletic trainer and the size of the sports medicine supply budget. The AMCAT offers an evaluation of medical care provided by interscholastic athletics programs. In South Carolina schools, athletic training services and the sports medicine

  3. Hydrophobic environment is a key factor for the stability of thermophilic proteins.

    PubMed

    Gromiha, M Michael; Pathak, Manish C; Saraboji, Kadhirvel; Ortlund, Eric A; Gaucher, Eric A

    2013-04-01

    The stability of thermophilic proteins has been viewed from different perspectives and there is yet no unified principle to understand this stability. It would be valuable to reveal the most important interactions for designing thermostable proteins for such applications as industrial protein engineering. In this work, we have systematically analyzed the importance of various interactions by computing different parameters such as surrounding hydrophobicity, inter-residue interactions, ion-pairs and hydrogen bonds. The importance of each interaction has been determined by its predicted relative contribution in thermophiles versus the same contribution in mesophilic homologues based on a dataset of 373 protein families. We predict that hydrophobic environment is the major factor for the stability of thermophilic proteins and found that 80% of thermophilic proteins analyzed showed higher hydrophobicity than their mesophilic counterparts. Ion pairs, hydrogen bonds, and interaction energy are also important and favored in 68%, 50%, and 62% of thermophilic proteins, respectively. Interestingly, thermophilic proteins with decreased hydrophobic environments display a greater number of hydrogen bonds and/or ion pairs. The systematic elimination of mesophilic proteins based on surrounding hydrophobicity, interaction energy, and ion pairs/hydrogen bonds, led to correctly identifying 95% of the thermophilic proteins in our analyses. Our analysis was also applied to another, more refined set of 102 thermophilic-mesophilic pairs, which again identified hydrophobicity as a dominant property in 71% of the thermophilic proteins. Further, the notion of surrounding hydrophobicity, which characterizes the hydrophobic behavior of residues in a protein environment, has been applied to the three-dimensional structures of elongation factor-Tu proteins and we found that the thermophilic proteins are enriched with a hydrophobic environment. The results obtained in this work highlight the

  4. Identification of transcriptional factors and key genes in primary osteoporosis by DNA microarray.

    PubMed

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

    2015-05-09

    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. 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. 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. 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.

  5. Direct transcriptional activation of BT genes by NLP transcription factors is a key component of the nitrate response in Arabidopsis.

    PubMed

    Sato, Takeo; Maekawa, Shugo; Konishi, Mineko; Yoshioka, Nozomi; Sasaki, Yuki; Maeda, Haruna; Ishida, Tetsuya; Kato, Yuki; Yamaguchi, Junji; Yanagisawa, Shuichi

    2017-01-29

    Nitrate modulates growth and development, functioning as a nutrient signal in plants. Although many changes in physiological processes in response to nitrate have been well characterized as nitrate responses, the molecular mechanisms underlying the nitrate response are not yet fully understood. Here, we show that NLP transcription factors, which are key regulators of the nitrate response, directly activate the nitrate-inducible expression of BT1 and BT2 encoding putative scaffold proteins with a plant-specific domain structure in Arabidopsis. Interestingly, the 35S promoter-driven expression of BT2 partially rescued growth inhibition caused by reductions in NLP activity in Arabidopsis. Furthermore, simultaneous disruption of BT1 and BT2 affected nitrate-dependent lateral root development. These results suggest that direct activation of BT1 and BT2 by NLP transcriptional activators is a key component of the molecular mechanism underlying the nitrate response in Arabidopsis.

  6. 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

    2014-04-09

    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.

  7. 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

  8. 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

  9. Key Factors for Providing Appropriate Medical Care in Secondary School Athletics: Athletic Training Services and Budget

    PubMed Central

    Wham, George S.; Saunders, Ruth; Mensch, James

    2010-01-01

    Abstract Context: Research suggests that appropriate medical care for interscholastic athletes is frequently lacking. However, few investigators have examined factors related to care. Objective: To examine medical care provided by interscholastic athletics programs and to identify factors associated with variations in provision of care. Design: Cross-sectional study. Setting: Mailed and e-mailed survey. Patients or Other Participants: One hundred sixty-six South Carolina high schools. Intervention(s): The 132-item Appropriate Medical Care Assessment Tool (AMCAT) was developed and pilot tested. It included 119 items assessing medical care based on the Appropriate Medical Care for Secondary School-Age Athletes (AMCSSAA) Consensus Statement and Monograph (test-retest reliability: r  =  0.89). Also included were items assessing potential influences on medical care. Presence, source, and number of athletic trainers; school size; distance to nearest medical center; public or private status; sports medicine supply budget; and varsity football regional championships served as explanatory variables, whereas the school setting, region of state, and rate of free or reduced lunch qualifiers served as control variables. Main Outcome Measure(s): The Appropriate Care Index (ACI) score from the AMCAT provided a quantitative measure of medical care and served as the response variable. The ACI score was determined based on a school's response to items relating to AMCSSAA guidelines. Results: Regression analysis revealed associations with ACI score for athletic training services and sports medicine supply budget (both P < .001) when controlling for the setting, region, and rate of free or reduced lunch qualifiers. These 2 variables accounted for 30% of the variance in ACI score (R2  =  0.302). Post hoc analysis showed differences between ACI score based on the source of the athletic trainer and the size of the sports medicine supply budget. Conclusions: The AMCAT offers an

  10. 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

  11. 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.

  12. A Robust and Anonymous Two Factor Authentication and Key Agreement Protocol for Telecare Medicine Information Systems.

    PubMed

    Xiong, Hu; Tao, Junyi; Chen, Yanan

    2016-11-01

    Nowadays people can get many services including health-care services from distributed information systems remotely via public network. By considering that these systems are built on public network, they are vulnerable to many malicious attacks. Hence it is necessary to introduce an effective mechanism to protect both users and severs. Recently many two-factor authentication schemes have been proposed to achieve this goal. In 2016, Li et al. demonstrated that Lee et al.'s scheme was not satisfactory to be deployed in practice because of its security weaknesses and then proposed a security enhanced scheme to overcome these drawbacks. In this paper, we analyze Li et al.'s scheme is still not satisfactory to be applied in telecare medicine information systems (TMIS) because it fails to withstand off-line dictionary attack and known session-specific temporary information attack. Moreover, their scheme cannot provide card revocation services for lost smart card. In order to solve these security problems, we propose an improved scheme. Then we analyze our scheme by using BAN-logic model and compare the improved scheme with related schemes to prove that our scheme is advantageous to be applied in practice.

  13. 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.

  14. 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

  15. Economic incentives to promote healthier food purchases: exploring acceptability and key factors for success.

    PubMed

    Ni Mhurchu, Cliona; Eyles, Helen; Dixon, Robyn; Matoe, Leonie; Teevale, Tasileta; Meagher-Lundberg, Patricia

    2012-09-01

    Despite increasing interest, little is known about the beliefs and views of the public in relation to the use of economic incentives as a means to promote healthy eating. This study explores views of ethnically and socioeconomically diverse shoppers regarding acceptability of economic incentives to promote healthier food purchases, and factors likely to affect the success of such schemes. Six focus groups (n = 36 participants; 14 Māori, 12 Pacific, 10 non-ethnic specific low income), were held in Auckland, New Zealand, in October 2009. A general inductive approach was used to identify common themes. The single most important reported food purchasing influence was cost. Focus group participants viewed the concept of economic incentives to promote healthy eating positively, as long as such schemes provided worthwhile incentives, and were simple and convenient to use. The preferred option for delivery was a pre-loaded electronic swipe card. Fruit and vegetables were the food group most participants said they would like to see incentivized. There was marked variability in the incentive amount thought sufficient to promote participation in such a scheme. Our findings suggest economic incentives hold promise as a means to promote healthier household food purchases, and their effectiveness should be evaluated using robust, randomized trials.

  16. 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.

  17. Corticotropin releasing factor: a key role in the neurobiology of addiction.

    PubMed

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

    2014-04-01

    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.

  18. The Transcription Factors T-bet and Eomes Control Key Checkpoints of Natural Killer Cell Maturation

    PubMed Central

    Gordon, Scott M.; Chaix, Julie; Rupp, Levi J.; Wu, Junmin; Madera, Sharline; Sun, Joseph C.; Lindsten, Tullia; Reiner, Steven L.

    2012-01-01

    Summary Natural killer (NK) cells play critical roles defending against tumors and pathogens. We show that mice lacking both transcription factors Eomesodermin (Eomes) and T-bet failed to develop NK cells. Developmental stability of immature NK cells constitutively expressing the death ligand TRAIL depended on T-bet. Conversely, maturation characterized by loss of constitutive TRAIL expression and induction of Ly49 receptor diversity and integrin CD49b (DX5+) required Eomes. Mature NK cells from which Eomes was deleted reverted to phenotypic immaturity if T-bet was present or downregulated NK lineage antigens if T-bet was absent, despite retaining expression of Ly49 receptors. Adult, hepatic and fetal hematopoiesis restricted Eomes expression and limited NK development to the T-bet-dependent, immature stage, whereas medullary hematopoiesis permitted Eomes-dependent NK maturation in adult mice. These findings reveal two sequential, genetically separable checkpoints of NK cell maturation, the progression of which is metered largely by the anatomic localization of hematopoiesis. PMID:22261438

  19. The transcription factors T-bet and Eomes control key checkpoints of natural killer cell maturation.

    PubMed

    Gordon, Scott M; Chaix, Julie; Rupp, Levi J; Wu, Junmin; Madera, Sharline; Sun, Joseph C; Lindsten, Tullia; Reiner, Steven L

    2012-01-27

    Natural killer (NK) cells play critical roles defending against tumors and pathogens. We show that mice lacking both transcription factors Eomesodermin (Eomes) and T-bet failed to develop NK cells. Developmental stability of immature NK cells constitutively expressing the death ligand TRAIL depended on T-bet. Conversely, maturation characterized by loss of constitutive TRAIL expression and induction of Ly49 receptor diversity and integrin CD49b (DX5(+)) required Eomes. Mature NK cells from which Eomes was deleted reverted to phenotypic immaturity if T-bet was present or downregulated NK lineage antigens if T-bet was absent, despite retaining expression of Ly49 receptors. Fetal and adult hepatic hematopoiesis restricted Eomes expression and limited NK development to the T-bet-dependent, immature stage, whereas medullary hematopoiesis permitted Eomes-dependent NK maturation in adult mice. These findings reveal two sequential, genetically separable checkpoints of NK cell maturation, the progression of which is metered largely by the anatomic localization of hematopoiesis. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. An exploratory study of older adults' comprehension of printed cancer information: is readability a key factor?

    PubMed

    Friedman, Daniela B; Hoffman-Goetz, Laurie

    2007-01-01

    Printed cancer information often is written at or beyond high school reading levels, despite lower average literacy abilities of the public. The objectives of this exploratory study were twofold: (1) to evaluate older adults' comprehension of breast (BC), prostate (PC), and colorectal (CC) cancer information; and (2) to determine if comprehension of BC, PC, and CC information varies according to text readability. Comprehension of printed cancer resources was evaluated with 44 community-dwelling older adults using the Cloze procedure and recall questions. Participants' comprehension scores were compared with Simple Measure of Gobbledegook (SMOG) readability scores (factors that influence comprehension. Use of plain language is recommended for CC resources.

  1. Membrane domain formation—a key factor for targeted intracellular drug delivery

    PubMed Central

    Popov-Čeleketić, Dušan; van Bergen en Henegouwen, Paul M. P.

    2014-01-01

    Protein molecules, toxins and viruses internalize into the cell via receptor-mediated endocytosis (RME) using specific proteins and lipids in the plasma membrane. The plasma membrane is a barrier for many pharmaceutical agents to enter into the cytoplasm of target cells. In the case of cancer cells, tissue-specific biomarkers in the plasma membrane, like cancer-specific growth factor receptors, could be excellent candidates for RME-dependent drug delivery. Recent data suggest that agent binding to these receptors at the cell surface, resulting in membrane domain formation by receptor clustering, can be used for the initiation of RME. As a result, these pharmaceutical agents are internalized into the cells and follow different routes until they reach their final intracellular targets like lysosomes or Golgi. We propose that clustering induced formation of plasma membrane microdomains enriched in receptors, sphingolipids, and inositol lipids, leads to membrane bending which functions as the onset of RME. In this review we will focus on the role of domain formation in RME and discuss potential applications for targeted intracellular drug delivery. PMID:25520666

  2. Pharmacy patronage: identifying key factors in the decision making process using the determinant attribute approach.

    PubMed

    Franic, Duska M; Haddock, Sarah M; Tucker, Leslie Tootle; Wooten, Nathan

    2008-01-01

    To use the determinant attribute approach, a research method commonly used in marketing to identify the wants of various consumer groups, to evaluate consumer pharmacy choice when having a prescription order filled in different pharmacy settings. Cross sectional. Community independent, grocery store, community chain, and discount store pharmacies in Georgia between April 2005 and April 2006. Convenience sample of adult pharmacy consumers (n = 175). Survey measuring consumer preferences on 26 attributes encompassing general pharmacy site features (16 items), pharmacist characteristics (5 items), and pharmacy staff characteristics (5 items). 26 potential determinant attributes for pharmacy selection. 175 consumers were surveyed at community independent (n = 81), grocery store (n = 44), community chain (n = 27), or discount store (n = 23) pharmacy settings. The attributes of pharmacists and staff at all four pharmacy settings were shown to affect pharmacy patronage motives, although consumers frequenting non-community independent pharmacies were also motivated by secondary convenience factors, e.g., hours of operation, and prescription coverage. Most consumers do not perceive pharmacies as merely prescription-distribution centers that vary only by convenience. Prescriptions are not just another economic good. Pharmacy personnel influence pharmacy selection; therefore, optimal staff selection and training is likely the greatest asset and most important investment for ensuring pharmacy success.

  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. The high affinity iron permease is a key virulence factor required for Rhizopus oryzae pathogenesis

    PubMed Central

    Ibrahim, Ashraf S.; Gebremariam, Teclegiorgis; Lin, Lin; Luo, Guanpingsheng; Husseiny, Mohamed I.; Skory, Christopher D.; Fu, Yue; French, Samuel W.; Edwards, John E.; Spellberg, Brad

    2010-01-01

    SUMMARY Rhizopus oryzaeis the most common cause of mucormycosis, an angioinvasive fungal infection that causes more then 50% mortality rate despite first-line therapy. Clinical and animal model data clearly demonstrate that the presence of elevated available serum iron predisposes the host to mucormycosis. The high affinity iron permease gene (FTR1) is required for R. oryzae iron transport in iron-depleted environments. Here we demonstrate that FTR1 is required for full virulence of R. oryzae in mice. We show that FTR1 is expressed during infection in diabetic ketoacidotic (DKA) mice. In addition, we disrupted FTR1 by double cross-over homologous recombination, but multinucleated R. oryzae could not be forced to segregate to a homokaryotic null allele. Nevertheless, a reduction of the relative copy number of FTR1 and inhibition of FTR1 expression by RNAi compromised the ability of R. oryzae to acquire iron in vitro and reduced its virulence in DKA mice. Importantly, passive immunization with anti-Ftr1p immune sera protected DKA mice from infection with R. oryzae. Thus FTR1 is a virulence factor for R. oryzae, and anti-Ftr1p passive immunotherapy deserves further evaluation as a strategy to improve outcomes of deadly mucormycosis. PMID:20545847

  5. Conformational dynamics as a key factor of signaling mediated by the receiver domain of sensor histidine kinase from Arabidopsis thaliana.

    PubMed

    Otrusinová, Olga; Demo, Gabriel; Padrta, Petr; Jaseňáková, Zuzana; Pekárová, Blanka; Gelová, Zuzana; Szmitkowska, Agnieszka; Kadeřávek, Pavel; Jansen, Séverine; Zachrdla, Milan; Klumpler, Tomáš; Marek, Jaromír; Hritz, Jozef; Janda, Lubomír; Iwaï, Hideo; Wimmerová, Michaela; Hejátko, Jan; Žídek, Lukáš

    2017-08-31

    Multistep phosphorelay (MSP) cascades mediate responses to a wide spectrum of stimuli, including plant hormonal signaling, but several aspects of MSP await elucidation. Here, we provide first insight into the key step of MSP-mediated phosphotransfer in a eukaryotic system, the phosphorylation of the receiver domain of the histidine kinase CYTOKININ INDEPENDENT 1 (CKI1RD) from Arabidopsis thaliana We observed that the crystal structures of free, Mg(2+)-bound, and beryllofluoridated CKI1RD (a stable analog of the labile phosphorylated form) were identical and similar to the active state of receiver domains of bacterial response regulators. However, the three CKI1RD variants exhibited different conformational dynamics in solution. NMR studies revealed that Mg(2+) binding and beryllofluoridation alter the conformational equilibrium of the β3-α3 loop close to the phosphorylation site. Mutations that perturbed the conformational behavior of the β3-α3 loop while keeping the active site aspartate intact resulted in suppression of CKI1 function. Mechanistically, homology modeling indicated that the β3-α3 loop directly interacts with the ATP-binding site of the CKI1 histidine kinase domain. The functional relevance of the conformational dynamics observed in the β3-α3 loop of CKI1RD was supported by a comparison with another A. thaliana histidine kinase, ETR1. In contrast to the highly dynamic β3-α3 loop of CKI1RD, the corresponding loop of the ETR1 receiver domain (ETR1RD) exhibited little conformational exchange and adopted a different orientation in crystals. Biochemical data indicated that ETR1RD is involved in phosphorylation-independent signaling, implying a direct link between conformational behavior and the ability of eukaryotic receiver domains to participate in MSP. Copyright © 2017, The American Society for Biochemistry and Molecular Biology.

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

    PubMed

    Carlfjord, Siw; Lindberg, Malou; Bendtsen, Preben; Nilsen, Per; Andersson, Agneta

    2010-08-23

    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. 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. 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. 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 innovation to be implemented, and of its

  7. 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

  8. MicroRNA and Transcription Factor: Key Players in Plant Regulatory Network

    PubMed Central

    Samad, Abdul F. A.; Sajad, Muhammad; Nazaruddin, Nazaruddin; Fauzi, Izzat A.; Murad, Abdul M. A.; Zainal, Zamri; Ismail, Ismanizan

    2017-01-01

    Recent achievements in plant microRNA (miRNA), a large class of small and non-coding RNAs, are very exciting. A wide array of techniques involving forward genetic, molecular cloning, bioinformatic analysis, and the latest technology, deep sequencing have greatly advanced miRNA discovery. A tiny miRNA sequence has the ability to target single/multiple mRNA targets. Most of the miRNA targets are transcription factors (TFs) which have paramount importance in regulating the plant growth and development. Various families of TFs, which have regulated a range of regulatory networks, may assist plants to grow under normal and stress environmental conditions. This present review focuses on the regulatory relationships between miRNAs and different families of TFs like; NF-Y, MYB, AP2, TCP, WRKY, NAC, GRF, and SPL. For instance NF-Y play important role during drought tolerance and flower development, MYB are involved in signal transduction and biosynthesis of secondary metabolites, AP2 regulate the floral development and nodule formation, TCP direct leaf development and growth hormones signaling. WRKY have known roles in multiple stress tolerances, NAC regulate lateral root formation, GRF are involved in root growth, flower, and seed development, and SPL regulate plant transition from juvenile to adult. We also studied the relation between miRNAs and TFs by consolidating the research findings from different plant species which will help plant scientists in understanding the mechanism of action and interaction between these regulators in the plant growth and development under normal and stress environmental conditions. PMID:28446918

  9. DNA lesions, inducible DNA repair, and cell division: Three key factors in mutagenesis and carcinogenesis

    SciTech Connect

    Ames, B.N.; Shigenaga, M.K.; Gold, L.S.

    1993-12-01

    DNA lesions that escape repair have a certain probability of giving rise to mutations when the cell divides. Endogenous DNA damage is high: 10{sup 6} oxidative lesions are present per rat cell. An exogenous mutagen produces an increment in lesions over the background rate of endogenous lesions. The effectiveness of a particular lesion depends on whether it is excised by a DNA repair system and the probability that it gives rise to a mutation when the cell divides. When the cell divides, an unrepaired DNA lesion has a certain probability of giving rise to a mutation. Thus, an important factor in the mutagenic effect of an exogenous agent whether it is genotoxic or non-genotoxic, is the increment it causes over the background cell division rate (mitogenesis) in cells that appear to matter most in cancer, the stem cells, which are not on their way to being discarded. Increasing their cell division rate increases by high doses of chemicals. If both the rate of DNA lesions and cell division are increased, then there will be a multiplicative effect on mutagenesis (and carcinogenesis), for example, by high doses of a mutagen that also increases mitogenesis through cell killing. The defense system against reactive electrophilic mutagens, such as the glutathione transferases, are also almost all inducible and buffer cells against increments in active forms of chemicals that can cause DNA lesions. A variety of DNA repair defense systems, almost all inducible, buffer the cell against any increment in DNA lesions. Therefore, the effect of a particular chemical insult depends on the level of each defense, which in turn depends on the past history of exposure. Exogenous agents can influence the induction and effectiveness of these defenses. Defenses can be partially disabled by lack of particular micronutrients in the diet (e.g., antioxidants).

  10. 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.

  11. Stearoyl-CoA desaturase-1 is a key factor for lung cancer-initiating cells

    PubMed Central

    Noto, A; Raffa, S; De Vitis, C; Roscilli, G; Malpicci, D; Coluccia, P; Di Napoli, A; Ricci, A; Giovagnoli, M R; Aurisicchio, L; Torrisi, M R; Ciliberto, G; Mancini, R

    2013-01-01

    In recent years, studies of cancer development and recurrence have been influenced by the cancer stem cells (CSCs)/cancer-initiating cells (CICs) hypothesis. According to this, cancer is sustained by highly positioned, chemoresistant cells with extensive capacity of self renewal, which are responsible for disease relapse after chemotherapy. Growth of cancer cells as three-dimensional non-adherent spheroids is regarded as a useful methodology to enrich for cells endowed with CSC-like features. We have recently reported that cell cultures derived from malignant pleural effusions (MPEs) of patients affected by adenocarcinoma of the lung are able to efficiently form spheroids in non-adherent conditions supplemented with growth factors. By expression profiling, we were able to identify a set of genes whose expression is significantly upregulated in lung tumor spheroids versus adherent cultures. One of the most strongly upregulated gene was stearoyl-CoA desaturase (SCD1), the main enzyme responsible for the conversion of saturated into monounsaturated fatty acids. In the present study, we show both by RNA interference and through the use of a small molecule inhibitor that SCD1 is required for lung cancer spheroids propagation both in stable cell lines and in MPE-derived primary tumor cultures. Morphological examination and image analysis of the tumor spheroids formed in the presence of SCD1 inhibitors showed a different pattern of growth characterized by irregular cell aggregates. Electron microscopy revealed that the treated spheroids displayed several features of cellular damage and immunofluorescence analysis on optical serial sections showed apoptotic cells positive for the M30 marker, most of them positive also for the stemness marker ALDH1A1, thus suggesting that the SCD1 inhibitor is selectively killing cells with stem-like properties. Furthermore, SCD1-inhibited lung cancer cells were strongly impaired in their in vivo tumorigenicity and ALDH1A1 expression. These

  12. Key Role of Amino Acid Repeat Expansions in the Functional Diversification of Duplicated Transcription Factors

    PubMed Central

    Radó-Trilla, Núria; Arató, Krisztina; Pegueroles, Cinta; Raya, Alicia; de la Luna, Susana; Albà, M. Mar

    2015-01-01

    The high regulatory complexity of vertebrates has been related to two rounds of whole genome duplication (2R-WGD) that occurred before the divergence of the major vertebrate groups. Following these events, many developmental transcription factors (TFs) were retained in multiple copies and subsequently specialized in diverse functions, whereas others reverted to their singleton state. TFs are known to be generally rich in amino acid repeats or low-complexity regions (LCRs), such as polyalanine or polyglutamine runs, which can evolve rapidly and potentially influence the transcriptional activity of the protein. Here we test the hypothesis that LCRs have played a major role in the diversification of TF gene duplicates. We find that nearly half of the TF gene families originated during the 2R-WGD contains LCRs. The number of gene duplicates with LCRs is 155 out of 550 analyzed (28%), about twice as many as the number of single copy genes with LCRs (15 out of 115, 13%). In addition, duplicated TFs preferentially accumulate certain LCR types, the most prominent of which are alanine repeats. We experimentally test the role of alanine-rich LCRs in two different TF gene families, PHOX2A/PHOX2B and LHX2/LHX9. In both cases, the presence of the alanine-rich LCR in one of the copies (PHOX2B and LHX2) significantly increases the capacity of the TF to activate transcription. Taken together, the results provide strong evidence that LCRs are important driving forces of evolutionary change in duplicated genes. PMID:25931513

  13. Pedoturbation by tree uprooting: the key pattern-forming factor in the forest soil

    NASA Astrophysics Data System (ADS)

    Bobrovsky, Maxim; Loyko, Sergey

    2017-04-01

    Treefalls with uprooting are the most powerful and ubiquitous biotic factor changing the structure of forest soil under free forest development. Practically every soil profile in a forest has a number of soil horizons anomalies which are located within the limits of the potential depth of treefall-related pedoturbations and these anomalies are indeed a result of treefalls in most cases. It is important to recognize signs of treefalls with uprooting in a soil profile even when signs of treefalls on the ground surface (pit-and-mound topography) are erased. Numerous field studies of forest soil in the European part of Russia and in the Western Siberia allowed us to generalize signs of treefalls in a soil profile, which can be used to distinguish the patterns of old treefall-related pedoturbations. We distinguish two main types of uprooting of a fallen tree: hinge and rotational tree uprooting (treefall). The signs of treefalls with uprooting in a soil profile are as follows: (1) treefall pits (cauldrons); (2) spotty or streaky structures of different degrees of contrast; (3) blocks of "buried material" from the upper soil layers; (4) washed (bleached) material depositing at the bottom of pits and filling soil pores and channels of various origins; (5) signs of hydrogenous changes of soil material resulting from water stagnation in the pits; (6) root channels at the bottom of the pit and (7) inclusions of litter and charcoal. We cleared that treefall-related pedoturbations affect soil profiles at a depth larger than the depth usually described by the soil horizons A, E, Bhs, etc. Therefore in most forest soils, the middle and lower parts of the profiles have patterns originating from the transfer of soil material upon treefalls. Age since the tree uprooting can be determined by dating of organic matter or charcoal located in old pits. We dated several tens of old tree uprooting pits by charcoal in sandy soil in the center and the east of the Russian Plain: they showed

  14. 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

  15. Privacy Protection for Telecare Medicine Information Systems Using a Chaotic Map-Based Three-Factor Authenticated Key Agreement Scheme.

    PubMed

    Zhang, Liping; Zhu, Shaohui; Tang, Shanyu

    2017-03-01

    Telecare medicine information systems (TMIS) provide flexible and convenient e-health care. However, the medical records transmitted in TMIS are exposed to unsecured public networks, so TMIS are more vulnerable to various types of security threats and attacks. To provide privacy protection for TMIS, a secure and efficient authenticated key agreement scheme is urgently needed to protect the sensitive medical data. Recently, Mishra et al. proposed a biometrics-based authenticated key agreement scheme for TMIS by using hash function and nonce, they claimed that their scheme could eliminate the security weaknesses of Yan et al.'s scheme and provide dynamic identity protection and user anonymity. In this paper, however, we demonstrate that Mishra et al.'s scheme suffers from replay attacks, man-in-the-middle attacks and fails to provide perfect forward secrecy. To overcome the weaknesses of Mishra et al.'s scheme, we then propose a three-factor authenticated key agreement scheme to enable the patient to enjoy the remote healthcare services via TMIS with privacy protection. The chaotic map-based cryptography is employed in the proposed scheme to achieve a delicate balance of security and performance. Security analysis demonstrates that the proposed scheme resists various attacks and provides several attractive security properties. Performance evaluation shows that the proposed scheme increases efficiency in comparison with other related schemes.

  16. A key role of nuclear factor Y in the refeeding response of fatty acid synthase in adipocytes.

    PubMed

    Nishi-Tatsumi, Makiko; Yahagi, Naoya; Takeuchi, Yoshinori; Toya, Naoki; Takarada, Ayako; Murayama, Yuki; Aita, Yuichi; Sawada, Yoshikazu; Piao, Xiaoying; Oya, Yukari; Shikama, Akito; Masuda, Yukari; Kubota, Midori; Izumida, Yoshihiko; Matsuzaka, Takashi; Nakagawa, Yoshimi; Sekiya, Motohiro; Iizuka, Yoko; Kawakami, Yasushi; Kadowaki, Takashi; Yamada, Nobuhiro; Shimano, Hitoshi

    2017-03-09

    Fatty acid synthase (Fasn) is a key component of energy metabolism that is dynamically induced by food intake. Although extensive studies have revealed a number of transcription factors involved in the fasting/refeeding transition of Fasn expression in hepatocytes, much less evidence is available for adipocytes. Using the in vivo Ad-luc analytical system, we identified the inverted CCAAT element (ICE) around -100 nucleotides in the Fasn promoter as a critical cis-element for the refeeding response in adipocytes. Electrophoretic mobility shift assays and chromatin immunoprecipitation show that nuclear factor Y (NF-Y) binds to ICE specifically in refeeding states. Notably, the NF-Y binding to ICE is differently regulated between adipocytes and hepatocytes. These findings provide insights into the specific mechanisms controlling energy metabolism in adipocytes. This article is protected by copyright. All rights reserved.

  17. Variability in the Contribution of Different Life Stages to Population Growth as a Key Factor in the Invasion Success of Pinus strobus

    PubMed Central

    Münzbergová, Zuzana; Hadincová, Věra; Wild, Jan; Kindlmannová, Jana

    2013-01-01

    Background Despite the increasing number of studies attempting to model population growth in various organisms, we still know relatively little about the population dynamics of long-lived species that reproduce only in the later stages of their life cycle, such as trees. Predictions of the dynamics of these species are, however, urgently needed for planning management actions when species are either endangered or invasive. In long-lived species, a single management intervention may have consequences for several decades, and detailed knowledge of long-term performance can therefore elucidate possible outcomes during the management planning phase. Methodology and Principal Findings We studied the population dynamics of an invasive tree species, Pinus strobus, in three habitat types represented by their position along the elevation gradient occupied by the species. In agreement with previous studies on the population dynamics of long-lived perennials, our results show that the survival of the largest trees exhibits the highest elasticity in all of the studied habitats. In contrast, life table response experiments (LTRE) analysis showed that different stages contribute the most to population growth rates in different habitats, with generative reproduction being more important in lower slopes and valley bottoms and survival being more important on rock tops and upper slopes. Conclusions The results indicate that P. strobus exhibits different growth strategies in different habitats that result in similar population growth rates. We propose that this plasticity in growth strategies is a key factor in the invasion success of the white pine. In all of the investigated habitats, the population growth rates are above 1, indicating that the population of the species is still increasing and has the ability to spread and occupy a wide range of habitats. PMID:23468896

  18. Lack of physician-patient communication as a key factor associated with malpractice litigation in neonatal brachial plexus palsy.

    PubMed

    Domino, Joseph; McGovern, Connie; Chang, Kate W C; Carlozzi, Noelle E; Yang, Lynda J S

    2014-02-01

    Perinatal disorders are prone to malpractice litigation. Neonatal brachial plexus palsy (NBPP) results from stretching the nerves in the perinatal period and may lead to paresis or paralysis and sensory loss in the affected arm. Little is known about the key factors associated with malpractice litigation by families of patients with NBPP and whether these factors reflect the practice environment or are inherent to the condition. In this study, the authors documented the percentage of families of NBPP patients at a specialty center that had filed a malpractice suit and described the key factors associated with that pursuit of legal action. The families/caregivers of 51 patients with NBPP who had presented to the University of Michigan Interdisciplinary Brachial Plexus Program participated in this study. A qualitative research design was applied using both a questionnaire to examine psychosocial factors and a dynamic tool to measure health outcomes from the patient perspective via parent proxy (Patient-Reported Outcomes Measurement Information System [PROMIS] assessment instruments). Statistical analysis included the Fisher exact test, chi-square test, and Student t-test. The study protocol was approved by the University of Michigan institutional review board. Forty-seven percent of the families pursued malpractice litigation. In comparing patient families that had pursued legal action with those that had not, significant differences were revealed in the perception that the sustained birth injury was unnecessary (p = 0.002), the information received in the perinatal period was inadequate (p = 0.003), family concerns were ignored in the perinatal period (p = 0.005), and family concerns were not adequately addressed (p < 0.001). Sixty-six percent of the families received external advice to pursue legal action. The PROMIS survey revealed significant group differences in depressive symptoms (p = 0.008), fatigue (p = 0.02), pain (p = 0.01), and anger (p = 0.004). In

  19. Integrated genome-wide chromatin occupancy and expression analyses identify key myeloid pro-differentiation transcription factors repressed by Myb.

    PubMed

    Zhao, Liang; Glazov, Evgeny A; Pattabiraman, Diwakar R; Al-Owaidi, Faisal; Zhang, Ping; Brown, Matthew A; Leo, Paul J; Gonda, Thomas J

    2011-06-01

    To gain insight into the mechanisms by which the Myb transcription factor controls normal hematopoiesis and particularly, how it contributes to leukemogenesis, we mapped the genome-wide occupancy of Myb by chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-Seq) in ERMYB myeloid progenitor cells. By integrating the genome occupancy data with whole genome expression profiling data, we identified a Myb-regulated transcriptional program. Gene signatures for leukemia stem cells, normal hematopoietic stem/progenitor cells and myeloid development were overrepresented in 2368 Myb regulated genes. Of these, Myb bound directly near or within 793 genes. Myb directly activates some genes known critical in maintaining hematopoietic stem cells, such as Gfi1 and Cited2. Importantly, we also show that, despite being usually considered as a transactivator, Myb also functions to repress approximately half of its direct targets, including several key regulators of myeloid differentiation, such as Sfpi1 (also known as Pu.1), Runx1, Junb and Cebpb. Furthermore, our results demonstrate that interaction with p300, an established coactivator for Myb, is unexpectedly required for Myb-mediated transcriptional repression. We propose that the repression of the above mentioned key pro-differentiation factors may contribute essentially to Myb's ability to suppress differentiation and promote self-renewal, thus maintaining progenitor cells in an undifferentiated state and promoting leukemic transformation.

  20. SND1, a NAC domain transcription factor, is a key regulator of secondary wall synthesis in fibers of Arabidopsis.

    PubMed

    Zhong, Ruiqin; Demura, Taku; Ye, Zheng-Hua

    2006-11-01

    Secondary walls in fibers and tracheary elements constitute the most abundant biomass produced by plants. Although a number of genes involved in the biosynthesis of secondary wall components have been characterized, little is known about the molecular mechanisms underlying the coordinated expression of these genes. Here, we demonstrate that the Arabidopsis thaliana NAC (for NAM, ATAF1/2, and CUC2) domain transcription factor, SND1 (for secondary wall-associated NAC domain protein), is a key transcriptional switch regulating secondary wall synthesis in fibers. We show that SND1 is expressed specifically in interfascicular fibers and xylary fibers in stems and that dominant repression of SND1 causes a drastic reduction in the secondary wall thickening of fibers. Ectopic overexpression of SND1 results in activation of the expression of secondary wall biosynthetic genes, leading to massive deposition of secondary walls in cells that are normally nonsclerenchymatous. In addition, we have found that SND1 upregulates the expression of several transcription factors that are highly expressed in fibers during secondary wall synthesis. Together, our results reveal that SND1 is a key transcriptional activator involved in secondary wall biosynthesis in fibers.

  1. 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

  2. Studying work practices: a key factor in understanding accidents on the level triggered by a balance disturbance.

    PubMed

    Derosier, C; Leclercq, S; Rabardel, P; Langa, P

    2008-12-01

    Accidents on the level (AOL) rank second amongst the most numerous and serious occupational accidents with days lost in France and are a major health and safety problem in every sector of activity. The case study described in this paper was conducted at a metallurgical company with 300 employees. The aims of this work were dual: 1) to extend the general knowledge required for preventing these accidents; 2) to propose prevention measures to this company. Existing data on company occupational accidents were gathered and analysed to identify a work situation that appeared likely to cause AOL. This work situation was analysed in detail. Several risk factors were identified within this work situation, by way of interviews with 12 operators. These risk factors concerned various dimensions of the work situation, particularly its physical dimension (e.g. templates structure) and organisational dimension (e.g. parts availability). Interviews were conducted, focusing on risk factors perceived by operators and involving allo-confrontations based on accounts of four AOL occurring in this situation. Allo-confrontations were interviews confronting operators with a risk occupational situation that was accidental for one of their colleagues, the latter being absent from the interview. Results highlighted the fact that the work practices implemented are key factors in understanding these accidents. This study underlines the role of work practices in AOL causality and prevention. It also provides explanations associated with various work situation dimensions involving adoption of more or less safe work practices. AOL are serious and frequent in occupational situations. Injury claims analysis and interviews in an industrial company emphasise the specific characteristics of an occupational situation and of prevention actions forming the basis of an intervention. The need for a better understanding of factors affecting work practice is highlighted in relation to research.

  3. An adipoinductive role of inflammation in adipose tissue engineering: key factors in the early development of engineered soft tissues.

    PubMed

    Lilja, Heidi E; Morrison, Wayne A; Han, Xiao-Lian; Palmer, Jason; Taylor, Caroline; Tee, Richard; Möller, Andreas; Thompson, Erik W; Abberton, Keren M

    2013-05-15

    Tissue engineering and cell implantation therapies are gaining popularity because of their potential to repair and regenerate tissues and organs. To investigate the role of inflammatory cytokines in new tissue development in engineered tissues, we have characterized the nature and timing of cell populations forming new adipose tissue in a mouse tissue engineering chamber (TEC) and characterized the gene and protein expression of cytokines in the newly developing tissues. EGFP-labeled bone marrow transplant mice and MacGreen mice were implanted with TEC for periods ranging from 0.5 days to 6 weeks. Tissues were collected at various time points and assessed for cytokine expression through ELISA and mRNA analysis or labeled for specific cell populations in the TEC. Macrophage-derived factors, such as monocyte chemotactic protein-1 (MCP-1), appear to induce adipogenesis by recruiting macrophages and bone marrow-derived precursor cells to the TEC at early time points, with a second wave of nonbone marrow-derived progenitors. Gene expression analysis suggests that TNFα, LCN-2, and Interleukin 1β are important in early stages of neo-adipogenesis. Increasing platelet-derived growth factor and vascular endothelial cell growth factor expression at early time points correlates with preadipocyte proliferation and induction of angiogenesis. This study provides new information about key elements that are involved in early development of new adipose tissue.

  4. An Adipoinductive Role of Inflammation in Adipose Tissue Engineering: Key Factors in the Early Development of Engineered Soft Tissues

    PubMed Central

    Lilja, Heidi E.; Morrison, Wayne A.; Han, Xiao-Lian; Palmer, Jason; Taylor, Caroline; Tee, Richard; Möller, Andreas; Thompson, Erik W.

    2013-01-01

    Tissue engineering and cell implantation therapies are gaining popularity because of their potential to repair and regenerate tissues and organs. To investigate the role of inflammatory cytokines in new tissue development in engineered tissues, we have characterized the nature and timing of cell populations forming new adipose tissue in a mouse tissue engineering chamber (TEC) and characterized the gene and protein expression of cytokines in the newly developing tissues. EGFP-labeled bone marrow transplant mice and MacGreen mice were implanted with TEC for periods ranging from 0.5 days to 6 weeks. Tissues were collected at various time points and assessed for cytokine expression through ELISA and mRNA analysis or labeled for specific cell populations in the TEC. Macrophage-derived factors, such as monocyte chemotactic protein-1 (MCP-1), appear to induce adipogenesis by recruiting macrophages and bone marrow-derived precursor cells to the TEC at early time points, with a second wave of nonbone marrow-derived progenitors. Gene expression analysis suggests that TNFα, LCN-2, and Interleukin 1β are important in early stages of neo-adipogenesis. Increasing platelet-derived growth factor and vascular endothelial cell growth factor expression at early time points correlates with preadipocyte proliferation and induction of angiogenesis. This study provides new information about key elements that are involved in early development of new adipose tissue. PMID:23231040

  5. Glucose and Insulin Stimulate Lipogenesis in Porcine Adipocytes: Dissimilar and Identical Regulation Pathway for Key Transcription Factors

    PubMed Central

    Hua, Zhang Guo; Xiong, Lu Jian; Yan, Chen; Wei, Dai Hong; YingPai, ZhaXi; Qing, Zhao Yong; Lin, Qiao Zi; Fei, Feng Ruo; Ling, Wang Ya; Ren, Ma Zhong

    2016-01-01

    Lipogenesis is under the concerted action of ChREBP, SREBP-1c and other transcription factors in response to glucose and insulin. The isolated porcine preadipocytes were differentiated into mature adipocytes to investigate the roles and interrelation of these transcription factors in the context of glucose- and insulin-induced lipogenesis in pigs. In ChREBP-silenced adipocytes, glucose-induced lipogenesis decreased by ~70%, however insulin-induced lipogenesis was unaffected. Moreover, insulin had no effect on ChREBP expression of unperturbed adipocytes irrespective of glucose concentration, suggesting ChREBP mediate glucose-induced lipogenesis. Insulin stimulated SREBP-1c expression and when SREBP-1c activation was blocked, and the insulin-induced lipogenesis decreased by ~55%, suggesting SREBP-1c is a key transcription factor mediating insulin-induced lipogenesis. LXRα activation promoted lipogenesis and lipogenic genes expression. In ChREBP-silenced or SREBP-1c activation blocked adipocytes, LXRα activation facilitated lipogenesis and SREBP-1c expression, but had no effect on ChREBP expression. Therefore, LXRα might mediate lipogenesis via SREBP-1c rather than ChREBP. When ChREBP expression was silenced and SREBP-1c activation blocked simultaneously, glucose and insulin were still able to stimulated lipogenesis and lipogenic genes expression, and LXRα activation enhanced these effects, suggesting LXRα mediated directly glucose- and insulin-induced lipogenesis. In summary, glucose and insulin stimulated lipogenesis through both dissimilar and identical regulation pathway in porcine adipocytes. PMID:27871177

  6. 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

  7. The EMT-activator Zeb1 is a key factor for cell plasticity and promotes metastasis in pancreatic cancer.

    PubMed

    Krebs, Angela M; Mitschke, Julia; Lasierra Losada, María; Schmalhofer, Otto; Boerries, Melanie; Busch, Hauke; Boettcher, Martin; Mougiakakos, Dimitrios; Reichardt, Wilfried; Bronsert, Peter; Brunton, Valerie G; Pilarsky, Christian; Winkler, Thomas H; Brabletz, Simone; Stemmler, Marc P; Brabletz, Thomas

    2017-05-01

    Metastasis is the major cause of cancer-associated death. Partial activation of the epithelial-to-mesenchymal transition program (partial EMT) was considered a major driver of tumour progression from initiation to metastasis. However, the role of EMT in promoting metastasis has recently been challenged, in particular concerning effects of the Snail and Twist EMT transcription factors (EMT-TFs) in pancreatic cancer. In contrast, we show here that in the same pancreatic cancer model, driven by Pdx1-cre-mediated activation of mutant Kras and p53 (KPC model), the EMT-TF Zeb1 is a key factor for the formation of precursor lesions, invasion and notably metastasis. Depletion of Zeb1 suppresses stemness, colonization capacity and in particular phenotypic/metabolic plasticity of tumour cells, probably causing the observed in vivo effects. Accordingly, we conclude that different EMT-TFs have complementary subfunctions in driving pancreatic tumour metastasis. Therapeutic strategies should consider these potential specificities of EMT-TFs to target these factors simultaneously.

  8. Review—Understanding and Mitigating Some of the Key Factors that Limit Non-Aqueous Lithium-Air Battery Performance

    SciTech Connect

    Lu, Jun; Lau, Kah Chun; Sun, Yang-Kook; Curtiss, Larry A.; Amine, Khalil

    2015-01-01

    In this article, we have reviewed our work on understanding and mitigating some of the key factors that limit non-aqueous Li-air battery performance. Advances in Li-air battery technology require fundamental understanding of the discharge and charge processes. We first summarize an investigation of Li-air batteries based on a well-defined cathode surfaces having size-selected silver clusters. This work provided key insight into the nucleation and growth mechanism of the discharge product and its relationship to lowering charge potentials. We then describe the development of new cathode materials including ones based on Pd and Mo2C nanoparticles that give very low charge potentials. This work has shown that it is possible to achieve very good round-trip efficiencies as well as up to 100 cycles in a Li-air cell. Finally, we discuss investigations of likely sources of electrolyte decomposition at the cathode and anode, which need to be resolved in order to achieve the long cycle life that is necessary to enable Li-air batteries.

  9. The Arabidopsis transcription factor AtTCP15 regulates endoreduplication by modulating expression of key cell-cycle genes.

    PubMed

    Li, Zi-Yu; Li, Bin; Dong, Ai-Wu

    2012-01-01

    Plant cells frequently undergo endoreduplication, a modified cell cycle in which genome is repeatedly replicated without cytokinesis. As the key step to achieve final size and function for cells, endoreduplication is prevalent during plant development. However, mechanisms to control the balance between endoreduplication and mitotic cell division are still poorly understood. Here, we show that the Arabidopsis TCP (CINCINNATA-like TEOSINTE BRANCHED1-CYCLOIDEA-PCF)-family transcription factor gene AtTCP15 is expressed in trichomes, as well as in rapidly dividing and vascular tissues. Expression of AtTCP15SRDX, AtTCP15 fused with a SRDX repressor domain, induces extra endoreduplication in trichomes and cotyledon cells in transgenic Arabidopsis. On the contrary, overexpression of AtTCP15 suppresses endoreduplication in trichomes and other examined cells. Misregulation of AtTCP15 affects the expression of several important genes involved in cell-cycle regulation. AtTCP15 protein binds directly to the promoter regions of CYCA2;3 and RETINOBLASTOMA-RELATED (RBR) genes, which play key roles in endoreduplication. Taken together, AtTCP15 plays an important role in regulating endoreduplication during Arabidopsis development.

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

    DOE PAGES

    Dogan, Nergiz; Wu, Weisheng; Morrissey, Christapher S.; ...

    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

  11. 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.

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

    PubMed

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

    2015-01-01

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

  13. Impaired inactivation of digestive proteases: The possible key factor for the high susceptibility of germ-free and antibiotic-treated animals to gut epithelial injury

    PubMed Central

    Qin, Xiaofa

    2017-01-01

    Recent study shows that germ-free and antibiotic-treated animals are highly susceptible to gut epithelial injury. This paper addresses that impaired inactivation of digestive proteases may be the key factor for the increased susceptibility. PMID:28251033

  14. Impaired inactivation of digestive proteases: The possible key factor for the high susceptibility of germ-free and antibiotic-treated animals to gut epithelial injury.

    PubMed

    Qin, Xiaofa

    2017-02-15

    Recent study shows that germ-free and antibiotic-treated animals are highly susceptible to gut epithelial injury. This paper addresses that impaired inactivation of digestive proteases may be the key factor for the increased susceptibility.

  15. Citizen science participation in research in the environmental sciences: key factors related to projects' success and longevity.

    PubMed

    Cunha, Davi G F; Marques, Jonatas F; Resende, Juliana C DE; Falco, Patrícia B DE; Souza, Chrislaine M DE; Loiselle, Steven A

    2017-06-29

    The potential impacts of citizen science initiatives are increasing across the globe, albeit in an imbalanced manner. In general, there is a strong element of trial and error in most projects, and the comparison of best practices and project structure between different initiatives remains difficult. In Brazil, the participation of volunteers in environmental research is limited. Identifying the factors related to citizen science projects' success and longevity within a global perspective can contribute for consolidating such practices in the country. In this study, we explore past and present projects, including a case study in Brazil, to identify the spatial and temporal trends of citizen science programs as well as their best practices and challenges. We performed a bibliographic search using Google Scholar and considered results from 2005-2014. Although these results are subjective due to the Google Scholar's algorithm and ranking criteria, we highlighted factors to compare projects across geographical and disciplinary areas and identified key matches between project proponents and participants, project goals and local priorities, participant profiles and engagement, scientific methods and funding. This approach is a useful starting point for future citizen science projects, allowing for a systematic analysis of potential inconsistencies and shortcomings in this emerging field.

  16. Mapping of transcription factor motifs in active chromatin identifies IRF5 as key regulator in classical Hodgkin lymphoma.

    PubMed

    Kreher, Stephan; Bouhlel, M Amine; Cauchy, Pierre; Lamprecht, Björn; Li, Shuang; Grau, Michael; Hummel, Franziska; Köchert, Karl; Anagnostopoulos, Ioannis; Jöhrens, Korinna; Hummel, Michael; Hiscott, John; Wenzel, Sören-Sebastian; Lenz, Peter; Schneider, Markus; Küppers, Ralf; Scheidereit, Claus; Giefing, Maciej; Siebert, Reiner; Rajewsky, Klaus; Lenz, Georg; Cockerill, Peter N; Janz, Martin; Dörken, Bernd; Bonifer, Constanze; Mathas, Stephan

    2014-10-21

    Deregulated transcription factor (TF) activities are commonly observed in hematopoietic malignancies. Understanding tumorigenesis therefore requires determining the function and hierarchical role of individual TFs. To identify TFs central to lymphomagenesis, we identified lymphoma type-specific accessible chromatin by global mapping of DNaseI hypersensitive sites and analyzed enriched TF-binding motifs in these regions. Applying this unbiased approach to classical Hodgkin lymphoma (HL), a common B-cell-derived lymphoma with a complex pattern of deregulated TFs, we discovered interferon regulatory factor (IRF) sites among the top enriched motifs. High-level expression of the proinflammatory TF IRF5 was specific to HL cells and crucial for their survival. Furthermore, IRF5 initiated a regulatory cascade in human non-Hodgkin B-cell lines and primary murine B cells by inducing the TF AP-1 and cooperating with NF-κB to activate essential characteristic features of HL. Our strategy efficiently identified a lymphoma type-specific key regulator and uncovered a tumor promoting role of IRF5.

  17. New Evidences of Key Factors Involved in "Silent Stones" Etiopathogenesis and Trace Elements: Microscopic, Spectroscopic, and Biochemical Approach.

    PubMed

    Cavalu, Simona; Popa, Adriana; Bratu, Ioan; Borodi, Gheorghe; Maghiar, Adrian

    2015-12-01

    The knowledge of the key factors involved in etiopathogenesis of the gallstone disease requires chemical, structural, and elemental composition analysis. The application of different complementary analytical techniques, both microscopic and spectroscopic, are aimed to provide a more comprehensive determination of the gallbladder calculi ultrastructure and trace element identification. High sensitivity techniques such as electron microscopy (SEM), Fourier transform infrared (FTIR), electron paramagnetic resonance (EPR) spectroscopy, and X-ray diffraction (XRD) along with biochemical analysis are used in a new attempt to investigate various factors which play a regulatory role in the pathogenesis of gallstones. The microstructure of different types of gallbladder stones has specific characteristics which are related to the elemental composition. The binding of metal ions with bile salts and bilirubin plays important roles in gallstone formation as revealed by FTIR spectrum of calcium bilirubinate complex in pigment gallstones. The EPR results demonstrated the generation of bilirubin free radicals and variation of its electronic structure and conjugation system in the skeleton of bilirubin molecule during complex formation. EPR spectra of pigment gallstones demonstrate the coexistence of four paramagnetic centers including stable bilirubin free radical, Mn2+, Cu2+, and Fe3+ with distinct magnetic parameters and well-resolved hyperfine structure in the case of Mn2+ ions. The result confirms a macromolecular network structure with proteins and the formation of bilirubin-coordinated polymer. Bilirubin and bilirubinate free radical complexes may play an important role in pigment gallstone formation.

  18. Mapping of transcription factor motifs in active chromatin identifies IRF5 as key regulator in classical Hodgkin lymphoma

    PubMed Central

    Kreher, Stephan; Bouhlel, M. Amine; Cauchy, Pierre; Lamprecht, Björn; Li, Shuang; Grau, Michael; Hummel, Franziska; Köchert, Karl; Anagnostopoulos, Ioannis; Jöhrens, Korinna; Hummel, Michael; Hiscott, John; Wenzel, Sören-Sebastian; Lenz, Peter; Schneider, Markus; Küppers, Ralf; Scheidereit, Claus; Giefing, Maciej; Siebert, Reiner; Rajewsky, Klaus; Lenz, Georg; Cockerill, Peter N.; Janz, Martin; Dörken, Bernd; Bonifer, Constanze; Mathas, Stephan

    2014-01-01

    Deregulated transcription factor (TF) activities are commonly observed in hematopoietic malignancies. Understanding tumorigenesis therefore requires determining the function and hierarchical role of individual TFs. To identify TFs central to lymphomagenesis, we identified lymphoma type-specific accessible chromatin by global mapping of DNaseI hypersensitive sites and analyzed enriched TF-binding motifs in these regions. Applying this unbiased approach to classical Hodgkin lymphoma (HL), a common B-cell–derived lymphoma with a complex pattern of deregulated TFs, we discovered interferon regulatory factor (IRF) sites among the top enriched motifs. High-level expression of the proinflammatory TF IRF5 was specific to HL cells and crucial for their survival. Furthermore, IRF5 initiated a regulatory cascade in human non-Hodgkin B-cell lines and primary murine B cells by inducing the TF AP-1 and cooperating with NF-κB to activate essential characteristic features of HL. Our strategy efficiently identified a lymphoma type-specific key regulator and uncovered a tumor promoting role of IRF5. PMID:25288773

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

    PubMed

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

    2017-01-01

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

  20. Identification of HNF-4α as a key transcription factor to promote ChREBP expression in response to glucose

    PubMed Central

    Meng, Jian; Feng, Ming; Dong, Weibing; Zhu, Yemin; Li, Yakui; Zhang, Ping; Wu, Lifang; Li, Minle; Lu, Ying; Chen, Hanbei; Liu, Xing; Lu, Yan; Sun, Haipeng; Tong, Xuemei

    2016-01-01

    Transcription factor carbohydrate responsive element binding protein (ChREBP) promotes glycolysis and lipogenesis in metabolic tissues and cancer cells. ChREBP-α and ChREBP-β, two isoforms of ChREBP transcribed from different promoters, are both transcriptionally induced by glucose. However, the mechanism by which glucose increases ChREBP mRNA levels remains unclear. Here we report that hepatocyte nuclear factor 4 alpha (HNF-4α) is a key transcription factor for glucose-induced ChREBP-α and ChREBP-β expression. Ectopic HNF-4α expression increased ChREBP transcription while knockdown of HNF-4α greatly reduced ChREBP mRNA levels in liver cancer cells and mouse primary hepatocytes. HNF-4α not only directly bound to an E-box-containing region in intron 12 of the ChREBP gene, but also promoted ChREBP-β transcription by directly binding to two DR1 sites and one E-box-containing site of the ChREBP-β promoter. Moreover, HNF-4α interacted with ChREBP-α and synergistically promoted ChREBP-β transcription. Functionally, HNF-4α suppression reduced glucose-dependent ChREBP induction. Increased nuclear abundance of HNF-4α and its binding to cis-elements of ChREBP gene in response to glucose contributed to glucose-responsive ChREBP transcription. Taken together, our results not only revealed the novel mechanism by which HNF-4α promoted ChREBP transcription in response to glucose, but also demonstrated that ChREBP-α and HNF-4α synergistically increased ChREBP-β transcription. PMID:27029511

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2017-01-01

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

  3. 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

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

    PubMed

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

    2015-01-01

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

  5. Carotenoid derivatives inhibit nuclear factor kappa B activity in bone and cancer cells by targeting key thiol groups.

    PubMed

    Linnewiel-Hermoni, Karin; Motro, Yair; Miller, Yifat; Levy, Joseph; Sharoni, Yoav

    2014-10-01

    Aberrant activation of the nuclear factor kappa B (NFkB) transcription system contributes to cancer progression, and has a harmful effect on bone health. Several major components of the NFkB pathway such as IkB Kinase (IKK) and the NFkB subunits contain cysteine residues that are critical for their activity. The interaction of electrophiles with these cysteine residues results in NFkB inhibition. Carotenoids, hydrophobic plant pigments, are devoid of electrophilic groups, and we have previously demonstrated that carotenoid derivatives, but not the native compounds activate the Nrf2 transcription system. The aim of the current study was to examine whether carotenoid derivatives inhibit NFkB, and, if so, to determine the molecular mechanism underpinning the inhibitory action. We report in the present study that a mixture of oxidized derivatives, prepared by ethanol extraction from partially oxidized lycopene preparation, inhibited NFkB reporter gene activity. In contrast, the intact carotenoid was inactive. A series of synthetic dialdehyde carotenoid derivatives inhibited reporter activity as well as several stages of the NFkB pathway in both cancer and bone cells. The activity of the carotenoid derivatives depended on the reactivity of the electrophilic groups in reactions such as Michael addition to sulfhydryl groups of proteins. Specifically, carotenoid derivatives directly interacted with two key proteins of the NFkB pathway: the IKKβ and the p65 subunit. Direct interaction with IKKβ was found in an in vitro kinase assay with a recombinant enzyme. The inhibition by carotenoid derivatives of p65 transcriptional activity was observed in a reporter gene assay performed in the presence of excess p65. This inhibition action resulted, at least in part, from direct interaction of the carotenoid derivative with p65 leading to reduced binding of the protein to DNA as evidenced by electrophoretic mobility shift assay (EMSA) experiments. Importantly, we found by using

  6. Genomics: Applications in Mechanism Elucidation

    PubMed Central

    Gresham, Venita; McLeod, Howard L.

    2009-01-01

    The inability to predict the pharmacology and toxicology of drug candidates in preclinical studies has led to the decline in the number of new drugs which make it to market and the rise in cost associated with drug development. Identifying molecular interactions associated with therapeutic and toxic drug effects early in development is a top priority. Traditional mechanism elucidation strategies are narrow, often focusing on the identification of solely the molecular target. Methods which can offer additional insight into wide-ranging molecular interactions required for drug effect and the biochemical consequences of these interactions are in demand. Genomic strategies have made impressive advances in defining a more global view of drug action are expected to increasingly be used a complimentary tool in drug discovery and development. PMID:19166886

  7. 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

  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.

  9. 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

  10. Improving the efficiency of isolated microspore culture in six-row spring barley: I-optimization of key physical factors.

    PubMed

    Esteves, Patricio; Belzile, François

    2014-06-01

    An improved isolated microspore culture protocol alleviating the recalcitrance typically observed in six-row spring barley was developed by optimizing four key physical factors to increase embryogenesis and reduce albinism. Doubled haploid (DH) plants are completely homozygous individuals that can be generated in just a few months via androgenesis in vitro. DHs are useful tools in genetic research and in plant breeding. Isolated microspore culture (IMC) is the most efficient way to produce DHs, but a strong genotype dependency imposes limitations to its wide application. Six-row, spring barley genotypes are considered as particularly recalcitrant due to a low frequency of embryogenesis and a high rate of albinism. Seeking to develop an efficient IMC protocol for this type of barley, we explored four important factors: (1) the harvest stage of immature spikes, (2) the type of pretreatment applied, (3) the osmotic potential in the induction medium, and (4) the plating density of microspores. This work was first performed using four barley genotypes: two typical six-row spring cultivars (ACCA and Léger), a two-row spring (Gobernadora) and a two-row winter (Igri) cultivar. First, by optimizing the harvest stage for each genotype we obtained a twofold to fourfold increase in the yield of embryogenic microspores. Second, two pretreatments (0.3 M mannitol for 2 days, or a combination of cold and heat over 15 days) both performed significantly better than the commonly used cold pretreatment (28 days at 4 °C). Third, an induction medium-containing mannitol (32 g/l) doubled green plant regeneration. Fourth, a plating density of 10(6) microspores/ml yielded the highest number of green regenerated plants. Our most important findings were then confirmed using sets of F1s from a six-row, spring-type breeding program.

  11. Receptor Activator for Nuclear Factor kappa B Ligand (RANKL) as an osteoimmune key regulator in bone physiology and pathology.

    PubMed

    Narducci, Paola; Bareggi, Renato; Nicolin, Vanessa

    2011-02-01

    The strength and integrity of the human skeleton depends on a delicate equilibrium between bone resorption and bone formation. Bone resorption is an elementary cellular activity in the modelling of the skeleton during growth and development. Later in life a most important physiological process in the skeleton is bone remodelling, which is locally initiated by resorption. During remodelling bone resorption is coupled to new bone formation that ensures renewal of bone with only minor local and temporary bone loss. Cells responsible for bone resorption and subsequent bone formation are the osteoclasts and osteoblasts, respectively. The osteoclast is derived from the pluripotent hematopoietic stem cell, which gives rise to a myeloid stem cell that can further differentiate into megakaryocytes, granulocytes, monocytes/macrophages and osteoclasts. The respective bone resorbing and forming actions of osteoclasts and osteoblasts are finely coupled, so that bone mass remains remarkably stable in a healthy adult. Imbalance between osteoclast and osteoblast activities can arise from a wide variety of hormonal changes or perturbations of inflammatory and growth factors resulting in postmenopausal osteoporosis, Paget's disease, lytic bone metastases, or rheumatoid arthritis, leading to increased bone resorption and crippling bone damage. In view of the critical role of osteoclasts in diverse pathology, there has been immense effort aimed at understanding the biology of this unique cell. The present review is focused on the current knowledge of the mechanisms that regulate the functional links between bone turnover and the immune system helping us to understand the main factors that lead to bone loss observed in osteoporosis, cancer and in rheumatoid arthritis. The aim of this review paper is to consider the key molecular interactions involved in the formation of osteoclast cells in normal and pathological conditions.

  12. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    PubMed

    Strbak, Oliver; Kanuchova, Zuzana; Krafcik, Andrej

    2016-11-01

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

    PubMed

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

    2014-06-01

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

  15. Deep sequencing of Lotus corniculatus L. reveals key enzymes and potential transcription factors related to the flavonoid biosynthesis pathway.

    PubMed

    Wang, Ying; Hua, Wenping; Wang, Jian; Hannoufa, Abdelali; Xu, Ziqin; Wang, Zhezhi

    2013-04-01

    Lotus corniculatus L. is used worldwide as a forage crop due to its abundance of secondary metabolites and its ability to grow in severe environments. Although the entire genome of L. corniculatus var. japonicus R. is being sequenced, the differences in morphology and production of secondary metabolites between these two related species have led us to investigate this variability at the genetic level, in particular the differences in flavonoid biosynthesis. Our goal is to use the resulting information to develop more valuable forage crops and medicinal materials. Here, we conducted Illumina/Solexa sequencing to profile the transcriptome of L. corniculatus. We produced 26,492,952 short reads that corresponded to 2.38 gigabytes of total nucleotides. These reads were then assembled into 45,698 unigenes, of which a large number associated with secondary metabolism were annotated. In addition, we identified 2,998 unigenes based on homology with L. japonicus transcription factors (TFs) and grouped them into 55 families. Meanwhile, a comparison of four tag-based digital gene expression libraries, built from the flowers, pods, leaves, and roots, revealed distinct patterns of spatial expression of candidate unigenes in flavonoid biosynthesis. Based on these results, we identified many key enzymes from L. corniculatus which were different from reference genes of L. japonicus, and five TFs that are potential enhancers in flavonoid biosynthesis. Our results provide initial genetics resources that will be valuable in efforts to manipulate the flavonoid metabolic pathway in plants.

  16. Spectrin-ankyrin interaction mechanics: A key force balance factor in the red blood cell membrane skeleton.

    PubMed

    Saito, Masakazu; Watanabe-Nakayama, Takahiro; Machida, Shinichi; Osada, Toshiya; Afrin, Rehana; Ikai, Atsushi

    2015-01-01

    As major components of red blood cell (RBC) cytoskeleton, spectrin and F-actin form a network that covers the entire cytoplasmic surface of the plasma membrane. The cross-linked two layered structure, called the membrane skeleton, keeps the structural integrity of RBC under drastically changing mechanical environment during circulation. We performed force spectroscopy experiments on the atomic force microscope (AFM) as a means to clarify the mechanical characteristics of spectrin-ankyrin interaction, a key factor in the force balance of the RBC cytoskeletal structure. An AFM tip was functionalized with ANK1-62k and used to probe spectrin crosslinked to mica surface. A force spectroscopy study gave a mean unbinding force of ~30 pN under our experimental conditions. Two energy barriers were identified in the unbinding process. The result was related to the well-known flexibility of spectrin tetramer and participation of ankyrin 1-spectrin interaction in the overall balance of membrane skeleton dynamics. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Research on key factors and their interaction effects of electromagnetic force of high-speed solenoid valve.

    PubMed

    Liu, Peng; Fan, Liyun; Hayat, Qaisar; 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.

  18. 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

  19. Susceptibility to Phytophthora ramorum in a key infectious host: landscape variation in host genotype, host phenotype, and environmental factors.

    PubMed

    Anacker, Brian L; Rank, Nathan E; Hüberli, Daniel; Garbelotto, Matteo; Gordon, Sarah; Harnik, Tami; Whitkus, Richard; Meentemeyer, Ross

    2008-01-01

    Sudden oak death is an emerging forest disease caused by the invasive pathogen Phytophthora ramorum. Genetic and environmental factors affecting susceptibility to P. ramorum in the key inoculum-producing host tree Umbellularia californica (bay laurel) were examined across a heterogeneous landscape in California, USA. Laboratory susceptibility trials were conducted on detached leaves and assessed field disease levels for 97 host trees from 12 225-m(2) plots. Genotype and phenotype characteristics were assessed for each tree. Effects of plot-level environmental conditions (understory microclimate, amount of solar radiation and topographic moisture potential) on disease expression were also evaluated. Susceptibility varied significantly among U. californica trees, with a fivefold difference in leaf lesion size. Lesion size was positively related to leaf area, but not to other phenotypic traits or to field disease level. Genetic diversity was structured at three spatial scales, but primarily among individuals within plots. Lesion size was significantly related to amplified fragment length polymorphism (AFLP) markers, but local environment explained most variation in field disease level. Thus, substantial genetic variation in susceptibility to P. ramorum occurs in its principal foliar host U. californica, but local environment mediates expression of susceptibility in nature.

  20. Identifying a key physical factor sensitive to the performance of Madden-Julian oscillation simulation in climate models

    NASA Astrophysics Data System (ADS)

    Kim, Go-Un; Seo, Kyong-Hwan

    2017-03-01

    A key physical factor in regulating the performance of Madden-Julian oscillation (MJO) simulation is examined by using 26 climate model simulations from the World Meteorological Organization's Working Group for Numerical Experimentation/Global Energy and Water Cycle Experiment Atmospheric System Study (WGNE and MJO-Task Force/GASS) global model comparison project. For this, intraseasonal moisture budget equation is analyzed and a simple, efficient physical quantity is developed. The result shows that MJO skill is most sensitive to vertically integrated intraseasonal zonal wind convergence (ZC). In particular, a specific threshold value of the strength of the ZC can be used as distinguishing between good and poor models. An additional finding is that good models exhibit the correct simultaneous convection and large-scale circulation phase relationship. In poor models, however, the peak circulation response appears 3 days after peak rainfall, suggesting unfavorable coupling between convection and circulation. For an improving simulation of the MJO in climate models, we propose that this delay of circulation in response to convection needs to be corrected in the cumulus parameterization scheme.

  1. 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

    2016-11-01

    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.

  2. Depression and key associated factors in female sex workers and women living with HIV/AIDS in the Dominican Republic.

    PubMed

    Rael, Christine T; Davis, Alissa

    2017-04-01

    Little is known about the mental health of female sex workers and women living with HIV/AIDS in the Dominican Republic, which impedes HIV prevention, testing, and treatment. This project estimates the prevalence of depression and identifies key contributing factors to this outcome in female sex workers, women living with HIV/AIDS, and a comparison group. Participants were female sex workers (N = 349), women living with HIV/AIDS (N = 213), and a comparison group of HIV-negative women who were not sex workers (N = 314) from the Dominican Republic. Participants completed questionnaires assessing demographic characteristics and depression. Female sex workers and women living with HIV/AIDS completed additional questionnaires ascertaining HIV or sex work-related internalized stigma. Depression was prevalent among female sex workers (70.2%), women living with HIV/AIDS (81.1%), and the comparison group (52.2%). Adjusted logistic regressions showed that internalized stigma was associated with depression for female sex workers (OR = 2.73; 95% CI = 1.95-3.84) and women living with HIV/AIDS (OR = 3.06; 95% CI = 1.86-5.05). Permanent income was associated with this outcome for female sex workers (OR = 0.08; 95% CI = 0.01-0.80) and the comparison group (OR = 0.04; 95% CI = 0.00-0.45).

  3. 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

    2016-07-29

    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.

  4. 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

  5. Information and professional support: key factors in the provision of family-centred early childhood intervention services.

    PubMed

    Fordham, L; Gibson, F; Bowes, J

    2012-09-01

    Much has been written on the principles of family-centred practice and on the service delivery methods and skills required of its practitioners. Far less has been written from the perspective of families whose children have a disability. The aims of this study were twofold: firstly to understand families' experiences of family-centred early childhood intervention services and secondly to explore other factors that might impact on these experiences. One hundred and thirty families attending two established early childhood intervention services in New South Wales, Australia completed a survey incorporating the Measure of Processes of Care-56, the Family Empowerment Scale, the Family Support Scale and the Parenting Daily Hassles Scale. Consistent with previous research using the Measure of Processes of Care-56, 'respectful and supportive care' was the domain of care families rated to occur most and 'provision of general information' was the domain they rated to occur least. Significant positive relationships existed between families' ratings of family-centred care and feelings of empowerment. Being provided with general information was strongly correlated with family empowerment. Families' social support networks played an important role but support from professionals was most strongly correlated with families' experiences of family-centred care. Finally, families whose children's early intervention services were co-ordinated by a professional experienced significantly better care. The provision of general information and professional support are key components of family-centred early childhood intervention services. © 2011 Blackwell Publishing Ltd.

  6. How the Adoption of the Big-Data Paradigm Affects the Key Factors That Influence the Effectiveness of an Information Assurance (IA) Framework: A Multiple-Case Study

    ERIC Educational Resources Information Center

    Apple, Benjamin G.

    2017-01-01

    This qualitative study identified those factors that influence the perceived effectiveness of traditional IA control frameworks. The key factors examined in this study are risk management, governance, access control, privacy protection, integrity, availability, reliability, and usability. The researcher endeavored to determine how the…

  7. 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…

  8. Regulation of Tacaribe Mammarenavirus Translation: Positive 5' and Negative 3' Elements and Role of Key Cellular Factors.

    PubMed

    Foscaldi, Sabrina; D'Antuono, Alejandra; Noval, María Gabriela; de Prat Gay, Gonzalo; Scolaro, Luis; Lopez, Nora

    2017-07-15

    Mammarenaviruses are enveloped viruses with a bisegmented negative-stranded RNA genome that encodes the nucleocapsid protein (NP), the envelope glycoprotein precursor (GPC), the RNA polymerase (L), and a RING matrix protein (Z). Viral proteins are synthesized from subgenomic mRNAs bearing a capped 5' untranslated region (UTR) and lacking 3' poly(A) tail. We analyzed the translation strategy of Tacaribe virus (TCRV), a prototype of the New World mammarenaviruses. A virus-like transcript that carries a reporter gene in place of the NP open reading frame and transcripts bearing modified 5' and/or 3' UTR were evaluated in a cell-based translation assay. We found that the presence of the cap structure at the 5' end dramatically increases translation efficiency and that the viral 5' UTR comprises stimulatory signals while the 3' UTR,specifically the presence of a terminal C+G-rich sequence and/or a stem-loop structure, down-modulates translation. Additionally, translation was profoundly reduced in eukaryotic initiation factor (eIF) 4G-inactivated cells, whereas depletion of intracellular levels of eIF4E had less impact on virus-like mRNA translation than on a cell-like transcript. Translation efficiency was independent of NP expression or TCRV infection. Our results indicate that TCRV mRNAs are translated using a cap-dependent mechanism, whose efficiency relies on the interplay between stimulatory signals in the 5' UTR and a negative modulatory element in the 3' UTR. The low dependence on eIF4E suggests that viral mRNAs may engage yet-unknown noncanonical host factors for a cap-dependent initiation mechanism.IMPORTANCE Several members of the Arenaviridae family cause serious hemorrhagic fevers in humans. In the present report, we describe the mechanism by which Tacaribe virus, a prototypic nonpathogenic New World mammarenavirus, regulates viral mRNA translation. Our results highlight the impact of untranslated sequences and key host translation factors on this process

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

    PubMed

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

    2017-01-01

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

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

    PubMed Central

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

    2017-01-01

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

  11. 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

  12. Elucidating Mechanisms of Extensive Chaos

    NASA Astrophysics Data System (ADS)

    Egolf, David A.; Melnikov, Ilarion V.; Pesch, Werner; Ecke, Robert E.

    2001-06-01

    We report studies of the mechanism for the generation of chaotic disorder in a phenomenon found in nature, Rayleigh-Bénard convection (RBC), in a regime exhaustively studied experimentally. Through large-scale, parallel-computational studies of the detailed space-time evolution of the dynamical degrees of freedom, we find that the Spiral Defect Chaos (SDC) state of RBC is spatially- and temporally- localized to defect creation/annihilation events (D.A. Egolf, I.V. Melnikov, W. Pesch, and R.E. Ecke, Nature, 404:733--736, 2000), and we elucidate how these divergent, but very brief, events lead to eventual macroscopic differences between initially similar flow patterns. We also demonstrate that SDC is extensively chaotic, in that the number of dynamical degrees of freedom (the fractal dimension) is proportional to the system size, suggesting the possibility for a hydrodynamic-like description of the long-wavelength properties of SDC. The computational technique employed shows promise for analyzing a wide variety of extended dynamical systems.

  13. Human CAP1 is a key factor in the recycling of cofilin and actin for rapid actin turnover.

    PubMed

    Moriyama, Kenji; Yahara, Ichiro

    2002-04-15

    Cofilin-ADF (actin-depolymerizing factor) is an essential driver of actin-based motility. We discovered two proteins, p65 and p55, that are components of the actin-cofilin complex in a human HEK293 cell extract and identified p55 as CAP1/ASP56, a human homologue of yeast CAP/SRV2 (cyclase-associated protein). CAP is a bifunctional protein with an N-terminal domain that binds to Ras-responsive adenylyl cyclase and a C-terminal domain that inhibits actin polymerization. Surprisingly, we found that the N-terminal domain of CAP1, but not the C-terminal domain, is responsible for the interaction with the actin-cofilin complex. The N-terminal domain of CAP1 was also found to accelerate the depolymerization of F-actin at the pointed end, which was further enhanced in the presence of cofilin and/or the C-terminal domain of CAP1. Moreover, CAP1 and its C-terminal domain were observed to facilitate filament elongation at the barbed end and to stimulate ADP-ATP exchange on G-actin, a process that regenerates easily polymerizable G-actin. Although cofilin inhibited the nucleotide exchange on G-actin even in the presence of the C-terminal domain of CAP1, its N-terminal domain relieved this inhibition. Thus, CAP1 plays a key role in speeding up the turnover of actin filaments by effectively recycling cofilin and actin and through its effect on both ends of actin filament.

  14. Protein kinase CK2/PTEN pathway plays a key role in platelet-activating factor-mediated murine anaphylactic shock.

    PubMed

    Kang, Nam-In; Yoon, Ha-Yong; Kim, Han-A; Kim, Kyoung-Jin; Han, Myung-Kwan; Lee, Young-Rae; Hwang, Pyoung-Han; Soh, Byoung-Yul; Shin, Sook-Jeong; Im, Suhn-Young; Lee, Hern-Ku

    2011-06-01

    Platelet-activating factor (PAF) is a major mediator in the induction of fatal hypovolemic shock in murine anaphylaxis. This PAF-mediated effect has been reported to be associated with PI3K/Akt-dependent eNOS-derived NO. The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is phosphatidylinositol phosphate phosphatase, which negatively controls PI3K by dephosphorylating the signaling lipid, phosphatidylinositol 3,4,5-triphosphate. In this study, we examined the possible involvement of PTEN in PAF-mediated anaphylactic shock. Induction of anaphylaxis or PAF injection resulted in a rapid decrease in PTEN activity, followed by increases in PI3K activity and phosphorylation of Akt and eNOS. Systemic administration of adenoviruses carrying PTEN cDNA (adenoviral PTEN), but not the control AdLacZ, not only attenuated anaphylactic symptoms, but also reversed anaphylaxis- or PAF-induced changes in PTEN and PI3K activities, as well as phosphorylation of Akt and eNOS. We found that the decreased PTEN activity was associated with PTEN phosphorylation, the latter effect being prevented by the protein kinase CK2 inhibitor, DMAT. DMAT also inhibited anaphylactic symptoms as well as the anaphylaxis- or PAF-mediated PTEN/PI3K/Akt/eNOS signaling cascade. CK2 activity was increased by PAF. The present data provide, as the key mechanism underlying anaphylactic shock, PAF triggers the upstream pathway CK2/PTEN, which ultimately leads to the activation of PI3K/Akt/eNOS. Therefore, CK2/PTEN may be a potent target in the control of anaphylaxis and other many PAF-mediated pathologic conditions.

  15. TeA is a key virulence factor for Alternaria alternata (Fr.) Keissler infection of its host.

    PubMed

    Kang, Ye; Feng, Hongwei; Zhang, Jingxu; Chen, Shiguo; Valverde, Bernal E; Qiang, Sheng

    2017-06-01

    A toxin-deficient mutant strain, HP001 mutant of Alternaria alternata, whose mycelium is unable to infect its host, produces little tenuazonic acid (TeA) toxin. How TeA plays a role in initiating host infection by A. alternata remains unclear. In this research we use Imaging-PAM based on chlorophyll fluorescence parameters and transmission electron microscopy to explore the role of TeA toxin during the infection process of A. alternata. Photosystem II damage began even before wild type mycelium infected the leaves of its host, croftonweed (Ageratina adenophora). Compared with the wild type, HP001 mutant produces morphologically different colonies, hyphae with thinner cell walls, has higher reactive oxygen species (ROS) content and lower peroxidase activity, and fails to form appressoria on the host surface. Adding TeA toxin allows the mutant to partially recover these characters and more closely resemble the wild type. Additionally, we found that the mutant is able to elicit disease symptoms when its mycelium is placed on leaves whose epidermis has been manually removed, which indicates that TeA may be determinant in the fungus recognition of its plant host. Lack of TeA toxin appears responsible for the loss of pathogenicity of the HP001 mutant. As a key virulence factor, TeA toxin not only damages the host plant but also is involved in maintaining ROS content, host recognition, inducing appressoria to infect the host and for allowing completion of the infection process. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  16. Sustained and therapeutic levels of human factor IX in hemophilia B mice implanted with microcapsules: key role of encapsulated cells.

    PubMed

    Wen, Jianping; Vargas, Andrew Gómez; Ofosu, Frederick A; Hortelano, Gonzalo

    2006-03-01

    A gene therapy delivery system based on microcapsules enclosing recombinant cells engineered to secrete a therapeutic protein was explored in this study. In order to prevent immune rejection of the delivered cells, they were enclosed in non-antigenic biocompatible alginate microcapsules prior to being implanted intraperitoneally into mice. We have shown that encapsulated C2C12 myoblasts can temporarily deliver therapeutic levels of factor IX (FIX) in mice, but the C2C12 myoblasts elicited an immune response to FIX. In this study we report the use of mouse fetal G8 myoblasts secreting hFIX in hemophilia mice. Mouse G8 myoblasts were transduced with MFG-FIX vector. A pool of recombinant G8 myoblasts secreting approximately 1500 ng hFIX/10(6) cells/24 h in vitro were enclosed in biocompatible alginate microcapsules and implanted intraperitoneally into immunocompetent C57BL/6 and hemophilic mice. Circulating levels of hFIX in treated mice reached approximately 400 ng/ml for at least 120 days (end of experiment). Interestingly, mice treated with encapsulated G8 myoblasts did not develop anti-hFIX antibodies. Activated partial thromboplastin time (APTT) of plasmas obtained from treated hemophilic mice was reduced from 107 to 82 sec on day 60 post-treatment, and whole blood clotting time (WBCT) was also corrected from 7-9 min before treatment to 3-5 min following microcapsule implantation. Further, mice were protected against bleeding following major trauma. Thus, the FIX delivery in vivo was biologically active. Our findings suggest that the type of cells encapsulated play a key role in the generation of immune responses against the transgene. Further, a judicious selection of encapsulated cells is critical for achieving sustained gene expression. Our findings support the feasibility of encapsulated G8 myoblasts as a gene therapy approach for hemophilia B.

  17. Master's level education in Jordan: a qualitative study of key motivational factors and perceived impact on practice.

    PubMed

    Zahran, Zainab

    2013-09-01

    To explore key motivational factors of Jordanian nurses to undertake a Master's degree and explore perceived impact on practice. In Jordan, there are postgraduate educational programmes offering a Master's degree in clinical nursing for registered nurses. These programmes are intended to prepare nurses to practise at an advanced level as potential clinical nurse specialists. Little is known about the motivation of nurses to undertake such Master's degree preparation programmes and their perceived impact on practice. Using an ethnographic design, narratives from semi-structured interviews with participants (n=37) from five Jordanian hospitals and two public universities were collected and thematically analysed. Four main themes emerged from the data: self development; broadening career opportunities; developing practice; and the perceived impact of Master's level nurses on practice. The majority of Jordanian nurses chose to undertake a Master's degree because of a desire for self and practice development. The majority of participants referred to M-level nurses in terms of knowledge transfer, highlighting their clinical teaching and in-service education activities. M-level nurses were also associated with managerial and supervisory roles in clinical practice. Controversy over the impact of M-level nurses in enhancing patient care is not limited to the Jordanian setting. Future research needs to focus on comparative studies between nurses with M-level qualifications and experienced nurses without either M-level qualifications or specialist courses to establish if there is any significant relationship between practice performance and educational preparation and experience. Evaluation research could be undertaken for the purpose of developing measurable and observable criteria related to educational and skill based outcomes. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. 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

  19. Granulocyte-macrophage colony-stimulating factor is a key mediator in experimental osteoarthritis pain and disease development

    PubMed Central

    2012-01-01

    Introduction Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to be important in the development of inflammatory models of rheumatoid arthritis and there is encouraging data that its blockade may have clinical relevance in patients with rheumatoid arthritis. The aims of the current study were to determine whether GM-CSF may also be important for disease and pain development in a model of osteoarthritis. Methods The role of GM-CSF was investigated using the collagenase-induced instability model of osteoarthritis. We studied both GM-CSF-/- mice and wild-type (C57BL/6) mice treated prophylactically or therapeutically with a monoclonal antibody to GM-CSF. Disease development (both early and late) was evaluated by histology and knee pain development was measured by assessment of weight distribution. Results In the absence of GM-CSF, there was less synovitis and matrix metalloproteinase-mediated neoepitope expression at week 2 post disease induction, and less cartilage damage at week 6. GM-CSF was absolutely required for pain development. Therapeutic neutralization of GM-CSF not only abolished the pain within 3 days but also led to significantly reduced cartilage damage. Conclusions GM-CSF is key to the development of experimental osteoarthritis and its associated pain. Importantly, GM-CSF neutralization by a therapeutic monoclonal antibody-based protocol rapidly and completely abolished existing arthritic pain and suppressed the degree of arthritis development. Our results suggest that it would be worth exploring the importance of GM-CSF for pain and disease in other osteoarthritis models and perhaps clinically for this form of arthritis. PMID:22995428

  20. In vivo tumor targeting and radionuclide imaging with self-assembled nanoparticles: mechanisms, key factors, and their implications.

    PubMed

    Cho, Yong Woo; Park, Soo Ah; Han, Tae Hee; Son, Dai Hyun; Park, Ji Sun; Oh, Seung Jun; Moon, Dae Hyuk; Cho, Kyung-Ja; Ahn, Cheol-Hee; Byun, Youngro; Kim, In-San; Kwon, Ick Chan; Kim, Sang Yoon

    2007-02-01

    The development of more selective delivery systems for cancer diagnosis and chemotherapy is one of the most important goals of current anticancer research. The purpose of this study is to evaluate various self-assembled nanoparticles as candidates to shuttle radionuclide and/or drugs into tumors and to investigate the mechanisms underlying the tumor targeting with self-assembled nanoparticles. By combining different hydrophobic moieties and hydrophilic polymer backbones, various self-assembled nanoparticles were prepared, and their in vivo distributions in tumor-bearing mice were studied by radionuclide imaging. One type of nanoparticles (fluorescein isothiocyanate-conjugated glycol chitosan (FGC) nanoparticles) exhibited highly selective tumoral localization. Scintigraphic images obtained 1 day after the intravenous injection of FGC nanoparticles clearly delineated the tumor against adjacent tissues. The mechanisms underlying the tumor targeting with self-assembled nanoparticles were investigated in terms of the physicochemical properties of nanoparticles and tumor microenvironments. FGC nanoparticles were preferentially localized in perivascular regions, implying their extravasation to tumors through the hyperpermeable tumor vasculature. The magnitude and pattern of tumoral distribution of self-assembled nanoparticles were influenced by several key factors--(i) in vivo colloidal stability: nanoparticles should maintain their intact nanostructures in vivo for a long period of time, (ii) particle size, (iii) intracellular uptake of nanoparticle: fast cellular uptake greatly facilitates the tumor targeting, (iv) tumor angiogenesis: pathological angiogenesis permits access of nanoparticles to tumors. We believe that this work can provide insight for the engineering of nanoparticles and be extended to cancer therapy and diagnosis, so as to deliver multiple therapeutic agents and imaging probes at high local concentrations.

  1. Characterization of key transcription factors as molecular signatures of HPV-positive and HPV-negative oral cancers.

    PubMed

    Verma, Gaurav; Vishnoi, Kanchan; Tyagi, Abhishek; Jadli, Mohit; Singh, Tejveer; Goel, Ankit; Sharma, Ankita; Agarwal, Kiran; Prasad, Subhash Chandra; Pandey, Durgatosh; Sharma, Shashi; Mehrotra, Ravi; Singh, Sukh Mahendra; Bharti, Alok Chandra

    2017-03-01

    Prior studies established constitutively active AP-1, NF-κB, and STAT3 signaling in oral cancer. Differential expression/activation of specific members of these transcription factors has been documented in HPV-positive oral lesions that respond better to therapy. We performed a comprehensive analysis of differentially expressed, transcriptionally active members of these pivotal signaling mediators to develop specific signatures of HPV-positive and HPV-negative oral lesions by immunohistochemical method that is applicable in low-resource settings. We examined a total of 31 prospective and 30 formalin-fixed, paraffin-embedded tissues from treatment-naïve, histopathologically and clinically confirmed cases diagnosed as oral or oropharyngeal squamous cell carcinoma (OSCC/OPSCC). Following determination of their HPV status by GP5 + /GP6 +  PCR, the sequential sections of the tissues were evaluated for expression of JunB, JunD, c-Fos, p50, p65, STAT3, and pSTAT3(Y705), along with two key regulatory proteins pEGFR and p16 by IHC. Independent analysis of JunB and p65 showed direct correlation with HPV positivity, whereas STAT3 and pSTAT3 were inversely correlated. A combined analysis of transcription factors revealed a more restrictive combination, characterized by the presence of AP-1 and NF-κB lacking involvement of STAT3 that strongly correlated with HPV-positive tumors. Presence of STAT3/pSTAT3 with NF-κB irrespective of the presence or absence of AP-1 members was present in HPV-negative lesions. Expression of pSTAT3 strongly correlated with all the AP-1/NF-κB members (except JunD), its upstream activator pEGFR(Y)(1092) , and HPV infection-related negative regulator p16. Overall, we show a simple combination of AP-1, NF-κB, and STAT3 members' expression that may serve as molecular signature of HPV-positive lesions or more broadly the tumors that show better prognosis.

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

    PubMed

    Schertel, Claus; Albarca, Monica; Rockel-Bauer, Claudia; Kelley, Nicholas W; Bischof, Johannes; Hens, Korneel; van Nimwegen, Erik; Basler, Konrad; Deplancke, Bart

    2015-04-01

    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.

  4. 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.

  5. 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

  6. An analysis of key stakeholders' attitudes and beliefs about barriers and facilitating factors in the development of a cervical cancer prevention program in South Africa.

    PubMed

    Francis, Shelley A; Leser, Kendall A; Esmont, Emma E; Griffith, Fareeda M

    2013-03-01

    Cervical cancer is the leading cause of cancer related deaths among women. Each year there are approximately 250,000 deaths; most of which occurred in Sub-Saharan Africa, South Asia, and Latin America. The purpose of this report is to examine key stakeholders experience and knowledge of HPV and cervical cancer, examine their experiences with the current cervical cancer screening and treatment policy, and identify barriers and facilitating factors to vaccine implementation and uptake. Fifteen indepth interviews were conducted with key stakeholders in Cape Town and Johannesburg, South Africa. The interviews revealed several key findings including: 1) knowledge about HPV and cervical cancer varied across participants, 2) knowledge about cervical cancer was also mixed while knowledge about the relationship between HPV and cervical cancer was low among participants. Our findings indicate that key stakeholders are concerned about women's health and wellbeing. In addition, they believe that the government, families, and the media need to play a prominent role in prevention efforts.

  7. A Study of the Relationship between Key Factors of Academic Innovation and Faculties' Teaching Goals--The Mediatory Role of Knowledge

    ERIC Educational Resources Information Center

    Mohammadi, Mehdi; Marzooghi, Rahmatullah; Dehghani, Fatemeh

    2017-01-01

    The following research tries to study the Relationship between key factors of academic innovations and faculties' teaching goals with the mediatory role of their pedagogical, technological and content knowledge. The statistical population in this research included faculty members of Shiraz University. By simple random sampling, 127 faculty members…

  8. Periods of child growth up to age 8 years in Ethiopia, India, Peru and Vietnam: key distal household and community factors.

    PubMed

    Schott, Whitney B; Crookston, Benjamin T; Lundeen, Elizabeth A; Stein, Aryeh D; Behrman, Jere R

    2013-11-01

    Recent research has demonstrated some growth recovery among children stunted in infancy. Less is known about key age ranges for such growth recovery, and what factors are correlates with this growth. This study characterized child growth up to age 1 year, and from ages 1 to 5 and 5 to 8 years controlling for initial height-for-age z-score (HAZ), and identified key distal household and community factors associated with these growth measures using longitudinal data on 7266 children in the Young Lives (YL) study in Ethiopia, India, Peru and Vietnam. HAZ at about age 1 year and age in months predicted much of the variation in HAZ at age 5 years, but 40-71% was not predicted. Similarly, HAZ at age 5 years and age in months did not predict 26-47% of variation in HAZ at 8 years. Multiple regression analysis suggests that parental schooling, consumption, and mothers' height are key correlates of HAZ at about age 1 and also are associated with unpredicted change in HAZ from ages 1 to 5 and 5 to 8 years, given initial HAZ. These results underline the importance of a child's starting point in infancy in determining his or her growth, point to key distal household and community factors that may determine early growth in early life and subsequent growth recovery and growth failure, and indicate that these factors vary some by country, urban/rural designation, and child sex. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. 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…

  10. 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…

  11. 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

  12. 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

  13. The Evaluation of Vehicle Mass Reduction and Material Choice in Life Cycle Assessments: Key Factors and Dynamic Industries

    EPA Science Inventory

    Developments in the realm of lightweight materials for automotive use continue to be announced by the industry and by academia. This session will provide new and updated information on new generation of materials. Additionally, this session will focus on the key topics involved i...

  14. The Evaluation of Vehicle Mass Reduction and Material Choice in Life Cycle Assessments: Key Factors and Dynamic Industries

    EPA Science Inventory

    Developments in the realm of lightweight materials for automotive use continue to be announced by the industry and by academia. This session will provide new and updated information on new generation of materials. Additionally, this session will focus on the key topics involved i...

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

    PubMed

    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 (δ(13)C) 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.

  16. 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 Central

    2013-01-01

    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

  17. Alginate synthesis by Pseudomonas aeruginosa: a key pathogenic factor in chronic pulmonary infections of cystic fibrosis patients.

    PubMed Central

    May, T B; Shinabarger, D; Maharaj, R; Kato, J; Chu, L; DeVault, J D; Roychoudhury, S; Zielinski, N A; Berry, A; Rothmel, R K

    1991-01-01

    Pulmonary infection by mucoid, alginate-producing Pseudomonas aeruginosa is the leading cause of mortality among patients suffering from cystic fibrosis. Alginate-producing P. aeruginosa is uniquely associated with the environment of the cystic fibrosis-affected lung, where alginate is believed to increase resistance to both the host immune system and antibiotic therapy. Recent evidence indicates that P. aeruginosa is most resistant to antibiotics when the infecting cells are present as a biofilm, as they appear to be in the lungs of cystic fibrosis patients. Inhibition of the protective alginate barrier with nontoxic compounds targeted against alginate biosynthetic and regulatory proteins may prove useful in eradicating P. aeruginosa from this environment. Our research has dealt with elucidating the biosynthetic pathway and regulatory mechanism(s) responsible for alginate synthesis by P. aeruginosa. This review summarizes reports on the role of alginate in cystic fibrosis-associated pulmonary infections caused by P. aeruginosa and provides details about the biosynthesis and regulation of this exopolysaccharide. PMID:1906371

  18. 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.

  19. Florida Keys

    NASA Image and Video Library

    2002-12-13

    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. http://photojournal.jpl.nasa.gov/catalog/PIA03890

  20. siRNA and shRNA screens advance key understanding of host factors required for HIV-1 replication.

    PubMed

    Kok, Kin-Hang; Lei, Ting; Jin, Dong-Yan

    2009-08-27

    A recent RNAi screen used a genome-wide shRNA library to search for cellular factors required for HIV-1 replication. This work complements three other siRNA-based screening studies and potentially opens the door to the discovery of factors that are important for HIV-1 replication in physiological host cells such as T lymphocytes. shRNA screens can be further improved, and they could promise to unravel new pathways and new facets of virus-cell interactions.

  1. Structural elucidation of rabeprazole sodium photodegradation products.

    PubMed

    Garcia, Cássia V; Nudelman, Norma S; Steppe, Martin; Schapoval, Elfrides E S

    2008-01-07

    Rabeprazole sodium is a proton pump inhibitor, used in acid-related disorders, like peptic ulcers and gastroesophageal reflux. It is known to be an acid-labile drug, however, few data about its stability under other factors are available. The aim of this work was to study the photodegradation of rabeprazole, to determine its kinetics and to elucidate the structures of the main degradation products. UVC-254 nm and metal-halide lamps were used. The analysis of the samples was carried out by HPLC. When the drug was in methanol solution, one main degradation product was formed; the degradation rate followed zero-order kinetics. The (1)H and (13)C NMR spectroscopic determinations revealed the product was the benzimidazolone. Another isolated product was identified as benzimidazole. The latter was confirmed against an authentic sample. A third photodegradation product was identified as the [4-(3-methoxy-propoxy)-3-methyl-pyridin-2-yl]methanol, by (1)H and (13)C NMR of the reaction mixture in chloroform-d. When powdered commercial tablets were exposed to UVC irradiation, they showed the same degradation products along with other unidentified, which appeared as traces; the degradation rate was slower than in solution. The intact tablets were stable after 50 days of exposition to the same light source.

  2. Independent Control of Organogenesis and Shoot Tip Abortion are Key Factors to Developmental Plasticity in Kiwifruit (Actinidia)

    PubMed Central

    Foster, Toshi M.; Seleznyova, Alla N.; Barnett, Andrew M.

    2007-01-01

    Background and Aims In kiwifruit (Actinidia), the number of nodes per shoot is highly variable and is influenced by genotype and environmental conditions. To understand this developmental plasticity, three key processes were studied: organogenesis by the shoot apical meristem during shoot growth; expansion of phytomers; and shoot tip abortion. Methods Studies were made of organogenesis and shoot tip abortion using light and scanning electron microscopy. The effect of temperature on shoot growth cessation was investigated using temperature indices over the budbreak period, and patterns of shoot tip abortion were quantified using stochastic modelling. Key Results All growing buds began organogenesis before budbreak. During shoot development, the number of phytomers initiated by the shoot apical meristem is correlated with the number of expanding phytomers and the mean internode length. Shoot tip abortion is preceded by growth cessation and is not brought about by the death of the shoot apical meristem, but occurs by tissue necrosis in the sub-apical zone. For most genotypes studied, the probability of shoot tip abortion is higher during expansion of the preformed part of the shoot. Lower temperatures during early growth result in a higher probability of shoot tip abortion. Conclusions Organogenesis and shoot tip abortion are controlled independently. All buds have the potential to become long shoots. Conditions that increase early growth rate postpone shoot tip abortion. PMID:17650513

  3. Analysis of transcription factors key for mouse pancreatic development establishes NKX2-2 and MNX1 mutations as causes of neonatal diabetes in man.

    PubMed

    Flanagan, Sarah E; De Franco, Elisa; Lango Allen, Hana; Zerah, Michele; Abdul-Rasoul, Majedah M; Edge, Julie A; Stewart, Helen; Alamiri, Elham; Hussain, Khalid; Wallis, Sam; de Vries, Liat; Rubio-Cabezas, Oscar; Houghton, Jayne A L; Edghill, Emma L; Patch, Ann-Marie; Ellard, Sian; Hattersley, Andrew T

    2014-01-07

    Understanding transcriptional regulation of pancreatic development is required to advance current efforts in developing beta cell replacement therapies for patients with diabetes. Current knowledge of key transcriptional regulators has predominantly come from mouse studies, with rare, naturally occurring mutations establishing their relevance in man. This study used a combination of homozygosity analysis and Sanger sequencing in 37 consanguineous patients with permanent neonatal diabetes to search for homozygous mutations in 29 transcription factor genes important for murine pancreatic development. We identified homozygous mutations in 7 different genes in 11 unrelated patients and show that NKX2-2 and MNX1 are etiological genes for neonatal diabetes, thus confirming their key role in development of the human pancreas. The similar phenotype of the patients with recessive mutations and mice with inactivation of a transcription factor gene support there being common steps critical for pancreatic development and validate the use of rodent models for beta cell development.

  4. Determining the key drivers and mitigating factors that influence the role of the Nurse and/or Midwife Consultant: a cross-sectional survey.

    PubMed

    Fernandez, Ritin S; Sheppard-Law, Suzanne; Manning, Vicki

    2017-06-01

    Globally, many nurses and midwives are working at an advanced practice level. The role of a Nurse and/or Midwife Consultant encompasses a diverse and complex interaction between five specified domains namely Clinical Service and Consultancy, Clinical Leadership, Research, Education, and Clinical Services Planning and Management. The objective of this replication study was to identify the key drivers and mitigating factors that impact the role of Australian Nurse and/or Midwife Consultants. Cross-sectional survey. The study was conducted in a large metropolitan health district in Sydney, Australia. Participants for this study consisted of all Nurse and/or Midwife Consultants working within a health district in New South Wales (NSW). Data were collected by an anonymous online survey. Key drivers and mitigating factors perceived to influence their role were identified using previously implemented instruments. Data were analysed using SPSS version 21. Responses were obtained from 122 Nurse and/or Midwife Consultants. The number of years of experience as a Nurse and/or Midwife Consultant ranged from 6 months to 25.5 years. Personal attributes which included personal motivation and own communication skills were identified as key drivers to role performance with a mean score of 7.7±0.6. Other key drivers included peer support, organisational culture, personal attributes, professional learning, Nurse and/or Midwife Consultant experience, and collaborative relationships. Of the 14 mitigating factors to the role, the most common factors were lack of resources to set up and develop the role (2.6 ± 0.9), lack of secretarial support (2.6 ± 1.1), lack of managerial support (2.45 ± 1.1), and lack of understanding of the role by other health professionals (2.40 ± 0.8). Understanding the key drivers and mitigating factors that influence the role of the Nurse and/or Midwife Consultant is important for healthcare managers. Given the changing landscape of nursing

  5. A systematic review of the key factors affecting tissue viability and rehabilitation outcomes of the residual limb in lower extremity traumatic amputees.

    PubMed

    Butler, Katrina; Bowen, Catherine; Hughes, Ann-Marie; Torah, Russel; Ayala, Ivo; Tudor, John; Metcalf, Cheryl D

    2014-08-01

    Most traumatic lower limb amputees ambulate using a prosthetic limb. Comfort, appearance of the missing limb and function are confirmed as being important during rehabilitation post-amputation. Emerging evidence suggests that impaired tissue viability of the stump affects rehabilitation and thus clinical ability to provide optimum care. The primary objective of this systematic review was to identify key factors relating to tissue viability of the residual limb in lower extremity traumatic amputees. A secondary objective was to identify factors that affect rehabilitation post-amputation. In total, 218 studies were assessed; 37 met pre-determined criteria. Studies were classified according to the WHO ICF framework and the NHMRC level of evidence. Five key themes emerged; Prosthetic Fit; The Residuum; Quality of Life; Amputee Care and Prosthetic Use. The evidence indicates that high frequencies of skin problems affecting tissue viability within this population are inherently linked to intolerance of the prosthesis. Stump integrity, amputee care regimen and pain were also identified as impacting on quality of life, affecting rehabilitation and the ability to become independently mobile. Levels of evidence within all studies were low and indicative of the majority being non-randomised cohort studies or case-control studies. As there are a limited number of interventional studies, further development of robust outcome measures, clinical trials and prospective studies are of utmost importance to unravel the links between tissue viability and the other key factors. This will inform clinical management strategies and help develop targeted therapies and care pathways.

  6. 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…

  7. Multi-level risk factors associated with sex trading among women living with HIV in Kazakhstan: A neglected key population.

    PubMed

    Davis, Alissa; Jiwatram-Negrón, Tina; Primbetova, Sholpan; Terlikbayeva, Assel; Bilokon, Yelena; Chubukova, Lyubov; El-Bassel, Nabila

    2017-01-01

    Little is known about the prevalence and risk factors associated with sex trading among HIV-positive women. A total of 242 HIV-positive women were recruited in five regions in Kazakhstan. These women completed a survey containing items on socio-demographics, HIV stigma, intimate partner violence, and partner risk behaviors. Multivariate regression was used to examine associations between risk factors and sex trading after controlling for socio-demographic factors. Fifty-six (23.1%) women reported trading sex in the past 90 days. Women who reported recent sex trading were more likely than women who did not trade sex in the past 90 days to experience intimate partner violence (adjusted odds ratio [AOR]: 2.25; 95% confidence interval [CI]: 1.08-4.73), to have been homeless in the past 90 days (AOR: 4.12; 95% CI: 1.19-14.29), and to know or suspect a male partner had a sexually transmitted infection (AOR: 2.20; 95% CI: 1.07-4.53), had sex with another partner (AOR: 4.53; 95% CI: 2.25-9.14), or injected drugs in the past year (AOR: 3.31; 95% CI: 1.64-6.65). These findings underscore the need for comprehensive HIV prevention and intervention programs that address the multi-level risk factors associated with sex trading for women infected with HIV.

  8. 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.

  9. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2016-10-01

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

  11. The ORCA2 transcription factor plays a key role in regulation of the terpenoid indole alkaloid pathway

    PubMed Central

    2013-01-01

    Background The terpenoid indole alkaloid (TIA) pathway leads to the production of pharmaceutically important drugs, such as the anticancer compounds vinblastine and vincristine. Unfortunately, these drugs are produced in trace amounts, causing them to be very costly. To increase production of these drugs, an improved understanding of the TIA regulatory pathway is needed. Towards this end, transgenic Catharanthus roseus hairy roots that overexpress the ORCA2 TIA transcriptional activator were generated and characterized. Results Transcriptional profiling experiments revealed that overexpression of ORCA2 results in altered expression of key genes from the indole and terpenoid pathways, which produce precursors for the TIA pathway, and from the TIA pathway itself. In addition, metabolite-profiling experiments revealed that overexpression of ORCA2 significantly affects the levels of several TIA metabolites. ORCA2 overexpression also causes significant increases in transcript levels of several TIA regulators, including TIA transcriptional repressors. Conclusions Results presented here indicate that ORCA2 plays a critical role in regulation of TIA metabolism. ORCA2 regulates expression of key genes from both feeder pathways, as well as the genes (STR and SGD) encoding the enzymes that catalyze the first two steps in TIA biosynthesis. ORCA2 may play an especially important role in regulation of the downstream branches of the TIA pathway, as it regulates four out of five genes characterized from this part of the pathway. Regulation of TIA transcriptional repressors by ORCA2 may provide a mechanism whereby increases in TIA metabolite levels in response to external stimuli are transient and limited in magnitude. PMID:24099172

  12. Long-Term Alcohol-Induced Activation of Mammalian Target of Rapamycin is a Key Risk Factor of Epilepsy.

    PubMed

    Fu, Xiaoling; Guo, Zhe; Gao, Chang; Chu, Qinying; Li, Jianhua; Ma, Hongying; Shu, Gangming

    2016-10-25

    BACKGROUND The aim of this study was to determine whether activation of mammalian target of rapamycin (mTOR) is a key epileptogenic mechanism in the development of alcohol-related seizure. MATERIAL AND METHODS C57BL/6 mice were administered 10% ethanol in drinking water for 9 weeks. Video-electroencephalography (EEG) monitoring was then used to assess seizure frequency after alcohol and rapamycin treatment. In addition, mouse neuroblastoma NG108-15 cells were treated ethanol for 3 days and subsequently treated with AKT inhibitor LY294002 for 2-12 h. The in vitro kinase assay was performed for determining mTOR activity. Western blot analysis was used to determine the expression of P-AKT, P-S6K, and P-S6. RESULTS Long-term ethanol treatment markedly increased the seizure frequency of C57/BL6 mice over time. Moreover, ethanol treatment increased the expression level of P-S6 over time. Ethanol-induced seizure can be reversed by rapamycin. In addition, the in vitro kinase assay showed mTOR activity was activated by ethanol. Compared with NG108-15 cells treated without both ethanol and LY294002, ethanol increased the expression level of P-AKT, P-S6K, and P-S6, whereas LY294002 had opposite effects on expression levels of these proteins. CONCLUSIONS Our findings indicate that long-term alcohol intake increases the risk of epilepsy via activation of mTOR signaling. Moreover, ethanol-induced mTOR activation may be dependent on the AKT-mTOR signaling pathway. The key molecules involved in AKT-mTOR signaling pathway may serve as potential targets in the treatment of epilepsy.

  13. 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

  14. 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.

  15. Identification methods of key contributing factors in crashes with high numbers of fatalities and injuries in China.

    PubMed

    Chen, Yikai; Li, Yiming; King, Mark; Shi, Qin; Wang, Changjun; Li, Pingfan

    2016-11-16

    In China, serious road traffic crashes (SRTCs) are those in which there are 10-30 fatalities, 50-100 serious injuries, or a total cost of 50-100 million RMB (U.S.$8-16 M), and particularly serious road traffic crashes (PSRTCs) are those that are more severe or costly. Due to the large number of fatalities and injuries as well as the negative public reaction they elicit, SRTCs and PSRTCs have become of great concern to China during recent years. The aim of this study is to identify the main factors contributing to these road traffic crashes and to propose preventive measures to reduce their number. 49 contributing factors of the SRTCs and PSRTCs that occurred from 2007 to 2013 were collected from the database "In-depth investigation and analysis system for major road traffic crashes" (IIASMRTC) and were analyzed through the integrated use of principal component analysis and hierarchical clustering to determine the primary and secondary groups of contributing factors. Speeding and overloading of passengers were the primary contributing factors, featuring in up to 66.3 and 32.6% of accidents, respectively. Two secondary contributing factors were road related: lack of or nonstandard roadside safety infrastructure and slippery roads due to rain, snow, or ice. The current approach to SRTCs and PSRTCs is focused on the attribution of responsibility and the enforcement of regulations considered relevant to particular SRTCs and PSRTCs. It would be more effective to investigate contributing factors and characteristics of SRTCs and PSRTCs as a whole to provide adequate information for safety interventions in regions where SRTCs and PSRTCs are more common. In addition to mandating a driver training program and publicization of the hazards associated with traffic violations, implementation of speed cameras, speed signs, markings, and vehicle-mounted Global Positioning Systems (GPS) are suggested to reduce speeding of passenger vehicles, while increasing regular checks by

  16. 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

  17. 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.

  18. Early stage of weathering of medieval-like potash-lime model glass: evaluation of key factors.

    PubMed

    Gentaz, Lucile; Lombardo, Tiziana; Loisel, Claudine; Chabas, Anne; Vallotto, Marta

    2011-02-01

    Throughout history, a consequent part of the medieval stained glass windows have been lost, mostly because of deliberate or accidental mechanic destruction during war or revolution, but, in some cases, did not withstand the test of time simply because of their low durability. Indeed, the glasses that remain nowadays are for many in a poor state of conservation and are heavily deteriorated. Under general exposure conditions, stained glass windows undergo different kinds of weathering processes that modify their optical properties, chemistry, and structure: congruent dissolution, leaching, and particle deposition (the combination of those two leading together to the formation of neocrystallisations and eventually crusts). Previous research has studied the weathering forms and the mechanisms from which they are originated, some others identified the main environmental parameters responsible for the deterioration and highlighted that both intrinsic (glass composition) and extrinsic (environmental parameters) factors influence glass degradation. Nevertheless, a clear quantification of the impact of the different deterioration extrinsic factors has not been performed. By analysing the results obtained with model glass (durable and nondurable) exposed in the field, this paper proposes a simple mathematical computation evaluating the contribution of the different weathering factors for the early stages of exposure of the stained glasses. In the case of non durable glass, water runoff was identified as the main factor inducing the leaching (83.4 ± 2.6% contribution), followed by gas (6.4 ± 1.5%) and particle deposition (6.8 ± 2.2%) and adsorbed water (3.4 ± 0.6%). Moreover, it was shown that the extrinsic stimuli superimposes with the impact of glass composition to the weathering. Those results show that the role played by dry deposition, even if less important than that of the wet deposition, cannot be neglected.

  19. Defense Advanced Research Projects Agency: Key Factors Drive Transition of Technologies, but Better Training and Data Dissemination Can Increase Success

    DTIC Science & Technology

    2015-11-01

    Data Dissemination Can Increase Success Report to Congressional Committees November 2015 GAO-16-5 United States Government Accountability...Factors Drive Transition of Technologies, but Better Training and Data Dissemination Can Increase Success 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c...Technologies, but Better Training and Data Dissemination Can Increase Success Why GAO Did This Study After the Soviet Union launched the first

  20. Systematic Selection of Key Logistic Regression Variables for Risk Prediction Analyses: A Five-Factor Maximum Model.

    PubMed

    Hewett, Timothy E; Webster, Kate E; Hurd, Wendy J

    2017-08-16

    The evolution of clinical practice and medical technology has yielded an increasing number of clinical measures and tests to assess a patient's progression and return to sport readiness after injury. The plethora of available tests may be burdensome to clinicians in the absence of evidence that demonstrates the utility of a given measurement. Thus, there is a critical need to identify a discrete number of metrics to capture during clinical assessment to effectively and concisely guide patient care. The data sources included Pubmed and PMC Pubmed Central articles on the topic. Therefore, we present a systematic approach to injury risk analyses and how this concept may be used in algorithms for risk analyses for primary anterior cruciate ligament (ACL) injury in healthy athletes and patients after ACL reconstruction. In this article, we present the five-factor maximum model, which states that in any predictive model, a maximum of 5 variables will contribute in a meaningful manner to any risk factor analysis. We demonstrate how this model already exists for prevention of primary ACL injury, how this model may guide development of the second ACL injury risk analysis, and how the five-factor maximum model may be applied across the injury spectrum for development of the injury risk analysis.

  1. PLASMINOGEN ACTIVATOR INHIBITOR-1 (PAI-1): A KEY FACTOR LINKING FIBRINOLYSIS AND AGE-RELATED SUBCLINICAL AND CLINICAL CONDITIONS

    PubMed Central

    Cesari, Matteo; Pahor, Marco; Incalzi, Raffaele Antonelli

    2010-01-01

    The close relationship existing between aging and thrombosis has growingly been studied in this last decade. The age-related development of a pro-thrombotic imbalance in the fibrinolysis homeostasis has been hypothesized at the basis of this increased cardiovascular and cerebrovascular risk. Fibrinolysis is the resulting of the interactions among multiple plasminogen activators and inhibitors constituing the enzymatic cascade, and ultimately leading to the degradation of fibrin. The plasminogen activator system plays a key role in a wide range of physiological and pathological processes. Plasminogen activator inhibitor-1 (PAI-1) is a member of the superfamily of serine-protease inhibitors (or serpins), and the principal inhibitor of both the tissue-type and the urinary-type plasminogen activator, the two plasminogen activators able to activate plasminogen. In this review, current evidence describing the central role played by PAI-1 in a number of age-related subclinical (i.e., inflammation, atherosclerosis, insulin resistance) and clinical (i.e., obesity, comorbidities, Werner syndrome) conditions is presented. Despite some controversial and unclear issues, PAI-1 represents an extremely promising marker which may become a biological parameter to be growingly considered in the prognostic evaluation, in the disease monitoring, and as treatment target of age-related conditions in the next future. PMID:20626406

  2. 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

  3. 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

  4. Identification of the key weather factors affecting overwintering success of Apolygus lucorum eggs in dead host tree branches.

    PubMed

    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.

  5. Contextual factors as a key to understanding the heterogeneity of effects of a maternal health policy in Burkina Faso?

    PubMed Central

    Belaid, Loubna; Ridde, Valéry

    2015-01-01

    Burkina Faso implemented a national subsidy for emergency obstetric and neonatal care (EmONC) covering 80% of the cost of normal childbirth in public health facilities. The objective was to increase coverage of facility-based deliveries. After implementation of the EmONC policy, coverage increased across the country, but disparities were observed between districts and between primary healthcare centres (PHC). To understand the variation in coverage, we assessed the contextual factors and the implementation of EmONC in six PHCs in a district. We conducted a contrasted multiple case study. We interviewed women (n = 71), traditional birth attendants (n = 7), clinic management committees (n = 11), and health workers and district health managers (n = 26). Focus groups (n = 62) were conducted within communities. Observations were carried out in the six PHCs. Implementation was nearly homogeneous in the six PHCs but the contexts and human factors appeared to explain the variations observed on the coverage of facility-based deliveries. In the PHCs of Nogo and Tara, the immediate increase in coverage was attributed to health workers’ leadership in creatively promoting facility-based deliveries and strengthening relationships of trust with communities, users’ positive perceptions of quality of care and the arrival of female professional staff. The change of healthcare team at Iata’s PHC and a penalty fee imposed for home births in Belem may have caused the delayed effects there. Finally, the unchanged coverage in the PHCs of Fati and Mata was likely due to lack of promotion of facility-based deliveries, users’ negative perceptions of quality of care, and conflicts between health workers and users. Before implementation, decision-makers should perform pilot studies to adapt policies according to contexts and human factors. PMID:24633914

  6. 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

  7. Thermal-oxidative effect of Kraft lignin antioxidant in polypropylene: Uncovering the key factor using correlation analysis model.

    PubMed

    Chen, Kai; Ye, Dezhan; Gu, Shaojin; Zhou, Yingshan

    2017-09-07

    Which factors are crucial to improving lignin antioxidant ability in polymers has been debated over years. Here, the structural effect of natural antioxidant from technical Kraft lignin (KL) on the oxidation induction time (OIT) of KL/polypropylene (PP) was quantitatively investigated using correlation analysis model instead of traditional linear fitting model. The correlation coefficient and significance value of their relationship clearly demonstrated the dominating role of non-condensed Phenolic OH (Ph-OH) in improving KL/PP thermal-oxidation stability, subsequently followed by M¯n, aliphatic OH/total Ph-OH, condensed Ph-OH and polydispersity. OIT is positive with non-condensed and total Ph-OH, while it declines with increase of the above other factors. Remarkably, the longest OIT (∼90min) was obtained even at extreme loading (0.5wt%), almost ∼911% and ∼201% huge increase in contrast to that of pure PP and crude KL/PP composite, respectively. Meanwhile, the mechanical properties of KL fractions/PP blends can be maintained at the same or better level than that of pure PP, due to strong interfacial adhesion strength. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Exploring key factors in the choice of e-health using an asthma care mobile service model.

    PubMed

    Lin, Shu-Ping; Yang, Hung-Yu

    2009-11-01

    Asthma care mobile service (ACMS) is a care platform for asthma patients using mobile phones to monitor asthma patients' real-time conditions. The anticipated benefits and development of the healthcare network platform rely on people's adoptive willingness and behavioral intention. The goal of this study is to understand and predict patients' acceptance behavior for ACMS as an application of e-health. The study is based on the technology acceptance model and integrates "subjective norm" and "innovativeness" to understand and predict the patient's attitude and behavioral intention. Employing a convenience sampling method, valid questionnaire responses were obtained from 229 patients. A confirmatory factor analysis examined the reliability and validity of the measurement model, while the structural equation modeling technique was employed to interpret the causal model. The model was used in the study to explain and predict the utilization of ACMS with a high explanatory power as a good-fit model. The results indicated the most critical factor that affects behavioral intentions related to ACMS is user attitude, followed by perceived usefulness, subjective norm, perceived ease of use, and innovativeness. The results provide the government developing high-tech, preventive medicine strategies the necessary data to define an appropriate policy to use in attracting greater participation in the effort.

  9. Participation a Key Factor for Life Recovery After Disaster: A Grounded Theory Study in an Iranian Context.

    PubMed

    Nakhaei, Maryam; Khankeh, Hamid Reza; Masoumi, Gholam Reza; Hosseini, Mohammad Ali; Parsa-Yekta, Zohreh

    2016-07-01

    Since life recovery after disasters is a subjective and multifaceted construct influenced by different factors, and survivors' main concerns and experiences are not clear, the researchers intended to explore this process. This study was conducted in 2011 - 2014 based on the grounded theory approach. Participants were selected by purposeful sampling followed by theoretical sampling to achieve conceptual and theoretical saturation. Data were collected through interviews, observation, focus group discussion, and document reviews. Data were analyzed by Strauss and Corbin's (2008) recommended approach. Transcribed data from 26 interviews (managers, health care providers, and receivers), field notes, and other documents were analyzed, and 1,652 open codes were identified. The codes were categorized, using constant comparative analysis, into five main categories including reactive exposure, subsiding emotions, need for comprehensive health recovery, improvement of normalization (new normality achievement), and contextual factors. The process of life recovery after disaster was also explored. The results clarified a deep perception of participants' experiences after disaster. The path of life recovery after disasters involves participants' striving to achieve a comprehensive health recovery, which starts with the need for all-inclusive health recovery as a main concern; this is the motivator for a responding strategy. This strategy is participatory, and the process is progressive; achievement of a new normality is the final goal, with new development and levels of empowerment.

  10. Participation a Key Factor for Life Recovery After Disaster: A Grounded Theory Study in an Iranian Context

    PubMed Central

    Nakhaei, Maryam; Khankeh, Hamid Reza; Masoumi, Gholam Reza; Hosseini, Mohammad Ali; Parsa-Yekta, Zohreh

    2016-01-01

    Background Since life recovery after disasters is a subjective and multifaceted construct influenced by different factors, and survivors’ main concerns and experiences are not clear, the researchers intended to explore this process. Materials and Methods This study was conducted in 2011 - 2014 based on the grounded theory approach. Participants were selected by purposeful sampling followed by theoretical sampling to achieve conceptual and theoretical saturation. Data were collected through interviews, observation, focus group discussion, and document reviews. Data were analyzed by Strauss and Corbin’s (2008) recommended approach. Results Transcribed data from 26 interviews (managers, health care providers, and receivers), field notes, and other documents were analyzed, and 1,652 open codes were identified. The codes were categorized, using constant comparative analysis, into five main categories including reactive exposure, subsiding emotions, need for comprehensive health recovery, improvement of normalization (new normality achievement), and contextual factors. The process of life recovery after disaster was also explored. Conclusions The results clarified a deep perception of participants’ experiences after disaster. The path of life recovery after disasters involves participants’ striving to achieve a comprehensive health recovery, which starts with the need for all-inclusive health recovery as a main concern; this is the motivator for a responding strategy. This strategy is participatory, and the process is progressive; achievement of a new normality is the final goal, with new development and levels of empowerment. PMID:27703797

  11. Identification of Key Items Regarding Personality, Environment, and Life Events to Assess Risk and Resilience Factors for Harmful Alcohol Drinking in Adolescents.

    PubMed

    Heinrich, Angela; Schumann, Gunter; Flor, Herta; Nees, Frauke

    2016-11-01

    Alcohol misuse often develops during adolescence involving interacting factors deriving from personality, environment and life events that can be assessed with well-established instruments. However, for specific research purposes, involving the assessment of large data sets, it may be beneficial having a short tool of key items representing the most important risk factors. We identified a set of key items from standard questionnaires assessed in about 2000 adolescents. In our longitudinal study we identified important items on personality, environment, and life events explaining alcohol drinking behaviour at the age of 14 years and the increase of alcohol consumption 2 years later. The key items explained 33.4% of variance in alcohol drinking behaviour (vs. 34.8% for original battery) and can be completed in six minutes. Our item list represents a powerful easy-to-use tool for the examination of alcohol drinking behaviour in adolescents. © The Author 2016. Medical Council on Alcohol and Oxford University Press. All rights reserved.

  12. A Novel Method of Evaluating Key Factors for Success in a Multifaceted Critical Care Fellowship Using Data Envelopment Analysis.

    PubMed

    Tiwari, Vikram; Kumar, Avinash B

    2017-07-21

    The current system of summative multi-rater evaluations and standardized tests to determine readiness to graduate from critical care fellowships has limitations. We sought to pilot the use of data envelopment analysis (DEA) to assess what aspects of the fellowship program contribute the most to an individual fellow's success. DEA is a nonparametric, operations research technique that uses linear programming to determine the technical efficiency of an entity based on its relative usage of resources in producing the outcome. Retrospective cohort study. Critical care fellows (n = 15) in an Accreditation Council for Graduate Medical Education (ACGME) accredited fellowship at a major academic medical center in the United States. After obtaining institutional review board approval for this retrospective study, we analyzed the data of 15 anesthesiology critical care fellows from academic years 2013-2015. The input-oriented DEA model develops a composite score for each fellow based on multiple inputs and outputs. The inputs included the didactic sessions attended, the ratio of clinical duty works hours to the procedures performed (work intensity index), and the outputs were the Multidisciplinary Critical Care Knowledge Assessment Program (MCCKAP) score and summative evaluations of fellows. A DEA efficiency score that ranged from 0 to 1 was generated for each of the fellows. Five fellows were rated as DEA efficient, and 10 fellows were characterized in the DEA inefficient group. The model was able to forecast the level of effort needed for each inefficient fellow, to achieve similar outputs as their best performing peers. The model also identified the work intensity index as the key element that characterized the best performers in our fellowship. DEA is a feasible method of objectively evaluating peer performance in a critical care fellowship beyond summative evaluations alone and can potentially be a powerful tool to guide individual performance during the fellowship.

  13. 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

  14. Organizational participatory research: a systematic mixed studies review exposing its extra benefits and the key factors associated with them.

    PubMed

    Bush, Paula L; Pluye, Pierre; Loignon, Christine; Granikov, Vera; Wright, Michael T; Pelletier, Jean-François; Bartlett-Esquilant, Gillian; Macaulay, Ann C; Haggerty, Jeannie; Parry, Sharon; Repchinsky, Carol

    2017-10-10

    In health, organizational participatory research (OPR) refers to health organization members participating in research decisions, with university researchers, throughout a study. This non-academic partner contribution to the research may take the form of consultation or co-construction. A drawback of OPR is that it requires more time from all those involved, compared to non-participatory research approaches; thus, understanding the added value of OPR, if any, is important. Thus, we sought to assess whether the OPR approach leads to benefits beyond what could be achieved through traditional research. We identified, selected, and appraised OPR health literature, and at each stage, two team members independently reviewed and coded the literature. We used quantitative content analysis to transform textual data into reliable numerical codes and conducted a logistic regression to test the hypothesis that a co-construction type OPR study yields extra benefits with a greater likelihood than consultation-type OPR studies. From 8873 abstracts and 992 full text papers, we distilled a sample of 107 OPR studies. We found no difference between the type of organization members' participation and the likelihood of exhibiting an extra benefit. However, the likelihood of an OPR study exhibiting at least one extra benefit is quadrupled when the impetus for the study comes from the organization, rather than the university researcher(s), or the organization and the university researcher(s) together (OR = 4.11, CI = 1.12-14.01). We also defined five types of extra benefits. This review describes the types of extra benefits OPR can yield and suggests these benefits may occur if the organization initiates the OPR. Further, this review exposes a need for OPR authors to more clearly describe the type of non-academic partner participation in key research decisions throughout the study. Detailed descriptions will benefit others conducting OPR and allow for a re-examination of the

  15. Identification of key factors in Accelerated Low Water Corrosion through experimental simulation of tidal conditions: influence of stimulated indigenous microbiota.

    PubMed

    Marty, Florence; Gueuné, Hervé; Malard, Emilie; Sánchez-Amaya, José M; Sjögren, Lena; Abbas, Ben; Quillet, Laurent; van Loosdrecht, Mark C M; Muyzer, Gerard

    2014-01-01

    Biotic and abiotic factors favoring Accelerated Low Water Corrosion (ALWC) on harbor steel structures remain unclear warranting their study under controlled experimental tidal conditions. Initial stimulation of marine microbial consortia by a pulse of organic matter resulted in localized corrosion and the highest corrosion rates (up to 12-times higher than non-stimulated conditions) in the low water zone, persisting after nine months exposure to natural seawater. Correlations between corrosion severity and the abundance and composition of metabolically active sulfate-reducing bacteria (SRB) indicated the importance and persistence of specific bacterial populations in accelerated corrosion. One phylotype related to the electrogenic SRB Desulfopila corrodens appeared as the major causative agent of the accelerated corrosion. The similarity of bacterial populations related to sulfur and iron cycles, mineral and tuberculation with those identified in ALWC support the relevance of experimental simulation of tidal conditions in the management of steel corrosion exposed to harbor environments.

  16. Paradigm of Professional Integration for Disabled People in Fundació Integralia Vallès: Key Success Factors.

    PubMed

    Gil, Ma Emilia; De Oña, Javier; Picola, Esteve

    2016-01-01

    Fundació Integralia Vallès is a pioneer contact center in Europe that has involved the creation of a healthcare reference center managed exclusively by people with disabilities and degenerative diseases to enable their professional development and ultimately integration into the labour market. The environment created under this project enables effective training and building of skills, capacity and work experience as well as promoting social responsibility among a population group that is at risk of exclusion. The major differentiating factor in Fundació Integralia Vallés is the quality of service provided by its staff, who are particularly sensitive to the issues of health, and who provide professional and human dimension in every attention.

  17. Heat shock transcription factor 1 is a key determinant of HCC development by regulating hepatic steatosis and metabolic syndrome

    PubMed Central

    Jin, Xiongjie; Moskophidis, Demetrius; Mivechi, Nahid F.

    2011-01-01

    Hepatocellular carcinoma (HCC) occurrence and progression is linked tightly to progressive hepatic metabolic syndrome associated with insulin resistance, hepatic steatosis, and chronic inflammation. Heat shock transcription factor 1 (HSF1), a major transactivator of stress proteins, increases survival by protecting cells against environmental stressors. It has been implicated in the pathogenesis of cancer, but specific mechanisms by which HSF1 supports cancer development remain elusive. We propose a pathogenic mechanism whereby HSF1 activation promotes growth of pre-malignant cells and HCC development by stimulating lipid biosynthesis and perpetuating chronic hepatic metabolic disease induced by carcinogens. Our work shows that inactivation of HSF1 impairs cancer progression, mitigating adverse effects of carcinogens on hepatic metabolism by enhancing insulin sensitivity and sensitizing activation of AMP-activated protein kinase (AMPK), an important regulator of energy homeostasis and inhibitor of lipid synthesis. HSF1 is a potential target for the control of hepatic steatosis, hepatic insulin resistance, and HCC development. PMID:21723507

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

    PubMed

    Makkena, Srilakshmi; Lamb, Rebecca S

    2013-05-01

    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.

  19. Npas4: a neuronal transcription factor with a key role in social and cognitive functions relevant to developmental disorders.

    PubMed

    Coutellier, Laurence; Beraki, Simret; Ardestani, Pooneh Memar; Saw, Nay Lui; Shamloo, Mehrdad

    2012-01-01

    Npas4 is a transcription factor, which is highly expressed in the brain and regulates the formation and maintenance of inhibitory synapses in response to excitatory synaptic activity. A deregulation of the inhibitory-excitatory balance has been associated with a variety of human developmental disorders such as schizophrenia and autism. However, not much is known about the role played by inhibitory synapses and inhibitory pathways in the development of nervous system disorders. We hypothesized that alterations in the inhibitory pathways induced by the absence of Npas4 play a major role in the expression of the symptoms observed in psychiatric disorders. To test this hypothesis we tested mice lacking the transcription factor (Npas4 knock-out mice (Npas4-KO)) in a battery of behavioral assays focusing on general activity, social behaviors, and cognitive functions. Npas4-KO mice are hyperactive in a novel environment, spend less time exploring an unfamiliar ovariectomized female, spend more time avoiding an unfamiliar male during a first encounter, show higher social dominance than their WT littermates, and display pre-pulse inhibition, working memory, long-term memory, and cognitive flexibility deficits. These behavioral deficits may replicate schizophrenia-related symptomatology such as social anxiety, hyperactivity, and cognitive and sensorimotor gating deficits. Immunohistochemistry analyses revealed that Npas4 expression is induced in the hippocampus after a social encounter and that Npas4 regulates the expression of c-Fos in the CA1 and CA3 regions of the hippocampus after a cognitive task. Our results suggest that Npas4 may play a major role in the regulation of cognitive and social functions in the brain with possible implications for developmental disorders such as schizophrenia and autism.

  20. A major latex-like protein is a key factor in crop contamination by persistent organic pollutants.

    PubMed

    Inui, Hideyuki; Sawada, Mami; Goto, Junya; Yamazaki, Kiyoshi; Kodama, Noriko; Tsuruta, Hiroki; Eun, Heesoo

    2013-04-01

    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.

  1. Soil pH and electrical conductivity are key edaphic factors shaping bacterial communities of greenhouse soils in Korea.

    PubMed

    Kim, Jeong Myeong; Roh, An-Sung; Choi, Seung-Chul; Kim, Eun-Jeong; Choi, Moon-Tae; Ahn, Byung-Koo; Kim, Sun-Kuk; Lee, Young-Han; Joa, Jae-Ho; Kang, Seong-Soo; Lee, Shin Ae; Ahn, Jae-Hyung; Song, Jaekyeong; Weon, Hang-Yeon

    2016-12-01

    Soil microorganisms play an essential role in soil ecosystem processes such as organic matter decomposition, nutrient cycling, and plant nutrient availability. The land use for greenhouse cultivation has been increasing continuously, which involves an intensive input of agricultural materials to enhance productivity; however, relatively little is known about bacterial communities in greenhouse soils. To assess the effects of environmental factors on the soil bacterial diversity and community composition, a total of 187 greenhouse soil samples collected across Korea were subjected to bacterial 16S rRNA gene pyrosequencing analysis. A total of 11,865 operational taxonomic units at a 97% similarity cutoff level were detected from 847,560 sequences. Among nine soil factors evaluated; pH, electrical conductivity (EC), exchangeable cations (Ca(2+), Mg(2+), Na(+), and K(+)), available P2O5, organic matter, and NO3-N, soil pH was most strongly correlated with bacterial richness (polynomial regression, pH: R(2) = 0.1683, P < 0.001) and diversity (pH: R(2) = 0.1765, P < 0.001). Community dissimilarities (Bray-Curtis distance) were positively correlated with Euclidean distance for pH and EC (Mantel test, pH: r = 0.2672, P < 0.001; EC: r = 0.1473, P < 0.001). Among dominant phyla (> 1%), the relative abundances of Proteobacteria, Gemmatimonadetes, Acidobacteria, Bacteroidetes, Chloroflexi, and Planctomycetes were also more strongly correlated with pH and EC values, compared with other soil cation contents, such as Ca(2+), Mg(2+), Na(+), and K(+). Our results suggest that, despite the heterogeneity of various environmental variables, the bacterial communities of the intensively cultivated greenhouse soils were particularly influenced by soil pH and EC. These findings therefore shed light on the soil microbial ecology of greenhouse cultivation, which should be helpful for devising effective management strategies to enhance soil microbial diversity and improving crop productivity.

  2. Key Survival Factor, Mcl-1, Correlates with Sensitivity to Combined Bcl-2/Bcl-xL Blockade.

    PubMed

    Williams, Michelle M; Lee, Linus; Hicks, Donna J; Joly, Meghan M; Elion, David; Rahman, Bushra; McKernan, Courtney; Sanchez, Violeta; Balko, Justin M; Stricker, Thomas; Estrada, Monica Valeria; Cook, Rebecca S

    2017-03-01

    An estimated 40,000 deaths will be attributed to breast cancer in 2016, underscoring the need for improved therapies. Evading cell death is a major hallmark of cancer, driving tumor progression and therapeutic resistance. To evade apoptosis, cancers use antiapoptotic Bcl-2 proteins to bind to and neutralize apoptotic activators, such as Bim. Investigation of antiapoptotic Bcl-2 family members in clinical breast cancer datasets revealed greater expression and more frequent gene amplification of MCL1 as compared with BCL2 or BCL2L1 (Bcl-xL) across three major molecular breast cancer subtypes, Luminal (A and B), HER2-enriched, and Basal-like. While Mcl-1 protein expression was elevated in estrogen receptor α (ERα)-positive and ERα-negative tumors as compared with normal breast, Mcl-1 staining was higher in ERα(+) tumors. Targeted Mcl-1 blockade using RNAi increased caspase-mediated cell death in ERα(+) breast cancer cells, resulting in sustained growth inhibition. In contrast, combined blockade of Bcl-2 and Bcl-xL only transiently induced apoptosis, as cells rapidly acclimated through Mcl-1 upregulation and enhanced Mcl-1 activity, as measured in situ using Mcl-1/Bim proximity ligation assays. Importantly, MCL1 gene expression levels correlated inversely with sensitivity to pharmacologic Bcl-2/Bcl-xL inhibition in luminal breast cancer cells, whereas no relationship was seen between the gene expression of BCL2 or BCL2L1 and sensitivity to Bcl-2/Bcl-xL inhibition. These results demonstrate that breast cancers rapidly deploy Mcl-1 to promote cell survival, particularly when challenged with blockade of other Bcl-2 family members, warranting the continued development of Mcl-1-selective inhibitors for targeted tumor cell killing.Implications: Mcl-1 levels predict breast cancer response to inhibitors targeting other Bcl-2 family members, and demonstrate the key role played by Mcl-1 in resistance to this drug class. Mol Cancer Res; 15(3); 259-68. ©2016 AACR. ©2016

  3. Replication and extension of a hierarchical model of social anxiety and depression: fear of positive evaluation as a key unique factor in social anxiety.

    PubMed

    Weeks, Justin W

    2015-01-01

    Wang, Hsu, Chiu, and Liang (2012, Journal of Anxiety Disorders, 26, 215-224) recently proposed a hierarchical model of social interaction anxiety and depression to account for both the commonalities and distinctions between these conditions. In the present paper, this model was extended to more broadly encompass the symptoms of social anxiety disorder, and replicated in a large unselected, undergraduate sample (n = 585). Structural equation modeling (SEM) and hierarchical regression analyses were employed. Negative affect and positive affect were conceptualized as general factors shared by social anxiety and depression; fear of negative evaluation (FNE) and disqualification of positive social outcomes were operationalized as specific factors, and fear of positive evaluation (FPE) was operationalized as a factor unique to social anxiety. This extended hierarchical model explicates structural relationships among these factors, in which the higher-level, general factors (i.e., high negative affect and low positive affect) represent vulnerability markers of both social anxiety and depression, and the lower-level factors (i.e., FNE, disqualification of positive social outcomes, and FPE) are the dimensions of specific cognitive features. Results from SEM and hierarchical regression analyses converged in support of the extended model. FPE is further supported as a key symptom that differentiates social anxiety from depression.

  4. Factors influencing frontline health service providers' likelihood to recommend a future, preventive HIV vaccine to key populations in Karnataka, south India.

    PubMed

    McClarty, Leigh M; Lorway, Robert R; Ramanaik, Satyanarayana; Wylie, John; Becker, Marissa L

    2015-01-29

    The HIV epidemic in the south Indian state of Karnataka disproportionately burdens key populations of men who have sex with men and female sex workers. Despite having successfully reduced HIV incidence among certain key populations through the use of targeted intervention, India's HIV epidemic remains one of its greatest public health issues. The best long-term strategy for managing the global HIV epidemic might involve a preventive vaccine; however, vaccine availability cannot guarantee its accessibility or acceptability. Vaccine recommendations from frontline health service providers have previously been identified as useful strategies to enhance vaccine uptake among target groups. This study used structured interviews to explore frontline health service providers' self-identified likelihood to recommend a future, preventive HIV vaccine to key populations in Karnataka. A modified social ecological model was then used to categorise factors that might prevent health service providers from recommending an HIV vaccine. Overall, 83% of health service providers reported that they would be very likely to recommend an HIV vaccine to men who have sex with men and female sex workers, while less than one-third of participants identified one or more barrier to vaccine recommendation. Intrapersonal, interpersonal, and structural/political factors were most commonly reported to act as potential barriers to future HIV vaccine recommendation among health service providers in Karnataka. This study adds to the limited body of literature focussing on future HIV vaccine acceptability in low- and middle-income countries and highlights some of the several complexities surrounding vaccine acceptability and uptake among key populations in Karnataka. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Coffee Drinking Is Widespread in the United States, but Usual Intake Varies by Key Demographic and Lifestyle Factors.

    PubMed

    Loftfield, Erikka; Freedman, Neal D; Dodd, Kevin W; Vogtmann, Emily; Xiao, Qian; Sinha, Rashmi; Graubard, Barry I

    2016-09-01

    Despite widespread popularity and possible health effects, the prevalence and distribution of coffee consumption in US adults are poorly characterized. We sought to estimate usual daily coffee intakes from all coffee-containing beverages, including decaffeinated and regular coffee, among US adults according to demographic, socioeconomic, and health-related factors. Dietary intake data from ≤2 nonconsecutive 24-h dietary recalls and a food-frequency questionnaire administered during the NHANES 2003-2006 were used to estimate the person-specific probability of consuming coffee on a particular day and the usual amount consumed on consumption days. Trends in population mean coffee consumption over time were evaluated by using multiple linear regression and 1-d 24-h recall data from NHANES 2003-2012. Analyses were weighted to be representative of the US adult population aged ≥20 y. An estimated 154 million adults, or 75% of the US population, aged ≥20 y reported drinking coffee; 49% reported drinking coffee daily. Prevalence did not vary by sex, education, income, or self-reported general health (all P ≥ 0.05) but did vary by age, race/ethnicity, smoking status, and alcohol drinking (all P < 0.05). Among coffee drinkers, the mean ± SE usual intake was 14.1 ± 0.5 fluid ounces/d (417 ± 15 mL/d). Mean usual intakes were higher in men than women, in older age groups than in those aged 20 to <30 y, in non-Hispanic whites than in non-Hispanic blacks or Hispanic/other races, in smokers than in never smokers, and in daily alcohol consumers than in nonconsumers (all P < 0.05). Population mean coffee consumption was stable from 2003 to 2012 (P-trend = 0.09). Coffee is widely consumed in the United States, with usual intakes varying by lifestyle and demographic factors, most notably by age. Longitudinal studies are needed to determine whether observed differences by age reflect birth cohort effects or changes in drinking patterns over the lifetime. © 2016 American