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Sample records for additional important factor

  1. Relative Importance and Additive Effects of Maternal and Infant Risk Factors on Childhood Asthma

    PubMed Central

    Rosas-Salazar, Christian; James, Kristina; Escobar, Gabriel; Gebretsadik, Tebeb; Li, Sherian Xu; Carroll, Kecia N.; Walsh, Eileen; Mitchel, Edward; Das, Suman; Kumar, Rajesh; Yu, Chang; Dupont, William D.; Hartert, Tina V.

    2016-01-01

    Background Environmental exposures that occur in utero and during early life may contribute to the development of childhood asthma through alteration of the human microbiome. The objectives of this study were to estimate the cumulative effect and relative importance of environmental exposures on the risk of childhood asthma. Methods We conducted a population-based birth cohort study of mother-child dyads who were born between 1995 and 2003 and were continuously enrolled in the PRIMA (Prevention of RSV: Impact on Morbidity and Asthma) cohort. The individual and cumulative impact of maternal urinary tract infections (UTI) during pregnancy, maternal colonization with group B streptococcus (GBS), mode of delivery, infant antibiotic use, and older siblings at home, on the risk of childhood asthma were estimated using logistic regression. Dose-response effect on childhood asthma risk was assessed for continuous risk factors: number of maternal UTIs during pregnancy, courses of infant antibiotics, and number of older siblings at home. We further assessed and compared the relative importance of these exposures on the asthma risk. In a subgroup of children for whom maternal antibiotic use during pregnancy information was available, the effect of maternal antibiotic use on the risk of childhood asthma was estimated. Results Among 136,098 singleton birth infants, 13.29% developed asthma. In both univariate and adjusted analyses, maternal UTI during pregnancy (odds ratio [OR] 1.2, 95% confidence interval [CI] 1.18, 1.25; adjusted OR [AOR] 1.04, 95%CI 1.02, 1.07 for every additional UTI) and infant antibiotic use (OR 1.21, 95%CI 1.20, 1.22; AOR 1.16, 95%CI 1.15, 1.17 for every additional course) were associated with an increased risk of childhood asthma, while having older siblings at home (OR 0.92, 95%CI 0.91, 0.93; AOR 0.85, 95%CI 0.84, 0.87 for each additional sibling) was associated with a decreased risk of childhood asthma, in a dose-dependent manner. Compared with vaginal

  2. Virulence factors of medically important fungi.

    PubMed Central

    Hogan, L H; Klein, B S; Levitz, S M

    1996-01-01

    Human fungal pathogens have become an increasingly important medical problem with the explosion in the number of immunocompromised patients as a result of cancer, steroid therapy, chemotherapy, and AIDS. Additionally, the globalization of travel and expansion of humankind into previously undisturbed habitats have led to the reemergence of old fungi and new exposure to previously undescribed fungi. Until recently, relatively little was known about virulence factors for the medically important fungi. With the advent of molecular genetics, rapid progress has now been made in understanding the basis of pathogenicity for organisms such as Aspergillus species and Cryptococcus neoformans. The twin technologies of genetic transformation and "knockout" deletion construction allowed for genetic tests of virulence factors in these organisms. Such knowledge will prove invaluable for the rational design of antifungal therapies. Putative virulence factors and attributes are reviewed for Aspergillus species, C. neoformans, the dimorphic fungal pathogens, and others, with a focus upon a molecular genetic approach. Candida species are excluded from coverage, having been the subject of numerous recent reviews. This growing body of knowledge about fungal pathogens and their virulence factors will significantly aid efforts to treat the serious diseases they cause. PMID:8894347

  3. The Importance of Carbon Fiber to Polymer Additive Manufacturing

    SciTech Connect

    Love, Lonnie J; Kunc, Vlastimil; Rios, Orlando; Duty, Chad E; Post, Brian K; Blue, Craig A

    2014-01-01

    Additive manufacturing holds tremendous promise in terms of revolutionizing manufacturing. However, fundamental hurdles limit mass adoption of the technology. First, production rates are extremely low. Second, the physical size of parts is generally small, less than a cubic foot. Third, while there is much excitement about metal additive manufacturing, the major growth area is in polymer additive manufacturing systems. Unfortunately, the mechanical properties of the polymer parts are poor, limiting the potential for direct part replacement. To address this issue, we describe three benefits of blending carbon fiber with polymer additive manufacturing. First, development of carbon fiber reinforced polymers for additive manufacturing achieves specific strengths approaching aerospace quality aluminum. Second, carbon fiber radically changes the behavior of the material during deposition, enabling large scale, out-of-the-oven, high deposition rate manufacturing. Finally, carbon fiber technology and additive manufacturing complement each other. Merging the two manufacturing processes enables the construction of complex components that would not be possible otherwise.

  4. DETERMINATION OF RELATIVE IMPORTANCE OF NONPROLIFERATION FACTORS

    SciTech Connect

    Richard Metcalf

    2009-07-01

    Methodologies to determine the proliferation resistance (PR) of nuclear facilities often rely on either expert elicitation, a resource-intensive approach without easily reproducible results, or numeric evaluations, which can fail to take into account the institutional knowledge and expert experience of the nonproliferation community. In an attempt to bridge the gap and bring the institutional knowledge into numeric evaluations of PR, a survey was conducted of 33 individuals to find the relative importance of a set of 62 nonproliferation factors, subsectioned into groups under the headings of Diversion, Transportation, Transformation, and Weaponization. One third of the respondents were self-described nonproliferation professionals, and the remaining two thirds were from secondary professions related to nonproliferation, such as industrial engineers or policy analysts. The factors were taken from previous work which used multi-attribute utility analysis with uniform weighting of attributes and did not include institutional knowledge. In both expert and non-expert groups, all four headings and the majority of factors had different relative importance at a confidence of 95% (p=0.05). This analysis and survey demonstrates that institutional knowledge can be brought into numeric evaluations of PR, if there is a sufficient investment of resources made prior to the evaluation.

  5. Drugs as important factors causing allergies

    PubMed Central

    Wróblewska, Paula; Adamczuk, Piotr; Zwoliński, Jacek; Oniszczuk, Anna; Wojtyła-Buciora, Paulina; Silny, Wojciech

    2015-01-01

    Medications can cause many adverse reactions, both non-immunologic and immunologic ones. Allergies can take many forms, allergic reactions include all types of reactions according to Gell and Coombs. Typically, allergic reactions to drugs are manifested by skin lesions such as maculopapular rash or urticaria and life-threatening systemic reactions such as anaphylaxis. Allergy to drugs is diagnosed based on medical history and a number of specific tests: skin tests, blood tests. In diagnosing the causes of anaphylaxis, the basophil activation test is used to exclude false negative and false positive results of skin tests and specific IgE levels. Allergic reactions to medications usually resolve themselves after discontinuation of the drug. Sometimes in the treatment anti-allergic drugs are used to inhibit the development of skin lesions. After observing any signs of drug allergy it is important to accurately diagnose the cause, since the subsequent exposure to the drug may lead to a strong anaphylactic reaction and consequently death. PMID:26759548

  6. Improvement of modal scaling factors using mass additive technique

    NASA Technical Reports Server (NTRS)

    Zhang, Qiang; Allemang, Randall J.; Wei, Max L.; Brown, David L.

    1987-01-01

    A general investigation into the improvement of modal scaling factors of an experimental modal model using additive technique is discussed. Data base required by the proposed method consists of an experimental modal model (a set of complex eigenvalues and eigenvectors) of the original structure and a corresponding set of complex eigenvalues of the mass-added structure. Three analytical methods,i.e., first order and second order perturbation methods, and local eigenvalue modification technique, are proposed to predict the improved modal scaling factors. Difficulties encountered in scaling closely spaced modes are discussed. Methods to compute the necessary rotational modal vectors at the mass additive points are also proposed to increase the accuracy of the analytical prediction.

  7. How important are the common factors in psychotherapy? An update

    PubMed Central

    Wampold, Bruce E

    2015-01-01

    The common factors have a long history in the field of psychotherapy theory, research and practice. To understand the evidence supporting them as important therapeutic elements, the contextual model of psychotherapy is outlined. Then the evidence, primarily from meta-analyses, is presented for particular common factors, including alliance, empathy, expectations, cultural adaptation, and therapist differences. Then the evidence for four factors related to specificity, including treatment differences, specific ingredients, adherence, and competence, is presented. The evidence supports the conclusion that the common factors are important for producing the benefits of psychotherapy. PMID:26407772

  8. 27 CFR 479.83 - Transfer tax in addition to import duty.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2011-04-01 2010-04-01 true Transfer tax in addition to import duty. 479.83 Section 479.83 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION MACHINE GUNS, DESTRUCTIVE...

  9. 27 CFR 479.83 - Transfer tax in addition to import duty.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2013-04-01 2013-04-01 false Transfer tax in addition to import duty. 479.83 Section 479.83 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION MACHINE GUNS,...

  10. 27 CFR 479.83 - Transfer tax in addition to import duty.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2010-04-01 2010-04-01 false Transfer tax in addition to import duty. 479.83 Section 479.83 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION MACHINE GUNS,...

  11. 27 CFR 479.83 - Transfer tax in addition to import duty.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2014-04-01 2014-04-01 false Transfer tax in addition to import duty. 479.83 Section 479.83 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION MACHINE GUNS,...

  12. 27 CFR 479.83 - Transfer tax in addition to import duty.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2012-04-01 2010-04-01 true Transfer tax in addition to import duty. 479.83 Section 479.83 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION MACHINE GUNS, DESTRUCTIVE...

  13. The Relative Importance of Job Factors: A New Measurement Approach.

    ERIC Educational Resources Information Center

    Nealey, Stanley M.

    This paper reports on a new two-phase measurement technique that permits a direct comparison of the perceived relative importance of economic vs. non-economic factors in a job situation in accounting for personnel retention, the willingness to produce, and job satisfaction. The paired comparison method was used to measure the preferences of 91…

  14. Identifying important motivational factors for professionals in Greek hospitals

    PubMed Central

    Kontodimopoulos, Nick; Paleologou, Victoria; Niakas, Dimitris

    2009-01-01

    Background The purpose of this study was to identify important motivational factors according to the views of health-care professionals in Greek hospitals and particularly to determine if these might differ in the public and private sectors. Methods A previously developed -and validated- instrument addressing four work-related motivators (job attributes, remuneration, co-workers and achievements) was used. Three categories of health care professionals, doctors (N = 354), nurses (N = 581) and office workers (N = 418), working in public and private hospitals, participated and motivation was compared across socio-demographic and occupational variables. Results The range of reported motivational factors was mixed and Maslow's conclusions that lower level motivational factors must be met before ascending to the next level were not confirmed. The highest ranked motivator for the entire sample, and by professional subgroup, was achievements (P < 0.001). Within subgroups, motivators were similar, and only one significant difference was observed, namely between doctors and nurses in respect to co-workers (P < 0.05). Remuneration (and salary in particular) was reported as a significant incentive only for professionals in managerial positions. Health professionals in private hospitals were motivated by all factors significantly more than their public-hospital counterparts. Conclusion The results are in agreement with the literature which focuses attention to management approaches employing both monetary and non-monetary incentives to motivate health care workers. This study showed that intrinsic factors are particularly important and should become a target for effective employee motivation. PMID:19754968

  15. Additives

    NASA Technical Reports Server (NTRS)

    Smalheer, C. V.

    1973-01-01

    The chemistry of lubricant additives is discussed to show what the additives are chemically and what functions they perform in the lubrication of various kinds of equipment. Current theories regarding the mode of action of lubricant additives are presented. The additive groups discussed include the following: (1) detergents and dispersants, (2) corrosion inhibitors, (3) antioxidants, (4) viscosity index improvers, (5) pour point depressants, and (6) antifouling agents.

  16. Important Factors For Resource Allocation In Applied Research And Development

    NASA Astrophysics Data System (ADS)

    Kotte, E. U.

    1989-01-01

    Competitiveness of modern societies requires optimum allocation of capital, qualified workforce and organizational infrastructure with the connecting link determined by information technology. Human resources of the scientific and technical community can compensate limited resources of other types supported by enhanced information promotion mechanisms in applied research and development. Descriptive features of the problem dimensions are given as a frame of reference, and important factors are reviewed for possible consideration in the fields of technology policy, resource allocation methods and management practices.

  17. Biosphere dose conversion Factor Importance and Sensitivity Analysis

    SciTech Connect

    M. Wasiolek

    2004-10-15

    This report presents importance and sensitivity analysis for the environmental radiation model for Yucca Mountain, Nevada (ERMYN). ERMYN is a biosphere model supporting the total system performance assessment (TSPA) for the license application (LA) for the Yucca Mountain repository. This analysis concerns the output of the model, biosphere dose conversion factors (BDCFs) for the groundwater, and the volcanic ash exposure scenarios. It identifies important processes and parameters that influence the BDCF values and distributions, enhances understanding of the relative importance of the physical and environmental processes on the outcome of the biosphere model, includes a detailed pathway analysis for key radionuclides, and evaluates the appropriateness of selected parameter values that are not site-specific or have large uncertainty.

  18. AP-42 ADDITIONS AND REVISIONS - TRANSPORTABILITY FACTORS FOR FUGITIVE DUST

    EPA Science Inventory

    The product is a table of factors, one for each county in the US, reflecting the portion of fugitive dust removed very close to the source via impaction on vegetation and similar mechanisms. Factors were based on land cover in area (county or grid cell) A praft final product was...

  19. Macitentan: An important addition to the treatment of pulmonary arterial hypertension

    PubMed Central

    Khadka, Anjan; Singh Brashier, Dick B; Tejus, Anantharamu; Sharma, Ashok Kumar

    2015-01-01

    Macitentan is an orphan drug for the treatment of pulmonary arterial hypertension (PAH). Endothelin-1 (ET-1) plays a critical role of pathophysiology of PAH. Macitentan, a new dual endothelin receptor antagonist, has reportedly improved prognosis of PAH patients by delaying the progression of disease. It prevents the binding of ET-1 to both endothelin A (ETA) and endothelin B (ETB) receptors. Macitentan displays higher efficacy, lesser adverse effects and drug interactions. It has completed phase III trials in 2012 for treatment of PAH and has been tried for ischemic digital ulcers in systemic sclerosis, recurrent glioblastoma and combination with chemotherapeutic agents against various cancers. Safety data for macitentan were obtained primarily from a placebo-controlled clinical study in 742 patients with PAH. The Food and Drug Administration (FDA) approved the drug on 13 October 2013. It is an important addition to long-term treatment of PAH. PMID:25709357

  20. Stellar Activity and CMEs: Important Factors of Planetary Evolution

    NASA Astrophysics Data System (ADS)

    Khodachenko, Maxim L.

    CME activity of the Sun is known to be an important impacting factor for the magnetospheres, atmospheres, and surfaces of solar system planets. Following an idea of a solar-stellar analogy, CME phenomena are expected on other stars as well. The main planetary impact factors of the stellar CMEs include the associated interplanetary shocks, plasma density and velocity disturbances, energetic particles accelerated in the shock regions, as well as distortions of the magnetic field direction and modulus. All these factors should be properly taken into account during the study of evolutionary processes on exoplanets and their atmospheric and plasma environments. The planetary impact of the stellar CME activity may vary depending on stellar age, stellar spectral type and the orbital distance of a planet. Because of the relatively short range of propagation of the majority of CMEs, they affect most strongly the magnetospheres and atmospheres of close-orbit ( < 0.1 AU) exoplanets. In this chapter we discuss an issue of the stellar CME activity in the context of several actual problems of modern exoplanetology, including planetary atmosphere mass loss, planet survival at close orbits, and definition of a criterion for habitability.

  1. Timing of predisposing factors is important in necrotic enteritis models.

    PubMed

    Van Waeyenberghe, Lieven; De Gussem, Maarten; Verbeke, Joren; Dewaele, Isabelle; De Gussem, Jeroen

    2016-06-01

    Since the ban of antimicrobial growth promotors, the importance of necrotic enteritis in broilers increases. Reliable and reproducible infection models are required for pathogenesis studies and product screening. Two major predisposing factors in necrotic enteritis models are fishmeal supplementation to feed and Eimeria infection. However, many unsolved issues regarding these predisposing factors still exist. Therefore, the influence of timepoint of fishmeal administration (onset on day 8 or day 18), timing of coccidiosis challenge (day 15 or day 19) and strain of coccidiosis challenge (field strain vs. commercial vaccine) on the induction of necrotic enteritis lesions was investigated. The birds were inoculated with Clostridium perfringens three times per day for four consecutive days (day 17 until day 20) and were scored for the presence of necrotic enteritis on days 22, 23, 24, 25 and 26. Supplementation of the diet with fishmeal from day 8 onwards increased the likelihood of necrotic enteritis compared to supplementation from day 18 onwards. Birds challenged on day 19 with coccidiosis were more likely to have necrotic enteritis on scoring days 23 and 24 compared to birds challenged on day 15. Differences on other scoring days were less pronounced. Finally, the strain of coccidiosis challenge had little influence on the induction of necrotic enteritis. Findings of this study can help researchers to set up successful necrotic enteritis infection models. PMID:26927291

  2. Depression and literacy are important factors for missed appointments.

    PubMed

    Miller-Matero, Lisa Renee; Clark, Kalin Burkhardt; Brescacin, Carly; Dubaybo, Hala; Willens, David E

    2016-09-01

    Multiple variables are related to missed clinic appointments. However, the prevalence of missed appointments is still high suggesting other factors may play a role. The purpose of this study was to investigate the relationship between missed appointments and multiple variables simultaneously across a health care system, including patient demographics, psychiatric symptoms, cognitive functioning and literacy status. Chart reviews were conducted on 147 consecutive patients who were seen by a primary care psychologist over a six month period and completed measures to determine levels of depression, anxiety, sleep, cognitive functioning and health literacy. Demographic information and rates of missed appointments were also collected from charts. The average rate of missed appointments was 15.38%. In univariate analyses, factors related to higher rates of missed appointments included younger age (p = .03), lower income (p = .05), probable depression (p = .05), sleep difficulty (p = .05) and limited reading ability (p = .003). There were trends for a higher rate of missed appointments for patients identifying as black (p = .06), government insurance (p = .06) and limited math ability (p = .06). In a multivariate model, probable depression (p = .02) and limited reading ability (p = .003) were the only independent predictors. Depression and literacy status may be the most important factors associated with missed appointments. Implications are discussed including regular screening for depression and literacy status as well as interventions that can be utilized to help improve the rate of missed appointments. PMID:26695719

  3. Determination of Important Topographic Factors for Landslide Mapping Analysis Using MLP Network

    PubMed Central

    Alkhasawneh, Mutasem Sh.; Ngah, Umi Kalthum; Mat Isa, Nor Ashidi; Al-batah, Mohammad Subhi

    2013-01-01

    Landslide is one of the natural disasters that occur in Malaysia. Topographic factors such as elevation, slope angle, slope aspect, general curvature, plan curvature, and profile curvature are considered as the main causes of landslides. In order to determine the dominant topographic factors in landslide mapping analysis, a study was conducted and presented in this paper. There are three main stages involved in this study. The first stage is the extraction of extra topographic factors. Previous landslide studies had identified mainly six topographic factors. Seven new additional factors have been proposed in this study. They are longitude curvature, tangential curvature, cross section curvature, surface area, diagonal line length, surface roughness, and rugosity. The second stage is the specification of the weight of each factor using two methods. The methods are multilayer perceptron (MLP) network classification accuracy and Zhou's algorithm. At the third stage, the factors with higher weights were used to improve the MLP performance. Out of the thirteen factors, eight factors were considered as important factors, which are surface area, longitude curvature, diagonal length, slope angle, elevation, slope aspect, rugosity, and profile curvature. The classification accuracy of multilayer perceptron neural network has increased by 3% after the elimination of five less important factors. PMID:24453846

  4. Diabetes mellitus: an important risk factor for reactivation of tuberculosis

    PubMed Central

    Rivera, Carmen; Mangual, Michelle; Martinez, José; Rivera, Kelvin; Fernandez, Ricardo

    2016-01-01

    Summary Diabetes mellitus was identified as a risk factor for developing tuberculosis (TB) infection, and relapse after therapy. The risk of acquiring TB is described as comparable to that of HIV population. The fact that diabetics are 3× times more prone to develop pulmonary TB than nondiabetics cannot be overlooked. With DM recognized as global epidemic, and TB affecting one-third of the world population, physicians must remain vigilant. We present a 45-year-old woman born in Dominican Republic (DR), with 10-year history of T2DM treated with metformin, arrived to our Urgency Room complaining of dry cough for the past 3months. Interview unveiled unintentional 15lbs weight loss, night sweats, occasional unquantified fever, and general malaise but denied bloody sputum. She traveled to DR 2years before, with no known ill exposure. Physical examination showed a thin body habitus, otherwise well appearing woman with stable vital signs, presenting solely right middle lung field ronchi. LDH, ESR, hsCRP and Hg A1C were elevated. Imaging revealed a right middle lobe cavitation. Sputum for AFB disclosed active pulmonary TB. Our case portrays that the consideration of TB as differential diagnosis in diabetics should be exercised with the same strength, as it is undertaken during the evaluation of HIV patients with lung cavitation. Inability to recognize TB will endanger the patient, hospital dwellers and staff, and perpetuate this global public health menace. Learning points Diabetes mellitus should be considered an important risk factor for the reactivation of pulmonary tuberculosis. High clinical suspicious should be taken into consideration as radiological findings for pulmonary tuberculosis in patients with diabetes mellitus may be atypical, involving middle and lower lobes. Inability to recognize pulmonary tuberculosis will endanger the patient, hospital dwellers and staff, and perpetuate this global public health menace. PMID:27482384

  5. Safety culture management: The importance of organizational factors

    SciTech Connect

    Haber, S.B.; Shurberg, D.A.; Jacobs, R.; Hofmann, D.

    1995-05-01

    The concept of safety culture has been used extensively to explain the underlying causes of performance based events, both positive and negative, across the nuclear industry. The work described in this paper represents several years of effort to identify, define and assess the organizational factors important to safe performance in nuclear power plants (NPPs). The research discussed in this paper is primarily conducted in support of the US Nuclear Regulatory Commission`s (NRC) efforts in understanding the impact of organizational performance on safety. As a result of a series of research activities undertaken by numerous NRC contractors, a collection of organizational dimensions has been identified and defined. These dimensions represent what is believed to be a comprehensive taxonomy of organizational elements that relate to the safe operation of nuclear power plants. Techniques were also developed by which to measure these organizational dimensions, and include structured interview protocols, behavioral checklists, and behavioral anchored rating scales (BARS). Recent efforts have focused on devising a methodology for the extraction of information related to the identified organizational dimensions from existing NRC documentation. This type of effort would assess the applicability of the organizational dimensions to existing NRC inspection and evaluation reports, refine the organizational dimensions previously developed so they are more relevant to the task of retrospective analysis, and attempt to rate plants based on the review of existing NRC documentation using the techniques previously developed for the assessment of organizational dimensions.

  6. Understanding the relative importance of global dengue risk factors.

    PubMed

    Lowe, Rachel

    2015-10-01

    Dengue is a mosquito-transmitted viral infection of major international public health concern. Global environmental and socio-economic change has created ideal conditions for the global expansion of dengue transmission. Innovative modelling tools help in understanding the global determinants of dengue risk and the relative impact of environmental and socio-economic factors on dengue transmission and spread. While climatic factors may act as a limiting factor on the global scale, other processes may play a dominant role at the local level. Understanding the spatial scales at which environmental and socio-economic factors dominate can help to target appropriate dengue control and prevention strategies. PMID:26311416

  7. Improved Growth Factor Directed Vascularization into Fibrin Constructs Through Inclusion of Additional Extracellular Molecules

    PubMed Central

    Smith, JD; Melhem, ME; Magge, KT; Waggoner, AS; Campbell, PG

    2009-01-01

    Using the chick chorioallantoic membrane assay (CAM) and a novel histological technique we investigated the ability of blood vessels to directly invade fibrin-based scaffolds. In our initial experiments utilizing vascular endothelial growth factor (VEGF165) we found no direct invasion. Instead, the fibrin was completely degraded and replaced with highly vascularized new tissue. Addition of fibroblast growth factor-2 (FGF-2), bone morphogenic protein-2 (BMP-2), or platelet-derived growth factor-BB (PDGF-BB) to the fibrin construct also did not result in construct vascularization. Because natural and regenerating tissues exhibit complex extracellular matrices (ECMs), we hypothesized that a more complex scaffold may improve blood vessel invasion. Addition of fibronectin, hyaluronic acid, and collagen type I within 20 mg/mL fibrin constructs resulted in no significant improvement. However, the same additive concentrations within 10 mg/mL fibrin constructs resulted in dramatic improvements, specifically with hyaluronic acid. Overall, we believe these results indicate the importance of structural and functional cues of not only in the initial scaffold but also as the construct is degraded and remodeled. Furthermore, the CAM assay may represent a useful model for understanding ECM interactions as well as for screening and designing tissue engineered scaffolds. PMID:17223139

  8. Learning to Solve Addition and Subtraction Word Problems in English as an Imported Language

    ERIC Educational Resources Information Center

    Verzosa, Debbie Bautista; Mulligan, Joanne

    2013-01-01

    This paper reports an intervention phase of a design study aimed to assist second-grade Filipino children in solving addition word problems in English, a language they primarily encounter only in school. With Filipino as the medium of instruction, an out-of-school pedagogical intervention providing linguistic and representational scaffolds was…

  9. 75 FR 29680 - Importation of Mexican Hass Avocados; Additional Shipping Options

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-27

    ... specify that the boxes, bins, or crates would have to be safeguarded from insects by covering with a lid, insect-proof mesh, or by some other barrier that prevents insects from entering the boxes or bins. Those... provide an additional layer of protection against insects of concern. The regulations also contain...

  10. 21 CFR 1311.115 - Additional requirements for two-factor authentication.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Additional requirements for two-factor... Additional requirements for two-factor authentication. (a) To sign a controlled substance prescription, the... authentication protocol that uses two of the following three factors: (1) Something only the practitioner...

  11. Psychopathy and Violence: The Importance of Factor Level Interactions

    ERIC Educational Resources Information Center

    Walsh, Zach; Kosson, David S.

    2008-01-01

    The power of scales based on the Psychopathy Checklist (PCL; R. D. Hare, 1980) for prediction of violent behavior is well established. Although evidence suggests that this relationship is chiefly due to the impulsive and antisocial lifestyle component (Factor 2), the predictive power of psychopathy for violence may also reflect the multiplicative…

  12. Implications of Export/Import Reporting Requirements in the United States - International Atomic Energy Agency Safeguards Additional Protocol

    SciTech Connect

    Killinger, Mark H.; Benjamin, Eugene L.; McNair, Gary W.

    2001-02-20

    The United States has signed but not ratified the US/IAEA Safeguards Additional Protocol. If ratified, the Additional Protocol will require the US to report to the IAEA certain nuclear-related exports and imports to the IAEA. This document identifies and assesses the issues associated with the US making those reports. For example, some regulatory changes appear to be necessary. The document also attempts to predict the impact on the DOE Complex by assessing the historical flow of exports and imports that would be reportable if the Additional Protocol were in force.

  13. Factors affecting breastfeeding duration in Greece: What is important?

    PubMed Central

    Tavoulari, Evangelia-Filothei; Benetou, Vassiliki; Vlastarakos, Petros V; Psaltopoulou, Theodora; Chrousos, George; Kreatsas, George; Gryparis, Alexandros; Linos, Athena

    2016-01-01

    AIM To investigate factors associated with breastfeeding duration (BD) in a sample of mothers living in Greece. METHODS Four hundred and twenty-eight mothers (438 infants) were initially recruited in a tertiary University Hospital. Monthly telephone interviews (1665 in total) using a structured questionnaire (one for each infant) were conducted until the sixth postpartum month. Cox regression analysis was used to assess factors influencing any BD. RESULTS Any breastfeeding rates in the first, third, and sixth month of the infant’s life reached 87.5%, 57.0% and 38.75%, respectively. In the multivariate analysis, maternal smoking in the lactation period [hazard-ratio (HR) = 4.20] and psychological status (HR = 1.72), and the introduction of a pacifier (HR = 2.08), were inversely associated, while higher maternal education (HRuniversity/college vs primary/high school = 0.53, HRmaster’s vs primary/high school = 0.20), and being an immigrant (HR = 0.35) were positively associated with BD. CONCLUSION Public health interventions should focus on campaigns against smoking during lactation, target women of lower educational status, and endorse the delayed introduction of pacifiers. PMID:27610353

  14. 34 CFR 477.22 - What additional factors does the Secretary consider?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION STATE PROGRAM ANALYSIS ASSISTANCE AND POLICY STUDIES PROGRAM How Does the Secretary Make an Award? § 477.22 What additional factors does the... 34 Education 3 2011-07-01 2011-07-01 false What additional factors does the Secretary...

  15. [The importance of biological and social factors in school success].

    PubMed

    Gorbachevskaia, N L; Davydova, E Iu; Petrova, S O; Tiushkevich, S A; Pashkevich, O I

    2010-01-01

    Three groups of children with learning difficulties (a total of 62 children) are dealt with in this study according to their cognitive and psychological special features. In the first group the difficulties are a symptom of the FMR1-gene dysfunction. In the second group the poor school performance is associated with social interaction problems and high intelligence level. In the third group of gifted children with low verbal intelligence parameters the poor school performance occurred because of unevenly developed verbal and non-verbal abili-ties. We demonstrate the importance of complex neurophysiological, neuropsychological and clinical psychological investigation for establishing the reasons for school difficulties. PMID:20586304

  16. Metabolic epistasis among apoptosis-inducing factor and the mitochondrial import factor CHCHD4

    PubMed Central

    Modjtahedi, Nazanine; Hangen, Emilie; Gonin, Patrick; Kroemer, Guido

    2015-01-01

    Abstract Hypomorphic mutation of apoptosis-inducing factor (AIF) in the whole body or organ-specific knockout of AIF compromises the activity of respiratory chain complexes I and IV, as it confers resistance to obesity and diabetes induced by high-fat diet. The mitochondrial defect induced by AIF deficiency can be explained by reduced AIF-dependent mitochondrial import of CHCHD4, which in turn is required for optimal import and assembly of respiratory chain complexes. Here we show that, as compared to wild type control littermates, mice with a heterozygous knockout of CHCHD4 exhibit reduced weight gain when fed with a Western style high-fat diet. This finding suggests widespread metabolic epistasis among AIF and CHCHD4. Targeting either of these proteins or their functional interaction might constitute a novel strategy to combat obesity. PMID:26178476

  17. Shale diagenesis: an important factor in development of secondary porosity

    SciTech Connect

    McMahon, D.A. Jr.

    1988-02-01

    Abundant secondary porosity due to the dissolution of feldspar grains, volcanic rock fragments, and carbonate cement has been observed in thin-section studies of reservoir sandstones in the McAllen Ranch field in south Texas. Secondary porosity develops in fluid flow pathways within the sandstones. Potentiometric profiles indicate that within the overpressured Oligocene strata, head gradients cause pore fluids to flow from the shales into the sandstones and toward major growth faults that bound the fields. The dissolution reactions responsible for the secondary porosity require that the pore fluid be acidic. Shale diagenesis provides an important source of hydrogen ions for these reactions. The transformation of smectite clay to illite has been well documented in the Oligocene shales in this area. The smectite to illite reaction (assuming mobile Al/sup +3/) is discussed as well as the reduction of Fe/sup +3/. Mass balance calculations in the study area indicate that the amount of acid produced by these reactions within the adjacent shales can easily account for the amount of secondary dissolution porosity observed in the sandstones. The exploration and exploitation of these types of sandstone reservoirs can be improved by a better understanding of the processes involved in the formation of secondary porosity.

  18. Land cover as an important factor for landslide risk assessment

    NASA Astrophysics Data System (ADS)

    Promper, C.; Glade, T.; Puissant, A.; Malet, J.-P.

    2012-04-01

    Landcover change is a crucial component of hazard and vulnerability in terms of quantification of possible future landslide risk, and the importance for spatial planners but also individuals is obvious. Damage of property, losses of agricultural land, loss of production but also damaged infrastructures and fatalities may be the result of landslide hazards. To avoid these economic damages as well as possible fatalities in the future, a method of assessing spatial but also temporal patterns of landslides is necessary. This study represents results of landcover modeling as a first step to the proposition of scenario of landslide risk for the future. The method used for future land cover analysis is the CLUE modeling framework combining past and actual observed landcover conditions. The model is based on a statistical relationship between the actual land cover and driving forces. The allocation of landcover pixel is modified by possible autonomous developments and competition between land use types. (Verburg et al. 1999) The study area is located in a district in the alpine foreland of Lower Austria: Waidhofen/Ybbs, of about 130km2. The topography is characterized by narrow valleys, flat plateau and steep slopes. The landcover is characterized by region of densely populated areas in the valley bottom along the Ybbs River, and a series of separated farm houses on the top of the plateau. Population density is about 90 persons / km2 which represent the observed population density of Austria. The initial landcover includes forest, grassland, culture, built-up areas and individual farms. Most of the observed developments are controlled by the topography (along the valleys) and the actual road network. The results of the landcover model show different scenarios of changes in the landslide prone landcover types. These maps will be implemented into hazard analysis but also into vulnerability assessment regarding elements at risk. Verburg, P.H., de Koning, G.H.J., Kok, K

  19. 34 CFR 658.34 - What additional factors does the Secretary consider in selecting grant recipients?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... does the Secretary consider in selecting grant recipients? In addition to applying the selection criteria in, as appropriate §§ 658.31, 658.32, and 658.33, the Secretary, to the extent practicable and... 34 Education 3 2014-07-01 2014-07-01 false What additional factors does the Secretary consider...

  20. 34 CFR 658.34 - What additional factors does the Secretary consider in selecting grant recipients?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... does the Secretary consider in selecting grant recipients? In addition to applying the selection criteria in, as appropriate §§ 658.31, 658.32, and 658.33, the Secretary, to the extent practicable and... 34 Education 3 2013-07-01 2013-07-01 false What additional factors does the Secretary consider...

  1. 34 CFR 658.34 - What additional factors does the Secretary consider in selecting grant recipients?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... does the Secretary consider in selecting grant recipients? In addition to applying the selection criteria in, as appropriate §§ 658.31, 658.32, and 658.33, the Secretary, to the extent practicable and... 34 Education 3 2012-07-01 2012-07-01 false What additional factors does the Secretary consider...

  2. 34 CFR 658.34 - What additional factors does the Secretary consider in selecting grant recipients?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... does the Secretary consider in selecting grant recipients? In addition to applying the selection criteria in, as appropriate §§ 658.31, 658.32, and 658.33, the Secretary, to the extent practicable and... 34 Education 3 2011-07-01 2011-07-01 false What additional factors does the Secretary consider...

  3. Importance-satisfaction analysis of street food sanitation and choice factor in Korea and Taiwan

    PubMed Central

    Joo, Nami; Park, Sanghyun; Lee, Bohee

    2015-01-01

    BACKGROUND/OBJECTIVES The present study investigated Korean and Taiwan adults on the importance of and the satisfaction with street food sanitation and street food choice factor, in order to present management and improvement measures for street foods. SUBJECTS/METHODS The present study conducted a survey on 400 randomly chosen adults (200 Korean, 200 Taiwanese). General characteristics, eating habits, street food intake frequency, and preference by type of street food of respondents were checked. Respondents' importance and satisfaction of street food hygiene and selection attributes were also measured. In order to test for the difference between groups, χ2-test and t-test were performed. ISA was also performed to analyze importance and satisfaction. RESULTS Results showed that the importance of sanitation was significantly higher than satisfaction on all items in both Korea and Taiwan, and the satisfaction with sanitation was higher in Taiwan than in Korea. According to ISA results with street food sanitation, satisfaction was low while importance was high in both Korea and Taiwan. In terms of street food choice factor, importance scores were significantly higher than satisfaction scores on all items. In addition, satisfaction scores on all items except 'taste' were significantly higher in Taiwan than in Korea. CONCLUSIONS A manual on sanitation management of street foods should be developed to change the knowledge and attitude toward sanitation by putting into practice a regularly conducted education. Considering the popularity of street foods and its potential as a tourism resource to easily publicize our food culture, thorough management measures should be prepared on sanitation so that safe street food culture should be created. PMID:26060542

  4. Are major behavioral and sociodemographic risk factors for mortality additive or multiplicative in their effects?

    PubMed

    Mehta, Neil; Preston, Samuel

    2016-04-01

    All individuals are subject to multiple risk factors for mortality. In this paper, we consider the nature of interactions between certain major sociodemographic and behavioral risk factors associated with all-cause mortality in the United States. We develop the formal logic pertaining to two forms of interaction between risk factors, additive and multiplicative relations. We then consider the general circumstances in which additive or multiplicative relations might be expected. We argue that expectations about interactions among socio-demographic variables, and their relation to behavioral variables, have been stated in terms of additivity. However, the statistical models typically used to estimate the relation between risk factors and mortality assume that risk factors act multiplicatively. We examine empirically the nature of interactions among five major risk factors associated with all-cause mortality: smoking, obesity, race, sex, and educational attainment. Data were drawn from the cross-sectional NHANES III (1988-1994) and NHANES 1999-2010 surveys, linked to death records through December 31, 2011. Our analytic sample comprised 35,604 respondents and 5369 deaths. We find that obesity is additive with each of the remaining four variables. We speculate that its additivity is a reflection of the fact that obese status is generally achieved later in life. For all pairings of socio-demographic variables, risks are multiplicative. For survival chances, it is much more dangerous to be poorly educated if you are black or if you are male. And it is much riskier to be a male if you are black. These traits, established at birth or during childhood, literally result in deadly combinations. We conclude that the identification of interactions among risk factors can cast valuable light on the nature of the process being studied. It also has public health implications by identifying especially vulnerable groups and by properly identifying the proportion of deaths

  5. 34 CFR 658.34 - What additional factors does the Secretary consider in selecting grant recipients?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false What additional factors does the Secretary consider in selecting grant recipients? 658.34 Section 658.34 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION UNDERGRADUATE...

  6. 34 CFR 655.32 - What additional factors does the Secretary consider in making grant awards?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION INTERNATIONAL EDUCATION... Secretary consider in making grant awards? Except for 34 CFR parts 656, 657, and 661, to the extent... 34 Education 3 2010-07-01 2010-07-01 false What additional factors does the Secretary consider...

  7. 34 CFR 490.22 - What additional factor does the Secretary consider?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false What additional factor does the Secretary consider? 490.22 Section 490.22 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION LIFE SKILLS FOR STATE AND...

  8. 34 CFR 411.22 - What additional factors may the Secretary consider?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 34 Education 3 2013-07-01 2013-07-01 false What additional factors may the Secretary consider? 411.22 Section 411.22 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION VOCATIONAL EDUCATION RESEARCH...

  9. 34 CFR 401.22 - What additional factors may the Secretary consider?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 3 2014-07-01 2014-07-01 false What additional factors may the Secretary consider? 401.22 Section 401.22 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION INDIAN VOCATIONAL EDUCATION PROGRAM...

  10. 34 CFR 401.22 - What additional factors may the Secretary consider?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false What additional factors may the Secretary consider? 401.22 Section 401.22 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION INDIAN VOCATIONAL EDUCATION PROGRAM...

  11. 34 CFR 401.22 - What additional factors may the Secretary consider?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 34 Education 3 2013-07-01 2013-07-01 false What additional factors may the Secretary consider? 401.22 Section 401.22 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION INDIAN VOCATIONAL EDUCATION PROGRAM...

  12. 34 CFR 411.22 - What additional factors may the Secretary consider?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false What additional factors may the Secretary consider? 411.22 Section 411.22 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION VOCATIONAL EDUCATION RESEARCH...

  13. 34 CFR 411.22 - What additional factors may the Secretary consider?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 3 2011-07-01 2011-07-01 false What additional factors may the Secretary consider? 411.22 Section 411.22 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION VOCATIONAL EDUCATION RESEARCH...

  14. 34 CFR 401.22 - What additional factors may the Secretary consider?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 3 2012-07-01 2012-07-01 false What additional factors may the Secretary consider? 401.22 Section 401.22 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION INDIAN VOCATIONAL EDUCATION PROGRAM...

  15. 34 CFR 411.22 - What additional factors may the Secretary consider?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 3 2012-07-01 2012-07-01 false What additional factors may the Secretary consider? 411.22 Section 411.22 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION VOCATIONAL EDUCATION RESEARCH...

  16. 34 CFR 401.22 - What additional factors may the Secretary consider?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 3 2011-07-01 2011-07-01 false What additional factors may the Secretary consider? 401.22 Section 401.22 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION INDIAN VOCATIONAL EDUCATION PROGRAM...

  17. 34 CFR 411.22 - What additional factors may the Secretary consider?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 3 2014-07-01 2014-07-01 false What additional factors may the Secretary consider? 411.22 Section 411.22 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION VOCATIONAL EDUCATION RESEARCH...

  18. 34 CFR 472.23 - What additional factor does the Secretary consider?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 3 2012-07-01 2012-07-01 false What additional factor does the Secretary consider? 472.23 Section 472.23 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION NATIONAL WORKPLACE LITERACY PROGRAM...

  19. 34 CFR 472.23 - What additional factor does the Secretary consider?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 3 2014-07-01 2014-07-01 false What additional factor does the Secretary consider? 472.23 Section 472.23 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION NATIONAL WORKPLACE LITERACY PROGRAM...

  20. 34 CFR 472.23 - What additional factor does the Secretary consider?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 3 2011-07-01 2011-07-01 false What additional factor does the Secretary consider? 472.23 Section 472.23 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION NATIONAL WORKPLACE LITERACY PROGRAM...

  1. 34 CFR 472.23 - What additional factor does the Secretary consider?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false What additional factor does the Secretary consider? 472.23 Section 472.23 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION NATIONAL WORKPLACE LITERACY PROGRAM...

  2. 34 CFR 472.23 - What additional factor does the Secretary consider?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 34 Education 3 2013-07-01 2013-07-01 false What additional factor does the Secretary consider? 472.23 Section 472.23 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION NATIONAL WORKPLACE LITERACY PROGRAM...

  3. 34 CFR 655.32 - What additional factors does the Secretary consider in making grant awards?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... PROGRAMS-GENERAL PROVISIONS How Does the Secretary Make a Grant? § 655.32 What additional factors does the Secretary consider in making grant awards? Except for 34 CFR parts 656, 657, and 661, to the extent... making grant awards? 655.32 Section 655.32 Education Regulations of the Offices of the Department...

  4. 34 CFR 655.32 - What additional factors does the Secretary consider in making grant awards?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... PROGRAMS-GENERAL PROVISIONS How Does the Secretary Make a Grant? § 655.32 What additional factors does the Secretary consider in making grant awards? Except for 34 CFR parts 656, 657, and 661, to the extent... making grant awards? 655.32 Section 655.32 Education Regulations of the Offices of the Department...

  5. 34 CFR 655.32 - What additional factors does the Secretary consider in making grant awards?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... PROGRAMS-GENERAL PROVISIONS How Does the Secretary Make a Grant? § 655.32 What additional factors does the Secretary consider in making grant awards? Except for 34 CFR parts 656, 657, and 661, to the extent... making grant awards? 655.32 Section 655.32 Education Regulations of the Offices of the Department...

  6. 34 CFR 655.32 - What additional factors does the Secretary consider in making grant awards?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 3 2014-07-01 2014-07-01 false What additional factors does the Secretary consider in making grant awards? 655.32 Section 655.32 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION INTERNATIONAL EDUCATION PROGRAMS-GENERAL PROVISIONS How Does...

  7. 34 CFR 477.22 - What additional factors does the Secretary consider?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false What additional factors does the Secretary consider? 477.22 Section 477.22 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION STATE PROGRAM ANALYSIS ASSISTANCE...

  8. MTHFR homozygous mutation and additional risk factors for cerebral infarction in a large Italian family.

    PubMed

    Del Balzo, Francesca; Spalice, Alberto; Perla, Massimo; Properzi, Enrico; Iannetti, Paola

    2009-01-01

    Several cases with cerebral infarctions associated with the C677T mutation in the methylenetetrahydrofolate reductase gene (MTHFR) have been reported. Given the large number of asymptomatic individuals with the MTHFR mutation, additional risk factors for cerebral infarction should be considered. This study describes a large family with the MTHFR mutation and a combination of heterozygous factor V Leiden mutations and different additional exogenous and endogenous thrombogenic risk factors. Psychomotor retardation and a left fronto-insular infarct associated with the MTHFR mutation together with diminished factor VII and low level of protein C was documented in the first patient. In the second patient, generalized epilepsy and a malacic area in the right nucleus lenticularis was associated with the MTHFR mutation and a low level of protein C. In the third patient, right hemiparesis and a left fronto-temporal porencephalic cyst were documented, together with the MTHFR mutation and hyperhomocysteinemia. An extensive search of additional circumstantial and genetic thrombogenic risk factors should be useful for prophylaxis and prognosis of infants with cerebral infarctions associated with the MTHFR mutation and of their related family members. PMID:19068258

  9. PTEN IDENTIFIED AS IMPORTANT RISK FACTOR OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE

    PubMed Central

    Hosgood, H Dean; Menashe, Idan; He, Xingzhou; Chanock, Stephen; Lan, Qing

    2009-01-01

    Common genetic variation may play an important role in altering chronic obstructive pulmonary disease (COPD) risk. In Xuanwei, China, the COPD rate is more than twice the Chinese national average, and COPD is strongly associated with in-home coal use. To identify genetic variation that may be associated with COPD in a population with substantial in-home coal smoke exposures, we evaluated 1,261 single nucleotide polymorphisms (SNPs) in 380 candidate genes potentially relevant for cancer and other human diseases in a population-based case-control study in Xuanwei (53 cases; 107 controls). PTEN was the most significantly associated gene with COPD in a minP analysis using 20,000 permutations (P = 0.00005). SNP-based analyses found that homozygote variant carriers of PTEN rs701848 (ORTT = 0.12, 95%CI = 0.03 - 0.47) had a significant decreased risk of COPD. PTEN, or phosphatase and tensin homolog, is an important regulator of cell cycle progression and cellular survival via the AKT signaling pathway. Our exploratory analysis suggests that genetic variation in PTEN may be an important risk factor of COPD in Xuanwei. However, due to the small sample size, additional studies are needed to evaluate these associations within Xuanwei and other populations with coal smoke exposures. PMID:19625176

  10. Interpersonal violence: an important risk factor for disease and injury in South Africa

    PubMed Central

    2010-01-01

    Background Burden of disease estimates for South Africa have highlighted the particularly high rates of injuries related to interpersonal violence compared with other regions of the world, but these figures tell only part of the story. In addition to direct physical injury, violence survivors are at an increased risk of a wide range of psychological and behavioral problems. This study aimed to comprehensively quantify the excess disease burden attributable to exposure to interpersonal violence as a risk factor for disease and injury in South Africa. Methods The World Health Organization framework of interpersonal violence was adapted. Physical injury mortality and disability were categorically attributed to interpersonal violence. In addition, exposure to child sexual abuse and intimate partner violence, subcategories of interpersonal violence, were treated as risk factors for disease and injury using counterfactual estimation and comparative risk assessment methods. Adjustments were made to account for the combined exposure state of having experienced both child sexual abuse and intimate partner violence. Results Of the 17 risk factors included in the South African Comparative Risk Assessment study, interpersonal violence was the second leading cause of healthy years of life lost, after unsafe sex, accounting for 1.7 million disability-adjusted life years (DALYs) or 10.5% of all DALYs (95% uncertainty interval: 8.5%-12.5%) in 2000. In women, intimate partner violence accounted for 50% and child sexual abuse for 32% of the total attributable DALYs. Conclusions The implications of our findings are that estimates that include only the direct injury burden seriously underrepresent the full health impact of interpersonal violence. Violence is an important direct and indirect cause of health loss and should be recognized as a priority health problem as well as a human rights and social issue. This study highlights the difficulties in measuring the disease burden from

  11. The importance of hyperhomocysteinemia as a risk factor for diseases: an overview.

    PubMed

    Herrmann, W

    2001-08-01

    Hyperhomocysteinemia is the result of a disturbed methionine metabolism. It results from enzyme and/or vitamin deficiency. Epidemiological studies have proven, that hyperhomocysteinemia is a risk factor for atherosclerotic cardiovascular diseases, stroke, peripheral arterial occlusive disease and venous thrombosis. Conflicting results come from prospective studies. Trials which are now in progress may clarify the "causality" of high homocysteine concentrations and will assess the value of homocysteine-lowering therapy. The induction of the atherogenic process by hyperhomocysteinemia seems to be associated with an alteration of endothelial and smooth muscle cell function leading to an accelerated formation of reactive oxygen species. An increased endothelial expression of adhesion molecules will then lead to an enhanced deposition of oxidized LDL in the vessel wall with the formation of foam cells. Additionally, hyperhomocysteinemia interferes with the coagulation system and thus also has prothrombotic effects. There is a high prevalence of hyperhomocysteinemia as a sign of a vitamin deficiency in elderly subjects which strongly increases with age. Elderly people have a high frequency of vitamin B12 deficiency which can be diagnosed more reliably by the measurement of serum methylmalonic acid (MMA) level than by serum vitamin B12. Subjects following a strict vegetarian diet also have a high prevalence of hyperhomocysteinemia caused by functional vitamin B12 deficiency (increased MMA level). Last but not least, hyperhomocysteinemia is a factor in the pathogenesis of neural tube defects and pre-eclampsia. An early diagnosis of vitamin B12 deficiency is important for the prevention of neurological damages. Homocysteine should be measured in patients with a history of atherothrombotic vessel diseases, in patients with diabetes or hyperlipidemia, in renal patients, in obese subjects, in elderly people, in postmenopausal women, and in early pregnancy. A specific diagnosis

  12. Phenological adjustment in arctic bird species: relative importance of snow melt and ecological factors

    USGS Publications Warehouse

    Liebezeit, Joseph R.; Gurney, K. E. B.; Budde, Michael E.; Zack, Steve; Ward, David H.

    2014-01-01

    Previous studies have documented advancement in clutch initiation dates (CIDs) in response to climate change, most notably for temperate-breeding passerines. Despite accelerated climate change in the Arctic, few studies have examined nest phenology shifts in arctic breeding species. We investigated whether CIDs have advanced for the most abundant breeding shorebird and passerine species at a long-term monitoring site in arctic Alaska. We pooled data from three additional nearby sites to determine the explanatory power of snow melt and ecological variables (predator abundance, green-up) on changes in breeding phenology. As predicted, all species (semipalmated sandpiper, Calidris pusilla, pectoral sandpiper, Calidris melanotos, red-necked phalarope, Phalaropus lobatus, red phalarope, Phalaropus fulicarius, Lapland longspur, Calcarius lapponicus) exhibited advanced CIDs ranging from 0.40 to 0.80 days/year over 9 years. Timing of snow melt was the most important variable in explaining clutch initiation advancement (“climate/snow hypothesis”) for four of the five species, while green-up was a much less important explanatory factor. We found no evidence that high predator abundances led to earlier laying dates (“predator/re-nest hypothesis”). Our results support previous arctic studies in that climate change in the cryosphere will have a strong impact on nesting phenology although factors explaining changes in nest phenology are not necessarily uniform across the entire Arctic. Our results suggest some arctic-breeding shorebird and passerine species are altering their breeding phenology to initiate nesting earlier enabling them to, at least temporarily, avoid the negative consequences of a trophic mismatch.

  13. Pre-treatment factors associated with detecting additional brain metastases at stereotactic radiosurgery.

    PubMed

    Wardak, Zabi; Augustyn, Alexander; Zhu, Hong; Mickey, Bruce E; Whitworth, Louis A; Madden, Christopher J; Barnett, Samuel L; Abdulrahman, Ramzi E; Nedzi, Lucien A; Timmerman, Robert D; Choe, Kevin S

    2016-06-01

    The number of brain metastases identified on diagnostic magnetic resonance imaging (MRI) is a key factor in consideration of stereotactic radiosurgery (SRS). However, additional lesions are often detected on high-resolution SRS-planning MRI. We investigated pre-treatment clinical characteristics that are associated with finding additional metastases at SRS. Patients treated with SRS for brain metastases between the years of 2009-2014 comprised the study cohort. All patients underwent frame-fixed, 1 mm thick MRI on the day of SRS. Patient, tumor, and treatment characteristics were analyzed for an association with increase in number of metastases identified on SRS-planning MRI. 289 consecutive SRS cases were analyzed. 725 metastases were identified on pre-treatment MRI and 1062 metastases were identified on SRS-planning MRI. An increase in the number of metastases occurred in 34 % of the cases. On univariate analysis, more than four metastases and the diameter of the largest lesion were significantly associated with an increase in number of metastases on SRS-planning MRI. When stratified by the diameter of the largest lesion into <2, 2-3, or ≥3 cm, additional metastases were identified in 37, 29, and 18 %, respectively. While this increase in the number of metastases is largely due to the difference in imaging technique, the number and size of the metastases were also associated with finding additional lesions. These clinical factors may be considered when determining treatment options for brain metastases. PMID:26966096

  14. Importance of environmental factors on the richness and distribution of benthic macroinvertebrates in tropical headwater streams

    EPA Science Inventory

    It is essential to understand the interactions between local environmental factors (e.g., physical habitat and water quality) and aquatic assemblages to conserve biodiversity in tropical and subtropical headwater streams. Therefore, we evaluated the relative importance of multipl...

  15. An Update on the Epidemiology of Schizophrenia with a Special Reference to Clinically Important Risk Factors

    ERIC Educational Resources Information Center

    El-Missiry, Ahmed; Aboraya, Ahmed Sayed; Manseur, Hader; Manchester, Johnna; France, Cheryl; Border, Katherine

    2011-01-01

    Schizophrenia is a chronic mental illness which poses a tremendous burden on the families, caregivers and the society. The purpose of this paper is to provide an updated review of the epidemiology of schizophrenia with a special attention to the clinically important risk factors such as drug abuse, hormonal factors and the new advances in genetic…

  16. From the Arctic to fetal life: physiological importance and structural basis of an 'additional' chloride-binding site in haemoglobin.

    PubMed Central

    De Rosa, M Cristina; Castagnola, Massimo; Bertonati, Claudia; Galtieri, Antonio; Giardina, Bruno

    2004-01-01

    Haemoglobins from mammals of sub-Arctic and Arctic species, as well as fetal human Hb, are all characterized by a significantly lower Delta H of oxygenation compared with the majority of mammalian haemoglobins from temperate species (exceptions are represented by some cold-resistant species, such as cow, horse and pig). This has been interpreted as an adaptive mechanism of great importance from a physiological point of view. To date, the molecular basis of this thermodynamic characteristic is still not known. In the present study, we show that binding of extra chloride (with respect to adult human Hb) ions to Hb would significantly contribute to lowering the overall heat of oxygenation, thus providing a molecular basis for the low effect of temperature on the oxygenation-deoxygenation cycle. To this aim, the oxygen binding properties of bovine Hb, bear (Ursus arctos) Hb and horse Hb, which are representative of this series of haemoglobins, have been studied with special regard to the effect of heterotropic ligands, such as organic phosphates (namely 2,3-diphosphoglycerate) and chloride. Functional results are consistent with a mechanism for ligand binding that involves an additional binding site for chloride ion. Analysis of computational chemistry results, obtained by the GRID program, further confirm the hypothesis that the reason for the lower Delta H of oxygenation is mainly due to an increase in the number of the oxygen-linked chloride-binding sites. PMID:14979874

  17. Synergistic and additive killing by antimicrobial factors found in human airway surface liquid.

    PubMed

    Singh, P K; Tack, B F; McCray, P B; Welsh, M J

    2000-11-01

    Airway surface liquid contains multiple factors thought to provide a first line of defense against bacteria deposited in the airways. Although the antimicrobial action of individual factors has been studied, less is known about how they work in combination. We examined the combined action of six antimicrobial peptides found in airway surface liquid. The paired combinations of lysozyme-lactoferrin, lysozyme-secretory leukocyte protease inhibitor (SLPI), and lactoferrin-SLPI were synergistic. The triple combination of lysozyme, lactoferrin, and SLPI showed even greater synergy. Other combinations involving the human beta-defensins, LL-37, and tobramycin (often administered to cystic fibrosis patients by inhalation) were additive. Because the airway surface liquid salt concentration may be elevated in cystic fibrosis patients, we examined the effect of salt on the synergistic combinations. As the ionic strength increased, synergistic interactions were lost. Our data suggest that the antibacterial potency of airway surface liquid may be significantly increased by synergistic and additive interactions between antimicrobial factors. These results also suggest that increased salt concentrations that may exist in cystic fibrosis could inhibit airway defenses by diminishing these synergistic interactions. PMID:11053013

  18. Estimate variable importance for recurrent event outcomes with an application to identify hypoglycemia risk factors.

    PubMed

    Duan, Ran; Fu, Haoda

    2015-08-30

    Recurrent event data are an important data type for medical research. In particular, many safety endpoints are recurrent outcomes, such as hypoglycemic events. For such a situation, it is important to identify the factors causing these events and rank these factors by their importance. Traditional model selection methods are not able to provide variable importance in this context. Methods that are able to evaluate the variable importance, such as gradient boosting and random forest algorithms, cannot directly be applied to recurrent events data. In this paper, we propose a two-step method that enables us to evaluate the variable importance for recurrent events data. We evaluated the performance of our proposed method by simulations and applied it to a data set from a diabetes study. PMID:25908216

  19. Mapping neural circuits with activity-dependent nuclear import of a transcription factor.

    PubMed

    Masuyama, Kaoru; Zhang, Yi; Rao, Yi; Wang, Jing W

    2012-03-01

    Abstract: Nuclear factor of activated T cells (NFAT) is a calcium-responsive transcription factor. We describe here an NFAT-based neural tracing method-CaLexA (calcium-dependent nuclear import of LexA)-for labeling active neurons in behaving animals. In this system, sustained neural activity induces nuclear import of the chimeric transcription factor LexA-VP16-NFAT, which in turn drives green fluorescent protein (GFP) reporter expression only in active neurons. We tested this system in Drosophila and found that volatile sex pheromones excite specific neurons in the olfactory circuit. Furthermore, complex courtship behavior associated with multi-modal sensory inputs activated neurons in the ventral nerve cord. This method harnessing the mechanism of activity-dependent nuclear import of a transcription factor can be used to identify active neurons in specific neuronal population in behaving animals. PMID:22236090

  20. The human factor: the critical importance of effective teamwork and communication in providing safe care.

    PubMed

    Leonard, M; Graham, S; Bonacum, D

    2004-10-01

    Effective communication and teamwork is essential for the delivery of high quality, safe patient care. Communication failures are an extremely common cause of inadvertent patient harm. The complexity of medical care, coupled with the inherent limitations of human performance, make it critically important that clinicians have standardised communication tools, create an environment in which individuals can speak up and express concerns, and share common "critical language" to alert team members to unsafe situations. All too frequently, effective communication is situation or personality dependent. Other high reliability domains, such as commercial aviation, have shown that the adoption of standardised tools and behaviours is a very effective strategy in enhancing teamwork and reducing risk. We describe our ongoing patient safety implementation using this approach within Kaiser Permanente, a non-profit American healthcare system providing care for 8.3 million patients. We describe specific clinical experience in the application of surgical briefings, properties of high reliability perinatal care, the value of critical event training and simulation, and benefits of a standardised communication process in the care of patients transferred from hospitals to skilled nursing facilities. Additionally, lessons learned as to effective techniques in achieving cultural change, evidence of improving the quality of the work environment, practice transfer strategies, critical success factors, and the evolving methods of demonstrating the benefit of such work are described. PMID:15465961

  1. Factor analysis models for structuring covariance matrices of additive genetic effects: a Bayesian implementation

    PubMed Central

    de los Campos, Gustavo; Gianola, Daniel

    2007-01-01

    Multivariate linear models are increasingly important in quantitative genetics. In high dimensional specifications, factor analysis (FA) may provide an avenue for structuring (co)variance matrices, thus reducing the number of parameters needed for describing (co)dispersion. We describe how FA can be used to model genetic effects in the context of a multivariate linear mixed model. An orthogonal common factor structure is used to model genetic effects under Gaussian assumption, so that the marginal likelihood is multivariate normal with a structured genetic (co)variance matrix. Under standard prior assumptions, all fully conditional distributions have closed form, and samples from the joint posterior distribution can be obtained via Gibbs sampling. The model and the algorithm developed for its Bayesian implementation were used to describe five repeated records of milk yield in dairy cattle, and a one common FA model was compared with a standard multiple trait model. The Bayesian Information Criterion favored the FA model. PMID:17897592

  2. Increasing Risk Factors for Imported and Domestic Gnathostomiasis in the United States.

    PubMed

    Diaz, James H

    2015-01-01

    importation of live freshwater species, such as Asian swamp eels (Monopterus spp.).1 Although raw seafood dishes are typically prepared with saltwater species, freshwater species, which harbor more parasites, are also used in these dishes, such as limejuice marinated tilapia or trout ceviche and eel-sashimi and sushi.2 In 2014, biologists from the US Geological Survey detected Gnathostoma species infective-stage larvae in nearly 30 percent of imported Monopterus species Asian swamp eels and in 4.5 percent of locally-caught Monopterus species freshwater swamp eels in three states.1 The investigators concluded that consumption of imported swamp eels from Gnathostoma-endemic regions of Asia could transmit gnathostomiasis to humans in the US.1 In addition, the release of live imported swamp eels or the disposal of their offal after filleting has introduced more Gnathostoma larvae into open and fish-farmed freshwaters infecting more native species.1 Since the US has all of the components to support Gnathostoma's life cycle, a zoonosis of infective Gnathostoma species, such as G. spinigerum and others, has become established in the US and will increase the risks of gnathostomiasis in humans consuming native, wildcaught, or farmed fish in ethnic dishes.1 As a result, the objectives of this review were to describe the biology and life cycle of Gnathostoma nematodes and the behavioral risk factors for gnathostomiasis; and to describe the clinical manifestations, diagnosis, management, and prevention of human gnathostomiasis. PMID:27159596

  3. Interaction of calcineurin with a domain of the transcription factor NFAT1 that controls nuclear import.

    PubMed Central

    Luo, C; Shaw, K T; Raghavan, A; Aramburu, J; Garcia-Cozar, F; Perrino, B A; Hogan, P G; Rao, A

    1996-01-01

    The nuclear import of the nuclear factor of activated T cells (NFAT)-family transcription factors is initiated by the protein phosphatase calcineurin. Here we identify a regulatory region of NFAT1, N terminal to the DNA-binding domain, that controls nuclear import of NFAT1. The regulatory region of NFAT1 binds directly to calcineurin, is a substrate for calcineurin in vitro, and shows regulated subcellular localization identical to that of full-length NFAT1. The corresponding region of NFATc likewise binds calcineurin, suggesting that the efficient activation of NFAT1 and NFATc by calcineurin reflects a specific targeting of the phosphatase to these proteins. The presence in other NFAT-family transcription factors of several sequence motifs from the regulatory region of NFAT1, including its probable nuclear localization sequence, indicates that a conserved protein domain may control nuclear import of all NFAT proteins. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8799126

  4. Three WRKY transcription factors additively repress abscisic acid and gibberellin signaling in aleurone cells.

    PubMed

    Zhang, Liyuan; Gu, Lingkun; Ringler, Patricia; Smith, Stanley; Rushton, Paul J; Shen, Qingxi J

    2015-07-01

    Members of the WRKY transcription factor superfamily are essential for the regulation of many plant pathways. Functional redundancy due to duplications of WRKY transcription factors, however, complicates genetic analysis by allowing single-mutant plants to maintain wild-type phenotypes. Our analyses indicate that three group I WRKY genes, OsWRKY24, -53, and -70, act in a partially redundant manner. All three showed characteristics of typical WRKY transcription factors: each localized to nuclei and yeast one-hybrid assays indicated that they all bind to W-boxes, including those present in their own promoters. Quantitative real time-PCR (qRT-PCR) analyses indicated that the expression levels of the three WRKY genes varied in the different tissues tested. Particle bombardment-mediated transient expression analyses indicated that all three genes repress the GA and ABA signaling in a dosage-dependent manner. Combination of all three WRKY genes showed additive antagonism of ABA and GA signaling. These results suggest that these WRKY proteins function as negative transcriptional regulators of GA and ABA signaling. However, different combinations of these WRKY genes can lead to varied strengths in suppression of their targets. PMID:26025535

  5. Effect of Addition of Chin Strap on PAP Compliance, Nightly Duration of Use, and Other Factors

    PubMed Central

    Knowles, Shelley R.; O'Brien, Daniel T.; Zhang, Shiling; Devara, Anupama; Rowley, James A.

    2014-01-01

    Study Objectives: A chinstrap is potentially useful to reduce unintentional air leak by preventing mouth opening during PAP treatment. This study examines whether the addition of a chinstrap to PAP therapy has any effect on adherence, nightly duration of use, air leak, and residual AHI. Methods: This was a retrospective study performed at an AASM-accredited VAMC sleep center. Clinical sleep data of veterans (n = 124) prescribed PAP therapy for sleep apnea was evaluated, and the effect of chinstrap use vs non-use on the above parameters was assessed. Results: Chinstrap users had significantly greater PAP adherence, longer nightly duration of PAP use, lower residual AHI and lower leak compared to chinstrap non-users at first follow up visit. Conclusions: The addition of a chin strap to PAP therapy is a simple and inexpensive method of increasing PAP adherence. Citation: Knowles SR; O'Brien DT; Zhang S; Devara A; Rowley JA. Effect of addition of chin strap on PAP compliance, nightly duration of use, and other factors. J Clin Sleep Med 2014;10(4):377-383. PMID:24733982

  6. The importance of oncogenic transcription factors for oral cancer pathogenesis and treatment.

    PubMed

    Yedida, Govinda Raju; Nagini, Siddavaram; Mishra, Rajakishore

    2013-08-01

    Oral squamous cell carcinoma is a major cause of morbidity and mortality worldwide. Current experimental evidence shows that most important risk factors for oral cancer include tobacco use and excessive alcohol consumption and less well-defined risks include viral infection and a diet deficient in antioxidants. The positive correlation between various risk/etiologic factors of oral cancer and the activation of various transcription factors (TFs) has been reported in the literature. Although initially, TFs were considered to be very difficult targets for use in clinical treatment, recent technological advances have provided the ability to control these factors of cancer progression. This review focuses on the role of oncogenic transcription factors in oral cancer, their modes of activation through various biological pathways, the promises and pitfalls in viewing them as potent oncotargets, the way they can be controlled based on the current understanding, and the future research to be done in this area. PMID:23619350

  7. Factors which Limit the Value of Additional Redundancy in Human Rated Launch Vehicle Systems

    NASA Technical Reports Server (NTRS)

    Anderson, Joel M.; Stott, James E.; Ring, Robert W.; Hatfield, Spencer; Kaltz, Gregory M.

    2008-01-01

    The National Aeronautics and Space Administration (NASA) has embarked on an ambitious program to return humans to the moon and beyond. As NASA moves forward in the development and design of new launch vehicles for future space exploration, it must fully consider the implications that rule-based requirements of redundancy or fault tolerance have on system reliability/risk. These considerations include common cause failure, increased system complexity, combined serial and parallel configurations, and the impact of design features implemented to control premature activation. These factors and others must be considered in trade studies to support design decisions that balance safety, reliability, performance and system complexity to achieve a relatively simple, operable system that provides the safest and most reliable system within the specified performance requirements. This paper describes conditions under which additional functional redundancy can impede improved system reliability. Examples from current NASA programs including the Ares I Upper Stage will be shown.

  8. PHASER 2.10 methodology for dependence, importance, and sensitivity: The role of scale factors, confidence factors, and extremes

    SciTech Connect

    Cooper, J.A.

    1996-09-01

    PHASER (Probabilistic Hybrid Analytical System Evaluation Routine) is a software tool that has the capability of incorporating subjective expert judgment into probabilistic safety analysis (PSA) along with conventional data inputs. An earlier report described the PHASER methodology, but only gave a cursory explanation about how dependence was incorporated in Version 1.10 and about how ``Importance`` and ``Sensitivity`` measures were to be incorporated in Version 2.00. A more detailed description is given in this report. The basic concepts involve scale factors and confidence factors that are associated with the stochastic variability and subjective uncertainty (which are common adjuncts used in PSA), and the safety risk extremes that are crucial to safety assessment. These are all utilized to illustrate methodology for incorporating dependence among analysis variables in generating PSA results, and for Importance and Sensitivity measures associated with the results that help point out where any major sources of safety concern arise and where any major sources of uncertainty reside, respectively.

  9. What Is Most Important: Social Factors, Health Selection, and Adolescent Educational Achievement

    ERIC Educational Resources Information Center

    Roos, Leslie L.; Hiebert, Brett; Manivong, Phongsack; Edgerton, Jason; Walld, Randy; MacWilliam, Leonard; de Rocquigny, Janelle

    2013-01-01

    This paper explores the relative importance of social factors and health measures in predicting educational achievement in early and late adolescence using population-based administrative data. The sample was made up of 41,943 children born in Manitoba, Canada between 1982 and 1989 and remaining in the province until age 18. Multilevel modeling…

  10. What Factors Are Important in Smoking Cessation Amongst Deprived Communities?: A Qualitative Study

    ERIC Educational Resources Information Center

    Henderson, Hazel J.; Memon, Anjum; Lawson, Kate; Jacobs, Barbara; Koutsogeorgou, Eleni

    2011-01-01

    Objective: There is limited evidence regarding effective smoking cessation interventions in deprived communities. This study explored what factors are considered most important in smoking cessation, from the perspective of a group of NHS Stop Smoking Service users from a deprived community. Design: A qualitative study. Setting: A deprived…

  11. Risk factors associated with elder abuse: the importance of differentiating by type of elder maltreatment.

    PubMed

    Jackson, Shelly L; Hafemeister, Thomas L

    2011-01-01

    Elder abuse research rarely differentiates by the type of elder maltreatment involved when identifying risk factors. The purpose of this study was to compare risk factors across four predominant types of elder maltreatment (financial exploitation, physical abuse, neglect by others, and hybrid financial exploitation [HFE]). Data were collected from two sources: interviews with victims of substantiated elder abuse, responding adult protective services (APS) caseworkers (N = 71), and third-party informants; and a statewide database that contained all substantiated cases over a corresponding 2-year period (N = 2,142). Using chi-square (interview data) and logistic regressions (Adult Services/Adult Protective Services [ASAPS] data), significant differences across the four types of elder maltreatment were found. These two datasets provide converging evidence for the importance of differentiating by type of maltreatment when identifying risk factors for elder maltreatment and for the importance of considering both the elderly victim and the abusive individual when predicting type of elder maltreatment. PMID:22288093

  12. Relative importance index (RII) in ranking of procrastination factors among university students

    NASA Astrophysics Data System (ADS)

    Aziz, Nazrina; Zain, Zakiyah; Mafuzi, Raja Muhammad Zahid Raja; Mustapa, Aini Mastura; Najib, Nur Hasibah Mohd; Lah, Nik Fatihah Nik

    2016-08-01

    Procrastination is the action of delaying or postponing something such as making a decision or starting or completing some tasks or activities. According to previous studies, students who have a strong tendency to procrastinate get low scores in their tests, resulting in poorer academic performance compared to those who do not procrastinate. This study aims to identify the procrastination factors in completing assignments among three groups of undergraduate students. The relative importance of procrastination factors was quantified by the relative importance index (RII) method prior to ranking. A multistage sampling technique was used in selecting the sample. The findings revealed that `too many works in one time' is one of the top three factors contributing to procrastination in all groups.

  13. RNA export factor Ddx19 is required for nuclear import of the SRF coactivator MKL1

    PubMed Central

    Rajakylä, Eeva Kaisa; Viita, Tiina; Kyheröinen, Salla; Huet, Guillaume; Treisman, Richard; Vartiainen, Maria K.

    2015-01-01

    Controlled transport of macromolecules between the cytoplasm and nucleus is essential for homeostatic regulation of cellular functions. For instance, gene expression entails coordinated nuclear import of transcriptional regulators to activate transcription and nuclear export of the resulting messenger RNAs for cytoplasmic translation. Here we link these two processes by reporting a novel role for the mRNA export factor Ddx19/Dbp5 in nuclear import of MKL1, the signal-responsive transcriptional activator of SRF. We show that Ddx19 is not a general nuclear import factor, and that its specific effect on MKL1 nuclear import is separate from its role in mRNA export. Both helicase and nuclear pore-binding activities of Ddx19 are dispensable for MKL1 nuclear import, but RNA binding is required. Mechanistically, Ddx19 operates by modulating the conformation of MKL1, which affects its interaction with Importin-β for efficient nuclear import. Thus, Ddx19 participates in mRNA export, translation and nuclear import of a key transcriptional regulator. PMID:25585691

  14. RNA export factor Ddx19 is required for nuclear import of the SRF coactivator MKL1.

    PubMed

    Rajakylä, Eeva Kaisa; Viita, Tiina; Kyheröinen, Salla; Huet, Guillaume; Treisman, Richard; Vartiainen, Maria K

    2015-01-01

    Controlled transport of macromolecules between the cytoplasm and nucleus is essential for homeostatic regulation of cellular functions. For instance, gene expression entails coordinated nuclear import of transcriptional regulators to activate transcription and nuclear export of the resulting messenger RNAs for cytoplasmic translation. Here we link these two processes by reporting a novel role for the mRNA export factor Ddx19/Dbp5 in nuclear import of MKL1, the signal-responsive transcriptional activator of SRF. We show that Ddx19 is not a general nuclear import factor, and that its specific effect on MKL1 nuclear import is separate from its role in mRNA export. Both helicase and nuclear pore-binding activities of Ddx19 are dispensable for MKL1 nuclear import, but RNA binding is required. Mechanistically, Ddx19 operates by modulating the conformation of MKL1, which affects its interaction with Importin-β for efficient nuclear import. Thus, Ddx19 participates in mRNA export, translation and nuclear import of a key transcriptional regulator. PMID:25585691

  15. Enhancement of antibody production by growth factor addition in perfusion and hollow-fiber culture systems.

    PubMed

    Omasa, T; Kobayashi, M; Nishikawa, T; Shioya, S; Suga, K; Uemura, S; Kitani, Y; Imamura, Y

    1995-12-20

    The effects of the high-molecular-weight growth factors, transferrin and bovine serum albumin (BSA), on antibody production were analyzed quantitatively in continuous hollow-fiber cultivation over a period of 60 days. Transferrin enhanced cell growth but had no significant effect on the specific antibody production rate, whereas BSA significantly enhanced antibody production. The antibody production rate was increased 4- and 14-fold respectively by feeding BSA at 2 and 5 g L(-1) into the EC side of the system (the side connected to the cell-containing outer part of the hollow-fiber unit) compared with the production achieved without BSA. Addition of 5 g L(1) BSA into the IC side of the system (the side connected to the inner part of the hollow-fiber unit) resulted in a 2.5-fold increase in the antibody production rate. The effect of BSA was also analyzed using the perfusion culture system with a separation unit. When fresh medium containing either 2 or 5 g L(-1) BSA was fed into the reactor, both the specific growth rate and specific death rate increased, while the specific antibody production rate was increased 2- and 25-fold, respectively, by feeding BSA at these two concentrations compared with no addition. Comparing the two systems, the increase in the antibody production rate achieved with the hollow-fiber system was threefold greater than that in the perfusion culture system with the same concentration of BSA feeding. (c) 1995 John Wiley & Sons, Inc. PMID:18623537

  16. Importance of the Compton-Getting Factor in Energetic Neutral Atom Imaging of the Heliosheath

    NASA Astrophysics Data System (ADS)

    Roelof, E. C.

    2012-12-01

    The Compton-Getting factor (CGF) enters into energetic neutral atom (ENA) imaging as a consequence of the generation of ENAs by a population of singly-charged energetic ions having a non-zero bulk plasma velocity with respect to the imager. There is an additional effect if the cold neutral atoms that produce the charge exchange also have their own relative bulk motion, but that will not be discussed here. The CGF follows from the general invariance of the ion phase-space density under a Lorentz transformation (Gallilean at non-relativistic energies), and it takes its simplest form under the approximation that the energetic ion distribution is isotropic in the plasma frame. Then one can write approximately j(v)=CGF*j0(v), where j(v) is the intensity in the frame of the imager for an ion with velocity (v), while j0(v), is the (assumedly isotropic) intensity in the plasma frame (evaluated at the same velocity v) and (k) is the local power-law index of the intensity energy spectrum (also in the plasma frame). For ENA imaging of the heliosheath, to good approximation CGF=R-2(k+1), where R=1+Vr/v involves the radial component of the plasma velocity V. The extraction of k requires further analysis, because the ENA spectrum is affected by the CGF. Plasma velocities Vr~100 km/s are measured within the heliosheath by both the Voyager spacecraft, and approximate values 1.530 keV) increases the estimate of the thickness of the heliosheath in the VGR2 pixel by 32%. Additional examples of how the CGF plays

  17. A new detrended semipartial cross-correlation analysis: Assessing the important meteorological factors affecting API

    NASA Astrophysics Data System (ADS)

    Shen, Chen-Hua

    2015-12-01

    To analyze the unique contribution of meteorological factors to the air pollution index (API), a new method, the detrended semipartial cross-correlation analysis (DSPCCA), is proposed. Based on both a detrended cross-correlation analysis and a DFA-based multivariate-linear-regression (DMLR), this method is improved by including a semipartial correlation technique, which is used to indicate the unique contribution of an explanatory variable to multiple correlation coefficients. The advantages of this method in handling nonstationary time series are illustrated by numerical tests. To further demonstrate the utility of this method in environmental systems, new evidence of the primary contribution of meteorological factors to API is provided through DMLR. Results show that the most important meteorological factors affecting API are wind speed and diurnal temperature range, and the explanatory ability of meteorological factors to API gradually strengthens with increasing time scales. The results suggest that DSPCCA is a useful method for addressing environmental systems.

  18. Patients’ experience of important factors in the healthcare environment in oncology care

    PubMed Central

    Browall, Maria; Koinberg, Ingalill; Falk, Hanna; Wijk, Helle

    2013-01-01

    Background and objective The aim of this study was to describe what factors of the healthcare environment are perceived as being important to patients in oncology care. Design A qualitative design was adopted using focus group interviews. Setting and participants The sample was 11 patients with different cancer diagnoses in an oncology ward at a university hospital in west Sweden. Results Analysis of the patients’ perceptions of the environment indicated a complex entity comprising several aspects. These came together in a structure consisting of three main categories: safety, partnership with the staff, and physical space. The care environment is perceived as a complex entity, made up of several physical and psychosocial aspects, where the physical factors are subordinated by the psychosocial factors. It is clearly demonstrated that the patients’ primary desire was a psychosocial environment where they were seen as a unique person; the patients wanted opportunities for good encounters with staff, fellow patients, and family members, supported by a good physical environment; and the patients valued highly a place to withdraw and rest. Conclusions This study presents those attributes that are valued by cancer patients as crucial and important for the support of their well-being and functioning. The results show that physical aspects were subordinate to psychosocial factors, which emerged strongly as being the most important in a caring environment. PMID:23924604

  19. RNA Helicase Important for Listeria monocytogenes Hemolytic Activity and Virulence Factor Expression

    PubMed Central

    Netterling, Sakura; Bäreclev, Caroline; Vaitkevicius, Karolis

    2015-01-01

    RNA helicases have been shown to be important for the function of RNA molecules at several levels, although their putative involvement in microbial pathogenesis has remained elusive. We have previously shown that Listeria monocytogenes DExD-box RNA helicases are important for bacterial growth, motility, ribosomal maturation, and rRNA processing. We assessed the importance of the RNA helicase Lmo0866 (here named CshA) for expression of virulence traits. We observed a reduction in hemolytic activity in a strain lacking CshA compared to the wild type. This phenomenon was less evident in strains lacking other RNA helicases. The reduced hemolysis was accompanied by lower expression of major listerial virulence factors in the ΔcshA strain, mainly listeriolysin O, but also to some degree the actin polymerizing factor ActA. Reduced expression of these virulence factors in the strain lacking CshA did not, however, correlate with a decreased level of the virulence regulator PrfA. When combining the ΔcshA knockout with a mutation creating a constitutively active PrfA protein (PrfA*), the effect of the ΔcshA knockout on LLO expression was negated. These data suggest a role for the RNA helicase CshA in posttranslational activation of PrfA. Surprisingly, although the expression of several virulence factors was reduced, the ΔcshA strain did not demonstrate any reduced ability to infect nonphagocytic cells compared to the wild-type strain. PMID:26483402

  20. Integrating products of Bessel functions with an additional exponential or rational factor

    NASA Astrophysics Data System (ADS)

    Van Deun, Joris; Cools, Ronald

    2008-04-01

    We provide two MATLAB programs to compute integrals of the form ex∏i=1kJν_i(ax)dxand 0∞xr+x∏i=1kJν_i(ax)dx with Jν_i(x) the Bessel function of the first kind and (real) order ν. The parameter m is a real number such that ∑ν+m>-1 (to assure integrability near zero), r is real and the numbers c and a are all strictly positive. The program can deliver accurate error estimates. Program summaryProgram title: BESSELINTR, BESSELINTC Catalogue identifier: AEAH_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEAH_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 1601 No. of bytes in distributed program, including test data, etc.: 13 161 Distribution format: tar.gz Programming language: Matlab (version ⩾6.5), Octave (version ⩾2.1.69) Computer: All supporting Matlab or Octave Operating system: All supporting Matlab or Octave RAM: For k Bessel functions our program needs approximately ( 500+140k) double precision variables Classification: 4.11 Nature of problem: The problem consists in integrating an arbitrary product of Bessel functions with an additional rational or exponential factor over a semi-infinite interval. Difficulties arise from the irregular oscillatory behaviour and the possible slow decay of the integrand, which prevents truncation at a finite point. Solution method: The interval of integration is split into a finite and infinite part. The integral over the finite part is computed using Gauss-Legendre quadrature. The integrand on the infinite part is approximated using asymptotic expansions and this approximation is integrated exactly with the aid of the upper incomplete gamma function. In the case where a rational factor is present, this factor is first expanded in a Taylor series around infinity. Restrictions: Some (and eventually all

  1. {beta}-Catenin can act as a nuclear import receptor for its partner transcription factor, lymphocyte enhancer factor-1 (lef-1)

    SciTech Connect

    Asally, Munehiro; Yoneda, Yoshihiro . E-mail: yyoneda@anat3.med.osaka-u.ac.jp

    2005-08-15

    Nuclear accumulation of {beta}-catenin plays an important role in the Wnt signaling pathway. In the nucleus, {beta}-catenin acts as a transcriptional co-activator for TCF/LEF family of transcription factors. It has been shown that lef-1 contains a typical basic type nuclear localization signal (NLS) and is transported into the nucleus by the conventional import pathway. In this study, we found that a mutant lef-1 lacking the classical NLS accumulated in the nucleus of living cells, when {beta}-catenin was co-expressed. In addition, in a cell-free import assay, lef-1 migrated into the nucleus in the presence of {beta}-catenin alone without any other soluble factors. In contrast, another mutant lef-1 lacking the {beta}-catenin binding domain failed to migrate into the nucleus, even in the presence of {beta}-catenin. These findings indicate that {beta}-catenin alone can mediate the nuclear import of lef-1 through the direct binding. Collectively, we propose that there are two distinct pathways for the nuclear import of lef-1: importin {alpha}/{beta}-mediated and {beta}-catenin-mediated one, which provides a novel paradigm for Wnt signaling pathway.

  2. Identifying Important Risk Factors for Survival in Kidney Graft Failure Patients Using Random Survival Forests

    PubMed Central

    HAMIDI, Omid; POOROLAJAL, Jalal; FARHADIAN, Maryam; TAPAK, Leili

    2016-01-01

    Background: Kidney transplantation is the best alternative treatment for end-stage renal disease. Several studies have been devoted to investigate predisposing factors of graft rejection. However, there is inconsistency between the results. The objective of the present study was to utilize an intuitive and robust approach for variable selection, random survival forests (RSF), and to identify important risk factors in kidney transplantation patients. Methods: The data set included 378 patients with kidney transplantation obtained through a historical cohort study in Hamadan, western Iran, from 1994 to 2011. The event of interest was chronic nonreversible graft rejection and the duration between kidney transplantation and rejection was considered as the survival time. RSF method was used to identify important risk factors for survival of the patients among the potential predictors of graft rejection. Results: The mean survival time was 7.35±4.62 yr. Thirty-seven episodes of rejection were occurred. The most important predictors of survival were cold ischemic time, recipient’s age, creatinine level at discharge, donors’ age and duration of hospitalization. RSF method predicted survival better than the conventional Cox-proportional hazards model (out-of-bag C-index of 0.965 for RSF vs. 0.766 for Cox model and integrated Brier score of 0.081 for RSF vs. 0.088 for Cox model). Conclusion: A RSF model in the kidney transplantation patients outperformed traditional Cox-proportional hazard model. RSF is a promising method that may serve as a more intuitive approach to identify important risk factors for graft rejection. PMID:27057518

  3. Age at onset of Alzheimer's disease: clue to the relative importance of etiologic factors

    SciTech Connect

    Horner, R.D.

    1987-09-01

    Clues to the relative importance of possible etiologic factors for dementia of the Alzheimer type may be gained by examining the fit of case series to Sartwell's model of the distribution of incubation periods. If age at disease onset is used as the incubation period of this disease, a genetic or environmental factor acting during the prenatal period is suggested if the distribution of these ages fits the lognormal curve; otherwise, environmental factors acting after birth are implicated. Case series were identified from the literature. Four case series were found which contained sufficiently detailed data to permit this secondary analysis; only one case series was population-based. The distribution of age at disease onset for each series was graphically and statistically assessed for fit to the logarithmic normal distribution. Each case series fit the lognormal curve well. This suggests that research into the etiology of dementia of the Alzheimer type should focus on the prenatal experiences of patients with this disease.

  4. Additional thyroid dose factor from transportation sources in Russia after the Chernobyl disaster.

    PubMed Central

    Parshkov, E M; Chebotareva, I V; Sokolov, V A; Dallas, C E

    1997-01-01

    Beginning approximately 4 years after the Chernobyl nuclear accident a steady increase in the incidence of thyroid cancer was observed in children and adolescents of the Bryansk Oblast, which received the highest level of radionuclide contaminants in Russia. We examined the spatial relationship between the residence location of patients with identified thyroid cancer (0-18 years old at the time of the accident) and a number of geographic parameters to better account for the etiology of thyroid cancer spatial distribution. Geographic parameters analyzed included spatial distribution of 137Cs and 131I in soil, population demographics, measurements and reconstructions. of absorbed thyroid 131I doses in the population, and maps of major transportation arteries. An interesting finding is the lack of a consistent correlation between the spatial distribution of radionuclides in the soil and thyroid cancer incidence. Instead, most of the thyroid cancer cases were diagnosed in settlements situated on major railways and roads. Correlating population with thyroid cancer cases and transportation arteries reveals a much higher cancer rate on or near major roads and railways than at a distance from them, again independent of radionuclide soil concentration. There are other important factors, of course, that must be considered in future evaluations of this phenomenon. These include the influence of iodine endemic zones, genetic predisposition to thyroid cancer, and duration of residence time in contaminated areas. The feasibility of radionuclide transport on railways and roads is discussed, together with the vectors for transfer of the contaminants to the human population. Developing a model to reconstruct the radiation dose to the thyroid over time in this geographic region is proposed in light of the impact of transportation arteries. Specific studies are outlined to provide the data necessary to develop this model as well as to better characterize the feasibility and

  5. The importance of seizure-inducing factors in the control of refractory forms of epilepsy.

    PubMed

    Aird, R B

    1983-10-01

    Of over 40 known epileptogenic mechanisms, some 10 vary from hour to hour, depending upon habit factors and the daily activities of the patients. Tension states, alterations of level of consciousness, sleep deprivation, disturbances of water and acid-base balances, sensory and drug stimulation, and drug withdrawal are the principal factors involved. Their importance varies widely in patients, as well as with time. This fact and the concentration of physicians upon drug therapy have served to deemphasize this aspect of antiepileptic therapy. This point was clearly verified by reviews of the literature. In a prospective study of 500 drug-resistant patients, such seizure-inducing mechanisms were studied. Methods of identification, evaluation, and regulation were developed. The results indicate that in selected patients the regulation of such factors may play a significant role in the stabilization and improvement of the underlying epileptic condition. In 17% of a refractory group, such factors were found to be of crucial importance. In spite of intensive efforts with drug therapy over the past 4 decades, the incidence of drug-resistant cases remains high. The more comprehensive approach suggested offers an attractive, partial solution to this difficult problem. PMID:6617587

  6. Cellular Promyelocytic Leukemia Protein Is an Important Dengue Virus Restriction Factor

    PubMed Central

    Giovannoni, Federico; Damonte, Elsa B.; García, Cybele C.

    2015-01-01

    The intrinsic antiviral defense is based on cellular restriction factors that are constitutively expressed and, thus, active even before a pathogen enters the cell. The promyelocytic leukemia (PML) nuclear bodies (NBs) are discrete nuclear foci that contain several cellular proteins involved in intrinsic antiviral responses against a number of viruses. Accumulating reports have shown the importance of PML as a DNA virus restriction factor and how these pathogens evade this antiviral activity. However, very little information is available regarding the antiviral role of PML against RNA viruses. Dengue virus (DENV) is an RNA emerging mosquito-borne human pathogen affecting millions of individuals each year by causing severe and potentially fatal syndromes. Since no licensed antiviral drug against DENV infection is currently available, it is of great importance to understand the factors mediating intrinsic immunity that may lead to the development of new pharmacological agents that can boost their potency and thereby lead to treatments for this viral disease. In the present study, we investigated the in vitro antiviral role of PML in DENV-2 A549 infected cells. PMID:25962098

  7. Electrical inhibition of lens epithelial cell proliferation: an additional factor in secondary cataract?

    PubMed Central

    Wang, Entong; Reid, Brian; Lois, Noemi; Forrester, John V.; McCaig, Colin D.; Zhao, Min

    2005-01-01

    Cataract is the most common cause of blindness but is at least curable by surgery. Unfortunately, many patients gradually develop the complication of posterior capsule opacification (PCO) or secondary cataract. This arises from stimulated cell growth within the lens capsule and can greatly impair vision. It is not fully understood why residual lens epithelial cell growth occurs after surgery. We propose and show that cataract surgery might remove an important inhibitory factor for lens cell growth, namely electric fields. The lens generates a unique pattern of electric currents constantly flowing out from the equator and entering the anterior and posterior poles. We show here that cutting and removing part of the anterior capsule as in cataract surgery significantly decreases the equatorial outward electric currents. Application of electric fields in culture inhibits proliferation of human lens epithelial cells. This inhibitory effect is likely to be mediated through a cell cycle control mechanism that decreases entry of cells into S phase from G1 phase by decreasing the G1-specific cell cycle protein cyclin E and increasing the cyclin-Cdk complex inhibitor p27kip1. Capsulorrhexis in vivo, which reduced endogenous lens electric fields, significantly increased LEC growth. This, together with our previous findings that electric fields have significant effects on the direction of lens cell migration, points to a controlling mechanism for the aberrant cell growth in posterior capsule opacification. A novel approach to control growth of lens epithelial cells using electric fields combined with other controlling mechanisms may be more effective in the prevention and treatment of this common complication of cataract surgery. PMID:15764648

  8. [Team-based community psychiatry: importance of context factors and transferability of evidence from studies].

    PubMed

    Weinmann, S; Gühne, U; Kösters, M; Gaebel, W; Becker, T

    2012-07-01

    The German Society for Psychiatry, Psychotherapy and Neurology (DGPPN) guidelines on psychosocial interventions for people with severe mental illness appraise the transferability of results of trials evaluating community-based mental health services to the German situation. This assessment has to draw on research results on factors determining effectiveness. This must be seen against the background of a lack of high-quality trials in Germany. The article discusses system, context and setting factors related to the transfer of evidence on community-based service models from other countries. These issues are discussed on the basis of evidence concerning the models of case management, assertive community treatment and community mental health teams. International differences in study findings are highlighted and the importance of treatment-as-usual in influencing study results is emphasized. The more control services including elements of community-based care there are and the less the pressure to reduce inpatient treatment (threshold to inpatient care admission), the smaller the relative effect sizes of innovative care models will be.In the absence of direct evidence, careful examination of transferability is required before introducing health care models. Research has revealed solid evidence for several factors influencing the effects of innovative community mental health care. Among key factors in the care of people with severe mental illness, home visits and joint team responsibility for both psychiatric and social care were identified. This evidence can facilitate the adaptation of successful mental health care models in Germany. PMID:22688090

  9. Non-clinical factors associated with TB: important for DOTS impact evaluation and disease elimination.

    PubMed

    Hill, Philip C; Whalen, Christopher C

    2014-09-01

    Initial optimism that DOTS (Directly Observed Treatment, Short-course) would have a dramatic effect on TB incidence rates in developing countries has not been supported by the evidence accumulated so far. Indeed, where TB incidence rates have decreased, non-clinical socio-economic factors appear to have played at least as great a role. We postulate that in those settings with little or no decrease in TB incidence, there are likely to be common pathway blockages that interfere with the effectiveness of DOTS implementation as socio-economic factors evolve. Measuring socio-economic trends, as well as DOTS implementation, is important for understanding TB control and opens up the opportunity for broader public health engagement. PMID:25059524

  10. The basic leucine zipper transcription factor ABSCISIC ACID RESPONSE ELEMENT-BINDING FACTOR2 is an important transcriptional regulator of abscisic acid-dependent grape berry ripening processes.

    PubMed

    Nicolas, Philippe; Lecourieux, David; Kappel, Christian; Cluzet, Stéphanie; Cramer, Grant; Delrot, Serge; Lecourieux, Fatma

    2014-01-01

    In grape (Vitis vinifera), abscisic acid (ABA) accumulates during fruit ripening and is thought to play a pivotal role in this process, but the molecular basis of this control is poorly understood. This work characterizes ABSCISIC ACID RESPONSE ELEMENT-BINDING FACTOR2 (VvABF2), a grape basic leucine zipper transcription factor belonging to a phylogenetic subgroup previously shown to be involved in ABA and abiotic stress signaling in other plant species. VvABF2 transcripts mainly accumulated in the berry, from the onset of ripening to the harvesting stage, and were up-regulated by ABA. Microarray analysis of transgenic grape cells overexpressing VvABF2 showed that this transcription factor up-regulates and/or modifies existing networks related to ABA responses. In addition, grape cells overexpressing VvABF2 exhibited enhanced responses to ABA treatment compared with control cells. Among the VvABF2-mediated responses highlighted in this study, the synthesis of phenolic compounds and cell wall softening were the most strongly affected. VvABF2 overexpression strongly increased the accumulation of stilbenes that play a role in plant defense and human health (resveratrol and piceid). In addition, the firmness of fruits from tomato (Solanum lycopersicum) plants overexpressing VvABF2 was strongly reduced. These data indicate that VvABF2 is an important transcriptional regulator of ABA-dependent grape berry ripening. PMID:24276949

  11. 21 CFR 1311.115 - Additional requirements for two-factor authentication.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... authentication. 1311.115 Section 1311.115 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE... requirements for two-factor authentication. (a) To sign a controlled substance prescription, the electronic... authentication protocol that uses two of the following three factors: (1) Something only the practitioner...

  12. 21 CFR 1311.115 - Additional requirements for two-factor authentication.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... authentication. 1311.115 Section 1311.115 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE... requirements for two-factor authentication. (a) To sign a controlled substance prescription, the electronic... authentication protocol that uses two of the following three factors: (1) Something only the practitioner...

  13. 21 CFR 1311.115 - Additional requirements for two-factor authentication.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... authentication. 1311.115 Section 1311.115 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE... requirements for two-factor authentication. (a) To sign a controlled substance prescription, the electronic... authentication protocol that uses two of the following three factors: (1) Something only the practitioner...

  14. 21 CFR 1311.115 - Additional requirements for two-factor authentication.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... authentication. 1311.115 Section 1311.115 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE... requirements for two-factor authentication. (a) To sign a controlled substance prescription, the electronic... authentication protocol that uses two of the following three factors: (1) Something only the practitioner...

  15. Perceptions of important retention and recruitment factors by therapists in northwestern Ontario.

    PubMed

    Solomon, P; Salvatori, P; Berry, S

    2001-01-01

    Recruitment and retention of health professionals in rural and remote communities are well-known challenges. Although the literature states that lifestyle factors and being from a rural background influence recruitment and retention, much of the research is dated and of limited relevance to rehabilitation professionals. This study reports on a survey of physical therapists (PTs) and occupational therapists (OTs) in northwestern Ontario. Seventy-four percent of the OTs and PTs from this geographically isolated region of Canada responded to a mail survey examining factors that influenced their job recruitment and retention decisions. Availability of leisure and recreation activities, proximity of family of origin, need for OTs and PTs and influence of spouse or partner frequently contributed to recruitment decisions and were also important in retention decisions. Although professional autonomy was an important source of job satisfaction for the respondents, almost one-third reported a feeling of professional isolation. Professional development initiatives appeared to influence job satisfaction but were unlikely to influence working life decisions. The findings suggest that recruitment and retention strategies should be multifaceted to reflect the complexity of therapists' decision-making. PMID:11765892

  16. Imported malaria in Albania and the risk factors that could allow its reappearance.

    PubMed

    Shkurti, Klodiana; Vyshka, Gentian; Velo, Enkelejda; Boçari, Arben; Kokici, Majlinda; Kraja, Dhimitër

    2013-01-01

    Malaria is an infectious disease gradually becoming a serious concern for public health institutions, even in European countries where the eradication of the disease was previously taken for granted. Albania was listed as an endemic area from the beginning of the 20th Century, but the disease was gradually under control and some decades after the World War II it was merely considered a historical curiosity. Nevertheless, for many reasons, since 1994 and in increasing trend, Albanian health facilities have registered several cases of malaria. Tracing the remnants of the autochthonous disease and finding links with the actual situation seems difficult, due to the relatively long period separating the proclaimed eradication of malaria with the re-appearance of the infection. Among major factors leading to such re-appearance might be massive migratory movements, and environmental changes such as the flooding of areas close to river deltas that flow into the Adriatic and Ionian Seas. These factors, combined with the constant presence of several Anopheles species, have led to newly-diagnosed imported malaria cases in Albania. Although all reported cases are considered imported, measures have to be put in place, in order to prevent reappearance of autochthonous malaria cases, and to control disease spread. PMID:23758911

  17. Dynamic regulation of Gata factor levels is more important than their identity.

    PubMed

    Ferreira, Rita; Wai, Albert; Shimizu, Ritsuko; Gillemans, Nynke; Rottier, Robbert; von Lindern, Marieke; Ohneda, Kinuko; Grosveld, Frank; Yamamoto, Masayuki; Philipsen, Sjaak

    2007-06-15

    Three Gata transcription factors (Gata1, -2, and -3) are essential for hematopoiesis. These factors are thought to play distinct roles because they do not functionally replace each other. For instance, Gata2 messenger RNA (mRNA) expression is highly elevated in Gata1-null erythroid cells, yet this does not rescue the defect. Here, we test whether Gata2 and -3 transgenes rescue the erythroid defect of Gata1-null mice, if expressed in the appropriate spatiotemporal pattern. Gata1, -2, and -3 transgenes driven by beta-globin regulatory elements, directing expression to late stages of differentiation, fail to rescue erythropoiesis in Gata1-null mutants. In contrast, when controlled by Gata1 regulatory elements, directing expression to the early stages of differentiation, Gata1, -2, and -3 do rescue the Gata1-null phenotype. The dramatic increase of endogenous Gata2 mRNA in Gata1-null progenitors is not reflected in Gata2 protein levels, invoking translational regulation. Our data show that the dynamic spatiotemporal regulation of Gata factor levels is more important than their identity and provide a paradigm for developmental control mechanisms that are hard-wired in cis-regulatory elements. PMID:17327407

  18. FNR Regulates Expression of Important Virulence Factors Contributing to Pathogenicity of Uropathogenic Escherichia coli

    PubMed Central

    Barbieri, Nicolle L.; Nicholson, Bryon; Hussein, Ashraf; Cai, Wentong; Wannemuehler, Yvonne M.; Dell'Anna, Giuseppe; Logue, Catherine M.; Horn, Fabiana; Nolan, Lisa K.

    2014-01-01

    Uropathogenic Escherichia coli (UPEC) is responsible for the majority of urinary tract infections (UTIs), which are some of the world's most common bacterial infections of humans. Here, we examined the role of FNR (fumarate and nitrate reduction), a well-known global regulator, in the pathogenesis of UPEC infections. We constructed an fnr deletion mutant of UPEC CFT073 and compared it to the wild type for changes in virulence, adherence, invasion, and expression of key virulence factors. Compared to the wild type, the fnr mutant was highly attenuated in the mouse model of human UTI and showed severe defects in adherence to and invasion of bladder and kidney epithelial cells. Our results showed that FNR regulates motility and multiple virulence factors, including expression of type I and P fimbriae, modulation of hemolysin expression, and expression of a novel pathogenicity island involved in α-ketoglutarate metabolism under anaerobic conditions. Our results demonstrate that FNR is a key global regulator of UPEC virulence and controls expression of important virulence factors that contribute to UPEC pathogenicity. PMID:25245807

  19. Hypoxia-inducible factors 1 and 2 are important transcriptional effectors in primary macrophages experiencing hypoxia.

    PubMed

    Fang, Hsin-Yu; Hughes, Russell; Murdoch, Craig; Coffelt, Seth B; Biswas, Subhra K; Harris, Adrian L; Johnson, Randall S; Imityaz, Hongxia Z; Simon, M Celeste; Fredlund, Erik; Greten, Florian R; Rius, Jordi; Lewis, Claire E

    2009-07-23

    Ischemia exists in many diseased tissues, including arthritic joints, atherosclerotic plaques, and malignant tumors. Macrophages accumulate in these sites and up-regulate hypoxia-inducible transcription factors (HIFs) 1 and 2 in response to the hypoxia present. Here we show that the gene expression profile in primary human and murine macrophages changes markedly when they are exposed to hypoxia for 18 hours. For example, they were seen to up-regulate the cell surface receptors, CXCR4 and GLUT1, and the potent, tumor-promoting cytokines, vascular endothelial growth factor A, interleukin (IL)-1beta and IL-8, adrenomedullin, CXCR4, and angiopoietin-2. Hypoxia also stimulated their expression and/or phosphorylation of various proteins in the nuclear factor-kappaB (NF-kappaB) signaling pathway. We then used both genetic and pharmacologic methods to manipulate the levels of HIFs-1alpha and 2alpha or NF-kappaB in primary macrophages to elucidate their role in the hypoxic induction of many of these key genes. These studies showed that both HIF-1 and -2, but not NF-kappaB, are important transcriptional effectors regulating the responses of macrophages to such a period of hypoxia. Further studies using experimental mouse models are now warranted to investigate the role of such macrophage responses in the progression of various diseased tissues, such as malignant tumors. PMID:19454749

  20. Leishmania parasites possess a platelet-activating factor acetylhydrolase important for virulence

    PubMed Central

    Pawlowic, Mattie C.; Zhang, Kai

    2012-01-01

    Leishmania parasites are intracellular protozoans capable of salvaging and remodeling lipids from the host. To understand the role of lipid metabolism in Leishmania virulence, it is necessary to characterize the enzymes involved in the uptake and turnover of phospholipids. This study focuses on a putative phospholipase A2 (PLA2)/platelet-activating factor acetylhydrolase (PAF-AH) in L. major. In mammals, PAF-AH is a subgroup of PLA2 catalyzing the hydrolysis/inactivation of platelet-activating factor (PAF), a potent mediator of many leukocyte functions. By immunofluorescence microscopy, L. major PLA2/PAF-AH is predominantly localized in the ER. While wild type L. major parasites are able to hydrolyze PAF, this activity is completely absent in the PLA2/PAF-AH-null mutants. Meanwhile, deletion of PLA2/PAF-AH had no significant effect on the turnover of common glycerophospholipids such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylglycerol. PLA2/PAF-AH is not required for the growth of L. major parasites in culture, or the production of GPI-anchored virulence factors. Nonetheless, it does play a key role in the mammalian host as the PLA2/PAF-AH null mutants exhibit attenuated virulence in BALB/c mice. In conclusion, these data suggest that Leishmania parasites possess a functional PAF-AH and the degradation of PAF or PAF-like lipids is an important step in infection. PMID:22954769

  1. 34 CFR 377.22 - What additional factors does the Secretary consider in making grants?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Secretary considers the following factors in making grants under this program: (a) The diversity of... funded projects. (b) The diversity of clients to be served, in order to ensure that a variety...

  2. 34 CFR 377.22 - What additional factors does the Secretary consider in making grants?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Secretary considers the following factors in making grants under this program: (a) The diversity of... funded projects. (b) The diversity of clients to be served, in order to ensure that a variety...

  3. 34 CFR 377.22 - What additional factors does the Secretary consider in making grants?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Secretary considers the following factors in making grants under this program: (a) The diversity of... funded projects. (b) The diversity of clients to be served, in order to ensure that a variety...

  4. 34 CFR 377.22 - What additional factors does the Secretary consider in making grants?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Secretary considers the following factors in making grants under this program: (a) The diversity of... funded projects. (b) The diversity of clients to be served, in order to ensure that a variety...

  5. 34 CFR 377.22 - What additional factors does the Secretary consider in making grants?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Secretary considers the following factors in making grants under this program: (a) The diversity of... funded projects. (b) The diversity of clients to be served, in order to ensure that a variety...

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

    PubMed Central

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

    2011-01-01

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

  7. Transcription factor ets-2 plays an important role in the pathogenesis of pulmonary fibrosis.

    PubMed

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

    2011-11-01

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

  8. Performance in the heat-physiological factors of importance for hyperthermia-induced fatigue.

    PubMed

    Nybo, Lars; Rasmussen, Peter; Sawka, Michael N

    2014-04-01

    This article presents a historical overview and an up-to-date review of hyperthermia-induced fatigue during exercise in the heat. Exercise in the heat is associated with a thermoregulatory burden which mediates cardiovascular challenges and influence the cerebral function, increase the pulmonary ventilation, and alter muscle metabolism; which all potentially may contribute to fatigue and impair the ability to sustain power output during aerobic exercise. For maximal intensity exercise, the performance impairment is clearly influenced by cardiovascular limitations to simultaneously support thermoregulation and oxygen delivery to the active skeletal muscle. In contrast, during submaximal intensity exercise at a fixed intensity, muscle blood flow and oxygen consumption remain unchanged and the potential influence from cardiovascular stressing and/or high skin temperature is not related to decreased oxygen delivery to the skeletal muscles. Regardless, performance is markedly deteriorated and exercise-induced hyperthermia is associated with central fatigue as indicated by impaired ability to sustain maximal muscle activation during sustained contractions. The central fatigue appears to be influenced by neurotransmitter activity of the dopaminergic system, but inhibitory signals from thermoreceptors arising secondary to the elevated core, muscle and skin temperatures and augmented afferent feedback from the increased ventilation and the cardiovascular stressing (perhaps baroreceptor sensing of blood pressure stability) and metabolic alterations within the skeletal muscles are likely all factors of importance for afferent feedback to mediate hyperthermia-induced fatigue during submaximal intensity exercise. Taking all the potential factors into account, we propose an integrative model that may help understanding the interplay among factors, but also acknowledging that the influence from a given factor depends on the exercise hyperthermia situation. PMID:24715563

  9. Factors Affecting the Retention of Individuals as Important People for Ex-Offenders in Early Recovery

    PubMed Central

    Jason, Leonard A.; Stone, Ariel; Stevens, Ed; Light, John M.

    2013-01-01

    Objective Few studies consider the retention of the individuals (alters) comprising the social networks of people in recovery. We conducted a longitudinal study exploring several possible factors predicting whether alters were retained six months after participants completed treatment. Method The Important Person Inventory was given to 270 ex-offenders (224 men, 46 women) transitioning from treatment to Oxford House residences, Safe Haven therapeutic communities, or to usual aftercare. A 6-month follow-up was completed by 176 participants (137 men, 39 women). Results We found that alters who were related to the participant, did not use drugs, were embedded in smaller networks, and had more frequent contact with the participant were significantly more likely to be retained as important people over 6 months, but found no effects based on alters’ drinking or criminal history. Conclusions Certain characteristics of important people are related to their retention in a social network. Understanding these relationships is essential for creating effective social interventions for addictions. PMID:24521088

  10. Factors affecting sports-related orofacial injuries and the importance of mouthguards.

    PubMed

    Tuna, Elif Bahar; Ozel, Emre

    2014-06-01

    Sports dentistry is one of the most recent and upcoming fields in dentistry. It includes mainly the prevention and management of sports-related orofacial injuries and associated oral diseases or traumas. The dentist can play a critical role in informing athletes, coaches, and patients and their parents about the importance of prevention, treatment, and diagnosis for orofacial injuries in sports. The most significant aspect in preventing sports-related orofacial injuries is wearing basic protective devices such as properly fitting helmets, face masks, and/or mouthguards. A properly fitted mouthguard prevents violent contact between the upper and lower dentition. According to the American Society for Testing and Materials, there are three types of mouthguards: custom-fabricated mouthguards, mouth-formed guards, and stock mouthguards. Essential properties of the various materials used in the manufacture of mouthguards include water absorption, density, and thickness as well as temperature transmission, energy absorption, and drawing strength (tensile strength) of custom-made mouthguards. Currently, a variety of materials is being used for mouthguards, most commonly polyvinyl acetate-polyethylene copolymer or ethylene vinyl acetate copolymer and polyvinyl chloride. Mouthguard use is significant for athletes, since dentists play an important role in the design and application of these in clinical practice. The purpose of this article is to review the importance of mouthguard use, the incidence and location of orofacial sports injuries, the risk factors for such injuries, and the types of mouthguards and their roles in the prevention of sports-related orofacial injuries. PMID:24647854

  11. An important factor powerfully influencing the Al Ni-based alloys' glass-forming ability

    NASA Astrophysics Data System (ADS)

    Bo, Zhang; Xiufang, Bian; Chunxia, Fu; Na, Han; Jiankun, Zhou; Weimin, Wang

    2005-12-01

    In order to get better glass-forming abilities (GFAs), Ni atoms are partially replaced by Cu and Co atoms in Al84Ni12Zr4 alloys. Thermal analysis shows that the reduced crystallization temperature Trx has no direct correlation with the GFA of the alloys. However, it is notable that prepeaks have been found in the total structure factors of the amorphous Al84Ni(12-x)Zr4Cux and Al84Ni(12-x)Zr4Cox alloys. In addition, the results prove that the intensity of the prepeaks influences the GFA powerfully. The amorphous alloys with larger intensity of the prepeak show better GFA. The influence of prepeaks on the GFA can be explained by the atomic configuration difference among the liquid, crystal and glass states.

  12. Relative importance of multiple factors on terrestrial loading of DOC to Arctic river networks

    SciTech Connect

    Kicklighter, David W.; Hayes, Daniel J; Mcclelland, James W; Peterson, Bruce; Mcguire, David; Melillo, Jerry

    2014-01-01

    Terrestrial carbon dynamics influence the contribution of dissolved organic carbon (DOC) to river networks in addition to controlling carbon fluxes between the land surface and the atmosphere. In this study, we use a biogeochemical process model to simulate the lateral transfer of DOC from land to the Arctic Ocean via riverine transport. We estimate that the pan-arctic watershed has contributed, on average, 32 Tg C/yr of DOC to the Arctic Ocean over the 20th century with most coming from the extensive area of boreal deciduous needle-leaved forests and forested wetlands in Eurasian watersheds. We also estimate that the rate of terrestrial DOC loading has been increasing by 0.037 Tg C/yr2 over the 20th century primarily as a result of increases in air temperatures and precipitation. These increases have been partially compensated by decreases in terrestrial DOC loading caused by wildfires. Other environmental factors (CO2 fertilization, ozone pollution, atmospheric nitrogen deposition, timber harvest, agriculture) are estimated to have relatively small effects on terrestrial DOC loading to arctic rivers. The effects of the various environmental factors on terrestrial carbon dynamics have both compensated and enhanced concurrent effects on hydrology to influence terrestrial DOC loading. Future increases in riverine DOC concentrations and export may occur from warming-induced increases in terrestrial DOC production associated with enhanced microbial metabolism and the exposure of additional organic matter from permafrost degradation along with decreases in water yield associated with warming-induced increases in evapotranspiration. Improvements in simulating terrestrial DOC loading to pan-arctic rivers in the future will require better information on the spatial distribution of precipitation and its temporal trends, carbon dynamics of larch-dominated ecosystems in eastern Siberia, and the role of industrial organic effluents on carbon budgets of rivers in western

  13. The Relative Importance of Spatial and Local Environmental Factors in Determining Beetle Assemblages in the Inner Mongolia Grassland

    PubMed Central

    Yu, Xiao-Dong; Lü, Liang; Wang, Feng-Yan; Luo, Tian-Hong; Zou, Si-Si; Wang, Cheng-Bin; Song, Ting-Ting; Zhou, Hong-Zhang

    2016-01-01

    The aim of this paper is to increase understanding of the relative importance of the input of geographic and local environmental factors on richness and composition of epigaeic steppe beetles (Coleoptera: Carabidae and Tenebrionidae) along a geographic (longitudinal/precipitation) gradient in the Inner Mongolia grassland. Specifically, we evaluate the associations of environmental variables representing climate and environmental heterogeneity with beetle assemblages. Beetles were sampled using pitfall traps at 25 sites scattered across the full geographic extent of the study biome in 2011–2012. We used variance partitioning techniques and multi-model selection based on the Akaike information criterion to assess the relative importance of the spatial and environmental variables on beetle assemblages. Species richness and abundance showed unimodal patterns along the geographic gradient. Together with space, climate variables associated with precipitation, water-energy balance and harshness of climate had strong explanatory power in richness pattern. Abundance pattern showed strongest association with variation in temperature and environmental heterogeneity. Climatic factors associated with temperature and precipitation variables and the interaction between climate with space were able to explain a substantial amount of variation in community structure. In addition, the turnover of species increased significantly as geographic distances increased. We confirmed that spatial and local environmental factors worked together to shape epigaeic beetle communities along the geographic gradient in the Inner Mongolia grassland. Moreover, the climate features, especially precipitation, water-energy balance and temperature, and the interaction between climate with space and environmental heterogeneity appeared to play important roles on controlling richness and abundance, and species compositions of epigaeic beetles. PMID:27138752

  14. The Relative Importance of Spatial and Local Environmental Factors in Determining Beetle Assemblages in the Inner Mongolia Grassland.

    PubMed

    Yu, Xiao-Dong; Lü, Liang; Wang, Feng-Yan; Luo, Tian-Hong; Zou, Si-Si; Wang, Cheng-Bin; Song, Ting-Ting; Zhou, Hong-Zhang

    2016-01-01

    The aim of this paper is to increase understanding of the relative importance of the input of geographic and local environmental factors on richness and composition of epigaeic steppe beetles (Coleoptera: Carabidae and Tenebrionidae) along a geographic (longitudinal/precipitation) gradient in the Inner Mongolia grassland. Specifically, we evaluate the associations of environmental variables representing climate and environmental heterogeneity with beetle assemblages. Beetles were sampled using pitfall traps at 25 sites scattered across the full geographic extent of the study biome in 2011-2012. We used variance partitioning techniques and multi-model selection based on the Akaike information criterion to assess the relative importance of the spatial and environmental variables on beetle assemblages. Species richness and abundance showed unimodal patterns along the geographic gradient. Together with space, climate variables associated with precipitation, water-energy balance and harshness of climate had strong explanatory power in richness pattern. Abundance pattern showed strongest association with variation in temperature and environmental heterogeneity. Climatic factors associated with temperature and precipitation variables and the interaction between climate with space were able to explain a substantial amount of variation in community structure. In addition, the turnover of species increased significantly as geographic distances increased. We confirmed that spatial and local environmental factors worked together to shape epigaeic beetle communities along the geographic gradient in the Inner Mongolia grassland. Moreover, the climate features, especially precipitation, water-energy balance and temperature, and the interaction between climate with space and environmental heterogeneity appeared to play important roles on controlling richness and abundance, and species compositions of epigaeic beetles. PMID:27138752

  15. Effect of ferrite addition above the base ferrite on the coupling factor of wireless power transfer for vehicle applications

    NASA Astrophysics Data System (ADS)

    Batra, T.; Schaltz, E.; Ahn, S.

    2015-05-01

    Power transfer capability of wireless power transfer systems is highly dependent on the magnetic design of the primary and secondary inductors and is measured quantitatively by the coupling factor. The inductors are designed by placing the coil over a ferrite base to increase the coupling factor and reduce magnetic emissions to the surroundings. Effect of adding extra ferrite above the base ferrite at different physical locations on the self-inductance, mutual inductance, and coupling factor is under investigation in this paper. The addition can increase or decrease the mutual inductance depending on the placement of ferrite. Also, the addition of ferrite increases the self-inductance of the coils, and there is a probability for an overall decrease in the coupling factor. Correct placement of ferrite, on the other hand, can increase the coupling factor relatively higher than the base ferrite as it is closer to the other inductor. Ferrite being a heavy compound of iron increases the inductor weight significantly and needs to be added judiciously. Four zones have been identified in the paper, which shows different sensitivity to addition of ferrite in terms of the two inductances and coupling factor. Simulation and measurement results are presented for different air gaps between the coils and at different gap distances between the ferrite base and added ferrite. This paper is beneficial in improving the coupling factor while adding minimum weight to wireless power transfer system.

  16. Calcifying nanoparticles (nanobacteria): an additional potential factor for urolithiasis in space flight crews.

    PubMed

    Jones, Jeffrey A; Ciftcioglu, Neva; Schmid, Josef F; Barr, Yael R; Griffith, Donald

    2009-01-01

    Spaceflight-induced microgravity appears to be a risk factor for the development of urinary calculi, resulting in urolithiasis during and after spaceflight. Calcifying nanoparticles, or nanobacteria, multiply more rapidly in simulated microgravity and create external shells of calcium phosphate. The question arises whether calcifying nanoparticles are nidi for calculi and contribute to the development of clinically significant urolithiasis in those who are predisposed to the development of urinary calculi because of intrinsic or extrinsic factors. This case report describes a calculus recovered after flight from an astronaut that, on morphologic and immunochemical analysis (including specific monoclonal antibody staining), demonstrated characteristics of calcifying nanoparticles. PMID:18718644

  17. Phenazine virulence factor binding to extracellular DNA is important for Pseudomonas aeruginosa biofilm formation

    PubMed Central

    Das, Theerthankar; Kutty, Samuel K.; Tavallaie, Roya; Ibugo, Amaye I.; Panchompoo, Janjira; Sehar, Shama; Aldous, Leigh; Yeung, Amanda W. S.; Thomas, Shane R.; Kumar, Naresh; Gooding, J. Justin; Manefield, Mike

    2015-01-01

    Bacterial resistance to conventional antibiotics necessitates the identification of novel leads for infection control. Interference with extracellular phenomena, such as quorum sensing, extracellular DNA integrity and redox active metabolite release, represents a new frontier to control human pathogens such as Pseudomonas aeruginosa and hence reduce mortality. Here we reveal that the extracellular redox active virulence factor pyocyanin produced by P. aeruginosa binds directly to the deoxyribose-phosphate backbone of DNA and intercalates with DNA nitrogenous base pair regions. Binding results in local perturbations of the DNA double helix structure and enhanced electron transfer along the nucleic acid polymer. Pyocyanin binding to DNA also increases DNA solution viscosity. In contrast, antioxidants interacting with DNA and pyocyanin decrease DNA solution viscosity. Biofilms deficient in pyocyanin production and biofilms lacking extracellular DNA show similar architecture indicating the interaction is important in P. aeruginosa biofilm formation. PMID:25669133

  18. Obstructive sleep apnea syndrome: An important piece in the puzzle of cardiovascular risk factors.

    PubMed

    Costa, Cátia; Santos, Beatriz; Severino, Davide; Cabanelas, Nuno; Peres, Marisa; Monteiro, Isabel; Leal, Margarida

    2015-01-01

    The obstructive sleep apnea syndrome (OSA) is a clinical entity characterized by recurring episodes of apnea and/or hypopnea during sleep, due to a total or partial collapse, respectively, of the upper airway. This collapse originates a set of pathophysiological changes that determine the appearance of several cardiovascular complications. OSA contributes for the development of hypertension, heart failure, arrhythmias and coronary heart disease. Nowadays it is recognized to be an important public health problem, taking into account not just its repercussions but also its prevalence, since the main risk factor for the disease is obesity, a growing problem worldwide, both in developed and developing countries. The present review summarizes the current knowledge about OSA, as regards its definition, pathophysiology, clinical manifestations, diagnosis, cardiovascular effects and treatment. PMID:25496654

  19. Seroprevalence and associated risk factors of important pig viral diseases in Bhutan.

    PubMed

    Monger, V R; Stegeman, J A; Koop, G; Dukpa, K; Tenzin, T; Loeffen, W L A

    2014-11-01

    A cross-sectional serological study was conducted in Bhutan between October 2011 and February 2012 to determine the prevalence of antibodies to classical swine fever virus (CSFV), porcine reproductive and respiratory syndrome virus (PRRSV), porcine circovirus type 2 (PCV2), swine influenza virus (SIV) subtype H1N1 and Aujeszky's disease virus (ADV). Furthermore, risk factors for the seropositive status were investigated. Antibodies to SIV, subtype H1N1 (likely pandemic H1N1 2009) were detected in 49% of the pigs in the government farms, and 8% of the village backyard pigs. For PCV2, these percentages were 73% and 37% respectively. For CSFV, the percentages were closer together, with 62% and 52% respectively. It should be taken into consideration that vaccination of piglets is routine in the government herds, and that piglets distributed to backyard farms are also vaccinated. No direct evidence of CSFV infections was found, either by clinical signs or virus isolation. Antibodies to PRRSV and Aujeszky's disease, on the other hand, were not found at all. Risk factors found are mainly related to practices of swill feeding and other biosecurity measures. For CSFV, these were swill feeding (OR=2.25, 95% CI: 1.01-4.99) and contact with neighbour's pigs (OR=0.31, 95% CI: 0.13-0.75). For PCV2 this was lending of boars for local breeding purposes (OR=3.30, 95% CI: 1.43-7.59). The results of this study showed that PCV2 and SIV infections are important in pigs in Bhutan and thus appropriate control strategies need to be designed and applied which could involve strict regulation on the import of live pigs and vaccination against these diseases. PMID:25081946

  20. Non-fatal strangulation is an important risk factor for homicide of women

    PubMed Central

    Glass, Nancy; Laughon, Kathryn; Campbell, Jacquelyn; Wolf Chair, Anna D.; Block, Carolyn Rebecca; Hanson, Ginger; Sharps, Phyllis W.; Taliaferro, Ellen

    2008-01-01

    The purpose of the study is to examine non-fatal strangulation by an intimate partner as a risk factor for major assault, or attempted or completed homicide of women. A case control design was used to describe non-fatal strangulation among complete homicides and attempted homicides (n =506) and abused controls (n = 427). Interviews of proxy respondents and survivors of attempted homicides were compared with data from abused controls. Data were derived using the Danger Assessment. Non-fatal strangulation was reported in 10% of abused controls, 45% of attempted homicides and 43% of homicides. Prior non-fatal strangulation was associated with greater than six-fold odds (OR 6.70, 95% CI 3.91–11.49) of becoming an attempted homicide, and over seven-fold odds (OR 7.48, 95% CI 4.53–12.35) of becoming a completed homicide. These results show non-fatal strangulation as an important risk factor for homicide of women, underscoring the need to screen for non-fatal strangulation when assessing abused women in emergency department settings. PMID:17961956

  1. Sodium Benzoate, a Metabolite of Cinnamon and a Food Additive, Upregulates Ciliary Neurotrophic Factor in Astrocytes and Oligodendrocytes.

    PubMed

    Modi, Khushbu K; Jana, Malabendu; Mondal, Susanta; Pahan, Kalipada

    2015-11-01

    Ciliary neurotrophic factor (CNTF) is a promyelinating trophic factor that plays an important role in multiple sclerosis (MS). However, mechanisms by which CNTF expression could be increased in the brain are poorly understood. Recently we have discovered anti-inflammatory and immunomodulatory activities of sodium benzoate (NaB), a metabolite of cinnamon and a widely-used food additive. Here, we delineate that NaB is also capable of increasing the mRNA and protein expression of CNTF in primary mouse astrocytes and oligodendrocytes and primary human astrocytes. Accordingly, oral administration of NaB and cinnamon led to the upregulation of astroglial and oligodendroglial CNTF in vivo in mouse brain. Induction of experimental allergic encephalomyelitis, an animal model of MS, reduced the level of CNTF in the brain, which was restored by oral administration of cinnamon. While investigating underlying mechanisms, we observed that NaB induced the activation of protein kinase A (PKA) and H-89, an inhibitor of PKA, abrogated NaB-induced expression of CNTF. The activation of cAMP response element binding (CREB) protein by NaB, the recruitment of CREB and CREB-binding protein to the CNTF promoter by NaB and the abrogation of NaB-induced expression of CNTF in astrocytes by siRNA knockdown of CREB suggest that NaB increases the expression of CNTF via the activation of CREB. These results highlight a novel myelinogenic property of NaB and cinnamon, which may be of benefit for MS and other demyelinating disorders. PMID:26399250

  2. Risk factors associated with endometriosis: importance of study population for characterizing disease in the ENDO Study

    PubMed Central

    Peterson, C. Matthew; Johnstone, Erica B.; Hammoud, Ahmad O.; Stanford, Joseph B.; Varner, Michael W.; Kennedy, Anne; Chen, Zhen; Sun, Liping; Fujimoto, Victor Y.; Hediger, Mary L.; Buck Louis, Germaine M.

    2014-01-01

    OBJECTIVE We sought to identify risk factors for endometriosis and their consistency across study populations in the Endometriosis: Natural History, Diagnosis, and Outcomes (ENDO) Study. STUDY DESIGN In this prospective matched, exposure cohort design, 495 women aged 18–44 years undergoing pelvic surgery (exposed to surgery, operative cohort) were compared to an age- and residence-matched population cohort of 131 women (unexposed to surgery, populationcohort). Endometriosis was diagnosed visually at laparoscopy/laparotomy or by pelvic magnetic resonance imaging in the operative and population cohorts, respectively. Logistic regression estimated the adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for each cohort. RESULTS The incidence of visualized endometriosis was 40% in the operative cohort (11.8% stage 3–4 by revised criteria from the American Society for Reproductive Medicine), and 11% stage 3–4 in the population cohort by magnetic resonance imaging. An infertility history increased the odds of an endometriosis diagnosis in both the operative (AOR, 2.43; 95% CI, 1.57–3.76) and population (AOR, 7.91; 95% CI, 1.69–37.2) cohorts. In the operative cohort only, dysmenorrhea (AOR, 2.46; 95% CI, 1.28–4.72) and pelvic pain (AOR, 3.67; 95% CI, 2.44–5.50) increased the odds of diagnosis, while gravidity (AOR, 0.49; 95% CI, 0.32–0.75), parity (AOR, 0.42; 95% CI, 0.28–0.64), and body mass index (AOR, 0.95; 95% CI, 0.93–0.98) decreased the odds of diagnosis. In all sensitivity analyses for different diagnostic subgroups, infertility history remained a strong risk factor. CONCLUSION An infertility history was a consistent risk factor for endometriosis in both the operative and population cohorts of the ENDO Study. Additionally, identified risk factors for endometriosis vary based upon cohort selection and diagnostic accuracy. Finally, endometriosis in the population may be more common than recognized. PMID:23454253

  3. Ligand Recognition by the TPR Domain of the Import Factor Toc64 from Arabidopsis thaliana

    PubMed Central

    Panigrahi, Rashmi; Adina-Zada, Abdussalam; Whelan, James; Vrielink, Alice

    2013-01-01

    The specific targeting of protein to organelles is achieved by targeting signals being recognised by their cognate receptors. Cytosolic chaperones, bound to precursor proteins, are recognized by specific receptors of the import machinery enabling transport into the specific organelle. The aim of this study was to gain greater insight into the mode of recognition of the C-termini of Hsp70 and Hsp90 chaperones by the Tetratricopeptide Repeat (TPR) domain of the chloroplast import receptor Toc64 from Arabidopsis thaliana (At). The monomeric TPR domain binds with 1∶1 stoichiometry in similar micromolar affinity to both Hsp70 and Hsp90 as determined by isothermal titration calorimetry (ITC). Mutations of the terminal EEVD motif caused a profound decrease in affinity. Additionally, this study considered the contributions of residues upstream as alanine scanning experiments of these residues showed reduced binding affinity. Molecular dynamics simulations of the TPR domain helices upon peptide binding predicted that two helices within the TPR domain move backwards, exposing the cradle surface for interaction with the peptide. Our findings from ITC and molecular dynamics studies suggest that AtToc64_TPR does not discriminate between C-termini peptides of Hsp70 and Hsp90. PMID:24391770

  4. Predicting Unprecedented Dengue Outbreak Using Imported Cases and Climatic Factors in Guangzhou, 2014

    PubMed Central

    Bi, Peng; Yang, Weizhong; Yang, Zhicong; Xu, Lei; Yang, Jun; Liu, Xiaobo; Jiang, Tong; Wu, Haixia; Chu, Cordia; Liu, Qiyong

    2015-01-01

    Introduction Dengue is endemic in more than 100 countries, mainly in tropical and subtropical regions, and the incidence has increased 30-fold in the past 50 years. The situation of dengue in China has become more and more severe, with an unprecedented dengue outbreak hitting south China in 2014. Building a dengue early warning system is therefore urgent and necessary for timely and effective response. Methodology and Principal Findings In the study we developed a time series Poisson multivariate regression model using imported dengue cases, local minimum temperature and accumulative precipitation to predict the dengue occurrence in four districts of Guangzhou, China. The time series data were decomposed into seasonal, trend and remainder components using a seasonal-trend decomposition procedure based on loess (STL). The time lag of climatic factors included in the model was chosen based on Spearman correlation analysis. Autocorrelation, seasonality and long-term trend were controlled in the model. A best model was selected and validated using Generalized Cross Validation (GCV) score and residual test. The data from March 2006 to December 2012 were used to develop the model while the data from January 2013 to September 2014 were employed to validate the model. Time series Poisson model showed that imported cases in the previous month, minimum temperature in the previous month and accumulative precipitation with three month lags could project the dengue outbreaks occurred in 2013 and 2014 after controlling the autocorrelation, seasonality and long-term trend. Conclusions Together with the sole transmission vector Aedes albopictus, imported cases, monthly minimum temperature and monthly accumulative precipitation may be used to develop a low-cost effective early warning system. PMID:26020627

  5. Nuclear import factor transportin and arginine methyltransferase 1 modify FUS neurotoxicity in Drosophila.

    PubMed

    Jäckel, Sandra; Summerer, Anna K; Thömmes, Catherine M; Pan, Xia; Voigt, Aaron; Schulz, Jörg B; Rasse, Tobias M; Dormann, Dorothee; Haass, Christian; Kahle, Philipp J

    2015-02-01

    Inclusions containing Fused in Sarcoma (FUS) are found in familial and sporadic cases of the incurable progressive motor neuron disease amyotrophic lateral sclerosis and in a common form of dementia, frontotemporal dementia. Most disease-associated mutations are located in the C-terminal proline-tyrosine nuclear localization sequence (PY-NLS) of FUS and impair its nuclear import. It has been shown in cell culture that the nuclear import of FUS is mediated by transportin, which binds the PY-NLS and the last arginine/glycine/glycine-rich (RGG) domain of FUS. Methylation of this last RGG domain by protein arginine methyltransferases (PRMTs) weakens transportin binding and therefore impairs nuclear translocation of FUS. To investigate the requirements for the nuclear import of FUS in an in vivo model, we generated different transgenic Drosophila lines expressing human FUS wild type (hFUS wt) and two disease-related variants P525L and R495X, in which the NLS is mutated or completely absent, respectively. To rule out effects caused by heterologous hFUS expression, we analysed the corresponding variants for the Drosophila FUS orthologue Cabeza (Caz wt, P398L, Q349X). Expression of these variants in eyes and motor neurons confirmed the PY-NLS-dependent nuclear localization of FUS/Caz and caused neurodegenerative effects. Surprisingly, FUS/Caz toxicity was correlated to the degree of its nuclear localization in this overexpression model. High levels of nuclear FUS/Caz became insoluble and reduced the endogenous Caz levels, confirming FUS autoregulation in Drosophila. RNAi-mediated knockdown of the two transportin orthologues interfered with the nuclear import of FUS/Caz and also enhanced the eye phenotype. Finally, we screened the Drosophila PRMT proteins (DART1-9) and found that knockdown of Dart1 led to a reduction in methylation of hFUS P525L and aggravated its phenotype. These findings show that the molecular mechanisms controlling the nuclear import of FUS/Caz and FUS

  6. Additive relationship between serum fibroblast growth factor 21 level and coronary artery disease

    PubMed Central

    2013-01-01

    Background Expression and activity of the fibroblast growth factor (FGF) 21 hormone-like protein are associated with development of several metabolic disorders. This study was designed to investigate whether serum FGF21 level was also associated with the metabolic syndrome-related cardiovascular disease, atherosclerosis, and its clinical features in a Chinese cohort. Methods Two-hundred-and-fifty-three subjects visiting the Cardiology Department (Sixth People's Hospital affiliated to Shanghai JiaoTong University) were examined by coronary arteriography (to diagnose coronary artery disease (CAD)) and hepatic ultrasonography (to diagnose non-alcoholic fatty liver disease (NAFLD)). Serum FGF21 level was measured by enzyme-linked immunosorbent assay and analyzed for correlation to subject and clinical characteristics. The independent factors of CAD were determined by multivariate logistic regression analysis. Results Subjects with NAFLD showed significantly higher serum FGF21 than those without NAFLD (388.0 pg/mL (253.0-655.4) vs. 273.3 pg/mL (164.9-383.7), P < 0.01). Subjects with CAD showed significantly higher serum FGF21, regardless of NAFLD diagnosis (P < 0.05). Serum FGF21 level significantly elevated with the increasing number of metabolic disorders (P for trend < 0.01). After adjustment of age, sex, and BMI, FGF21 was positively correlated with total cholesterol (P < 0.05) and triglyceride (P < 0.01). FGF21 was identified as an independent factor of CAD (odds ratio = 2.984, 95% confidence interval: 1.014-8.786, P < 0.05). Conclusions Increased level of serum FGF21 is associated with NAFLD, metabolic disorders and CAD. PMID:23981342

  7. Molecular cloning and expression of an additional epidermal growth factor receptor-related gene.

    PubMed Central

    Plowman, G D; Whitney, G S; Neubauer, M G; Green, J M; McDonald, V L; Todaro, G J; Shoyab, M

    1990-01-01

    Epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), and amphiregulin are structurally and functionally related growth regulatory proteins. These secreted polypeptides all bind to the 170-kDa cell-surface EGF receptor, activating its intrinsic kinase activity. However, amphiregulin exhibits different activities than EGF and TGF-alpha in a number of biological assays. Amphiregulin only partially competes with EGF for binding EGF receptor, and amphiregulin does not induce anchorage-independent growth of normal rat kidney cells (NRK) in the presence of TGF-beta. Amphiregulin also appears to abrogate the stimulatory effect of TGF-alpha on the growth of several aggressive epithelial carcinomas that overexpress EGF receptor. These findings suggest that amphiregulin may interact with a separate receptor in certain cell types. Here we report the cloning of another member of the human EGF receptor (HER) family of receptor tyrosine kinases, which we have named "HER3/ERRB3." The cDNA was isolated from a human carcinoma cell line, and its 6-kilobase transcript was identified in various human tissues. We have generated peptide-specific antisera that recognizes the 160-kDa HER3 protein when transiently expressed in COS cells. These reagents will allow us to determine whether HER3 binds amphiregulin or other growth regulatory proteins and what role HER3 protein plays in the regulation of cell growth. Images PMID:2164210

  8. ERK5 Pathway Regulates Transcription Factors Important for Monocytic Differentiation of Human Myeloid Leukemia Cells†

    PubMed Central

    Wang, Xuening; Pesakhov, Stella; Harrison, Jonathan S; Danilenko, Michael; Studzinski, George P

    2014-01-01

    Mitogen-activated protein kinases (MAPKs) are important transducers of external signals for cell growth, survival and other cellular responses including cell differentiation. Several MAPK cascades are known with the MEK1/2-ERK1/2, JNK, and p38MAPKs receiving most attention, but the role of MEK5-ERK5 in intracellular signaling deserves more scrutiny, as this pathway transmits signals that can complement ERK/2 signaling. We hypothesized that the ERK5 pathway plays a role in the control of monocytic differentiation, which is disturbed in myeloid leukemia. We therefore examined the cellular phenotype and key molecular events which occur when human myeloid leukemia cells, acute (AML) or chronic (CML), are forced to differentiate by vitamin D derivatives (VDDs). This study was performed using established cell lines HL60 and U937, and primary cultures of blasts from 10 patients with ML. We found that ERK5 and its direct downstream target transcription factor MEF2C are upregulated by 1,25D in parallel with monocytic differentiation. Further, inhibition of ERK5 activity by specific pharmacological agents BIX02189 and XMD8-92 alters the phenotype of these cells by reducing the abundance of the VDD-induced surface monocytic marker CD14, and concomitantly increasing surface expression of the general myeloid marker CD11b. Similar results were obtained when the expression of ERK5 was reduced by siRNA or short hairpin (sh) RNA. ERK5 inhibition resulted in an expected decrease in MEF2C activation. We also found that in AML the transcription factor C/EBPβ is positively regulated, while C/EBPα is negatively regulated by ERK5. These findings provide new understanding of dysregulated differentiation in human myeloid leukemia. PMID:24264602

  9. ERK5 pathway regulates transcription factors important for monocytic differentiation of human myeloid leukemia cells.

    PubMed

    Wang, Xuening; Pesakhov, Stella; Harrison, Jonathan S; Danilenko, Michael; Studzinski, George P

    2014-07-01

    Mitogen-activated protein kinases (MAPKs) are important transducers of external signals for cell growth, survival, and other cellular responses including cell differentiation. Several MAPK cascades are known with the MEK1/2-ERK1/2, JNK, and p38MAPKs receiving most attention, but the role of MEK5-ERK5 in intracellular signaling deserves more scrutiny, as this pathway transmits signals that can complement ERK/2 signaling. We hypothesized that the ERK5 pathway plays a role in the control of monocytic differentiation, which is disturbed in myeloid leukemia. We therefore examined the cellular phenotype and key molecular events which occur when human myeloid leukemia cells, acute (AML) or chronic (CML), are forced to differentiate by vitamin D derivatives (VDDs). This study was performed using established cell lines HL60 and U937, and primary cultures of blasts from 10 patients with ML. We found that ERK5 and its direct downstream target transcription factor MEF2C are upregulated by 1,25D in parallel with monocytic differentiation. Further, inhibition of ERK5 activity by specific pharmacological agents BIX02189 and XMD8-92 alters the phenotype of these cells by reducing the abundance of the VDD-induced surface monocytic marker CD14, and concomitantly increasing surface expression of the general myeloid marker CD11b. Similar results were obtained when the expression of ERK5 was reduced by siRNA or short hairpin (sh) RNA. ERK5 inhibition resulted in an expected decrease in MEF2C activation. We also found that in AML cells the transcription factor C/EBPβ is positively regulated, while C/EBPα is negatively regulated by ERK5. These findings provide new understanding of dysregulated differentiation in human myeloid leukemia. PMID:24264602

  10. Generalized Ligamentous Laxity: An Important Predisposing Factor for Shoulder Injuries in Athletes

    PubMed Central

    Saremi, Hossein; Yavarikia, Alireza; Jafari, Nasibeh

    2016-01-01

    Background Generalized ligamentous laxity is defined as an increased range of joint motion compared to that of the general population. It is a predisposing factor for sports injuries, especially in the lower extremities. Nevertheless, there is little evidence about the relationship between generalized ligamentous laxity and sports injuries in the upper extremities. Objectives To evaluate the relationship of generalized ligamentous laxity with acute and chronic shoulder injuries in athletes. Patients and Methods Our study comprised 118 volunteer athletes with a history of at least six months of sports activities and a shoulder injury in the three years prior to participation in our study. The athletes were divided into two groups: those with or without generalized ligamentous laxity. Acute and chronic shoulder injuries, shoulder pain, shoulder instability, and functional status assessed via the QuickDASH measure were determined and compared between the two groups. A P value of less than 0.05 was considered significant. Results Group A (with ligamentous laxity) consisted of 43 participants (36.4%) and group B (without ligamentous laxity) consisted of 75 participants (63.6%). The athletes in group A had more shoulder pain (P = 0.016), chronic shoulder injuries (P = 0.032), and shoulder instability (P = 0.004), and less functionality (P = 0.030) than those in group B. If fracture were not considered an acute injury in both groups, the athletes with generalized ligamentous laxity would have had more acute shoulder injuries. Conclusions Generalized ligamentous laxity is an important predisposing factor for acute and chronic shoulder injuries in athletes. Prescreening programs for beginners and rehabilitation shoulder programs for sports athletes at high risk are strongly recommended. PMID:27621940

  11. Cigarette smoking: an important renal risk factor – far beyond carcinogenesis

    PubMed Central

    Orth, SR

    2003-01-01

    In recent years, it has become apparent that smoking has a negative impact on renal function, being one of the most important remediable renal risk factors. It has been clearly shown that the risk for high-normal urinary albumin excretion and microalbuminuria is increased in smoking compared to non-smoking subjects of the general population. Data from the Multiple Risk Factor Intervention Trial (MRFIT) indicate that at least in males, smoking increases the risk to reach end-stage renal failure. Smoking is particularly "nephrotoxic" in older subjects, subjects with essential hypertension and patients with preexisting renal disease. Of interest, the magnitude of the adverse renal effect of smoking seems to be independent of the underlying renal disease. Death-censored renal graft survival is decreased in smokers, indicating that smoking also damages the renal transplant. Cessation of smoking has been show to reduce the rate of progression of renal failure both in patients with renal disease or a renal transplant. The mechanisms of smoking-induced renal damage are only partly understood and comprise acute hemodynamic (e.g., increase in blood pressure and presumably intraglomerular pressure) and chronic effects (e.g., endothelial cell dysfunction). Renal failure per se leads to an increased cardiovascular risk. The latter is further aggravated by smoking. Particularly survival of smokers with diabetes mellitus on hemodialysis is abysmal. In the present review article the current state of knowledge about the renal risks of smoking is reviewed. It is the aim of the article to point out that smoking not only increases the risk of renal cell carcinoma or uroepithelial cell carcinoma, but also the risk of a faster decline of renal function. The latter is a relatively new negative aspect which has not been widely recognized. PMID:19570254

  12. Cigarette smoking: an important renal risk factor – far beyond carcinogenesis

    PubMed Central

    Orth, SR

    2003-01-01

    In recent years, it has become apparent that smoking has a negative impact on renal function, being one of the most important remediable renal risk factors. It has been clearly shown that the risk for high-normal urinary albumin excretion and microalbuminuria is increased in smoking compared to non-smoking subjects of the general population. Data from the Multiple Risk Factor Intervention Trial (MRFIT) indicate that at least in males, smoking increases the risk to reach end-stage renal failure. Smoking is particularly "nephrotoxic" in older subjects, subjects with essential hypertension and patients with preexisting renal disease. Of interest, the magnitude of the adverse renal effect of smoking seems to be independent of the underlying renal disease. Death-censored renal graft survival is decreased in smokers, indicating that smoking also damages the renal transplant. Cessation of smoking has been show to reduce the rate of progression of renal failure both in patients with renal disease or a renal transplant. The mechanisms of smoking-induced renal damage are only partly understood and comprise acute hemodynamic (e.g., increase in blood pressure and presumably intraglomerular pressure) and chronic effects (e.g., endothelial cell dysfunction). Renal failure per se leads to an increased cardiovascular risk. The latter is further aggravated by smoking. Particularly survival of smokers with diabetes mellitus on hemodialysis is abysmal. In the present review article the current state of knowledge about the renal risks of smoking is reviewed. It is the aim of the article to point out that smoking not only increases the risk of renal cell carcinoma or uroepithelial cell carcinoma, but also the risk of a faster decline of renal function. The latter is a relatively new negative aspect which has not been widely recognized.

  13. Ribosome Modulation Factor, an Important Protein for Cell Viability Encoded by the Polyamine Modulon*

    PubMed Central

    Terui, Yusuke; Tabei, Yuzuru; Akiyama, Mariko; Higashi, Kyohei; Tomitori, Hideyuki; Yamamoto, Kaneyoshi; Ishihama, Akira; Igarashi, Kazuei; Kashiwagi, Keiko

    2010-01-01

    We searched for proteins whose synthesis is enhanced by polyamines at the stationary phase of cell growth using an Escherichia coli polyamine-requiring mutant in which cell viability is greatly decreased by polyamine deficiency. The synthesis of ribosome modulation factor (RMF) was strongly enhanced by polyamines at the level of translation at the stationary phase of cell growth. In rmf mRNA, a Shine-Dalgarno (SD) sequence is located 11 nucleotides upstream of the initiation codon AUG. When the SD sequence was moved to the more common position 8 nucleotides upstream of the initiation codon, the degree of polyamine stimulation was reduced, although the level of RMF synthesis was markedly increased. Polyamine stimulation of RMF synthesis was found to be caused by a selective structural change of the bulged-out region of the initiation site of rmf mRNA. The decrease in cell viability caused by polyamine deficiency was prevented by the addition of a modified rmf gene whose synthesis is not influenced by polyamines. The results indicate that polyamines enhance cell viability of E. coli at least in part by enhancing RMF synthesis. PMID:20628056

  14. 34 CFR 359.32 - What additional factors does the Secretary consider in making a grant under this program?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 2 2010-07-01 2010-07-01 false What additional factors does the Secretary consider in making a grant under this program? 359.32 Section 359.32 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION DISABILITY AND...

  15. 34 CFR 359.32 - What additional factors does the Secretary consider in making a grant under this program?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 2 2014-07-01 2013-07-01 true What additional factors does the Secretary consider in making a grant under this program? 359.32 Section 359.32 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION DISABILITY AND...

  16. 34 CFR 359.32 - What additional factors does the Secretary consider in making a grant under this program?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 2 2012-07-01 2012-07-01 false What additional factors does the Secretary consider in making a grant under this program? 359.32 Section 359.32 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION DISABILITY AND...

  17. Commercial kidney transplantation is an important risk factor in long-term kidney allograft survival.

    PubMed

    Prasad, G V Ramesh; Ananth, Sailesh; Palepu, Sneha; Huang, Michael; Nash, Michelle M; Zaltzman, Jeffrey S

    2016-05-01

    Transplant tourism, a form of transplant commercialization, has resulted in serious short-term adverse outcomes that explain reduced short-term kidney allograft survival. However, the nature of longer-term outcomes in commercial kidney transplant recipients is less clear. To study this further, we identified 69 Canadian commercial transplant recipients of 72 kidney allografts transplanted during 1998 to 2013 who reported to our transplant center for follow-up care. Their outcomes to 8 years post-transplant were compared with 702 domestic living donor and 827 deceased donor transplant recipients during this period using Kaplan-Meier survival plots and multivariate Cox regression analysis. Among many complications, notable specific events included hepatitis B or C seroconversion (7 patients), active hepatitis and/or fulminant hepatic failure (4 patients), pulmonary tuberculosis (2 patients), and a type A dissecting aortic aneurysm. Commercial transplantation was independently associated with significantly reduced death-censored kidney allograft survival (hazard ratio 3.69, 95% confidence interval 1.88-7.25) along with significantly delayed graft function and eGFR 30 ml/min/1.73 m(2) or less at 3 months post-transplant. Thus, commercial transplantation represents an important risk factor for long-term kidney allograft loss. Concerted arguments and efforts using adverse recipient outcomes among the main premises are still required in order to eradicate transplant commercialization. PMID:27083285

  18. Usage patterns of personal care products: important factors for exposure assessment.

    PubMed

    Biesterbos, Jacqueline W H; Dudzina, Tatsiana; Delmaar, Christiaan J E; Bakker, Martine I; Russel, Frans G M; von Goetz, Natalie; Scheepers, Paul T J; Roeleveld, Nel

    2013-05-01

    Complete information regarding the use of personal care products (PCPs) by consumers is limited, but such information is crucial for realistic consumer exposure assessment. To fill this gap, a database was created with person-oriented information regarding usage patterns and circumstances of use for 32 different PCPs. Out of 2700 potential participants from the Netherlands, 516 men and women completed a digital questionnaire. The prevalence of use varied by gender, age, level of education and skin type. A high frequency of use was observed for some products (e.g. lip care products), while toothpaste, deodorant and day cream were generally used once or twice a day. The frequency of use for other PCPs varied over a wide range. The amounts of use varied largely between and within different product groups. Body lotion, sunscreen and after sun lotion were often applied on adjacent body parts. The majority of PCPs were applied in the morning, but some products, such as night cream and after sun, were predominantly applied in the evening or night. As expected, the participants used several PCPs simultaneously. The database yields important personalized exposure factors which can be used in aggregate consumer exposure assessment for substances that are components of PCPs. PMID:23174517

  19. Ethnobotanical knowledge in rural communities of Cordoba (Argentina): the importance of cultural and biogeographical factors

    PubMed Central

    2009-01-01

    Background The possibility to better understand the relationships within the men, the nature and their culture has extreme importance because allows the characterisation of social systems through their particular environmental perception, and provides useful tools for the development of conservation policies. Methods The present study was planned to disentangle environmental and cultural factors that are influencing the perception, knowledge and uses of edible and medicinal plants in rural communities of Cordoba (Argentina). Interviews an participant observation were conducted in nine rural communities located in three different biogeographical areas. Data about knowledge of medicinal and edible plants and sociocultural variables were obtained. Data were analysed by Principal Components Analysis (PCA). Results The analysis of data confirmed that medicinal species are widely used whereas the knowledge on edible plants is eroding. The PCA showed four groups of communities, defined by several particular combinations of sociocultural and/or natural variables. Conclusion This comprehensive approach suggests that in general terms the cultural environment has a stronger influence than the natural environment on the use of medicinal and edible plants in rural communities of Cordoba (Argentina). PMID:20003502

  20. Hypoxia inducible factors 1 and 2 are important transcriptional effectors in primary macrophages experiencing hypoxia

    PubMed Central

    Fang, Hsin-Yu; Hughes, Russell; Murdoch, Craig; Coffelt, Seth; Biswas, Subhra K.; Harris, Adrian L.; Johnson, Randall S.; Imityaz, Hongxia Z.; Simon, M. Celeste; Fredlund, Erik; Greten, Florian; Rius, Jordi; Lewis, Claire E.

    2010-01-01

    Ischemia exists in many diseased tissues including arthritic joints, atherosclerotic plaques and malignant tumors. Macrophages accumulate in these sites and upregulate hypoxia-inducible transcription factors (HIFs) 1 and 2 in response to the hypoxia present. Here we show that the gene expression profile in primary human and murine macrophages changes markedly when they are exposed to hypoxia for 18h. For example, they were seen to upregulate the cell surface receptors, CXCR4 and GLUT1, and the potent, tumor-promoting cytokines, VEGFA, interleukins 1β and 8, adrenomedullin, CXCR4 and angiopoietin-2. Hypoxia also stimulated their expression and/or phosphorylation of various proteins in the NF-κB signalling pathway. We then used both genetic and pharmacological methods to manipulate the levels of HIFs 1α and 2α or NF-κB in primary macrophages in order to elucidate their role in the hypoxic induction of many of these key genes. These studies showed that both HIFs 1 and 2, but not NF-κB, are important transcriptional effectors regulating the responses of macrophages to such a period of hypoxia. Further studies using experimental mouse models are now warranted to investigate the role of such macrophage responses in the progression of various diseased tissues like malignant tumors. PMID:19454749

  1. Fibronectin Interaction and Enhancement of Growth Factors: Importance for Wound Healing

    PubMed Central

    Sawicka, Katarzyna M.; Seeliger, Markus; Musaev, Tagai; Macri, Lauren K.; Clark, Richard A.F.

    2015-01-01

    Significance: This critical review focuses on interactions between cells, fibronectin (FN), and growth factors (GF). Recent Advances: Initially, the extracellular matrix (ECM) was thought to serve simply as a reservoir for GFs that would be released as soluble ligands during proteolytic degradation of ECM. This view was rather quickly extended by the observation that ECM could concentrate GFs to the pericellular matrix for more efficient presentation to cell surface receptors. However, recent reports support much more complex interactions among GFs and ECM molecules, particularly FN, and the way these interactions can fine-tune cell responses to the microenvironment. Critical Issues: Wounds that are unable to synthesize and sustain a functional ECM cannot optimally benefit from endogenous or exogenous GFs. Therefore, GF treatments have recently focused on utilizing ECM molecules as delivery vehicles. Thus, ECM can influence GF stability and activity, and GFs can modulate the ECM activity. Hence, both individually and together, ECM and GFs modulate cells that in turn control the type and level of GFs and ECM in the pericellular environment that ultimately results in new tissue generation. Although many ECM components are important for optimal tissue regeneration and wound healing, FN stands out as absolutely critical not only for wound healing and tissue regeneration but also for embryogenesis and morphogenesis. Future Directions: Understanding ECM/GF interactions will greatly facilitate our understanding of normal wound repair and regeneration, the failure of wounds to heal, and how the latter can be salvaged with proper ECM/GF combinations. PMID:26244103

  2. Seclusion and the importance of contextual factors: An innovation project revisited.

    PubMed

    Boumans, Christien E; Egger, Jos I M; Bouts, Richard A; Hutschemaekers, Giel J M

    2015-01-01

    Variation in seclusion rates between psychiatric facilities cannot be adequately explained by patient characteristics alone and there is a growing awareness of the influence of 'cultural' and staff factors on the use of seclusion. In this study, staff variables as well as seclusion parameters were investigated during the implementation of an innovation project, against the background of an institutional program to reduce the use of coercive measures. The results demonstrate the impact of confidence within the team, staffing level and communication with the patient on nurses' decisions on seclusion. The importance of the organizational context is further illustrated by the negative effects of organizational instability on nurses' attitudes and decision making with respect to seclusion, and on seclusion rates. A reduction in the use of seclusion was achieved after the implementation of the innovation project; however, during a period of organizational turmoil, the work engagement scores of staff decreased and the use of seclusion increased. The results of this study show the vulnerability of innovations within the continuously changing organizational context of mental health care. PMID:25846558

  3. Patterns of contraceptive use in the United States: the importance of religious factors.

    PubMed

    Goldscheider, C; Mosher, W D

    1991-01-01

    Previous research has shown that the major religious communities in the US have all shifted their expected family size downward but significant differences in contraceptive use styles continue to characterize Catholics, Protestants, Jews, and those of no religious affiliation. This paper examines data from Cycle IV of the National Survey of Family Growth (1988) to extend the time period covered by previous research by comparing the emerging contraceptive use patterns and fertility expectations among women in the late 1980s with earlier cohorts from previous national studies, beginning in the 1960s. The categories of religious affiliation are extended to include specific religious denominations (fundamentalist Protestants, Baptists, and other denominations, as well as Mormons) and include measures of religiosity--church attendance, the extent of receiving communion among Catholics, and attendance at church-related schools. These data are examined for blacks, Hispanics, and non-Hispanic whites. The analysis suggests how religious affiliation and religiosity continue to be important factors in the contraceptive paths to low fertility under general conditions of controlled fertility and in the context of secularization. PMID:1858103

  4. Aitchbone hanging and ageing period are additive factors influencing pork eating quality.

    PubMed

    Channon, H A; Taverner, M R; D'Souza, D N; Warner, R D

    2014-01-01

    The effects of abattoir, carcase weight (60 or 80 kg HCW), hanging method (Achilles or aitchbone) and ageing period (2 or 7 day post-slaughter) on eating quality attributes of pork were investigated in this 3×2×2×2 factorial study. A total of 144 Large White×Landrace female pigs were slaughtered at one of three abattoirs and sides hung from either the Achilles tendon or the aitchbone. After 24 h chilling, loin (M. longissimus thoracis et lumborum) and topside (M. semimembranosus) muscles were individually vacuum packaged and aged for 2 or 7 days post-slaughter. Consumers (n=852) evaluated eating quality. Neither abattoir nor carcase weight influenced tenderness, flavour or overall liking of pork. Improvements in tenderness, flavour and overall liking were found due to aitchbone hanging (P<0.001) and ageing (P<0.001) for 7 days compared with Achilles-hung carcases and pork aged for 2 days, respectively. This study demonstrated that aitchbone hanging and 7 day ageing can improve eating quality, but these effects were additive as the interaction term was not significant. PMID:24013699

  5. [Virulence factors in Proteus spp. bacteria isolated from urinary tract infections: their detection and importance].

    PubMed

    2011-08-01

    Nosocomial infections associated with biofilm formation have been a serious problem in recent years. Up to 32 % of them are urinary tract infections in patients with long-dwelling catheters. Catheters represent an ideal surface for bacterial adhesion, facilitating easier colonization of the urinary tract. Important pathogens causing these infections are bacteria of the genus Proteus that colonize catheters not only by biofilm formation but also using other virulence factors. Those were developed for survival in the host organism and are also used by bacteria to infect the host or fight the defence mechanisms. The study focused on the following selected virulence factors: swimming, swarming and twitching motility, swarming motility across various types of urinary catheters, biofilm formation in various media, formation of biofilm on catheters, haemolysin and urease production. A total of 102 strains isolated from urinary catheters and 50 strains isolated from stools were analyzed. In twitching motility, a difference between strains isolated from catheters and stools was statistically significant (p = 0.012). In swimming and swarming motility, the difference was not significant (p = 0.074 and p = 0.809, respectively). In motility across various catheter types, a statistically significant difference was found in strains isolated from both catheters and stools (p « 0.01 in both cases). For biofilm formation analyses, BHI and BHI with 4 % glucose were used. In BHI, biofilm was produced by all strains, with 65% of catheter strains and 88 % of strains from stools being strong producers. Similarly, all strains produced biofilm in BHI with 4 % glucose, with strong producers in 94 % and 92 % of strains isolated from catheters and stools, respectively. In formation of biofilm on catheters, there was a statistical difference between strains from catheters and stools (p = 0.00008). All strains isolated from both catheters and stools produced urease; no difference in urease

  6. Data integration for identification of important transcription factors of STAT6-mediated cell fate decisions.

    PubMed

    Jargosch, M; Kröger, S; Gralinska, E; Klotz, U; Fang, Z; Chen, W; Leser, U; Selbig, J; Groth, D; Baumgrass, R

    2016-01-01

    Data integration has become a useful strategy for uncovering new insights into complex biological networks. We studied whether this approach can help to delineate the signal transducer and activator of transcription 6 (STAT6)-mediated transcriptional network driving T helper (Th) 2 cell fate decisions. To this end, we performed an integrative analysis of publicly available RNA-seq data of Stat6-knockout mouse studies together with STAT6 ChIP-seq data and our own gene expression time series data during Th2 cell differentiation. We focused on transcription factors (TFs), cytokines, and cytokine receptors and delineated 59 positively and 41 negatively STAT6-regulated genes, which were used to construct a transcriptional network around STAT6. The network illustrates that important and well-known TFs for Th2 cell differentiation are positively regulated by STAT6 and act either as activators for Th2 cells (e.g., Gata3, Atf3, Satb1, Nfil3, Maf, and Pparg) or as suppressors for other Th cell subpopulations such as Th1 (e.g., Ar), Th17 (e.g., Etv6), or iTreg (e.g., Stat3 and Hif1a) cells. Moreover, our approach reveals 11 TFs (e.g., Atf5, Creb3l2, and Asb2) with unknown functions in Th cell differentiation. This fact together with the observed enrichment of asthma risk genes among those regulated by STAT6 underlines the potential value of the data integration strategy used here. Thus, our results clearly support the opinion that data integration is a useful tool to delineate complex physiological processes. PMID:27420972

  7. The importance of climatic factors and outliers in predicting regional monthly campylobacteriosis risk in Georgia, USA

    NASA Astrophysics Data System (ADS)

    Weisent, J.; Seaver, W.; Odoi, A.; Rohrbach, B.

    2014-01-01

    Incidence of Campylobacter infection exhibits a strong seasonal component and regional variations in temperate climate zones. Forecasting the risk of infection regionally may provide clues to identify sources of transmission affected by temperature and precipitation. The objectives of this study were to (1) assess temporal patterns and differences in campylobacteriosis risk among nine climatic divisions of Georgia, USA, (2) compare univariate forecasting models that analyze campylobacteriosis risk over time with those that incorporate temperature and/or precipitation, and (3) investigate alternatives to supposedly random walk series and non-random occurrences that could be outliers. Temporal patterns of campylobacteriosis risk in Georgia were visually and statistically assessed. Univariate and multivariable forecasting models were used to predict the risk of campylobacteriosis and the coefficient of determination (R 2) was used for evaluating training (1999-2007) and holdout (2008) samples. Statistical control charting and rolling holdout periods were investigated to better understand the effect of outliers and improve forecasts. State and division level campylobacteriosis risk exhibited seasonal patterns with peaks occurring between June and August, and there were significant associations between campylobacteriosis risk, precipitation, and temperature. State and combined division forecasts were better than divisions alone, and models that included climate variables were comparable to univariate models. While rolling holdout techniques did not improve predictive ability, control charting identified high-risk time periods that require further investigation. These findings are important in (1) determining how climatic factors affect environmental sources and reservoirs of Campylobacter spp. and (2) identifying regional spikes in the risk of human Campylobacter infection and their underlying causes.

  8. Importance of Natural and Anthropogenic Environmental Factors to Fish Communities of the Fox River in Illinois

    NASA Astrophysics Data System (ADS)

    Schnier, Spencer; Cai, Ximing; Cao, Yong

    2016-02-01

    The dominant environmental determinants of aquatic communities have been a persistent topic for many years. Interactions between natural and anthropogenic characteristics within the aquatic environment influence fish communities in complex ways that make the effect of a single characteristic difficult to ascertain. Researchers are faced with the question of how to deal with a large number of variables and complex interrelationships. This study utilized multiple approaches to identify key environmental variables to fish communities of the Fox River Basin in Illinois: Pearson and Spearman correlations, an algorithm based on information theory called mutual information, and a measure of variable importance built into the machine learning algorithm Random Forest. The results are based on a dataset developed for this study, which uses a fish index of biological integrity (IBI) and its ten component metrics as response variables and a range of environmental variables describing geomorphology, stream flow statistics, climate, and both reach-scale and watershed-scale land use as independent variables. Agricultural land use and the magnitude and duration of low flow events were ranked by the algorithms as key factors for the study area. Reach-scale characteristics were dominant for native sunfish, and stream flow metrics were rated highly for native suckers. Regression tree analyses of environmental variables on fish IBI identified breakpoints in percent agricultural land in the watershed (~64 %), duration of low flow pulses (~12 days), and 90-day minimum flow (~0.13 cms). The findings should be useful for building predictive models and design of more effective monitoring systems and restoration plans.

  9. Importance of Natural and Anthropogenic Environmental Factors to Fish Communities of the Fox River in Illinois.

    PubMed

    Schnier, Spencer; Cai, Ximing; Cao, Yong

    2016-02-01

    The dominant environmental determinants of aquatic communities have been a persistent topic for many years. Interactions between natural and anthropogenic characteristics within the aquatic environment influence fish communities in complex ways that make the effect of a single characteristic difficult to ascertain. Researchers are faced with the question of how to deal with a large number of variables and complex interrelationships. This study utilized multiple approaches to identify key environmental variables to fish communities of the Fox River Basin in Illinois: Pearson and Spearman correlations, an algorithm based on information theory called mutual information, and a measure of variable importance built into the machine learning algorithm Random Forest. The results are based on a dataset developed for this study, which uses a fish index of biological integrity (IBI) and its ten component metrics as response variables and a range of environmental variables describing geomorphology, stream flow statistics, climate, and both reach-scale and watershed-scale land use as independent variables. Agricultural land use and the magnitude and duration of low flow events were ranked by the algorithms as key factors for the study area. Reach-scale characteristics were dominant for native sunfish, and stream flow metrics were rated highly for native suckers. Regression tree analyses of environmental variables on fish IBI identified breakpoints in percent agricultural land in the watershed (~64%), duration of low flow pulses (~12 days), and 90-day minimum flow (~0.13 cms). The findings should be useful for building predictive models and design of more effective monitoring systems and restoration plans. PMID:26404430

  10. 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

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

    PubMed

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

    2016-06-01

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

  12. Climate Factors as Important Determinants of Dengue Incidence in Curaçao.

    PubMed

    Limper, M; Thai, K T D; Gerstenbluth, I; Osterhaus, A D M E; Duits, A J; van Gorp, E C M

    2016-03-01

    Macro- and microclimates may have variable impact on dengue incidence in different settings. We estimated the short-term impact and delayed effects of climate variables on dengue morbidity in Curaçao. Monthly dengue incidence data from 1999 to 2009 were included to estimate the short-term influences of climate variables by employing wavelet analysis, generalized additive models (GAM) and distributed lag nonlinear models (DLNM) on rainfall, temperature and relative humidity in relation to dengue incidence. Dengue incidence showed a significant irregular 4-year multi-annual cycle associated with climate variables. Based on GAM, temperature showed a U-shape, while humidity and rainfall exhibited a dome-shaped association, suggesting that deviation from mean temperature increases and deviation from mean humidity and rainfall decreases dengue incidence, respectively. Rainfall was associated with an immediate increase in dengue incidence of 4.1% (95% CI: 2.2-8.1%) after a 10-mm increase, with a maximum increase of 6.5% (95% CI: 3.2-10.0%) after 1.5 month lag. A 1 °C decrease of mean temperature was associated with a RR of 17.4% (95% CI: 11.2-27.0%); the effect was inversed for a 1°C increase of mean temperature (RR= 0.457, 95% CI: 0.278-0.752). Climate variables are important determinants of dengue incidence and provide insight into its short-term effects. An increase in mean temperature was associated with lower dengue incidence, whereas lower temperatures were associated with higher dengue incidence. PMID:26122819

  13. Steatosis Grade is the Most Important Risk Factor for Development of Endothelial Dysfunction in NAFLD

    PubMed Central

    Sapmaz, Ferdane; Uzman, Metin; Basyigit, Sebahat; Ozkan, Selcuk; Yavuz, Bunyamin; Yeniova, Abdullah; Kefeli, Ayse; Asilturk, Zeliha; Nazligül, Yasar

    2016-01-01

    Abstract It is shown that there are strong associations between nonalcoholic fatty liver disease (NAFLD) and endothelial dysfunction. The aim of our study was to reveal whether steatosis or fibrosis score is more important in the development of endothelial dysfunction in patients with NAFLD in a prospective manner. This cross-sectional study included 266 subjects. These subjects were divided into 2 groups depending on presence of hepatosteatosis sonographically. Patients with hepatosteatosis were also divided into 3 subgroups depending on degree of steatosis: grade 1, 2, and 3. In all patients, Aspartate aminotransferase-to-Platelet Ratio Index and Fibrosis-4 (FIB4) scores were calculated. In addition, flow-mediated dilatation (FMD) measurements were recorded. There was NAFLD in 176 (66.2%) of 266 patients included. There were no significant differences in sex and age distributions between patients with NAFLD (group 1) and controls without NAFLD (group 2) (P = 0.05). Mean Aspartate aminotransferase-to-Platelet Ratio Index score was significantly higher in group 1 compared with the control group (P = 0.001), whereas no significant difference was detected regarding FIB4 scores between groups (P = 0.4). Mean FMD value was found to be significantly lower in group 1 (P = 0.008). Patients with grade 3 hepatosteatosis had significantly lower FMD values than those with grade 1 steatosis and controls (P = 0.001). In univariate and multivariate analyses in group 1, no significant difference was detected regarding mean FMD measurements (P = 0.03). Again, no significant difference was detected in mean FMD measurement between FIB4 subgroups among patients with NAFLD and the whole study group (P = 0.09). The endothelial dysfunction is associated with steatosis in patients with NAFLD. PMID:27057890

  14. The importance of residues 195-206 of human blood clotting factor VII in the interaction of factor VII with tissue factor

    SciTech Connect

    Wildgoose, P.; Kisiel, W.; Kazim, A.L. )

    1990-09-01

    Previous studies indicated that human and bovine factor VII exhibit 71% amino acid sequence identity. In the present study, competition binding experiments revealed that the interaction of human factor VII with cell-surface human tissue factor was not inhibited by 100-fold molar excess of bovine factor VII. This finding indicated that bovine and human factor VII are not structurally homologous in the region(s) where human factor VII interacts with human tissue factor. On this premise, the authors synthesized three peptides corresponding to regions of human factor VII that exhibited marked structural dissimilarity to bovine factor VII; these regions of dissimilarity included residues 195-206, 263-274, and 314-326. Peptide 195-206 inhibited the interaction of factor VII with cell-surface tissue factor and the activation of factor X by a complex of factor VIIa and tissue factor half-maximally at concentrations of 1-2 mM. A structurally rearranged form of peptide 195-206 containing an aspartimide residue inhibited these reactions half-maximally at concentrations of 250-300 {mu}M. In contrast, neither peptide 263-274 nor peptide 314-326, at 2 mM concentration, significantly affected either factor VIIa interaction with tissue factor or factor VIIa-mediated activation of factor X. The data provide presumptive evidence that residues 195-206 of human factor VII are involved in the interaction of human factor VII with the extracellular domain of human tissue factor apoprotein.

  15. Tissue-specific factors additively increase the probability of the all-or-none formation of a hypersensitive site.

    PubMed Central

    Boyes, J; Felsenfeld, G

    1996-01-01

    DNase I-hypersensitive sites lack a canonical nucleosome and have binding sites for various transcription factors. To understand how the hypersensitivity is generated and maintained, we studied the chicken erythroid-specific beta(A)/epsilon globin gene enhancer, a region where both tissue-specific and ubiquitous transcription factors can bind. Constructions containing mutations of this enhancer were stably introduced into a chicken erythroid cell line. We found that the hypersensitivity was determined primarily by the erythroid factors and that their binding additively increased the accessibility. The fraction of accessible sites in clonal cell lines was quantitated using restriction endonucleases; these data implied that the formation of each hypersensitive site was an all-or-none phenomenon. Use of DNase I and micrococcal nuclease probes further indicated that the size of the hypersensitive site was influenced by the binding of transcription factors which then determined the length of the nucleosome-free gap. Our data are consistent with a model in which hypersensitive sites are generated stochastically: mutations that reduce the number of bound factors reduce the probability that these factors will prevail over a nucleosome; thus, the fraction of sites in the population that are accessible is also diminished. Images PMID:8665857

  16. Persist or Withdraw: The Importance of External Factors in Students' Departure Intentions

    ERIC Educational Resources Information Center

    Leveson, Lynne; McNeil, Nicola; Joiner, Therese

    2013-01-01

    The role of institutional factors in students' intentions to persist with or withdraw from their studies is well established in the literature. More recently, the influence of factors external to the institution has been highlighted as well. This study investigates the relationship between levels of engagement of first-year students…

  17. Transforming growth factor-β: an important mediator in Helicobacter pylori-associated pathogenesis

    PubMed Central

    Li, Nianshuang; Xie, Chuan; Lu, Nong-Hua

    2015-01-01

    Helicobacter pylori (H.pylori) is a Gram-negative, microaerophilic, helical bacillus that specifically colonizes the gastric mucosa. The interaction of virulence factors, host genetic factors, and environmental factors contributes to the pathogenesis of H. pylori-associated conditions, such as atrophic gastritis and intestinal metaplasia. Infection with H. pylori has recently been recognized as the strongest risk factor for gastric cancer. As a pleiotropic cytokine, transforming growth factor (TGF)-β regulates various biological processes, including cell cycle, proliferation, apoptosis, and metastasis. Recent studies have shed new light on the involvement of TGF-β signaling in the pathogenesis of H. pylori infection. This review focuses on the potential etiological roles of TGF-β in H. pylori-mediated gastric pathogenesis. PMID:26583078

  18. Identifying the Most Important Factors Promoting Aflatoxin and Fumonisin Contamination in Maize (Corn): Effects of Temperature and Bt-Status

    Technology Transfer Automated Retrieval System (TEKTRAN)

    1. Background Maize (corn, Zea mays L.) is grown worldwide in both industrialized and developing countries. Maize is unusually susceptible to mycotoxin contamination, with aflatoxin being the most important mycotoxin. Our research program seeks to identify what pre-harvest factors are most important...

  19. To transplant or not? The importance of psychosocial and behavioural factors before lung transplantation.

    PubMed

    Dobbels, F; Verleden, G; Dupont, L; Vanhaecke, J; De Geest, S

    2006-01-01

    The gratifying results of lung transplantation in terms of survival and quality of life stimulate the referral of an ever-increasing number of patients with end-stage lung disease. This in turn compounds the organ shortage, which is the limiting factor in the transplantation rate. In the absence of good alternative treatment modalities, an evidence-based pretransplant screening process is a prerequisite to determine which patients will benefit most from transplantation. Within this evidence-based screening process, medical selection criteria are well established. There is a growing awareness that psychosocial and behavioural factors may determine outcome after transplantation as well. This paper reviews the available evidence for psychosocial and behavioural factors in the screening process for lung transplantation. The relation of various factors with post-transplant outcome was explored. Psychosocial characteristics before transplantation consist of 1) anxiety and depression, 2) personality disorders, 3) neurocognitive problems, and 4) lack of social support. Pretransplant behavioural factors include 1) noncompliance with medication, 2) alcohol abuse or dependence, 3) smoking, 4) noncompliance with dietary guidelines, and 5) noncompliance with monitoring of vital parameters and infections. It appears that the lack of rigorous studies limit the feasibility of an evidence-based screening process. Prospective studies are crucial to this further investigation of the relationship between psychosocial and behavioural determinants before transplantation and outcomes after transplantation, in terms of compliance, morbidity, and mortality. Identification of modifiable risk factors for poor outcome before transplantation is a first step in developing interventions. PMID:16509176

  20. What factors are important for deprescribing in Australian long-term care facilities? Perspectives of residents and health professionals

    PubMed Central

    Edwards, Susan; Stanners, Melinda; Shakib, Sepehr; Bell, J Simon

    2016-01-01

    Objectives Polypharmacy and multimorbidity are common in long-term care facilities (LTCFs). Reducing polypharmacy may reduce adverse events and maintain quality of life. Deprescribing refers to reducing medications after consideration of therapeutic goals, benefits and risks, and medical ethics. The objective was to use nominal group technique (NGT) to generate then rank factors that general medical practitioners (GPs), nurses, pharmacists and residents or their representatives perceive are most important when deciding whether or not to deprescribe medications. Design Qualitative research using NGT. Setting Participants were invited if they worked with, or resided in LTCFs across metropolitan and regional South Australia. Participants 11 residents/representatives, 19 GPs, 12 nurses and 14 pharmacists participated across six separate groups. Methods Individual groups of GPs, nurses, pharmacists and residents/representatives were convened. Using NGT each group ranked factors perceived to be most important when deciding whether or not to deprescribe. Then, using NGT, the prioritised factors from individual groups were discussed and prioritised by a multidisciplinary metropolitan and regional group comprised of resident representatives, GPs, nurses and pharmacists. Results No two groups had the same priorities. GPs ranked ‘evidence for deprescribing’ and ‘communication with family/resident’ as most important factors. Nurses ranked ‘GP receptivity to deprescribing’ and ‘nurses ability to advocate for residents’ as most important. Pharmacists ranked ‘clinical appropriateness of therapy’ and ‘identifying residents’ goals of care’ as most important. Residents ranked ‘wellbeing of the resident’ and ‘continuity of nursing staff’ as most important. The multidisciplinary groups ranked ‘adequacy of medical and medication history’ and ‘identifying residents’ goals of care’ as most important. Conclusions While each group prioritised

  1. Expression, purification, and characterization of a diabody against the most important angiogenesis cell receptor: Vascular endothelial growth factor receptor 2.

    PubMed

    Behdani, Mahdi; Zeinali, Sirous; Karimipour, Morteza; Khanahmad, Hossein; Asadzadeh, Nader; Azadmanesh, Kayhan; Seyed, Negar; Baniahmad, Seyed Farzad; Anbouhi, Mahdi Habibi

    2012-01-01

    Antibodies and their derivative fragments have long been used as tools in a variety of applications, in fundamental research work, biotechnology, diagnosis, and therapy. Camels produce single heavy-chain antibodies (VHH) in addition to usual antibodies. These minimal-sized binders are very robust and bind the antigen with high affinity in a monomeric state. Vascular endothelial growth factor recepror-2 (VEGFR2) is an important tumor-associated receptor that blockade of its signaling can lead to the inhibition of neovascularization and tumor metastasis. Here, we describe the construction, expression, and purification VEGFR2-specific Diabody. Two variable fragments of a same camel anti-VEGFR2 antibody were linked together by the upper hinge segment of antibody to make a diabody. We showed the ability of diabody to recognition of VEGFR2 on the cell surface by FACS. Diabodies can be produced in the low-cost prokaryotic expression system, so they are suitable molecules for diagnostic and therapeutic issues. PMID:23326765

  2. [Determinants of the rural exodus: the importance of place of origin factors, Chile, 1965-1970].

    PubMed

    Raczynski, D

    1982-07-01

    Trends in rural-urban migration in Chile during the period 1965-1970 are analyzed, with a focus on the impact of the combination of structural factors and socioeconomic processes in rural areas. Factors of population retention and expulsion are examined in terms of agrarian structure, the process of agrarian reform, urbanization of the countryside, and the availability of basic social services. Rural-urban migration rates in the central and southern areas of the country are compared, and migration rates of males and females are examined. PMID:12313739

  3. Context Matters: The Experience of 14 Research Teams in Systematically Reporting Contextual Factors Important for Practice Change

    PubMed Central

    Tomoaia-Cotisel, Andrada; Scammon, Debra L.; Waitzman, Norman J.; Cronholm, Peter F.; Halladay, Jacqueline R.; Driscoll, David L.; Solberg, Leif I.; Hsu, Clarissa; Tai-Seale, Ming; Hiratsuka, Vanessa; Shih, Sarah C.; Fetters, Michael D.; Wise, Christopher G.; Alexander, Jeffrey A.; Hauser, Diane; McMullen, Carmit K.; Scholle, Sarah Hudson; Tirodkar, Manasi A.; Schmidt, Laura; Donahue, Katrina E.; Parchman, Michael L.; Stange, Kurt C.

    2013-01-01

    PURPOSE We aimed to advance the internal and external validity of research by sharing our empirical experience and recommendations for systematically reporting contextual factors. METHODS Fourteen teams conducting research on primary care practice transformation retrospectively considered contextual factors important to interpreting their findings (internal validity) and transporting or reinventing their findings in other settings/situations (external validity). Each team provided a table or list of important contextual factors and interpretive text included as appendices to the articles in this supplement. Team members identified the most important contextual factors for their studies. We grouped the findings thematically and developed recommendations for reporting context. RESULTS The most important contextual factors sorted into 5 domains: (1) the practice setting, (2) the larger organization, (3) the external environment, (4) implementation pathway, and (5) the motivation for implementation. To understand context, investigators recommend (1) engaging diverse perspectives and data sources, (2) considering multiple levels, (3) evaluating history and evolution over time, (4) looking at formal and informal systems and culture, and (5) assessing the (often nonlinear) interactions between contextual factors and both the process and outcome of studies. We include a template with tabular and interpretive elements to help study teams engage research participants in reporting relevant context. CONCLUSIONS These findings demonstrate the feasibility and potential utility of identifying and reporting contextual factors. Involving diverse stakeholders in assessing context at multiple stages of the research process, examining their association with outcomes, and consistently reporting critical contextual factors are important challenges for a field interested in improving the internal and external validity and impact of health care research. PMID:23690380

  4. Factors Important for Work Participation Among Older Workers with Depression, Cardiovascular Disease, and Osteoarthritis: A Mixed Method Study.

    PubMed

    Boot, Cécile R L; de Kruif, Anja Th C M; Shaw, William S; van der Beek, Allard J; Deeg, Dorly J; Abma, Tineke

    2016-06-01

    Purpose The aim of this study was to gain insight into differences and similarities in factors important for work participation in older (58-65 years) workers among three different chronic diseases: depression (D), cardiovascular disease (C), and osteoarthritis (O). Methods A mixed method design was used, with a qualitative part (in-depth interviews) with 14 patients with D, C or O and a quantitative part based on the 2002-2003 cohort of the Longitudinal Aging Study Amsterdam. We analysed and compared 3-year (response 93 %) predictors of paid work in 239 participants with D, C, or O using regression analyses. The qualitative findings were integrated with the quantitative findings aiming at complementarity. Results Common factors important for work participation were: working at baseline; male gender; lower age; partner with paid work; better physical and mental health; and higher mastery scores. The qualitative analyses added autonomy in work and provided contextual information regarding the perceived importance of working as factors important for participation in paid work. For D and C, work gave purpose in life and enhanced social contacts. Participation in work was perceived as necessary to structure life only for D. Conclusion Most factors important for work participation were similar for D, C, and O. However, the interviews revealed that for D, the context and the meaning attributed to these factors differed. PMID:26210996

  5. IMPORTANCE OF PHYSICAL SCALING FACTORS TO BENTHIC MARINE INVERTEBRATE RECOLONIZATION OF LABORATORY MICROCOSMS

    EPA Science Inventory

    Five laboratory studies of benthic macroinvertebrate recolonization were conducted for 6-wk periods to evaluate the effects of physical factors (i.e., microcosm size, seawater flow rates and sediment depth) on benthic community structure. esign variables included4 open-faced acry...

  6. KM Critical Success Factors: A Comparison of Perceived Importance Versus Implementation in Malaysian ICT Companies

    ERIC Educational Resources Information Center

    Chong, Siong Choy

    2006-01-01

    Purpose: This research examines the level of perception and implementation of 11 identified knowledge management (KM) success factors and their differences among the information and communication technology (ICT) companies operating in Malaysia. Design/methodology/approach: The survey data was obtained from a study of 427 middle managers from 194…

  7. Test Cheating in a Rural College: Studying the Importance of Individual and Situational Factors

    ERIC Educational Resources Information Center

    Robinson, Erin; Amburgey, Rita; Swank, Eric; Faulkner, Cynthia

    2004-01-01

    There is a long line of studies on academic cheating. This literature has established a litany of different individual and contextual factors that seem to inspire student conformity of the official rules of test taking. This study draws on this literature by using fourteen independent variables to explain the cheating habits of students in a…

  8. Position paper on the importance of psychosocial factors in cardiology: Update 2013

    PubMed Central

    Ladwig, Karl-Heinz; Lederbogen, Florian; Albus, Christian; Angermann, Christiane; Borggrefe, Martin; Fischer, Denise; Fritzsche, Kurt; Haass, Markus; Jordan, Jochen; Jünger, Jana; Kindermann, Ingrid; Köllner, Volker; Kuhn, Bernhard; Scherer, Martin; Seyfarth, Melchior; Völler, Heinz; Waller, Christiane; Herrmann-Lingen, Christoph

    2014-01-01

    Background: The rapid progress of psychosomatic research in cardiology and also the increasing impact of psychosocial issues in the clinical daily routine have prompted the Clinical Commission of the German Heart Society (DGK) to agree to an update of the first state of the art paper on this issue which was originally released in 2008. Methods: The circle of experts was increased, general aspects were implemented and the state of the art was updated. Particular emphasis was dedicated to coronary heart diseases (CHD), heart rhythm diseases and heart failure because to date the evidence-based clinical knowledge is most advanced in these particular areas. Differences between men and women and over the life span were considered in the recommendations as were influences of cognitive capability and the interactive and synergistic impact of classical somatic risk factors on the affective comorbidity in heart disease patients. Results: A IA recommendation (recommendation grade I and evidence grade A) was given for the need to consider psychosocial risk factors in the estimation of coronary risks as etiological and prognostic risk factors. Furthermore, for the recommendation to routinely integrate psychosocial patient management into the care of heart surgery patients because in these patients, comorbid affective disorders (e.g. depression, anxiety and post-traumatic stress disorder) are highly prevalent and often have a malignant prognosis. A IB recommendation was given for the treatment of psychosocial risk factors aiming to prevent the onset of CHD, particularly if the psychosocial risk factor is harmful in itself (e.g. depression) or constrains the treatment of the somatic risk factors. Patients with acute and chronic CHD should be offered anti-depressive medication if these patients suffer from medium to severe states of depression and in this case medication with selective reuptake inhibitors should be given. In the long-term course of treatment with implanted

  9. The functional importance of telomere clustering: Global changes in gene expression result from SIR factor dispersion

    PubMed Central

    Taddei, Angela; Van Houwe, Griet; Nagai, Shigeki; Erb, Ionas; van Nimwegen, Erik; Gasser, Susan M.

    2009-01-01

    Budding yeast telomeres and cryptic mating-type loci are enriched at the nuclear envelope, forming foci that sequester silent information regulators (SIR factors), much as heterochromatic chromocenters in higher eukaryotes sequester HP1. Here we examine the impact of such subcompartments for regulating transcription genome-wide. We show that the efficiency of subtelomeric reporter gene repression depends not only on the strength of SIR factor recruitment by cis-acting elements, but also on the accumulation of SIRs in such perinuclear foci. To monitor the effects of disrupting this subnuclear compartment, we performed microarray analyses under conditions that eliminate telomere anchoring, while preserving SIR complex integrity. We found 60 genes reproducibly misregulated. Among those with increased expression, 22% were within 20 kb of a telomere, confirming that the nuclear envelope (NE) association of telomeres helps repress natural subtelomeric genes. In contrast, loci that were down-regulated were distributed over all chromosomes. Half of this ectopic repression was SIR complex dependent. We conclude that released SIR factors can promiscuously repress transcription at nontelomeric genes despite the presence of “anti-silencing” mechanisms. Bioinformatic analysis revealed that promoters bearing the PAC (RNA Polymerase A and C promoters) or Abf1 binding consenses are consistently down-regulated by mislocalization of SIR factors. Thus, the normal telomeric sequestration of SIRs both favors subtelomeric repression and prevents promiscuous effects at a distinct subset of promoters. This demonstrates that patterns of gene expression can be regulated by changing the spatial distribution of repetitive DNA sequences that bind repressive factors. PMID:19179643

  10. The importance of heat evolution during the overcharge process and the protection mechanism of electrolyte additives for prismatic lithium ion batteries

    NASA Astrophysics Data System (ADS)

    Chen, Yi-Shiun; Hu, Chi-Chang; Li, Yuan-Yao

    In this work, the rate of heat generation in the overcharge period for 103450 prismatic lithium ion batteries (LIBs) of the LiCoO 2-graphite jellyroll type with a basic electrolyte consisting of 1 M LiPF 6-PC/EC/EMC (1/3/5 in weight ratio) has been found to be more important than the gas evolution which was traditionally considered as the main reason in the overcharge protection mechanism. The cell voltage, charge current, and skin temperature were monitored during the charge process. For a single battery or batteries in parallel, LIBs without any additives is an acceptable design if the cell voltage is not charged above 4.55 V under the common charge program. The rate of heat generation from the polymerization of 3 wt% cyclohexyl benzene (CHB) is high enough to cause the explosion or thermal runaway of a battery, which is not found for an LIB containing 2 wt% CHB + 1 wt% tert-amyl benzene (TAB). In the 12 V overcharge test at 1C, the thermal fuse was broken by the high skin temperature (ca. 80 °C) due to the polymerization of 3 wt% CHB, which was also the case for LIBs containing 2 wt% CHB + 1 wt% TAB. The disconnection of the thermal fuse, however, did not interrupt the thermal runaway of LIBs without any additives because the battery voltage was too high (ca. 4.9 V). The influence of specific surface area of active materials in the anode on the polymerization kinetics of additives has to be carefully considered in order to add correct amount of overcharge protection agents.

  11. Prognostic factors in pediatric high-grade astrocytoma: the importance of accurate pathologic diagnosis.

    PubMed

    Hales, Russell K; Shokek, Ori; Burger, Peter C; Paynter, Nina P; Chaichana, Kaisorn L; Quiñones-Hinojosa, Alfredo; Jallo, George I; Cohen, Kenneth J; Song, Danny Y; Carson, Benjamin S; Wharam, Moody D

    2010-08-01

    To characterize a population of pediatric high-grade astrocytoma (HGA) patients by confirming the proportion with a correct diagnosis, and determine prognostic factors for survival in a subset diagnosed with uniform pathologic criteria. Sixty-three children diagnosed with HGA were treated at the Johns Hopkins Hospital between 1977 and 2004. A single neuropathologist (P.C.B.) reviewed all available histologic samples (n = 48). Log-rank analysis was used to compare survival by patient, tumor, and treatment factors. Median follow-up was 16 months for all patients and 155 months (minimum 54 months) for surviving patients. Median survival for all patients (n = 63) was 14 months with 10 long-term survivors (survival >48 months). At initial diagnosis, 27 patients were grade III (43%) and 36 grade IV (57%). Forty-eight patients had pathology slides available for review, including seven of ten long-term surviving patients. Four patients had non-HGA pathology, all of whom were long term survivors. The remaining 44 patients with confirmed HGG had a median survival of 14 months and prognostic analysis was confined to these patients. On multivariate analysis, five factors were associated with inferior survival: performance status (Lansky) <80% (13 vs. 15 months), bilaterality (13 vs. 19 months), parietal lobe location (13 vs. 16 months), resection less than gross total (13 vs. 22 months), and radiotherapy dose <50 Gy (9 vs. 16 months). Among patients with more than one of the five adverse factors (n = 27), median survival and proportion of long-term survivors were 12.9 months and 0%, compared with 41.4 months and 18% for patients with 0-1 adverse factors (n = 17). In an historical cohort of children with HGA, the potential for long term survival was confined to the subset with less than two of the following adverse prognostic factors: low performance status, bilaterality, parietal lobe site, less than gross total resection, and radiotherapy dose <50 Gy. Pathologic misdiagnosis

  12. Obesity as an Important Risk Factor for Certain Types of Cancer

    PubMed Central

    Davoodi, Sayed Hossain; Malek-Shahabi, Talieh; Malekshahi-Moghadam, Ali; Shahbazi, Roghieh; Esmaeili, Saeideh

    2013-01-01

    Cancer could be described as the uncontrolled and unrestricted growth of malignant cells in any place of the body. It is a multifactorial disease which either heredity or environmental factors (such as nutrition, physical inactivity, alcohol, obesity, exposure to sun, environmental pollutants, infections) chip in incidence of cancer. In recent years, several researchers have focused on obesity as a potent cancer risk factor. Scientificevidences have suggested that obesity has associated with increased risk for a plenty of different types of cancer. The evidences are the most consistent for endometrial cancer, breast cancer between the postmenopausal women, and renal cell cancer. More contradictoryresults have reported about the colorectal, prostate, and pancreatic cancer. Although numerous studies have done according to the obesity and cancer relation or joint, but the molecular mechanisms in which obesity could increase the risks of cancer, have been poorly understood. PMID:25250133

  13. Labour complications remain the most important risk factors for perinatal mortality in rural Kenya.

    PubMed Central

    Weiner, Renay; Ronsmans, Carine; Dorman, Ed; Jilo, Hilton; Muhoro, Anne; Shulman, Caroline

    2003-01-01

    OBJECTIVES: To identify and quantify risk factors for perinatal mortality in a Kenyan district hospital and to assess the proportion of perinatal deaths attributable to labour complications, maternal undernutrition, malaria, anaemia and human immunodeficiency virus (HIV). METHODS: A cross-sectional study of 910 births was conducted between January 1996 and July 1997 and risk factors for perinatal mortality were analysed. FINDINGS: The perinatal mortality rate was 118 per 1000 births. Complications of labour such as haemorrhage, premature rupture of membranes/premature labour, and obstructed labour/ malpresentation increased the risk of death between 8- and 62-fold, and 53% of all perinatal deaths were attributable to labour complications. Placental malaria and maternal HIV, on the other hand, were not associated with perinatal mortality. CONCLUSIONS: Greater attention needs to be given to the quality of obstetric care provided in the rural district-hospital setting. PMID:14576887

  14. Trends of male factor infertility, an important cause of infertility: A review of literature

    PubMed Central

    Kumar, Naina; Singh, Amit Kant

    2015-01-01

    Infertility and problems of impaired fecundity have been a concern through ages and is also a significant clinical problem today, which affects 8–12% of couples worldwide. Of all infertility cases, approximately 40–50% is due to “male factor” infertility and as many as 2% of all men will exhibit suboptimal sperm parameters. It may be one or a combination of low sperm concentration, poor sperm motility, or abnormal morphology. The rates of infertility in less industrialized nations are markedly higher and infectious diseases are responsible for a greater proportion of infertility. The present literature will help in knowing the trends of male factor infertility in developing nations like India and to find out in future, various factors that may be responsible for male infertility. PMID:26752853

  15. The effects of genotype and infant weight on adult plasma levels of fibrinogen, factor VII, and LDL cholesterol are additive.

    PubMed Central

    Henry, J A; Bolla, M; Osmond, C; Fall, C; Barker, D J; Humphries, S E

    1997-01-01

    High circulating levels of cholesterol, particularly low density lipoprotein (LDL) cholesterol and the clotting factors fibrinogen and factor VII, are associated with increased risk of myocardial infarction. Variations in the plasma levels of these factors are determined in part by polymorphisms in the genes concerned and also by weight at 1 year (infant weight). We have looked at the possibility of interactions between these genetic factors and infant weight in a sample of 290 men and 192 women from Hertfordshire using the beta-fibrinogen G/A-455, factor VII R353Q, and ApoE polymorphisms. The rare allele frequencies of the three polymorphisms were 0.19 for beta-fibrinogen, 0.10 for factor VII, and 0.07 and 0.13 for the 2 and 4 alleles of ApoE, and these frequencies were not different in subjects of different infant weight. In this sample, the polymorphisms showed the expected effects on plasma levels of fibrinogen, factor VII, and LDL cholesterol. The A-455 allele was associated with higher fibrinogen levels but the effect was only statistically significant in women (p = 0.003). The R353 allele was associated with higher factor VII activity in both men and women (p < 0.0001 for both). The ApoE2 allele was associated with lower levels of LDL cholesterol (p = 0.03 in men, p = 0.006 in women), while the ApoE4 allele was associated with higher levels (p < 0.001 in men, not significant in women). In this sample of men and women the effect of low infant weight was only associated with significant effects on fibrinogen and LDL cholesterol in the group of men (p = 0.005 and p = 0.008 respectively). Compared with the E3E3 subjects, the LDL lowering effect of the E2 allele and the raising effect of the E4 allele was greater in those with low infant weight compared with those with high infant weight (low v high infant weight for E2: 12.7% v 9.4%; for E4 12.7% v 8.5%). Although in this sample the interactive effect did not reach statistical significance, the additive effect

  16. Important Factors Underlying Ethical Intentions of Students: Implications for Marketing Education

    ERIC Educational Resources Information Center

    Singhapakdi, Anusorn

    2004-01-01

    This study analyzes the relative influences of perceived ethical problems, perceived importance of ethics, idealism, relativism, and gender on ethical intention of students. The potential impacts of grade point average and education level of students were also investigated. The results from a survey of students in marketing classes from two major…

  17. [Triglycerides--a long known risk factor for cardiovascular disease. Subgroup analysis shows the importance after acute coronary syndrome].

    PubMed

    Olsson, Anders

    2015-01-01

    An increased blood concentration of triglycerides (TG) has long been recognized as an important risk factor for cardiovascular disease. Through competition from HDL cholesterol and the arrival of statin treatment for high LDL cholesterol the importance of TG as risk factor was largely forgotten. A high concentration of TG indicates high blood levels of TG-rich lipoproteins including cholesterol rich remnant particles. Studies using Mendelian randomizations have demonstrated that a low HDL cholesterol does not carry a direct atherogenic function and that remnant particles do so. New efforts should be exercised in order to diminish residual cardiovascular risk during statin treatment through decreasing TG rich lipoproteins. PMID:26371484

  18. Imported Flood-Related Leptospirosis From Palau: Awareness of Risk Factors Leads to Early Treatment.

    PubMed

    Matono, Takashi; Kutsuna, Satoshi; Koizumi, Nobuo; Fujiya, Yoshihiro; Takeshita, Nozomi; Hayakawa, Kayoko; Kanagawa, Shuzo; Kato, Yasuyuki; Ohmagari, Norio

    2015-01-01

    We describe two Japanese travelers with leptospirosis who visited Palau. Both travelers swam in Ngardmau Falls, which was flooded for two days after typhoon Phanfone. The diagnoses were confirmed by microscopic agglutination test or polymerase chain reaction. This is the first report of leptospirosis in travelers who returned from Palau. It should be noted that choosing the appropriate test to biologically confirm leptospirosis was highly time-dependent. Awareness of the risk factors for leptospirosis, mainly that of the exposure to contaminated fresh water after a flooding, would lead to an early and appropriate treatment before the confirmed diagnosis. PMID:26503094

  19. A strain-dependent diffusivity model to study the nuclear import of mechanobiological transcription factors.

    PubMed

    Nava, Michele M; Fedele, Roberto; Raimondi, Manuela T

    2015-08-01

    Nuclear spreading plays a crucial role in stem cell fate determination. In previous works, we reported evidence of multipotency maintenance of mesenchymal stromal cells cultured on three-dimensional engineered niche substrates fabricated via two-photon laser polymerization (2PP). We correlated multipotency maintenance to a more roundish nuclear morphology of cells cultured in the 2PP-fabricated niches, with respect to those on flat substrates. To interpret these findings, here we present a multiphysics model coupling nuclear strains induced by cell adhesion to diffusive transport across the cell nucleus. We reconstructed the cell nuclear geometry from confocal Z-stack images of 2PP-cultured cells, and we estimated the volume, surface and shape factors. The levels of nuclear spreading significantly varied depending on the cell localization within the niche architecture. We assumed the cell diffusivity as a function of the local volumetric strain. The computational model also indicate that the larger the nuclear deformation (e.g. in spread nuclei), the higher the nuclear flux of small solutes such as transcription factors through the nuclear membrane. Our results point towards nuclear deformation as a primary mechanism by which the stem cell translates its shape into a fate decision, i.e. through a strain-dependent amplification of the diffusive flow of signaling molecules into the nucleus. PMID:26736643

  20. Beyond overweight: nutrition as an important lifestyle factor influencing timing of puberty.

    PubMed

    Cheng, Guo; Buyken, Anette E; Shi, Lijie; Karaolis-Danckert, Nadina; Kroke, Anja; Wudy, Stefan A; Degen, Gisela H; Remer, Thomas

    2012-03-01

    Early onset of puberty may confer adverse health consequences. Thus, modifiable factors influencing the timing of puberty are of public health interest. Childhood overweight as a factor in the earlier onset of menarche has been supported by prospective evidence; nonetheless, its overall contribution may have been overemphasized, since secular trends toward a younger age at menarche have not been a universal finding during the recent obesity epidemic. Current observational studies suggest notable associations between dietary intakes and pubertal timing beyond contributions to an energy imbalance: children with the highest intakes of vegetable protein or animal protein experience pubertal onset up to 7 months later or 7 months earlier, respectively. Furthermore, girls with high isoflavone intakes may experience the onset of breast development and peak height velocity approximately 7-8 months later. These effect sizes are on the order of those observed for potentially neuroactive steroid hormones. Thus, dietary patterns characterized by higher intakes of vegetable protein and isoflavones and lower intakes of animal protein may contribute to a lower risk of breast cancer or a lower total mortality. PMID:22364156

  1. What factors were important for dietary improvement in emergency shelters after the Great East Japan Earthquake?

    PubMed

    Tsuboyama-Kasaoka, Nobuyo; Hoshi, Yuko; Onodera, Kazue; Mizuno, Shoichi; Sako, Kazuko

    2014-01-01

    The Great East Japan Earthquake of 2011 left many evacuees with insufficient food and emergency shelter. However, there is no evidence concerning the factors affecting dietary circumstances in emergency shelters after disasters. To clarify the factors that influenced the provision of meals, we reanalyzed a data set from a dietary survey conducted in emergency shelters one month after the Great East Japan Earthquake (2011). Among the 69 shelters in "city A," 53 (79.1%) had food shortages. The possibility of cooking in the emergency shelter improved the provision of meals to evacuees. When comparing emergency shelters with and without cooking equipment, the shelters with cooking equipment provided more meals, as well as more dishes containing grains and vegetables. When there was a gas supply, the twice per day provision of "balanced" meals (containing grains, vegetables, and meat/fish) was more frequent than when there was no gas supply. Interestingly, neither the water supply nor the electricity supply affected the provision of balanced meals. Further, emergency shelters with larger numbers of evacuees had a lower possibility of cooking and lower availability of gas supply. Our results demonstrate that early improvements to post-disaster meal provision may maintain the health of evacuees. Such improvements could be achieved by 1) the speedy restoration of the gas supply to enable cooking, and 2) limiting the number of evacuees per emergency shelter. PMID:24561984

  2. Analysis of factors important for the occurrence of Campylobacter in Danish broiler flocks.

    PubMed

    Sommer, H M; Heuer, O E; Sørensen, A I V; Madsen, M

    2013-08-01

    For more than a decade human campylobacteriosis has been the leading zoonosis in many developed countries. Consumption of poultry or poultry products has been identified as the primary source of infection in humans. This study was conducted to identify risk factors for the occurrence of Campylobacter in Danish broiler flocks. The study was based on a large data set consisting of Campylobacter positive status for nearly 6000 broiler flocks and 43 explanatory variables. Data were obtained from the Danish Campylobacter surveillance programme in poultry and from the responses to a standardized questionnaire answered via interviews with broiler farm owners. Two hundred and forty broiler farms, comprising 539 broiler houses, were included in the study and their Campylobacter status was followed over a 2-year period (1999-2000). The large number of observations made it possible to carry out a multivariate analysis including all 43 variables. A multivariate analysis was conducted using a generalized linear model, and the correlations between the houses from the same farms were accounted for by adding a variance structure to the model. The procedures for analyses included backward elimination, forward selection and expanding of the number of observations used in the variance analysis along with the reduction of the number of parameters in the model. The unit of analysis was 'broiler house', meaning that all results from a broiler house were aggregated into one prevalence figure (number of positive flocks/total number of flocks delivered over the 2-year period). The following factors were found to be significantly associated with the occurrence of Campylobacter in the broiler flocks: old broiler houses, late introduction of whole wheat in the feed, relatively high broiler age at slaughter, improper rodent control, large number of chimneys on the broiler house, farm located in an area with a high density of cattle farms, having more than one broiler house on the farm, and

  3. Sex differences in visuospatial ability: do performance factors play such an important role?

    PubMed

    Delgado, A R; Prieto, G

    1996-07-01

    This study was designed to analyze some performance factors as a possible source of sex-related bias in psychometric tests of visuospatial aptitude. Goldstein, Haldane, and Mitchell (1990) explored the effect of two response styles-slowness of performance and reluctance to guess-by using a 3-D mental rotation test (the task showing the largest cognitive sex difference) and found that time limits and raw scores contributed substantially to the male advantage. We applied two tests in the speed-power continuum to a representative sample of 621 males and 821 females in their last year of high school in a 2 x 2 (gender x time) full factorial design. Reluctance to guess was similar for males and females. Males obtained more correct responses on both tests, and for both time conditions, than did females. These results are not only statistically significant but also are of substantial practical consequence. PMID:8757498

  4. Role of bilirubin overproduction in revealing Gilbert's syndrome: is dyserythropoiesis an important factor?

    PubMed Central

    Metreau, J M; Yvart, J; Dhumeaux, D; Berthelot, P

    1978-01-01

    Gilbert's syndrome was diagnosed in 37 patients with unconjugated hyperbilirubinaemia without overt haemolysis or structural liver abnormality, who had a marked reduction in hepatic bilirubin UDP-glucuronosyltransferase activity (B-GTA) (as compared with that of 23 normal subjects). No significant correlation existed in these patients between serum bilirubin level and the values of B-GTA, thus suggesting that factors other than a low B-GTA must influence the degree of hyperbilirubinaemia in Gilbert's syndrome. Studies of 51Cr erythrocyte survival and 59Fe kinetics in 10 unselected patients demonstrated slight haemolysis in eight, whereas mild ineffective erythropoiesis was suggested in all from a low 24-hour incorporation of radioactive iron into circulating red cells. This overproduction of bilirubin resulting from mild haemolysis and perhaps dyserythropoiesis might reflect only an extreme degree of the normal situation. It certainly contributes to the hyperbilirubinaemia of Gilbert's syndrome and may play a major role in the manifestation of this condition. PMID:101425

  5. Liver Stiffness Measurement in Psoriasis: Do Metabolic or Disease Factors Play the Important Role?

    PubMed Central

    Pongpit, Jamrus; Porntharukchareon, Saneerat; Kaewduang, Piyaporn; Promson, Kwannapa; Stitchantrakul, Wasana; Petraksa, Supanna; Thakkinstian, Ammarin; Kositchaiwat, Chomsri; Rajatanavin, Natta; Sobhonslidsuk, Abhasnee

    2016-01-01

    Background. An increased prevalence of metabolic syndrome including nonalcoholic fatty liver disease (NAFLD) was reported in psoriasis. NAFLD can progress to nonalcoholic steatohepatitis and fibrosis. Transient elastography (TE) is a noninvasive liver fibrosis assessment. We evaluated the prevalence of significant liver fibrosis or high liver stiffness measurement (LSM) using the LSM cutoff over 7 kPa and its associated factors in psoriatic patients. Methods. Subjects underwent TE and ultrasonography. Univariate and multivariate analysis were performed for the associated factors. Results. One hundred and sixty-eight patients were recruited. Three patients were excluded due to TE failure. Mean BMI was 24.8 ± 4.7 kg/m2. NAFLD, metabolic syndrome, and diabetes were seen in 105 (63.6%), 83 (50.3%), and 31 (18.8%) patients. The total cumulative dose of methotrexate over 1.5 g was seen in 39 (23.6%) patients. Mean LSM was 5.3 ± 2.9 kPa. High LSM was found in 18 (11.0%) patients. Waist circumference (OR: 1.24; 95% CI: 1.11–1.38; P = 0.0002), diabetes (OR: 12.70; 95% CI: 1.84–87.70; P = 0.010), and AST (OR: 1.08; 95% CI: 1.02–1.16; P = 0.017) were associated with high LSM. Conclusion. 11% of psoriatic patients had significant liver fibrosis by high LSM. Waist circumference, diabetes, and AST level were the independent predictors. PMID:27006950

  6. Liver Stiffness Measurement in Psoriasis: Do Metabolic or Disease Factors Play the Important Role?

    PubMed

    Pongpit, Jamrus; Porntharukchareon, Saneerat; Kaewduang, Piyaporn; Promson, Kwannapa; Stitchantrakul, Wasana; Petraksa, Supanna; Thakkinstian, Ammarin; Kositchaiwat, Chomsri; Rajatanavin, Natta; Sobhonslidsuk, Abhasnee

    2016-01-01

    Background. An increased prevalence of metabolic syndrome including nonalcoholic fatty liver disease (NAFLD) was reported in psoriasis. NAFLD can progress to nonalcoholic steatohepatitis and fibrosis. Transient elastography (TE) is a noninvasive liver fibrosis assessment. We evaluated the prevalence of significant liver fibrosis or high liver stiffness measurement (LSM) using the LSM cutoff over 7 kPa and its associated factors in psoriatic patients. Methods. Subjects underwent TE and ultrasonography. Univariate and multivariate analysis were performed for the associated factors. Results. One hundred and sixty-eight patients were recruited. Three patients were excluded due to TE failure. Mean BMI was 24.8 ± 4.7 kg/m(2). NAFLD, metabolic syndrome, and diabetes were seen in 105 (63.6%), 83 (50.3%), and 31 (18.8%) patients. The total cumulative dose of methotrexate over 1.5 g was seen in 39 (23.6%) patients. Mean LSM was 5.3 ± 2.9 kPa. High LSM was found in 18 (11.0%) patients. Waist circumference (OR: 1.24; 95% CI: 1.11-1.38; P = 0.0002), diabetes (OR: 12.70; 95% CI: 1.84-87.70; P = 0.010), and AST (OR: 1.08; 95% CI: 1.02-1.16; P = 0.017) were associated with high LSM. Conclusion. 11% of psoriatic patients had significant liver fibrosis by high LSM. Waist circumference, diabetes, and AST level were the independent predictors. PMID:27006950

  7. [The role of the team of family physician in prevention of changing risk factors important in development of arterial hypertension].

    PubMed

    Beganlić, Azijada; Batić-Mujanović, Olivera; Tulumović, Ajsa; Zilzić, Muharem

    2005-01-01

    Arterial hypertension (AH) is one of the commonest noninfective chronic disease according to its important and the role in the morbidity and mortality, which is the reason for patients coming to the family phisician. Detection and treatment of high blood pressure are the major responsibility of physician in the primary care. If the family physician team (physician and nurse) make a good assessment of the risk factors which is important in development of arterial hypertension, the appearance of disease and its complications can be prevented or delayed. The most important for prevention of arterial hypertension is adoption a healthy lifestyle and it is nonseparate part of arterial hypertension treatment. PMID:16268072

  8. Statistical Analyses of Scatterplots to Identify Important Factors in Large-Scale Simulations

    SciTech Connect

    Kleijnen, J.P.C.; Helton, J.C.

    1999-04-01

    The robustness of procedures for identifying patterns in scatterplots generated in Monte Carlo sensitivity analyses is investigated. These procedures are based on attempts to detect increasingly complex patterns in the scatterplots under consideration and involve the identification of (1) linear relationships with correlation coefficients, (2) monotonic relationships with rank correlation coefficients, (3) trends in central tendency as defined by means, medians and the Kruskal-Wallis statistic, (4) trends in variability as defined by variances and interquartile ranges, and (5) deviations from randomness as defined by the chi-square statistic. The following two topics related to the robustness of these procedures are considered for a sequence of example analyses with a large model for two-phase fluid flow: the presence of Type I and Type II errors, and the stability of results obtained with independent Latin hypercube samples. Observations from analysis include: (1) Type I errors are unavoidable, (2) Type II errors can occur when inappropriate analysis procedures are used, (3) physical explanations should always be sought for why statistical procedures identify variables as being important, and (4) the identification of important variables tends to be stable for independent Latin hypercube samples.

  9. Saliva between normal and pathological. Important factors in determining systemic and oral health.

    PubMed

    Iorgulescu, Gabriela

    2009-01-01

    There is a tendency in current medical research to explore the importance and symptomatology of saliva. The question to which increasingly more researchers from the medico-legal, systemic and dental fields tried to answer and bring together arguments for a greater emphasis is referring to the role of saliva in the health of the patient. Up until our time, people have looked at the importance of saliva from another perspective: saliva helped in pasting envelopes or stamps, or mostly in reported cases of public speakers faced with the impossibility of having a coherent speech due to sensations of dry mouth. This 'dry mouth' condition, named xerostomia in medical terms, has been used since antiquity as a test in detecting lies, knowing since then that the inhibition of emotional salivary glands, the feeling of 'dry mouth' is caused by anxiety, thus being a potential incrimination. Although hundreds of publications have insisted on the etiology and complications of the salivary gland hypofunction, only a few health professionals used to harvest saliva tests. As in the case of urine and blood, saliva quality and quantity are affected by a multitude of medical conditions and treatments, as well as the patient's psychological state. A review of the formation, function and dysfunction of salivary glands may convey the significant role played by saliva in health and disease, especially in detection and recognition of salivary gland hypofunction, systemic disease, and the psychological states, and thus prevent complications caused by these conditions. PMID:20112475

  10. Diversity and distribution of transcription factors: their partner domains play an important role in regulatory plasticity in bacteria.

    PubMed

    Rivera-Gómez, Nancy; Segovia, Lorenzo; Pérez-Rueda, Ernesto

    2011-08-01

    The ability of bacteria to deal with diverse environmental changes depends on their repertoire of genes and their ability to regulate their expression. In this process, DNA-binding transcription factors (TFs) have a fundamental role because they affect gene expression positively and/or negatively depending on operator context and ligand-binding status. Here, we show an exhaustive analysis of winged helix-turn-helix domains (wHTHs), a class of DNA-binding TFs. These proteins were identified in high proportions and widely distributed in bacteria, representing around half of the total TFs identified so far. In addition, we evaluated the repertoire of wHTHs in terms of their partner domains (PaDos), identifying a similar trend, as with TFs, i.e. they are abundant and widely distributed in bacteria. Based on the PaDos, we defined three main groups of families: (i) monolithic, those families with little PaDo diversity, such as LysR; (ii) promiscuous, those families with a high PaDo diversity; and (iii) monodomain, with families of small sizes, such as MarR. These findings suggest that PaDos have a very important role in the diversification of regulatory responses in bacteria, probably contributing to their regulatory complexity. Thus, the TFs discriminate over longer regions on the DNA through their diverse DNA-binding domains. On the other hand, the PaDos would allow a great flexibility for transcriptional regulation due to their ability to sense diverse stimuli through a variety of ligand-binding compounds. PMID:21636649

  11. GLI1 expression is an important prognostic factor that contributes to the poor prognosis of rhabdomyosarcoma.

    PubMed

    Wang, Yuanyuan; Sun, Chao; Jiang, Jinfang; Xie, Yuwen; Li, Bingcheng; Cui, Xiaobin; Chen, Yunzhao; Liu, Chunxia; Li, Feng

    2016-03-01

    The GLI1 and MDM2 genes are amplified or exhibit copy number gains in rhabdomyosarcoma (RMS). Here, we used immunohistochemistry to determine the relationships between GLI1 and MDM2 protein expression and several clinicopathological variables of RMS. GLI1 and MDM2-positivity rates were 61.36% and 13.64%, respectively. GLI1 expression correlated with presence of the PAX3-FOXO1 fusion gene (P=0.040) and lymph node metastasis (P=0.034), and a significant association was found between GLI1 expression and overall survival (OS) (P=0.008). However, there was no association between MDM2 expression and any of the clinicopathological parameters or OS. Thus, GLI1 may be a biomarker of poor prognosis in RMS patients, and could itself be a therapeutic target. This contrasts with the apparent lack of clinical importance of MDM2 in RMS pathology, at least in the cohorts we examined. PMID:26544916

  12. Nonmotor Features in Parkinson's Disease: What Are the Most Important Associated Factors?

    PubMed

    Kadastik-Eerme, Liis; Muldmaa, Mari; Lilles, Stella; Rosenthal, Marika; Taba, Nele; Taba, Pille

    2016-01-01

    Introduction. The purpose of this study was to demonstrate the frequency and severity of nonmotor symptoms and their correlations with a wide range of demographic and clinical factors in a large cohort of patients with Parkinson's disease (PD). Methods. 268 PD patients were assessed using the validated Movement Disorders Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS), the Beck Depression Inventory (BDI), Parkinson's Disease Questionnaire (PDQ-39), the Hoehn and Yahr scale (HY), the Schwab and England Activities of Daily Living (SE-ADL) Scale, and the Minimental State Examination (MMSE). Results. Nonmotor symptoms had a strong positive relationship with depression and lower quality of life. Also, age, duration and severity of PD, cognitive impairment, daily dose, and duration of levodopa treatment correlated with the burden of nonmotor symptoms. Patients with postural instability and gait disorder (PIGD) dominance or with the presence of motor complications had higher MDS-UPDRS Part I scores expressing the load of nonmotor features, compared to participants with other disease subtypes or without motor complications. Conclusions. Though the severity of individual nonmotor symptoms was generally rated by PD patients as "mild" or less, we found a significant cumulative effect of nonmotor symptoms on patients' mood, daily activities, and quality of life. PMID:27195172

  13. Polycystic Ovary Syndrome: Important Underrecognised Cardiometabolic Risk Factor in Reproductive-Age Women

    PubMed Central

    Baldani, Dinka Pavicic; Skrgatic, Lana; Ougouag, Roya

    2015-01-01

    Polycystic ovary syndrome (PCOS) is the most common endocrine disorder amongst women of reproductive age. Although PCOS is diagnosed exclusively based on reproductive criteria, it is also a metabolic disorder. Insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, obesity, and dyslipidemia are more common in women with PCOS than in age-comparable women without PCOS. Many of the metabolic abnormalities that manifest in PCOS are worsened by the concurrent incidence of obesity. However, some of these metabolic perturbations occur even in lean women with PCOS and therefore are rightfully recognized as intrinsic to PCOS. The intrinsic factors that produce these metabolic disturbances are reviewed in this paper. The consequences of obesity and the other metabolic aberrations are also discussed. The metabolic perturbations in PCOS patients lead to chronic low-grade inflammation and to cardiovascular impairments that heighten the risk of having cardiovascular disease. Even though many studies have shown an elevation in surrogate biomarkers of cardiovascular disease in PCOS women, it is still not clear to what extent and magnitude the elevation precipitates more frequent and earlier events. PMID:26124830

  14. Nonmotor Features in Parkinson's Disease: What Are the Most Important Associated Factors?

    PubMed Central

    Kadastik-Eerme, Liis; Muldmaa, Mari; Lilles, Stella; Rosenthal, Marika; Taba, Nele; Taba, Pille

    2016-01-01

    Introduction. The purpose of this study was to demonstrate the frequency and severity of nonmotor symptoms and their correlations with a wide range of demographic and clinical factors in a large cohort of patients with Parkinson's disease (PD). Methods. 268 PD patients were assessed using the validated Movement Disorders Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS), the Beck Depression Inventory (BDI), Parkinson's Disease Questionnaire (PDQ-39), the Hoehn and Yahr scale (HY), the Schwab and England Activities of Daily Living (SE-ADL) Scale, and the Minimental State Examination (MMSE). Results. Nonmotor symptoms had a strong positive relationship with depression and lower quality of life. Also, age, duration and severity of PD, cognitive impairment, daily dose, and duration of levodopa treatment correlated with the burden of nonmotor symptoms. Patients with postural instability and gait disorder (PIGD) dominance or with the presence of motor complications had higher MDS-UPDRS Part I scores expressing the load of nonmotor features, compared to participants with other disease subtypes or without motor complications. Conclusions. Though the severity of individual nonmotor symptoms was generally rated by PD patients as “mild” or less, we found a significant cumulative effect of nonmotor symptoms on patients' mood, daily activities, and quality of life. PMID:27195172

  15. The hematopoietic cytokine granulocyte-macrophage colony stimulating factor is important for cognitive functions

    PubMed Central

    Krieger, Markus; Both, Martin; Kranig, Simon A.; Pitzer, Claudia; Klugmann, Matthias; Vogt, Gerhard; Draguhn, Andreas; Schneider, Armin

    2012-01-01

    We recently reported expression of hematopoietic growth factor GM-CSF and its receptor (GM-CSFR) in CNS neurons. Here we evaluated this system in learning and memory formation using GM-CSF deficient mice. In complementation, GM-CSF signalling was manipulated specifically in adult murine hippocampus by adeno-associated virus (AAV)-mediated GM-CSFR alpha overexpression or knock-down. GM-CSF ablation caused various hippocampus and amygdala-dependent deficits in spatial and fear memory while rendering intact basic parameters like motor function, inherent anxiety, and pain threshold levels. Corroborating these data, spatial memory of AAV-injected mice was positively correlated with GM-CSFRα expression levels. Hippocampal neurons of knock-out mice showed markedly pruned dendritic trees, reduced spine densities, and lower percentages of mature spines. Despite such morphological alterations, long-term potentiation (LTP) was unimpaired in the knock-out hippocampus. Collectively, these results suggest that GM-CSF signalling plays a major role in structural plasticity relevant to learning and memory. PMID:23019518

  16. Non-alcoholic fatty liver disease: a new and important cardiovascular risk factor?

    PubMed

    Bhatia, Lokpal S; Curzen, Nicholas P; Calder, Philip C; Byrne, Christopher D

    2012-05-01

    Non-alcoholic fatty liver disease (NAFLD) affects up to a third of the population worldwide and may confer increased cardiometabolic risk with consequent adverse cardiovascular outcomes independent of traditional cardiovascular risk factors and the metabolic syndrome. It is characterized almost universally by insulin resistance and is strongly associated with type 2 diabetes and obesity. Non-alcoholic fatty liver disease is a marker of pathological ectopic fat accumulation combined with a low-grade chronic inflammatory state. This results in several deleterious pathophysiological processes including abnormal glucose, fatty acid and lipoprotein metabolism, increased oxidative stress, deranged adipokine profile, hypercoaguability, endothelial dysfunction, and accelerated progression of atherosclerosis. This ultimately leads to a dysfunctional cardiometabolic phenotype with cardiovascular mortality representing the main mode of premature death in NAFLD. This review is aimed at introducing NAFLD to the clinical cardiologist by discussing in-depth the evidence to date linking NAFLD with cardiovascular disease, reviewing the likely mechanisms underlying this association, as well as summarizing from a cardiologist's perspective, current and potential future treatment options for this increasingly prevalent disease. PMID:22408036

  17. Important Factors for Early Market Microgrids: Demand Response and Plug-in Electric Vehicle Charging

    NASA Astrophysics Data System (ADS)

    White, David Masaki

    Microgrids are evolving concepts that are growing in interest due to their potential reliability, economic and environmental benefits. As with any new concept, there are many unresolved issues with regards to planning and operation. In particular, demand response (DR) and plug-in electric vehicle (PEV) charging are viewed as two key components of the future grid and both will likely be active technologies in the microgrid market. However, a better understanding of the economics associated with DR, the impact DR can have on the sizing of distributed energy resource (DER) systems and how to accommodate and price PEV charging is necessary to advance microgrid technologies. This work characterizes building based DR for a model microgrid, calculates the DER systems for a model microgrid under DR through a minimization of total cost, and determines pricing methods for a PEV charging station integrated with an individual building on the model microgrid. It is shown that DR systems which consist only of HVAC fan reductions provide potential economic benefits to the microgrid through participation in utility DR programs. Additionally, peak shaving DR reduces the size of power generators, however increasing DR capacity does not necessarily lead to further reductions in size. As it currently stands for a microgrid that is an early adopter of PEV charging, current installation costs of PEV charging equipment lead to a system that is not competitive with established commercial charging networks or to gasoline prices for plug-in hybrid electric vehicles (PHEV).

  18. Lentiviral hepatitis B pseudotype entry requires sodium taurocholate co-transporting polypeptide and additional hepatocyte-specific factors.

    PubMed

    Meredith, L W; Hu, K; Cheng, X; Howard, C R; Baumert, T F; Balfe, P; van de Graaf, K F; Protzer, U; McKeating, J A

    2016-01-01

    Hepatitis B virus (HBV) is one of the world's major unconquered infections, resulting in progressive liver disease, and current treatments rarely cure infection. A limitation to discovering new therapies is our limited knowledge of HBV entry and dissemination pathways that hinders the development of in vitro culture systems. To address this gap in our understanding we optimized the genesis of infectious lentiviral pseudoparticles (HBVpps). The recent discovery that the bile salt transporter sodium taurocholate co-transporting polypeptide (NTCP) acts as a receptor for HBV enabled us to assess the receptor dependency of HBVpp infection. HBVpps preferentially infect hepatoma cells expressing NTCP, whereas other non-liver cells engineered to express NTCP do not support infection, suggesting that additional hepatocyte-specific factors are required for HBVpp internalization. These results highlight the value of the HBVpp system to dissect the pathways of HBV entry and dissemination. PMID:26474824

  19. Insulin receptor isoform A and insulin-like growth factor II as additional treatment targets in human osteosarcoma.

    PubMed

    Avnet, Sofia; Sciacca, Laura; Salerno, Manuela; Gancitano, Giovanni; Cassarino, Maria Francesca; Longhi, Alessandra; Zakikhani, Mahvash; Carboni, Joan M; Gottardis, Marco; Giunti, Armando; Pollak, Michael; Vigneri, Riccardo; Baldini, Nicola

    2009-03-15

    Despite the frequent presence of an insulin-like growth factor I receptor (IGFIR)-mediated autocrine loop in osteosarcoma (OS), interfering with this target was only moderately effective in preclinical studies. Here, we considered other members of the IGF system that might be involved in the molecular pathology of OS. We found that, among 45 patients with OS, IGF-I and IGFBP-3 serum levels were significantly lower, and IGF-II serum levels significantly higher, than healthy controls. Increased IGF-II values were associated with a decreased disease-free survival. After tumor removal, both IGF-I and IGF-II levels returned to normal values. In 23 of 45 patients, we obtained tissue specimens and found that all expressed high mRNA level of IGF-II and >IGF-I. Also, isoform A of the insulin receptor (IR-A) was expressed at high level in addition to IGFIR and IR-A/IGFIR hybrids receptors (HR(A)). These receptors were also expressed in OS cell lines, and simultaneous impairment of IGFIR, IR, and Hybrid-Rs by monoclonal antibodies, siRNA, or the tyrosine kinase inhibitor BMS-536924, which blocks both IGFIR and IR, was more effective than selective anti-IGFIR strategies. Also, anti-IGF-II-siRNA treatment in low-serum conditions significantly inhibited MG-63 OS cells that have an autocrine circuit for IGF-II. In summary, IGF-II rather than IGF-I is the predominant growth factor produced by OS cells, and three different receptors (IR-A, HR(A), and IGFIR) act complementarily for an IGF-II-mediated constitutive autocrine loop, in addition to the previously shown IGFIR/IGF-I circuit. Cotargeting IGFIR and IR-A is more effective than targeting IGF-IR alone in inhibiting OS growth. PMID:19258511

  20. Importance of sunscreen products spreading protocol and substrate roughness for in vitro sun protection factor assessment.

    PubMed

    Fageon, L; Moyal, D; Coutet, J; Candau, D

    2009-12-01

    The purpose of this study was to evaluate the impact of substrate roughness and of product spreading method on in vitro sun protection factor (SPF) measurement and to define the experimental conditions most appropriate to reach the best level of correlation to in vivo SPF. In vitro SPF assessment was carried out on 13 products (including different formulation types with SPF from 20 to 75) using various in vitro SPF protocols and comparing related predictive potential regarding in vivo SPF. In the first part, two spreading methods were compared on two types of PMMA (Polymethyl methacrylate plate with different roughness. The impact of a second spreading step after product drying was also evaluated. From the various investigated parameters, it was shown that (i) a higher roughness (Ra = 4, 5 microm) was preferred for O/W formulations (ii) using a defined sequence of light linear and circular strokes was more adequate than monitoring product spreading in terms of time and pressure (iii) both correlation to in vivo SPF and results variability were improved when a second spreading step was added. The altered protocol showed a good predictive potential regarding in vivo SPF values for O/W formulations (correlation coefficient 0.92, correlation curve slope 0.98) and coefficient of variation of in vitro results (14% of the mean SPF value) close to what is usually obtained in vivo. The repeatability of the protocol was also demonstrated. In the second part, we evaluated the impact of PMMA plate pre-treatment with paraffinum liquidum before spreading the product to get a better correlation between in vivo and in vitro SPF values for W/O formulations. This allowed us to define a protocol suitable for both O/W and W/O formulations. PMID:19627381

  1. Venous insufficiency after prolonged standing: Is joint hypermobility an important risk factor?

    PubMed Central

    Azma, Kamran; Mottaghi, Peyman; Hosseini, Alireza; Salek, Shadi; Bina, Roya

    2015-01-01

    Background: Varicose veins are extremely common disease which is due to elevated superficial venous pressures. We aimed to know that if joint hypermobility causes the venous insufficiency following the prolonged standing. Materials and Methods: This prospective cohort study conducted on the soldiers of training periods in a military base of Iran Army in Isfahan in 2013. The active-duty soldiers were first examined by a physician and their Beighton scores (BSs) were obtained. At the onset of the training period, the presence of chronic venous insufficiency was clinically evaluated according to the C class of clinical, etiological, anatomical, and pathological classification. After 3 months, soldiers with and without joint hypermobility were reexamined for manifestations of venous insufficiency based on clinical examination. Results: Of 718 soldiers, 211 subjects were diagnosed for joint hypermobility syndrome (29.3%). The mean BS was significantly higher in hypermobility soldiers (5.5 ± 1.5) than the healthy ones (1.2 ± 1.1). Before the training period, the prevalence of spider and varicose veins in soldiers with joint hypermobility was significantly higher than healthy subjects (P > 0.001). After the training period, the prevalence of venous insufficiency significantly increased in soldiers with joint hypermobility (P > 0.001) while there was no significant difference in healthy group before and after the period of training (P = 0.25). Conclusion: Hypermobility could be considered as a risk factor for the development of venous insufficiency, so it seems necessary to evaluate the population who need to be standing for a long time for evidence of joint hypermobility. PMID:26015924

  2. What are the most important factors determining different vegetation types in the Chapada Diamantina, Brazil?

    PubMed

    Neves, S P S; Funch, R; Conceição, A A; Miranda, L A P; Funch, L S

    2016-06-01

    A transect was used to examine the environmental and biological descriptors of a compact vegetation mosaic in the Chapada Diamantina in northeastern Brazil, including the floristic composition, spectrum of plant life forms, rainfall, and soil properties that defined areas of cerrado (Brazilian savanna), caatinga (seasonally dry tropical forest thorny, deciduous shrub/arboreal vegetation) and cerrado-caatinga transition vegetation. The floristic survey was made monthly from April/2009 to March/2012. A dendrogram of similarity was generated using the Jaccard Index based on a matrix of the species that occurred in at least two of the vegetation types examined. The proportions of life forms in each vegetation type were compared using the chi-square test. Composite soil samples were analyzed by simple variance (ANOVA) to examine relationships between soil parameters of each vegetation type and the transition area. The monthly precipitation levels in each vegetation type were measured and compared using the chi-square test. A total of 323 species of angiosperms were collected distributed in 193 genera and 54 families. The dendrogram demonstrated strong difference between the floristic compositions of the cerrado and caatinga, sharing 2% similarity. The chi-square test did not demonstrate any significant statistical differences between the monthly values of recorded rainfall. The organic matter and clay contents of the soilsin the caatinga increased while sand decreased, and the proportions of therophyte, hemicryptophyte, and chamaephyte life forms decreased and phanerophytes increased. We can therefore conclude that the floristic composition and the spectrum of life forms combined to define the cerrado and caatinga vegetation along the transect examined, with soil being the principal conditioning factor determining the different vegetation types, independent of precipitation levels. PMID:26934155

  3. Railway noise annoyance and the importance of number of trains, ground vibration, and building situational factors.

    PubMed

    Gidlöf-Gunnarsson, Anita; Ögren, Mikael; Jerson, Tomas; Öhrström, Evy

    2012-01-01

    Internationally accepted exposure-response relationships show that railway noise causes less annoyance than road traffic and aircraft noise. Railway transport, both passenger and freight transport, is increasing, and new railway lines are planned for environmental reasons. The combination of more frequent railway traffic and faster and heavier trains will, most probably, lead to more disturbances from railway traffic in the near future. To effectively plan for mitigations against noise and vibration from railway traffic, new studies are needed to obtain a better basis of knowledge. The main objectives of the present study was to investigate how the relationship between noise levels from railway traffic and general annoyance is influenced by (i) number of trains, (ii) the presence of ground borne vibrations, and (iii) building situational factors, such as orientation of balcony/patio and bedroom window. Socio-acoustic field studies were executed in residential areas; (1) with relatively intense railway traffic; (2) with strong vibrations, and; (3) with the most intense railway traffic in the country. Data was obtained for 1695 respondents exposed to sound levels ranging from L(Aeq,24h) 45 to 65 dB. Both number of trains and presence of ground-borne vibrations, and not just the noise level per se, are of relevance for how annoying railway noise is perceived. The results imply that, for the proportion annoyed to be equal, a 5 - 7 dB lower noise level is needed in areas where the railway traffic causes strong ground-borne vibrations and in areas with a very large number of trains. General noise annoyance was twice as high among residents in dwellings with balcony / patio oriented towards the railway and about 1.5 times higher among residents with bedroom windows facing the railway. PMID:22918150

  4. Hygiene training of food handlers in hospital settings: important factor in the prevention of nosocomial infections.

    PubMed

    Lazarević, Konstansa; Stojanović, Dusica; Bogdanović, Dragan; Dolićanin, Zana

    2013-09-01

    The aim of this study was to evaluate the effects of food hygiene training of food handlers on sanitary-hygienic conditions in hospital kitchens, based on microbiological analysis of smears taken in hospital kitchens. The study was conducted in the 1995-2009 period at the Clinical Centre Nis, Serbia. The food hygiene training was conducted in February 2005, by an infection control officer. 1,076 smears in the central kitchen and 4,025 smears in distributive kitchens were taken from hands and work clothes, work surfaces, equipment, and kitchen utensils. Microbiological analysis of smears was carried out in an accredited laboratory of the Public Health Institute Nis (Serbia). A significantly lower percentage of smears with isolates of bacteria (p < 0.001) taken from hands and work clothes, work surfaces, equipment and kitchen utensils in the central and distributive kitchens was observed in the period following the food safety education programme (2005-2009). The most commonly isolated bacteria was: Enterobacter spp., Acinetobacter spp., Citrobacter spp., and E. coli. Our results confirmed that food hygiene training improved hygiene and is also an important component for the prevention of nosocomial infection. PMID:24344539

  5. Important factors determining the nanoscale tracking precision of dynamic microtubule ends.

    PubMed

    Bohner, G; Gustafsson, N; Cade, N I; Maurer, S P; Griffin, L D; Surrey, T

    2016-01-01

    Tracking dynamic microtubule ends in fluorescence microscopy movies provides insight into the statistical properties of microtubule dynamics and is vital for further analysis that requires knowledge of the trajectories of the microtubule ends. Here we analyse the performance of a previously developed automated microtubule end tracking routine; this has been optimized for comparatively low signal-to-noise image sequences that are characteristic of microscopy movies of dynamic microtubules growing in vitro. Sequences of simulated microtubule images were generated assuming a variety of different experimental conditions. The simulated movies were then tracked and the tracking errors were characterized. We found that the growth characteristics of the microtubules within realistic ranges had a negligible effect on the tracking precision. The fluorophore labelling density, the pixel size of the images, and the exposure times were found to be important parameters limiting the tracking precision which could be explained using concepts of single molecule localization microscopy. The signal-to-noise ratio was found to be a good single predictor of the tracking precision: typical experimental signal-to-noise ratios lead to tracking precisions in the range of tens of nanometres, making the tracking program described here a useful tool for dynamic microtubule end tracking with close to molecular precision. PMID:26444439

  6. Important factors determining the nanoscale tracking precision of dynamic microtubule ends

    PubMed Central

    BOHNER, G.; GUSTAFSSON, N.; CADE, N.I.; MAURER, S.P.; GRIFFIN, L.D.

    2016-01-01

    Summary Tracking dynamic microtubule ends in fluorescence microscopy movies provides insight into the statistical properties of microtubule dynamics and is vital for further analysis that requires knowledge of the trajectories of the microtubule ends. Here we analyse the performance of a previously developed automated microtubule end tracking routine; this has been optimized for comparatively low signal‐to‐noise image sequences that are characteristic of microscopy movies of dynamic microtubules growing in vitro. Sequences of simulated microtubule images were generated assuming a variety of different experimental conditions. The simulated movies were then tracked and the tracking errors were characterized. We found that the growth characteristics of the microtubules within realistic ranges had a negligible effect on the tracking precision. The fluorophore labelling density, the pixel size of the images, and the exposure times were found to be important parameters limiting the tracking precision which could be explained using concepts of single molecule localization microscopy. The signal‐to‐noise ratio was found to be a good single predictor of the tracking precision: typical experimental signal‐to‐noise ratios lead to tracking precisions in the range of tens of nanometres, making the tracking program described here a useful tool for dynamic microtubule end tracking with close to molecular precision. PMID:26444439

  7. Basal transcription factor 3 plays an important role in seed germination and seedling growth of rice.

    PubMed

    Wang, Wenyi; Xu, Mengyun; Wang, Ya; Jamil, Muhammad

    2014-01-01

    BTF3 has been recognized to be involved in plant growth and development. But its function remains mostly unknown during seed germination and seedling stage. Here, we have analyzed OsBTF3-related sequences in Oryza sativa L. subspecies, japonica, which resembles with the conserved domain of a nascent polypeptide associated complex (NAC) with different homologs of OsBTF3 and human BTF3. Inhibition of Osj10gBTF3 has led to considerable morphological changes during seed germination and seedling growth. Germination percentage was not influenced by the application of GA3, ABA, and NaCl but all concentrations caused wild-type (WT) seeds to germinate more rapidly than the RNAi (Osj10gBTF3 (Ri)) transgenic lines. Seedling inhibition was more severe in the Osj10gBTF3 (Ri) seedlings compared with their WT especially when treated with 100 or 200 μM GA3; 50% reduction in shoots was observed in Osj10gBTF3 (Ri) seedlings. The expression of Osj3g1BTF3, Osj3g2BTF3 and Osj10gBTF3 was primarily constitutive and generally modulated by NaCl, ABA, and GA3 stresses in both Osj10gBTF3 (Ri) lines and WT at the early seedling stage, suggesting that Osj3g1BTF3 and Osj10gBTF3 are much similar but different from Osj3g2BTF3 in biological function. These results show that OsBTF3 plays an important role in seed germination and seedling growth gives a new perception demonstrating that more multifaceted regulatory functions are linked with BTF3 in plants. PMID:24971328

  8. Sex, Race, and the Quality of Life Factors Most Important to Patients’ Well-Being Among Those Seeking Bariatric Surgery

    PubMed Central

    Davis, Roger B.; Jones, Dan B.; Apovian, Caroline A.; Chiodi, Sarah; Huskey, Karen W.; Hamel, Mary B.

    2016-01-01

    Background Evidence suggests obesity-related social stigma and impairment in work function may be the two most detrimental quality of life (QOL) factors to overall well-being among patients seeking weight loss surgery (WLS); whether the relative importance of QOL factors varies across patient sex and race/ethnicity is unclear. Methods We interviewed 574 patients seeking WLS at two centers. We measured patient’s health utility (preference-based well-being measure) as determined via standard gamble scenarios assessing patients’ willingness to risk death to achieve weight loss or perfect health. Multivariable models assessed associations between patients’ utility and five weight-related QOL domains stratified by gender and race: social stigma, self-esteem, physical function, public distress (weight stigma), and work life. Results Depending on patients’ sex and race/ethnicity, mean utilities ranged from 0.85 to 0.91, reflecting an average willingness to assume a 9–15 % risk of death to achieve their most desired health/weight state. After adjustment, African Americans (AAs) reported higher utility than Caucasians (+ 0.054, p=0.03), but utilities did not vary significantly by sex. Among Caucasian and AA men, impairment in physical functioning was the most important factor associated with diminished utility; social stigma was also a leading factor for Caucasian men. Among Caucasian women, self-esteem and work function appeared equally important. Social stigma was the leading contributor to utility among AA women; QOL factors did not appear as important among Hispanic patients. Conclusion AAs reported higher utilities than Caucasian patients. Individual QOL domains that drive diminished well-being varied across race/ethnicity and sex. PMID:26630951

  9. 25 CFR 39.1101 - Addition of pre-kindergarten as a weight factor to the Indian School Equalization Formula in...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 1 2013-04-01 2013-04-01 false Addition of pre-kindergarten as a weight factor to the Indian School Equalization Formula in fiscal year 1982. 39.1101 Section 39.1101 Indians BUREAU OF INDIAN... Programs § 39.1101 Addition of pre-kindergarten as a weight factor to the Indian School...

  10. 25 CFR 39.1101 - Addition of pre-kindergarten as a weight factor to the Indian School Equalization Formula in...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 1 2011-04-01 2011-04-01 false Addition of pre-kindergarten as a weight factor to the Indian School Equalization Formula in fiscal year 1982. 39.1101 Section 39.1101 Indians BUREAU OF INDIAN... Programs § 39.1101 Addition of pre-kindergarten as a weight factor to the Indian School...

  11. 25 CFR 39.1101 - Addition of pre-kindergarten as a weight factor to the Indian School Equalization Formula in...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Addition of pre-kindergarten as a weight factor to the Indian School Equalization Formula in fiscal year 1982. 39.1101 Section 39.1101 Indians BUREAU OF INDIAN... Programs § 39.1101 Addition of pre-kindergarten as a weight factor to the Indian School...

  12. 25 CFR 39.1101 - Addition of pre-kindergarten as a weight factor to the Indian School Equalization Formula in...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 1 2014-04-01 2014-04-01 false Addition of pre-kindergarten as a weight factor to the Indian School Equalization Formula in fiscal year 1982. 39.1101 Section 39.1101 Indians BUREAU OF INDIAN... Programs § 39.1101 Addition of pre-kindergarten as a weight factor to the Indian School...

  13. 25 CFR 39.1101 - Addition of pre-kindergarten as a weight factor to the Indian School Equalization Formula in...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 1 2012-04-01 2011-04-01 true Addition of pre-kindergarten as a weight factor to the Indian School Equalization Formula in fiscal year 1982. 39.1101 Section 39.1101 Indians BUREAU OF INDIAN... Programs § 39.1101 Addition of pre-kindergarten as a weight factor to the Indian School...

  14. What are the most important factors that determine the overall quality of dermatology residency training: A resident survey.

    PubMed

    Guffey, Darren; Feldman, Steven R; Huang, William W

    2015-10-01

    Currently no broadly accepted and standardized objective ranking system for dermatology residency programs exist. A new ranking system was recently developed in an attempt to address this issue. However, it remains unclear if the algorithm employed is based on factors that have a tangible impact on the quality of training provided by dermatology residency programs [1]. Our authors surveyed all current dermatology residents in order to investigate the factors that they feel are most important in determining the strength of training provided by a residency program. PMID:26632809

  15. Trajectories of Childhood Weight Gain: The Relative Importance of Local Environment versus Individual Social and Early Life Factors

    PubMed Central

    Carter, Megan A.; Dubois, Lise; Tremblay, Mark S.; Taljaard, Monica; Jones, Bobby L.

    2012-01-01

    Objective To determine the association between local environmental factors with child weight status in a longitudinal study, using a semi-parametric, group-based method, while also considering social and early life factors. Methods Standardized, directly measured BMI from 4–10 y of age, and group-based trajectory modeling (PROC TRAJ) were used to estimate developmental trajectories of weight change in a Québec birth cohort (n = 1,566). Associations between the weight trajectories and living location, social cohesion, disorder, and material and social deprivation were estimated after controlling for social and early life factors. Results Four weight trajectory groups were estimated: low-increasing (9.7%); low-medium, accelerating (36.2%); medium-high, increasing (43.0%); and high-stable (11.1%). In the low-increasing and medium-high trajectory groups, living in a semi-urban area was inversely related to weight, while living in a rural area was positively related to weight in the high-stable group. Disorder was inversely related to weight in the low-increasing group only. Other important risk factors for high-stable weight included obesity status of the mother, smoking during pregnancy, and overeating behaviors. Conclusions In this study, associations between local environment factors and weight differed by trajectory group. Early life factors appear to play a more consistent role in weight status. Further work is needed to determine the influence of place on child weight. PMID:23077545

  16. Type 1 Diabetes in the Spanish Population: additional factors to Class II HLA-DR3 and -DR4

    PubMed Central

    Urcelay, Elena; Santiago, José L; de la Calle, Hermenegildo; Martínez, Alfonso; Méndez, Julián; Ibarra, José M; Maluenda, Carlos; Fernández-Arquero, Miguel; de la Concha, Emilio G

    2005-01-01

    Background The Major Histocompatibility Complex is the main genetic contributor to susceptibility to type 1 diabetes (T1D); genome-wide scans have consistently mapped increased predisposition to this region. The highest disease risk has been associated with HLA-DR3 and HLA-DR4. In particular, the DR3-positive ancestral haplotype 18.2 was reported as highly diabetogenic. We aimed to corroborate whether this haplotype increases the susceptibility conferred by the DQ2-DR3 alleles in a Mediterranean population. We also searched for additional susceptibility factors to the classic DQ2-DR3 and DQ8-DR4. Results Genetic MHC markers were analysed in a case-control study with 302 T1D patients and 529 ethnically matched controls. DR3-TNFa1b5 carrier rate was significantly higher in DR3-positive heterozygous T1D patients than in DR3-positive heterozygous controls (p = 0.0019; odds ratio OR [95% confidence interval CI] = 2.26 [1.3–3.93]). This data was confirmed analysing the allelic frequency, which includes the information corresponding to the DR3-homozygous individuals (p = 0.001; OR = 2.09) and by using the Arlequin software to check the DR3-positive haplotypes (p = 0.004;OR = 1.93). The present results provide strong evidence of a second susceptibility region in the ancestral haplotype 18.2 in the Spanish population. Moreover, we searched for T1D susceptibility factors in addition to the MHC classical ones, within the DR2-DQ6/DR3-DQ2/DR4-DQ8 negative population. Several genetic markers in both MHC class II (DQA1*0101-DQB1*0501 [p = 0.007;OR = 2.81], DQA1*0201-DQB1*0202 [p = 0.03; OR = 2.35]) and III (TNFa2b1 [p = 0.01 OR = 2.74], BAT-2*2 [p = 0.004; OR = 3.19]) were found. These different alleles associated with T1D were not independent and we observed linkage disequilibrium among them leading us to describe two new risk haplotypes (DQA1*0101-DQB1*0501-TNFa2b1 and DQA1*0201-DQB1*0202- BAT-2*2). Finally, we studied a T1D susceptibility/protection marker located in

  17. Randomised Controlled Feasibility Trial of an Evidence-Informed Behavioural Intervention for Obese Adults with Additional Risk Factors

    PubMed Central

    Sniehotta, Falko F.; Dombrowski, Stephan U.; Avenell, Alison; Johnston, Marie; McDonald, Suzanne; Murchie, Peter; Ramsay, Craig R.; Robertson, Kim; Araujo-Soares, Vera

    2011-01-01

    Background Interventions for dietary and physical activity changes in obese adults may be less effective for participants with additional obesity-related risk factors and co-morbidities than for otherwise healthy individuals. This study aimed to test the feasibility and acceptability of the recruitment, allocation, measurement, retention and intervention procedures of a randomised controlled trial of an intervention to improve physical activity and dietary practices amongst obese adults with additional obesity related risk factors. Method Pilot single centre open-labelled outcome assessor-blinded randomised controlled trial of obese (Body Mass Index (BMI)≥30 kg/m2) adults (age≥18 y) with obesity related co-morbidities such as type 2 diabetes, impaired glucose tolerance or hypertension. Participants were randomly allocated to a manual-based group intervention or a leaflet control condition in accordance to a 2∶1 allocation ratio. Primary outcome was acceptability and feasibility of trial procedures, secondary outcomes included measures of body composition, physical activity, food intake and psychological process measures. Results Out of 806 potentially eligible individuals identified through list searches in two primary care general medical practices N = 81 participants (63% female; mean-age = 56.56(11.44); mean-BMI = 36.73(6.06)) with 2.35(1.47) co-morbidities were randomised. Scottish Index of Multiple Deprivation (SIMD) was the only significant predictor of providing consent to take part in the study (higher chances of consent for invitees with lower levels of deprivation). Participant flowcharts, qualitative and quantitative feedback suggested good acceptance and feasibility of intervention procedures but 34.6% of randomised participants were lost to follow-up due to overly high measurement burden and sub-optimal retention procedures. Participants in the intervention group showed positive trends for most psychological, behavioural and body

  18. Feeling too hot or cold after breast cancer: Is it just a nuisance or a potentially important prognostic factor?

    PubMed Central

    KOKOLUS, KATHLEEN M.; HONG, CHI-CHEN; REPASKY, ELIZABETH A.

    2010-01-01

    There is widespread recognition among both patients and caregivers that breast cancer patients often experience debilitating deficiencies in their ability to achieve thermal comfort, feeling excessively hot or cold under circumstances when others are comfortable. However, this symptom receives little clinical or scientific attention beyond identification and testing of drugs that minimise menopausal-like symptoms. Could some of these symptoms represent an important prognostic signal? Could thermal discomfort be among other cytokine-driven sickness behaviour symptoms seen in many breast cancer patients? While the literature reveals a strong link between treatment for breast cancer and some menopausal vasomotor symptoms (e.g. hot flashes also known as “hot flushes”), there is little data on quantitative assessment of severity of different types of symptoms and their possible prognostic potential. However, recent, intriguing studies indicating a correlation between the presence of hot flashes and reduced development of breast cancer recurrence strongly suggests that more study on this topic is needed. In comparison to reports on the phenomenon of breast cancer-associated hot flashes, there is essentially no scientific study on the large number of women who report feeling excessively cold after breast cancer treatment. Since similar acquired thermal discomfort symptoms can occur in patients with cancers other than breast cancer, there may be as yet unidentified cancer – or treatment-driven factor related to temperature dysregulation. In general, there is surprisingly little information on the physiological relationship between body temperature regulation, vasomotor symptoms, and cancer growth and progression. The goal of this article is twofold: (1) to review the scientific literature egarding acquired deficits inthermoregulation among breast cancer survivors and (2) to propose some speculative ideas regarding the possible basis for thermal discomfort among some

  19. Structural and calorimetric studies demonstrate that the hepatocyte nuclear factor 1β (HNF1β) transcription factor is imported into the nucleus via a monopartite NLS sequence.

    PubMed

    Wiedmann, Mareike M; Aibara, Shintaro; Spring, David R; Stewart, Murray; Brenton, James D

    2016-09-01

    The transcription factor hepatocyte nuclear factor 1β (HNF1β) is ubiquitously overexpressed in ovarian clear cell carcinoma (CCC) and is a potential therapeutic target. To explore potential approaches that block HNF1β transcription we have identified and characterised extensively the nuclear localisation signal (NLS) for HNF1β and its interactions with the nuclear protein import receptor, Importin-α. Pull-down assays demonstrated that the DNA binding domain of HNF1β interacted with a spectrum of Importin-α isoforms and deletion constructs tagged with eGFP confirmed that the HNF1β (229)KKMRRNR(235) sequence was essential for nuclear localisation. We further characterised the interaction between the NLS and Importin-α using complementary biophysical techniques and have determined the 2.4Å resolution crystal structure of the HNF1β NLS peptide bound to Importin-α. The functional, biochemical, and structural characterisation of the nuclear localisation signal present on HNF1β and its interaction with the nuclear import protein Importin-α provide the basis for the development of compounds targeting transcription factor HNF1β via its nuclear import pathway. PMID:27346421

  20. The importance of genetic and shared environmental factors for the associations between job demands, control, support and burnout.

    PubMed

    Blom, Victoria; Bodin, Lennart; Bergström, Gunnar; Hallsten, Lennart; Svedberg, Pia

    2013-01-01

    Within occupational health research, one of the most influential models is the Job Demands-Control-Support model. Numerous studies have applied the model to different domains, with both physical and psychological health outcomes, such as burnout. The twin design provides a unique and powerful research methodology for examining the effects of environmental risk factors on burnout while taking familial factors (genetic and shared environment) into account. The aim of the present study was to investigate the impact of familial factors on the associations of burnout with job demands, control and support. A total of 14,516 individuals from the Swedish Twin Registry, who were born between 1959 and 1986, and who participated in the Study of Twin Adults: Genes and Environment (STAGE) by responding to a web-based questionnaire in 2005, were included in the analyses. Of these, there were 5108 individuals in complete same-sex twin pairs. Co-twin control analyses were performed using linear mixed modeling, comparing between-pairs effects and within-pair effects, stratified also by zygosity and sex. The results indicate that familial factors are of importance in the association between support and burnout in both women and men, but not between job demands and burnout. There are also tendencies towards familial factors being involved in the association between control and burnout in men. These results offer increased understanding of the mechanisms involved in the associations between work stress and burnout. PMID:24086520

  1. Being at peace as an important factor in acquiring teaching competency by Iranian nurse teachers: a qualitative study.

    PubMed

    Emamzadeh Ghasemi, Hormat Sadat; Rafii, Forough; Farahani, Mansoureh A; Mohammadi, Nooreddin

    2014-05-01

    It is imperative to understand the factor that influence teaching competency. Therefore, it is necessary to study those that have an impact on the process of acquiring teaching competency. Competent nurse teachers have an important role in the achievement of nursing students and improving the quality of nursing education. However, few researches have focused specifically on the process of acquiring teaching competency in nurse teachers and its related factors. This study as a part of more extensive research aims to explore the factors influencing acquisition of teaching competency by Iranian nurse teachers. Grounded theory was chosen as the method. Eleven teachers from three nursing schools in Tehran were recruited. Data was generated by semi structured interviews during May 2011 to March 2013 and was analyzed through using constant comparison. Three main categories were emerged including "individual characteristics" (spirituality, professional interest, ethical conducts, knowledge expansion and reflective practice), "organizational factors" (management of educational systems, solidarity culture, student characteristics) and "socio-cultural factors" (social situations, and public definition of nursing). Nurse teachers who deal peacefully with the nursing profession and colleagues are responsible and committed to acquiring teaching competency. A suitable organization in nursing educational systems that is structured and ordered also encourages a peaceful approach by nurse teachers. PMID:24762353

  2. Keep them in school: the importance of education as a protective factor against HIV infection among young South African women

    PubMed Central

    Pettifor, Audrey E; Levandowski, Brooke A; MacPhail, Catherine; Padian, Nancy S; Cohen, Myron S; Rees, Helen V

    2008-01-01

    Objective To identify risk factors for HIV infection among young women aged 15–24 years reporting one lifetime partner in South Africa. Design In 2003, we conducted a nationally representative household survey of sexual behaviour and HIV testing among 11 904 young people aged 15–24 years in South Africa. This analysis focuses on the subset of sexually experienced young women with only one reported lifetime sex partner (n = 1708). Methods Using the proximate determinants framework and the published literature we identified factors associated with HIV in young women. The associations between these factors and HIV infection were explored in multivariable logistic regression models. Results Of the young women, 15% reporting one lifetime partner were HIV positive. In multivariable analyses, young women who had not completed high school were more likely to be infected with HIV compared with those that had completed high school (AOR 3.75; 95% CI 1.34–10.46). Conclusions Young South African women in this population were at high risk of HIV infection despite reporting only having one lifetime partner. Few individual level factors were associated with HIV infection, emphasizing the importance of developing HIV prevention interventions that address structural and partner level risk factors. PMID:18614609

  3. Additional diagnostic and clinical value of anti-cyclic citrullinated peptide antibodies compared with rheumatoid factor isotypes in rheumatoid arthritis.

    PubMed

    Vallbracht, Inka; Helmke, Klaus

    2005-07-01

    In the past decade significant advantages have been made in the treatment of rheumatoid arthritis (RA) and therapeutic strategies have changed a lot. These days, highly effective disease modifying anti-rheumatic drugs enable intervention early in the disease process, in order to prevent major joint damage. For years, serological support in the diagnosis of RA has been limited to the presence of rheumatoid factors, although not very specific for RA. During the last years a variety of circulating non-RF antibodies have been discovered and reported to be of potential diagnostic value. CCP2 proved to be a very disease-specific and even sensitive marker for RA. In addition to the diagnostic properties, CCP showed to be a good prognostic marker, CCP helps to predict the erosive or nonerosive progression of the disease, and CCP is already present early in the disease. This diagnostic tool enables the clinician to choose the optimal therapeutic management for each single RA patient. PMID:16081030

  4. Are delta-aminolevulinate dehydratase inhibition and metal concentrations additional factors for the age-related cognitive decline?

    PubMed

    Baierle, Marília; Charão, Mariele F; Göethel, Gabriela; Barth, Anelise; Fracasso, Rafael; Bubols, Guilherme; Sauer, Elisa; Campanharo, Sarah C; Rocha, Rafael C C; Saint'Pierre, Tatiana D; Bordignon, Suelen; Zibetti, Murilo; Trentini, Clarissa M; Avila, Daiana S; Gioda, Adriana; Garcia, Solange C

    2014-01-01

    Aging is often accompanied by cognitive impairments and influenced by oxidative status and chemical imbalances. Thus, this study was conducted to examine whether age-related cognitive deficit is associated with oxidative damage, especially with inhibition of the enzyme delta-aminolevulinate dehydratase (ALA-D), as well as to verify the influence of some metals in the enzyme activity and cognitive performance. Blood ALA-D activity, essential (Fe, Zn, Cu, Se) and non-essential metals (Pb, Cd, Hg, As, Cr, Ni, V) were measured in 50 elderly and 20 healthy young subjects. Cognitive function was assessed by tests from Consortium to Establish a Registry for Alzheimer's Disease (CERAD) battery and other. The elderly group presented decreased ALA-D activity compared to the young group. The index of ALA-D reactivation was similar to both study groups, but negatively associated with metals. The mean levels of essential metals were within the reference values, while the most toxic metals were above them in both groups. Cognitive function impairments were observed in elderly group and were associated with decreased ALA-D activity, with lower levels of Se and higher levels of toxic metals (Hg and V). Results suggest that the reduced ALA-D activity in elderly can be an additional factor involved in cognitive decline, since its inhibition throughout life could lead to accumulation of the neurotoxic compound ALA. Toxic metals were found to contribute to cognitive decline and also to influence ALA-D reactivation. PMID:25329536

  5. The Importance of Patient-Specific Preoperative Factors: An Analysis of The Society of Thoracic Surgeons Congenital Heart Surgery Database

    PubMed Central

    Jacobs, Jeffrey Phillip; O'Brien, Sean M.; Pasquali, Sara K.; Kim, Sunghee; Gaynor, J. William; Tchervenkov, Christo Ivanov; Karamlou, Tara; Welke, Karl F.; Lacour-Gayet, Francois; Mavroudis, Constantine; Mayer, John E.; Jonas, Richard A.; Edwards, Fred H.; Grover, Frederick L.; Shahian, David M.; Jacobs, Marshall Lewis

    2014-01-01

    Background The most common fonns of risk adjustment for pediatric and congenital heart surgery used today are based mainly on the estimated risk of mortality of the primary procedure of the operation. The goals of this analysis were to assess the association of patient-specific preoperative factors with mortality and to determine which of these preoperative factors to include in future pediatric and congenital cardiac surgical risk models. Methods All index cardiac operations in The Society of Thoracic Surgeons Congenital Heart Surgery Database (STS-CHSD) during 2010 through 2012 were eligible for inclusion. Patients weighing less than 2.5 kg undergoing patent ductus arteriosus closure were excluded. Centers with more than 10% missing data and patients with missing data for discharge mortality or other key variables were excluded. Rates of discharge mortality for patients with or without specific preoperative factors were assessed across age groups and were compared using Fisher's exact test. Results In all, 25,476 operations were included (overall discharge mortality 3.7%, n = 943). The prevalence of common preoperative factors and their associations with discharge mortality were determined. Associations of the following preoperative factors with discharge mortality were all highly significant (p < 0.0001) for neonates, infants, and children: mechanical circulatory support, renal dysfunction, shock, and mechanical ventilation. Conclusions Current STS-CHSD risk adjustment is based on estimated risk of mortality of the primary procedure of the operation as well as age, weight, and prematurity. The inclusion of additional patient-specific preoperative factors in risk models for pediatric and congenital cardiac surgery could lead to increased precision in predicting risk of operative mortality and comparison of observed to expected outcomes. PMID:25262395

  6. Importance of Relativistic Effects and Electron Correlation in Structure Factors and Electron Density of Diphenyl Mercury and Triphenyl Bismuth.

    PubMed

    Bučinský, Lukáš; Jayatilaka, Dylan; Grabowsky, Simon

    2016-08-25

    This study investigates the possibility of detecting relativistic effects and electron correlation in single-crystal X-ray diffraction experiments using the examples of diphenyl mercury (HgPh2) and triphenyl bismuth (BiPh3). In detail, the importance of electron correlation (ECORR), relativistic effects (REL) [distinguishing between total, scalar and spin-orbit (SO) coupling relativistic effects] and picture change error (PCE) on the theoretical electron density, its topology and its Laplacian using infinite order two component (IOTC) wave functions is discussed. This is to develop an understanding of the order of magnitude and shape of these different effects as they manifest in the electron density. Subsequently, the same effects are considered for the theoretical structure factors. It becomes clear that SO and PCE are negligible, but ECORR and scalar REL are important in low- and medium-order reflections on absolute and relative scales-not in the high-order region. As a further step, Hirshfeld atom refinement (HAR) and subsequent X-ray constrained wavefunction (XCW) fitting have been performed for the compound HgPh2 with various relativistic and nonrelativistic wave functions against the experimental structure factors. IOTC calculations of theoretical structure factors and relativistic HAR as well as relativistic XCW fitting are presented for the first time, accounting for both scalar and spin-orbit relativistic effects. PMID:27434184

  7. Nuclear Import of the Parsley bZIP Transcription Factor CPRF2 Is Regulated by Phytochrome Photoreceptors

    PubMed Central

    Kircher, Stefan; Wellmer, Frank; Nick, Peter; Rügner, Alexander; Schäfer, Eberhard; Harter, Klaus

    1999-01-01

    In plants, light perception by photoreceptors leads to differential expression of an enormous number of genes. An important step for differential gene expression is the regulation of transcription factor activities. To understand these processes in light signal transduction we analyzed the three well-known members of the common plant regulatory factor (CPRF) family from parsley (Petroselinum crispum). Here, we demonstrate that these CPRFs, which belong to the basic- region leucine-zipper (bZIP) domain-containing transcription factors, are differentially distributed within parsley cells, indicating different regulatory functions within the regulatory networks of the plant cell. In particular, we show by cell fractionation and immunolocalization approaches that CPRF2 is transported from the cytosol into the nucleus upon irradiation due to action of phytochrome photoreceptors. Two NH2-terminal domains responsible for cytoplasmic localization of CPRF2 in the dark were characterized by deletion analysis using a set of CPRF2-green fluorescent protein (GFP) gene fusion constructs transiently expressed in parsley protoplasts. We suggest that light-induced nuclear import of CPRF2 is an essential step in phytochrome signal transduction. PMID:9922448

  8. Mercury in soils, lakes, and fish in Voyageurs National Park (Minnesota): Importance of atmospheric deposition and ecosystem factors

    USGS Publications Warehouse

    Wiener, J.G.; Knights, B.C.; Sandheinrich, M.B.; Jeremiason, J.D.; Brigham, M.E.; Engstrom, D.R.; Woodruff, L.G.; Cannon, W.F.; Balogh, S.J.

    2006-01-01

    Concentrations of methylmercury in game fish from many interior lakes in Voyageurs National Park (MN, U.S.A.) substantially exceed criteria for the protection of human health. We assessed the importance of atmospheric and geologic sources of mercury to interior lakes and watersheds within the Park and identified ecosystem factors associated with variation in methylmercury contamination of lacustrine food webs. Geologic sources of mercury were small, based on analyses of underlying bedrock and C-horizon soils, and nearly all mercury in the O- and A-horizon soils was derived from atmospheric deposition. Analyses of dated sediment cores from five lakes showed that most (63% ?? 13%) of the mercury accumulated in lake sediments during the 1900s was from anthropogenic sources. Contamination of food webs was assessed by analysis of whole, 1-year-old yellow perch (Perca flavescens), a regionally important prey fish. The concentrations of total mercury in yellow perch and of methylmercury in lake water varied substantially among lakes, reflecting the influence of ecosystem processes and variables that affect the microbial production and abundance of methylmercury. Models developed with the information-theoretic approach (Akaike Information Criteria) identified lake water pH, dissolved sulfate, and total organic carbon (an indicator of wetland influence) as factors influencing methylmercury concentrations in lake water and fish. We conclude that nearly all of the mercury in fish in this seemingly pristine landscape was derived from atmospheric deposition, that most of this bioaccumulated mercury was from anthropogenic sources, and that both watershed and lacustrine factors exert important controls on the bioaccumulation of methylmercury. ?? 2006 American Chemical Society.

  9. Radiation-induced nausea and vomiting: Is ABO blood group as important as radiation and patient-related factors? An observational study.

    PubMed

    Habibi, Mohsen; Namimoghadam, Amir; Korouni, Roghaye; Fashiri, Paria; Borzoueisileh, Sajad; Elahimanesh, Farideh; Amiri, Fatemeh; Moradi, Ghobad

    2016-08-01

    Despite the improvements in cancer screening and treatment, it still remains as one of the leading causes of mortality worldwide. Nausea and vomiting as the side effects of different cancer treatment modalities, such as radiotherapy, are multifactorial and could affect the treatment continuation and patient quality of life. Therefore, the aim of this study was to assess the possible linkage between ABO blood groups and radiation-induced nausea and vomiting (RINV), also its incidence and affecting factors.One hundred twenty-eight patients referring to Tohid hospital of Sanandaj, Iran, were selected and the patients and treatment-related factors were determined in a cross-sectional study. Patients' nausea and vomiting were recorded from the onset of treatment until 1 week after treatment accomplishment. Also, previous possible nausea and vomiting were recorded. The frequencies of nausea and vomiting and their peak time were examined during the treatment period.The association between ABO blood group and the incidence of radiotherapy-induced nausea and vomiting (RINV) were significant and it seems that A blood group patients are the most vulnerable individuals to these symptoms. The association between Rhesus antigen and the time of maximum severity of RINV may indicate that Rhesus antigen affects the time of maximum severity of RINV. The incidence of RINV was not affected by karnofsky performance status, but it was related to the severity of RINV. Furthermore, among the factors affecting the incidence of nausea and vomiting, nausea and vomiting during patient's previous chemotherapy, radiotherapy region, and background gastrointestinal disease were shown to be three important factors.In addition to familiar RINV-affecting factors, ABO blood group may play an important role and these results address the needs for further studies with larger sample size. PMID:27495037

  10. Clinical importance of F-waves as a prognostic factor in Guillain-Barré syndrome in children

    PubMed Central

    Lee, Eung-Bin; Lee, Yun Young; Lee, Jae Min; Son, Su Min; Hwang, Su-Kyeong; Kwon, Soonhak

    2016-01-01

    Purpose A limited number of studies have examined the link between F-wave abnormalities and clinical presentation in pediatric Guillain-Barré syndrome (GBS). Therefore, this study examined the importance of F-wave abnormalities as a prognostic factor in pediatric GBS patients. Methods The records and electrodiagnostic studies (EDS) of 70 GBS patients were retrospectively evaluated, and divided into 2 groups according to the results of EDS. Group A (n=33) presented with F-wave abnormalities, and group B (n=26) exhibited normal findings. We compared laboratory reports, clinical features, response to treatment, and prognosis between the 2 groups. Results Motor weakness was the most frequently observed symptom for either group. Clinically, the incidence of fever and upper respiratory symptoms differed between the 2 groups, while the prevalence of abnormal deep tendon reflex (DTR) was significantly higher in group A than B (P<0.05). Patients diagnosed with GBS had received intravenous immunoglobulin treatment: 94% in group A and 58% in group B. Furthermore, significantly greater numbers of patients in group A showed H-reflex abnormalities and poor prognosis compared with group B (P<0.05). Conclusion This study demonstrated that F-waves are a clinically important prognostic factor in GBS. F-wave abnormalities were associated with abnormal DTR and poor prognosis in patients. Limited studies have examined the link between F-wave abnormalities and clinical results; therefore, further randomized controlled studies are needed to confirm the clinical characteristics and efficacy of treatments. PMID:27462356

  11. Important Factors in the Cognitive Development of Children with Hearing Impairment: Case Studies of Candidates for Cochlear Implants

    PubMed Central

    Nasralla, Heloisa Romeiro; Goffi Gomez, Maria Valéria Schimidt; Magalhaes, Ana Tereza; Bento, Ricardo Ferreira

    2014-01-01

    Introduction The factors that affect the development of children with and without hearing disabilities are similar, provided their innate communication abilities are taken into account. Parents need to mourn the loss of the expected normally hearing child, and it is important that parents create bonds of affection with their child. Objective To conduct a postevaluation of the development and cognition of 20 candidates for cochlear implants between 1 and 13 years of age and to observe important factors in their development. Methods The following instruments were used in accordance with their individual merits: interviews with parents; the Vineland Social Maturity Scale; the Columbia Maturity Scale; free drawings; Bender and Pre-Bender testing; and pedagogical tests. Results The results are described. Conclusion Parental acceptance of a child's deafness proved to be the starting point for the child's verbal or gestural communication development, as well as for cognitive, motor, and emotional development. If the association between deafness and fine motor skills (with or without multiple disabilities) undermines the development of a child's speech, it does not greatly affect communication when the child interacts with his or her peers and receives maternal stimulation. Overprotection and poor sociability make children less independent, impairs their development, and causes low self-esteem. Further observational studies are warranted to determine how cochlear implants contribute to patient recovery. PMID:25992122

  12. Important factors in the cognitive development of children with hearing impairment: case studies of candidates for cochlear implants.

    PubMed

    Nasralla, Heloisa Romeiro; Goffi Gomez, Maria Valéria Schimidt; Magalhaes, Ana Tereza; Bento, Ricardo Ferreira

    2014-10-01

    Introduction The factors that affect the development of children with and without hearing disabilities are similar, provided their innate communication abilities are taken into account. Parents need to mourn the loss of the expected normally hearing child, and it is important that parents create bonds of affection with their child. Objective To conduct a postevaluation of the development and cognition of 20 candidates for cochlear implants between 1 and 13 years of age and to observe important factors in their development. Methods The following instruments were used in accordance with their individual merits: interviews with parents; the Vineland Social Maturity Scale; the Columbia Maturity Scale; free drawings; Bender and Pre-Bender testing; and pedagogical tests. Results The results are described. Conclusion Parental acceptance of a child's deafness proved to be the starting point for the child's verbal or gestural communication development, as well as for cognitive, motor, and emotional development. If the association between deafness and fine motor skills (with or without multiple disabilities) undermines the development of a child's speech, it does not greatly affect communication when the child interacts with his or her peers and receives maternal stimulation. Overprotection and poor sociability make children less independent, impairs their development, and causes low self-esteem. Further observational studies are warranted to determine how cochlear implants contribute to patient recovery. PMID:25992122

  13. Risk factors for chronic undernutrition among children in India: Estimating relative importance, population attributable risk and fractions.

    PubMed

    Corsi, Daniel J; Mejía-Guevara, Iván; Subramanian, S V

    2016-05-01

    Nearly 40% of the world's stunted children live in India and the prevalence of undernutrition has been persistently high in recent decades. Given numerous available interventions for reducing undernutrition in children, it is not clear of the relative importance of each within a multifactorial framework. We assess the simultaneous contribution of 15 known risk factors for child chronic undernutrition in India. Data are from the 3rd Indian National Family Health Survey (NFHS-3), a nationally representative cross-sectional survey undertaken in 2005-2006. The study population consisted of children aged 6-59 months [n = 26,842 (stunting/low height-for-age), n = 27,483 (underweight/low weight-for-age)]. Risk factors examined for their association with undernutrition were: vitamin A supplementation, vaccination, use of iodized salt, household air quality, improved sanitary facilities, safe disposal of stools, improved drinking water, prevalence of infectious disease, initiation of breastfeeding, dietary diversity, age at marriage, maternal BMI, height, education, and household wealth. Age/sex-adjusted and multivariable adjusted effect sizes (odds ratios) were calculated for risk factors along with Population Attributable Risks (PAR) and Fractions (PAF) using logistic regression. In the mutually adjusted models, the five most important predictors of childhood stunting/underweight were short maternal stature, mother having no education, households in lowest wealth quintile, poor dietary diversity, and maternal underweight. These five factors had a combined PAR of 67.2% (95% CI: 63.3-70.7) and 69.7% (95% CI: 66.3-72.8) for stunting and underweight, respectively. The remaining factors were associated with a combined PAR of 11.7% (95% CI: 6.0-17.4) and 15.1% (95% CI: 8.9-21.3) for stunting and underweight, respectively. Implementing strategies focused on broader progress on social circumstances and infrastructural domains as well as investments in nutrition specific

  14. Importance of Rhodococcus strains in a bacterial consortium degrading a mixture of hydrocarbons, gasoline, and diesel oil additives revealed by metatranscriptomic analysis.

    PubMed

    Auffret, Marc D; Yergeau, Etienne; Labbé, Diane; Fayolle-Guichard, Françoise; Greer, Charles W

    2015-03-01

    A bacterial consortium (Mix3) composed of microorganisms originating from different environments (soils and wastewater) was obtained after enrichment in the presence of a mixture of 16 hydrocarbons, gasoline, and diesel oil additives. After addition of the mixture, the development of the microbial composition of Mix3 was monitored at three different times (35, 113, and 222 days) using fingerprinting method and dominant bacterial species were identified. In parallel, 14 bacteria were isolated after 113 days and identified. Degradation capacities for Mix3 and the isolated bacterial strains were characterized and compared. At day 113, we induced the expression of catabolic genes in Mix3 by adding the substrate mixture to resting cells and the metatranscriptome was analyzed. After addition of the substrate mixture, the relative abundance of Actinobacteria increased at day 222 while a shift between Rhodococcus and Mycobacterium was observed after 113 days. Mix3 was able to degrade 13 compounds completely, with partial degradation of isooctane and 2-ethylhexyl nitrate, but tert-butyl alcohol was not degraded. Rhodococcus wratislaviensis strain IFP 2016 isolated from Mix3 showed almost the same degradation capacities as Mix3: these results were not observed with the other isolated strains. Transcriptomic results revealed that Actinobacteria and in particular, Rhodococcus species, were major contributors in terms of total and catabolic gene transcripts while other species were involved in cyclohexane degradation. Not all the microorganisms identified at day 113 were active except R. wratislaviensis IFP 2016 that appeared to be a major player in the degradation activity observed in Mix3. PMID:25343979

  15. Insulin is an important risk factor of endometrial cancer among premenopausal women: a case-control study in China.

    PubMed

    Shao, Yanli; Cheng, Shijie; Hou, Jianqing; Zuo, Ying; Zheng, Wei; Xia, Min; Mu, Nan

    2016-04-01

    The aim of the article was to evaluate the important role played by insulin in the development of endometrial cancer (EC) among Chinese premenopausal women. In this study, 128 endometrial cancer patients and 294 controls who were all premenopausal were included. Baseline characteristics data were collected and serum insulin, C-peptide, sex hormone-binding globulin, C-reaction protein, interleukin-6, and tumor necrosis factor-α levels were measured. Paired t test, χ(2) test, Spearman correlation coefficients, and univariate and multivariate logistic regression models were used in data analysis. Furthermore, insulin levels were categorized into quartiles, and likelihood ratio was calculated for the four categories. Blood insulin levels of the patients were significantly higher than those of the controls (P < 0.001). Factor analysis identified insulin (OR = 2.46; 95 % confidence interval (CI) = 1.55-3.91; P < 0.001) as the independent risk factor of EC. When insulin levels were categorized into quartiles, we found that insulin was positively associated with endometrial cancer risk [HR comparing extreme quartiles (HR q4-q1) = 4.44; 95 % CI = 2.59-7.62; P trend = 0.025]. After adjustment for body mass index (BMI) or waist-hip ratio (WHR), this association was attenuated, but still significant. In conclusion, insulin plays an important role in the carcinogenesis of EC among premenopausal women. Treatment targeting down-regulation of blood insulin levels seems effective in the prevention of this malignancy. PMID:26511973

  16. Insulin-like growth factor-II is produced by, signals to and is an important survival factor for the mature podocyte in man and mouse.

    PubMed

    Hale, L J; Welsh, G I; Perks, C M; Hurcombe, J A; Moore, S; Hers, I; Saleem, M A; Mathieson, P W; Murphy, A J; Jeansson, M; Holly, J M; Hardouin, S N; Coward, R J

    2013-05-01

    Podocytes are crucial for preventing the passage of albumin into the urine and, when lost, are associated with the development of albuminuria, renal failure and cardiovascular disease. Podocytes have limited capacity to regenerate, therefore pro-survival mechanisms are critically important. Insulin-like growth factor-II (IGF-II) is a potent survival and growth factor; however, its major function is thought to be in prenatal development, when circulating levels are high. IGF-II has only previously been reported to continue to be expressed in discrete regions of the brain into adulthood in rodents, with systemic levels being undetectable. Using conditionally immortalized human and ex vivo adult mouse cells of the glomerulus, we demonstrated the podocyte to be the major glomerular source and target of IGF-II; it signals to this cell via the IGF-I receptor via the PI3 kinase and MAPK pathways. Functionally, a reduction in IGF signalling causes podocyte cell death in vitro and glomerular disease in vivo in an aged IGF-II transgenic mouse that produces approximately 60% of IGF-II due to a lack of the P2 promoter of this gene. Collectively, this work reveals the fundamental importance of IGF-II in the mature podocyte for glomerular health across mammalian species. PMID:23299523

  17. Importance of physicians’ attire: factors influencing the impression it makes on patients, a cross-sectional study

    PubMed Central

    2014-01-01

    Objective The aim of the present study was to determine the importance of physician attire in inspiring confidence in patients, patient preferences and factors influencing the impression made by the clothing worn by doctors. Methods Self-administered questionnaires were distributed and completed in five pharmacies across Japan (April–October 2012) to patients or their carers (aged ≥20 years). The survey was performed over 2 consecutive days in each pharmacy. To estimate patient confidence in doctors, questions were asked addressing six items, namely doctors’ attire, speech (way of speaking, volume, tone etc.), age, gender, title (professor, PhD etc.) and reputation. Participants were shown photographs of five different types of attire for male and female doctors (i.e. white coats, scrubs, semiformal, smart casual and casual wear) and asked to rate the appropriateness of each clothing style using a five-point Likert scale. Results Of the 1411 patients or carers who attended the pharmacies, 530 responded to the questionnaire, with 491 complete responses used in subsequent analyses. The mean age of respondents was 51.9 years and 40.3% were male. Speech was the most important factor (mean score 4.60) in determining confidence in doctors, followed by reputation (4.06) and attire (4.00). With regard to attire, regardless of a doctor’s gender, the white coat was judged to be the most appropriate style of dress, followed by surgical scrubs. Only the preference for scrubs was significantly affected by age, gender and region (P < 0.05). Using binomial logistic regression analysis, we evaluated the effects of age on the appropriateness (Likert score 3–5) versus inappropriateness (score 1–2) of scrubs. There was a significant increase in the number of subjects aged 50–64 and >65 years of age who thought scrubs were inappropriate compared with those aged 20–34 years (adjusted odds ratios of 4.30 and 12.7 for male doctors, and 3.66 and 6.91 for female

  18. The Importance of Evaluating Frailty and Social-behavioral Factors for Managing Drugs and Dialysis Prescription in Elderly Patients.

    PubMed

    Musso, C G; Vilas, M; de Quirós, F G B; Núñez, J F M

    2016-04-01

    Ageing is characterized by a progressive loss of complexity, which is an essential condition for making the organism capable of keeping homeostasis. Thus, senile loss of complexity makes old individuals frail: a syndrome characterized by the presence of shrinking (sarcopenia), weakness, poor endurance and energy, slowness, and low physical activity. Moreover, renal ageing progressively leads to a glomerular filtration rate (GFR) reduction, one of the main pharmacokinetic senile changes, which is not detectable by simply evaluating serum urea or creatinine values but measuring or calculating patient's GFR. Finally, current epidemiology has documented that detrimental social-behavioral factors such as low education level, poor financial-resource, depression, and isolation, also influence the onset and progression of chronic diseases, and even overall mortality, particularly in the elderly. Thus, we propose that these 3 variables: frailty phenotype, senile GFR, and detrimental social-behavioral factors, should be considered at time of prescribing drugs or medical procedures in the elderly. Additionally, they should also be considered for following patient's response to prescribed therapies in elderly patients suffering from chronic diseases (diabetes mellitus, chronic kidney disease, etc.), or on organ replacement treatments (dialysis and transplantation). PMID:26575015

  19. DeepCAGE Transcriptomics Reveal an Important Role of the Transcription Factor MAFB in the Lymphatic Endothelium.

    PubMed

    Dieterich, Lothar C; Klein, Sarah; Mathelier, Anthony; Sliwa-Primorac, Adriana; Ma, Qiaoli; Hong, Young-Kwon; Shin, Jay W; Hamada, Michito; Lizio, Marina; Itoh, Masayoshi; Kawaji, Hideya; Lassmann, Timo; Daub, Carsten O; Arner, Erik; Carninci, Piero; Hayashizaki, Yoshihide; Forrest, Alistair R R; Wasserman, Wyeth W; Detmar, Michael

    2015-11-17

    VEGF-C/VEGFR-3 signaling plays a central role in lymphatic development, regulating the budding of lymphatic progenitor cells from embryonic veins and maintaining the expression of PROX1 during later developmental stages. However, how VEGFR-3 activation translates into target gene expression is still not completely understood. We used cap analysis of gene expression (CAGE) RNA sequencing to characterize the transcriptional changes invoked by VEGF-C in LECs and to identify the transcription factors (TFs) involved. We found that MAFB, a TF involved in differentiation of various cell types, is rapidly induced and activated by VEGF-C. MAFB induced expression of PROX1 as well as other TFs and markers of differentiated LECs, indicating a role in the maintenance of the mature LEC phenotype. Correspondingly, E14.5 Mafb(-/-) embryos showed impaired lymphatic patterning in the skin. This suggests that MAFB is an important TF involved in lymphangiogenesis. PMID:26549461

  20. Telomerase RNA TLC1 shuttling to the cytoplasm requires mRNA export factors and is important for telomere maintenance.

    PubMed

    Wu, Haijia; Becker, Daniel; Krebber, Heike

    2014-09-25

    Telomerases protect the ends of linear chromosomes from shortening. They are composed of an RNA (TLC1 in S. cerevisiae) and several proteins. TLC1 undergoes several maturation steps before it is exported into the cytoplasm to recruit the Est proteins for complete assembly. The mature telomerase is subsequently reimported into the nucleus, where it fulfills its function on telomeres. Here, we show that TLC1 export into the cytoplasm requires not only the Ran GTPase-dependent karyopherin Crm1/Xpo1 but also the mRNA export machinery. mRNA export factor mutants accumulate mature and export-competent TLC1 RNAs in their nuclei. Moreover, TLC1 physically interacts with the mRNA transport factors Mex67 and Dbp5/Rat8. Most importantly, we show that the nuclear export of TLC1 is an essential step for the formation of the functional RNA containing enzyme, because blocking TLC1 export in the mex67-5 xpo1-1 double mutant prevents its cytoplasmic maturation and leads to telomere shortening. PMID:25220466

  1. Erythroid Krüppel-like factor (EKLF) contains a multifunctional transcriptional activation domain important for inter- and intramolecular interactions.

    PubMed Central

    Chen, X; Bieker, J J

    1996-01-01

    Erythroid Krüppel-like factor (EKLF) is a red cell-restricted transcriptional activator that plays a dominant role in establishing high levels of beta-globin gene expression during erythroid ontogeny. Although its DNA binding domain belongs to the well-studied class of Krüppel-like zinc fingers, its proline-rich activation region has not been thoroughly examined. We have analyzed this region by monitoring the functional effects of its mutagenesis upon EKLF activity in vivo and in vitro. First, using co-transfection assays, we find that the transactivation region contains discrete stimulatory and inhibitory subdomains. Second, in vitro binding assays indicate that the inhibitory domain exerts its effect in cis by interfering with DNA binding. Third, in vivo competition assays demonstrate that EKLF interacts with a positive-acting cellular factor, and that the domain responsible for this trans interaction lies within a 40 amino acid sequence that is coincident with the EKLF minimal transactivation domain. Finally, site-directed mutagenesis of this domain implies that conformation and/or phosphorylation status of its central core may be critical for such interactions. These results point towards post-translational steric and/or allosteric control of EKLF function that may be important not just for its DNA binding ability, but also for its potential to interact with other proteins that fully establish the correct stereospecific array leading to efficient switching of beta-globin transcription during development. Images PMID:8918466

  2. The Basic Leucine Zipper Transcription Factor ABSCISIC ACID RESPONSE ELEMENT-BINDING FACTOR2 Is an Important Transcriptional Regulator of Abscisic Acid-Dependent Grape Berry Ripening Processes1[W][OPEN

    PubMed Central

    Nicolas, Philippe; Lecourieux, David; Kappel, Christian; Cluzet, Stéphanie; Cramer, Grant; Delrot, Serge; Lecourieux, Fatma

    2014-01-01

    In grape (Vitis vinifera), abscisic acid (ABA) accumulates during fruit ripening and is thought to play a pivotal role in this process, but the molecular basis of this control is poorly understood. This work characterizes ABSCISIC ACID RESPONSE ELEMENT-BINDING FACTOR2 (VvABF2), a grape basic leucine zipper transcription factor belonging to a phylogenetic subgroup previously shown to be involved in ABA and abiotic stress signaling in other plant species. VvABF2 transcripts mainly accumulated in the berry, from the onset of ripening to the harvesting stage, and were up-regulated by ABA. Microarray analysis of transgenic grape cells overexpressing VvABF2 showed that this transcription factor up-regulates and/or modifies existing networks related to ABA responses. In addition, grape cells overexpressing VvABF2 exhibited enhanced responses to ABA treatment compared with control cells. Among the VvABF2-mediated responses highlighted in this study, the synthesis of phenolic compounds and cell wall softening were the most strongly affected. VvABF2 overexpression strongly increased the accumulation of stilbenes that play a role in plant defense and human health (resveratrol and piceid). In addition, the firmness of fruits from tomato (Solanum lycopersicum) plants overexpressing VvABF2 was strongly reduced. These data indicate that VvABF2 is an important transcriptional regulator of ABA-dependent grape berry ripening. PMID:24276949

  3. Silencing of core transcription factors in human EC cells highlights the importance of autocrine FGF signaling for self-renewal

    PubMed Central

    Greber, Boris; Lehrach, Hans; Adjaye, James

    2007-01-01

    Background Despite their distinct origins, human embryonic stem (hES) and embryonic carcinoma (hEC) cells share a number of similarities such as surface antigen expression, growth characteristics, the ability to either self-renew or differentiate, and control of the undifferentiated state by the same core transcription factors. To obtain further insights into the regulation of self-renewal, we have silenced hES/hEC cell-specific genes in NCCIT hEC cells and analysed the downstream effects by means of microarrays. Results RNAi-mediated silencing of OCT4 and SOX2 induced differentiation with mesodermal characteristics. Markers of trophoblast induction were only transiently up-regulated in the OCT4 knock-down. Independent knock-downs of NANOG produced a proliferation rather than a differentiation phenotype, which may be due to high NANOG expression levels in the cell line used. Published ChIP-chip data from hES cells were used to identify putative direct targets. RNAi-mediated differentiation was accompanied by direct down-regulation of known hES/hEC cell markers. This included all three core transcription factors in the case of the OCT4 and SOX2 knock-downs, confirming previous findings of reciprocal activation in ES cells. Furthermore, large numbers of histone genes as well as epigenetic regulators were differentially expressed, pointing at chromatin remodeling as an additional regulatory level in the differentiation process. Moreover, loss of self-renewal was accompanied by the down-regulation of genes involved in FGF signaling. FGF receptor inhibition for short and prolonged periods of time revealed that the ERK/MAPK cascade is activated by endogenously expressed fibroblast growth factors and that FGF signaling is cruicial for maintaining the undifferentiated state of hEC cells, like in hES cells. Conclusion Control of self-renewal appears to be very similar in hEC and hES cells. This is supported by large numbers of common transcription factor targets and the

  4. An Additional Potential Factor for Kidney Stone Formation during Space Flights: Calcifying Nanoparticles (Nanobacteria): A Case Report

    NASA Technical Reports Server (NTRS)

    Jones, Jeffrey A.; Ciftcioglu, Neva; Schmid, Joseph; Griffith, Donald

    2007-01-01

    Spaceflight-induced microgravity appears to be a risk factor for the development of urinary calculi due to skeletal calcium liberation and other undefined factors, resulting in stone disease in crewmembers during and after spaceflight. Calcifying nanoparticles, or nanobacteria, reproduce at a more rapid rate in simulated microgravity conditions and create external shells of calcium phosphate in the form of apatite. The questions arises whether calcifying nanoparticles are niduses for calculi and contribute to the development of clinical stone disease in humans, who possess environmental factors predisposing to the development of urinary calculi and potentially impaired immunological defenses during spaceflight. A case of a urinary calculus passed from an astronaut post-flight with morphological characteristics of calcifying nanoparticles and staining positive for a calcifying nanoparticle unique antigen, is presented.

  5. Employing Lead Thiocyanate Additive to Reduce the Hysteresis and Boost the Fill Factor of Planar Perovskite Solar Cells.

    PubMed

    Ke, Weijun; Xiao, Chuanxiao; Wang, Changlei; Saparov, Bayrammurad; Duan, Hsin-Sheng; Zhao, Dewei; Xiao, Zewen; Schulz, Philip; Harvey, Steven P; Liao, Weiqiang; Meng, Weiwei; Yu, Yue; Cimaroli, Alexander J; Jiang, Chun-Sheng; Zhu, Kai; Al-Jassim, Mowafak; Fang, Guojia; Mitzi, David B; Yan, Yanfa

    2016-07-01

    Lead thiocyanate in the perovskite precursor can increase the grain size of a perovskite thin film and reduce the conductivity of the grain boundaries, leading to perovskite solar cells with reduced hysteresis and enhanced fill factor. A planar perovskite solar cell with grain boundary and interface passivation achieves a steady-state efficiency of 18.42%. PMID:27145346

  6. Predictive factors for erectile dysfunction in men with prostate cancer after brachytherapy: Is dose to the penile bulb important?

    SciTech Connect

    Macdonald, A. Graham . E-mail: gmacdonald@easynet.co.uk; Keyes, Mira; Kruk, Alexandra; Duncan, Graeme; Moravan, Veronika; Morris, W. James

    2005-09-01

    Purpose: To determine predictive factors for postimplant erectile dysfunction (ED) in a cohort of patients, according to prospectively collected data; specifically, to assess the impact of penile bulb volume and D50 and D95 (dose covering 50% and 95% of the penile bulb volume, respectively) on ED. Methods and Materials: Three hundred forty-two patients were identified who were potent before implant and who had at least 2 years' follow-up. Patient, tumor, treatment, and dosimetric data were collected on all patients. Postimplant ED was defined according to both physician-documented and patient-documented outcome data. Binary logistic regression analysis was used to create multivariable models of predictors for ED at 1, 2, and 3 years after implant. Results: Physician-documented rates of ED were 57%, 48%, and 38% at 1, 2, and 3 years after implant, respectively. Patient-documented rates of ED were 70% and 66% at 1 and 2 years, respectively. Multivariable analyses revealed age and degree of preimplant erectile function to be consistently significant predictors of ED. Use of hormones was significant at the 1-year physician-documented ED endpoint but not thereafter, in keeping with the time course of testosterone recovery. Penile bulb volume, D50, and D95 were not found to be predictive for ED at any time point, in contrast to previous studies. In addition, planning ultrasound target volume, number of needles, and institutional case sequence number were significant predictors of ED at various time points, consistent with a traumatic etiology of ED. Conclusions: We found no evidence to support penile bulb dosimetry as an independent predictive factor for ED after implant, using physician-documented or patient-documented outcomes.

  7. UAP56 is an important mediator of Angiotensin II/platelet derived growth factor induced vascular smooth muscle cell DNA synthesis and proliferation

    SciTech Connect

    Sahni, Abha; Wang, Nadan; Alexis, Jeffrey

    2013-02-15

    Highlights: ► Knockdown of UAP56 inhibits Angiotensin II/PDGF induced vascular smooth muscle cell proliferation. ► UAP56 is a positive regulator of E2F transcriptional activation. ► UAP56 is present in the vessel wall of low flow carotid arteries. -- Abstract: Angiotensin (Ang) II and platelet-derived growth factor (PDGF) are important mediators of pathologic vascular smooth muscle cell (VSMC) proliferation. Identifying downstream mediators of Ang II and PDGF signaling may provide insights for therapies to improve vascular proliferative diseases. We have previously demonstrated that breakpoint cluster region (Bcr) is an important mediator of Ang II/PDGF signaling in VSMC. We have recently reported that the DExD/H box protein UAP56 is an interacting partner of Bcr in regulating VSMC DNA synthesis. We hypothesized that UAP56 itself is an important regulator of VSMC proliferation. In this report we demonstrate that knockdown of UAP56 inhibits Ang II/PDGF induced VSMC DNA synthesis and proliferation, and inhibits E2F transcriptional activity. In addition, we demonstrate that UAP56 is present in the vessel wall of low-flow carotid arteries. These findings suggest that UAP56 is a regulator of VSMC proliferation and identify UAP56 as a target for preventing vascular proliferative disease.

  8. Overexpression of hepatocyte growth factor in SBMA model mice has an additive effect on combination therapy with castration.

    PubMed

    Ding, Ying; Adachi, Hiroaki; Katsuno, Masahisa; Huang, Zhe; Jiang, Yue-Mei; Kondo, Naohide; Iida, Madoka; Tohnai, Genki; Nakatsuji, Hideaki; Funakoshi, Hiroshi; Nakamura, Toshikazu; Sobue, Gen

    2015-12-25

    Spinal and bulbar muscular atrophy (SBMA) is an inherited motor neuron disease caused by the expansion of a polyglutamine (polyQ)-encoding tract within the androgen receptor (AR) gene. The pathologic features of SBMA are motor neuron loss in the spinal cord and brainstem and diffuse nuclear accumulation and nuclear inclusions of mutant AR in residual motor neurons and certain visceral organs. Hepatocyte growth factor (HGF) is a polypeptide growth factor which has neuroprotective properties. To investigate whether HGF overexpression can affect disease progression in a mouse model of SBMA, we crossed SBMA transgenic model mice expressing an AR gene with an expanded CAG repeat with mice overexpressing HGF. Here, we report that high expression of HGF induces Akt phosphorylation and modestly ameliorated motor symptoms in an SBMA transgenic mouse model treated with or without castration. These findings suggest that HGF overexpression can provide a potential therapeutic avenue as a combination therapy with disease-modifying therapies in SBMA. PMID:26551462

  9. Smoking and polymorphisms in xenobiotic metabolism and DNA repair genes are additive risk factors affecting bladder cancer in Northern Tunisia.

    PubMed

    Rouissi, Kamel; Ouerhani, Slah; Hamrita, Bechr; Bougatef, Karim; Marrakchi, Raja; Cherif, Mohamed; Ben Slama, Mohamed Riadh; Bouzouita, Mohamed; Chebil, Mohamed; Ben Ammar Elgaaied, Amel

    2011-12-01

    Cancer epidemiology has undergone marked development since the nineteen-fifties. One of the most spectacular and specific contributions was the demonstration of the massive effect of smoking and genetic polymorphisms on the occurrence of bladder cancer. The tobacco carcinogens are metabolized by various xenobiotic metabolizing enzymes, such as the super-families of N-acetyltransferases (NAT) and glutathione S-transferases (GST). DNA repair is essential to an individual's ability to respond to damage caused by tobacco carcinogens. Alterations in DNA repair genes may affect cancer risk by influencing individual susceptibility to this environmental exposure. Polymorphisms in NAT2, GST and DNA repair genes alter the ability of these enzymes to metabolize carcinogens or to repair alterations caused by this process. We have conducted a case-control study to assess the role of smoking, slow NAT2 variants, GSTM1 and GSTT1 null, and XPC, XPD, XPG nucleotide excision-repair (NER) genotypes in bladder cancer development in North Tunisia. Taken alone, each gene unless NAT2 did not appear to be a factor affecting bladder cancer susceptibility. For the NAT2 slow acetylator genotypes, the NAT2*5/*7 diplotype was found to have a 7-fold increased risk to develop bladder cancer (OR = 7.14; 95% CI: 1.30-51.41). However, in tobacco consumers, we have shown that Null GSTM1, Wild GSTT1, Slow NAT2, XPC (CC) and XPG (CC) are genetic risk factors for the disease. When combined together in susceptible individuals compared to protected individuals these risk factors give an elevated OR (OR = 61). So, we have shown a strong cumulative effect of tobacco and different combinations of studied genetic risk factors which lead to a great susceptibility to bladder cancer. PMID:21647780

  10. Preceding infection as an important risk factor for ischaemic brain infarction in young and middle aged patients

    PubMed Central

    Syrjänen, Jaana; Valtonen, Ville V; Iivanainen, Matti; Kaste, Markku; Huttunen, Jussi K

    1988-01-01

    The role of preceding infection as a risk factor for ischaemic stroke was investigated in a case-control study of 54 consecutive patients under 50 years of age with brain infarction and 54 randomly selected controls from the community matched for sex and age. Information about previous illnesses, smoking, consumption of alcohol, and use of drugs was taken. A blood sample was analysed for standard biochemical variables and serum cholesterol, high density lipoprotein cholesterol, triglyceride, and fasting blood glucose concentrations determined. Titres of antimicrobial antibodies against various bacteria, including Staphylococcus, Streptococcus, Yersinia, and Salmonella and several viruses were determined. Febrile infection was found in patients during the month before the brain infarction significantly more often than in controls one month before their examination (19 patients v three controls; estimated relative risk 9·0 (95% confidence interval 2·2 to 80·0)). The most common preceding febrile infection was respiratory infection (80%). Infections preceding brain infarction were mostly of bacterial origin based on cultural, serological, and clinical data. In conditional logistic regression analysis for matched pairs the effect of preceding febrile infection remained significant (estimated relative risk 14·5 (95% confidence interval 1·9 to 112·3)) when tested with triglyceride concentration, hypertension, smoking, and preceding intoxication with alcohol. Although causality cannot be inferred from these data and plausible underlying mechanisms remain undetermined, preceding febrile infection may play an important part in the development of brain infarction in young and middle aged patients. PMID:3132245

  11. The diameter of the ileal J-pouch-anal anastomosis as an important risk factor of pouchitis – clinical observations

    PubMed Central

    Banasiewicz, Tomasz; Marciniak, Ryszard; Kaczmarek, Elżbieta; Meissner, Wiktor; Krokowicz, Piotr; Paszkowski, Jacek; Walkowiak, Jarosław; Majewski, Przemysław; Marszałek, Andrzej; Drews, Michał

    2011-01-01

    Summary Background Patients’ quality of life after restorative proctocolectomy depends on the potential complications. Stricture of the ileal pouch-anal anastomosis is one of the complications following restorative proctocolectomy. Material/Methods We analyzed the correlation between the diameter of the anastomosis and clinical parameters, including pouchitis disease activity index (PDAI), the activity of fecal M2-pyruvate kinase and maximum tolerable volume of the pouch. The study group consisted of 31 patients in whom covering ileostomy had been closed 72±50 months before enrolement to the study. Restorative proctocolectomy for ulcerative colitis or familial adenomatous polyposis coli had been performed in this group. Results The study did not show any correlation between the diameter of the anastomosis and primary indication for surgery, the time elapsed after restoration of the bowel continuity, the activity of fecal M2-pyruvate kinase, or maximum tolerable volume. However, meaningful correlations between the stricture of the anastomosis and the presence and activity of pouchitis, together with the ileal villi atrophy, were detected. Conclusions Stricture of the anastomosis appears to be an important factor increasing the incidence of pouchitis, and is independent of the underlying condition and time after the operation. Dilation of the anastomosis and prevention of stricture should constitute a permanent element of postoperative follow-up. PMID:21278694

  12. Bacterial 'cosmopolitanism' and importance of local environmental factors for community composition in remote high-altitude lakes.

    PubMed

    Sommaruga, Ruben; Casamayor, Emilio O

    2009-05-01

    In October 2004, plankton samples were collected from six permanent lakes located between 4960 and 5440 m a.s.l. in the Mount Everest region (Nepal) to assess how spatial and local environmental factors affect natural bacterial community composition. Fingerprinting analysis of the bacterial 16S rRNA gene fragment was done by denaturing gradient gel electrophoresis (DGGE).The number of DGGE bands (range: 12-23) was not correlated with lake area or remoteness, but there was a strong negative correlation with the ratio of catchment to lake area (r = -0.826, P < 0.05), suggesting that hydraulic retention time affects the establishment of the bacterial community in these seepage lakes.Most dominant sequences belonged to Betaproteobacteria except in two lakes where members of Bacteroidetes made the largest relative contribution. Up to 81% of the phylotypes had high similarity (>98 to 100%) in partial 16S rRNA gene sequence to those reported from other alpine lakes and glaciers around the world, suggesting the presence of 'cosmopolitan' bacteria.An analysis based on dissimilarity matrices and the Mantel test revealed the existence of dissimilarities in bacterial community composition related to geographical distance over a small spatial scale (<6 km), but determined by local environmental constraints.Our results suggest that several bacterial phylotypes are ubiquitous in the freshwater aquatic realm, but taxon sorting by local environmental constraints is important. PMID:20543908

  13. Food additives.

    PubMed

    Berglund, F

    1978-01-01

    The use of additives to food fulfils many purposes, as shown by the index issued by the Codex Committee on Food Additives: Acids, bases and salts; Preservatives, Antioxidants and antioxidant synergists; Anticaking agents; Colours; Emulfifiers; Thickening agents; Flour-treatment agents; Extraction solvents; Carrier solvents; Flavours (synthetic); Flavour enhancers; Non-nutritive sweeteners; Processing aids; Enzyme preparations. Many additives occur naturally in foods, but this does not exclude toxicity at higher levels. Some food additives are nutrients, or even essential nutritents, e.g. NaCl. Examples are known of food additives causing toxicity in man even when used according to regulations, e.g. cobalt in beer. In other instances, poisoning has been due to carry-over, e.g. by nitrate in cheese whey - when used for artificial feed for infants. Poisonings also occur as the result of the permitted substance being added at too high levels, by accident or carelessness, e.g. nitrite in fish. Finally, there are examples of hypersensitivity to food additives, e.g. to tartrazine and other food colours. The toxicological evaluation, based on animal feeding studies, may be complicated by impurities, e.g. orthotoluene-sulfonamide in saccharin; by transformation or disappearance of the additive in food processing in storage, e.g. bisulfite in raisins; by reaction products with food constituents, e.g. formation of ethylurethane from diethyl pyrocarbonate; by metabolic transformation products, e.g. formation in the gut of cyclohexylamine from cyclamate. Metabolic end products may differ in experimental animals and in man: guanylic acid and inosinic acid are metabolized to allantoin in the rat but to uric acid in man. The magnitude of the safety margin in man of the Acceptable Daily Intake (ADI) is not identical to the "safety factor" used when calculating the ADI. The symptoms of Chinese Restaurant Syndrome, although not hazardous, furthermore illustrate that the whole ADI

  14. The relative importance of climatic, environmental, and anthropogenic factors on fire activity in Africa using the MODIS active fire product

    NASA Astrophysics Data System (ADS)

    Powell, R. L.; Eckmann, T. C.; Still, C. J.

    2006-12-01

    Wildland fires are local-scale phenomena that have global-scale impacts due to emissions of greenhouse gases and aerosols. Fires are also thought to fundamentally influence ecosystem structure and function, particularly in grasslands and savannas. Satellite observations of fire events facilitate studies of the spatial distribution and frequency of fire activity, even on continental scales, and yet few studies have explored in detail the controls on such fire events. In a preliminary effort to contribute to these broad scientific issues, we integrate several sources of satellite and other spatially explicit datasets to investigate the relative importance of climate and ecosystem controls on fire activity in woody- and herbaceous-dominated biomes. Specifically, for a single year, we analyze fire occurrence in Africa--as detected by the MODIS active fire product--as a function of latitude, time of year, land-cover type, vegetation growth form, climate, and percentage C4 vegetation cover. Additionally, we integrate satellite-observed lightning activity and a spatially explicit dataset of human population density to categorize fire regimes as either human dominated (i.e., majority of ignitions are related to anthropogenic activity) or 'natural' fire ecosystems (i.e., majority of ignitions are related to lightning activity). This work will be the basis of future modeling efforts to assess the relationships among climate, fire activity, and vegetation structure, particularly in C4 grass-dominated biomes, which are thought to be dependent on regular fires for their maintenance and growth.

  15. Breeding site selection by coho salmon (Oncorhynchus kisutch) in relation to large wood additions and factors that influence reproductive success

    USGS Publications Warehouse

    Clark, Steven M.; Dunham, Jason B.; McEnroe, Jeffery R.; Lightcap, Scott W.

    2014-01-01

    The fitness of female Pacific salmon (Oncorhynchus spp.) with respect to breeding behavior can be partitioned into at least four fitness components: survival to reproduction, competition for breeding sites, success of egg incubation, and suitability of the local environment near breeding sites for early rearing of juveniles. We evaluated the relative influences of habitat features linked to these fitness components with respect to selection of breeding sites by coho salmon (Oncorhynchus kisutch). We also evaluated associations between breeding site selection and additions of large wood, as the latter were introduced into the study system as a means of restoring habitat conditions to benefit coho salmon. We used a model selection approach to organize specific habitat features into groupings reflecting fitness components and influences of large wood. Results of this work suggest that female coho salmon likely select breeding sites based on a wide range of habitat features linked to all four hypothesized fitness components. More specifically, model parameter estimates indicated that breeding site selection was most strongly influenced by proximity to pool-tail crests and deeper water (mean and maximum depths). Linkages between large wood and breeding site selection were less clear. Overall, our findings suggest that breeding site selection by coho salmon is influenced by a suite of fitness components in addition to the egg incubation environment, which has been the emphasis of much work in the past.

  16. The importance of basic factors in innovation processes and their effects on innovation capability of Malaysian-owned manufacturing companies

    NASA Astrophysics Data System (ADS)

    Suradi, Nur Riza Mohd; Omar, Aminuddin; Shahabuddin, Faridatulazna Ahmad

    2015-02-01

    Innovation is the core ingredient in the competitiveness of today's businesses. Any company that cannot innovate will be losing its competitiveness. While the study on innovation at conceptual level is widely available, there is still lack of deep understanding of how innovation factors impact each stage of the processes of innovation that happen in Malaysian companies. This process-factor approach and understanding may help the government focuses its assistance on relevant factors at relevant process according to the size of the company. This study examines how companies are affected by fundamental factors needed in innovation. Based on results of MYTIC Study 2012 on the level of Technological Innovation Capability (TIC) of Malaysian companies using the RDCB framework, the significance of each innovation factor in each innovation process is determined. This study shows that human resource factor gives more impact than other factors in most processes. Also, financial and human resource factors are likely dictated by the size of the company.

  17. The Extracytoplasmic Function Sigma Factor SigY Is Important for Efficient Maintenance of the Spβ Prophage That Encodes Sublancin in Bacillus subtilis

    PubMed Central

    Mendez, Rebecca; Gutierrez, Alba; Reyes, Jasmin

    2012-01-01

    Many strains of the soil bacterium Bacillus subtilis are capable of producing and being resistant to the antibiotic sublancin because they harbor the Spβ prophage. This 135 kb viral genome is integrated into the circular DNA chromosome of B. subtilis, and contains genes for the production of and resistance to sublancin. We investigated the role of SigY in sublancin production and resistance, finding that it is important for efficient maintenance of the Spβ prophage. We were unable to detect the prophage in mutants lacking SigY. Additionally, these mutants were no longer able to produce sublancin, were sensitive to killing by this factor, and displayed a delay in sporulation. Wild-type cells with normal SigY activity were found to partially lose the Spβ prophage during growth and early sporulation, suggesting a mechanism for the bistable outcome of sibling cells capable of killing and of being killed. The appropriate regulation of SigY appears to be essential for growth as evidenced by the inability to disrupt the gene for its putative antisigma. Our results confirm a role for SigY in antibiotic production and resistance, as has been found for other members of the extracytoplasmic function sigma factor family in B. subtilis, and shows that this role is achieved by affecting maintenance of the Spβ prophage. PMID:22400495

  18. A mammalian homologue of GCN2 protein kinase important for translational control by phosphorylation of eukaryotic initiation factor-2alpha.

    PubMed Central

    Sood, R; Porter, A C; Olsen, D A; Cavener, D R; Wek, R C

    2000-01-01

    A family of protein kinases regulates translation in response to different cellular stresses by phosphorylation of the alpha subunit of eukaryotic initiation factor-2 (eIF-2alpha). In yeast, an eIF-2alpha kinase, GCN2, functions in translational control in response to amino acid starvation. It is thought that uncharged tRNA that accumulates during amino acid limitation binds to sequences in GCN2 homologous to histidyl-tRNA synthetase (HisRS) enzymes, leading to enhanced kinase catalytic activity. Given that starvation for amino acids also stimulates phosphorylation of eIF-2alpha in mammalian cells, we searched for and identified a GCN2 homologue in mice. We cloned three different cDNAs encoding mouse GCN2 isoforms, derived from a single gene, that vary in their amino-terminal sequences. Like their yeast counterpart, the mouse GCN2 isoforms contain HisRS-related sequences juxtaposed to the kinase catalytic domain. While GCN2 mRNA was found in all mouse tissues examined, the isoforms appear to be differentially expressed. Mouse GCN2 expressed in yeast was found to inhibit growth by hyperphosphorylation of eIF-2alpha, requiring both the kinase catalytic domain and the HisRS-related sequences. Additionally, lysates prepared from yeast expressing mGCN2 were found to phosphorylate recombinant eIF-2alpha substrate. Mouse GCN2 activity in both the in vivo and in vitro assays required the presence of serine-51, the known regulatory phosphorylation site in eIF-2alpha. Together, our studies identify a new mammalian eIF-2alpha kinase, GCN2, that can mediate translational control. PMID:10655230

  19. Stereochemical arrangement of hydroxyl groups in sugar and polyalcohol molecules as an important factor in effective cryopreservation.

    PubMed

    Turner, S; Senaratna, T; Touchell, D; Bunn, E; Dixon, K; Tan, B

    2001-02-01

    The efficacy of several sugars and polyalcohols in preculture medium was investigated using Anigozanthos viridis ssp terraspectans Hopper (Haemodoraceae), a threatened plant species endemic to the south west of Western Australia. A vitrification protocol involving preculturing of shoot apices for 3 days on different concentrations of sugars and polyalcohols, followed by incubation in plant vitrification solution 2 (PVS2) for 25 min, prior to immersion in liquid nitrogen (LN) and warming resulted in shoot tip survival ranging from 34 to 84%. High levels of survival were obtained with polyalcohols, compared to sucrose, glucose, trehalose and raffinose when used at the same molarity (0.4 M) or at the equivalent concentration of total hydroxyl (OH) groups present in molecules. In both cases glycerol proved more effective. When polyalcohols (ribitol and erythritol) with similar stereochemical arrangement of OH groups as glycerol were examined, at the same molarity (0.4 M) and with equivalent OH numbers, higher survival was achieved when the total number of OH groups present was the same as glycerol. Additionally, when the structural isomers mannitol/sorbitol and ribitol/xylitol were compared at the same molarity (0.4 M), the isomer with the higher number of OH groups along the same side resulted in significantly higher levels of post-LN survival. We propose that the mode of action of polyalcohols is based not on molarity, but on the total number of OH groups present in the medium. Furthermore, based on these results we propose that the orientation of OH groups is a determining factor in effective cryopreservation. PMID:11166436

  20. Factors associated with HCV risk practices in methadone-maintained patients: the importance of considering the couple in prevention interventions

    PubMed Central

    2014-01-01

    Background One important public health issue associated with opioid use today is the risk of hepatitis C (HCV) infection. Although methadone maintenance may help to decrease HCV-related risk practices, HCV risk behaviors persist and are strongly associated with specific substance use patterns, mental status and social context. The ANRS-Methaville study gave us the opportunity to better disentangle the different relationships between these various factors and HCV risk practices. Methods The ANRS-Methaville multisite randomized trial was designed to assess the feasibility of initiating methadone in primary care by comparing it with methadone initiation in specialized centers. This study recruited 195 participants initiating methadone maintenance and followed up for 12 months. Longitudinal data from this trial was used to acquire a greater understanding of HCV risk practices and their pattern of correlates in this population. We selected 176 patients who had data on HCV risk practices at M0 and M12, accounting for 312 visits. HCV risk practices were defined as follows: sharing needles or syringes, sharing drug paraphernalia, getting a tattoo or having a piercing in a non-professional context, sharing toiletry items. To identify factors associated with HCV risk practices, we performed a mixed logistic regression analysis. Results HCV risk practices were reported by 19% and 15% of participants at baseline and M12, respectively. After adjustment for age, cocaine use and alcohol dependence as well as suicidal risk, living in a couple with a non-drug user and in a couple with a drug user were both independent predictors of HCV risk practices (OR[CI95%] = 4.16 [1.42-12.12]; OR[CI95%] = 9.85 [3.13-31.06], respectively). Conclusions Identifying individuals at risk of HCV transmission during methadone treatment such as stimulant users, alcohol dependent individuals, and those at suicidal risk is necessary to optimize response to treatment. Innovative prevention

  1. The importance of growth factors for the treatment of chronic wounds in the case of diabetic foot ulcers

    PubMed Central

    Buchberger, Barbara; Follmann, Markus; Freyer, Daniela; Huppertz, Hendrik; Ehm, Alexandra; Wasem, Jürgen

    2010-01-01

    studies was affected by significant deficiencies. The results showed becaplermin being cost-effective whereas no obvious statement can be made regarding Dermagraft and Apligraf because of diverging cost bases and incremental cost-effectiveness ratios. Discussion Differences in standard wound care are complicating the comparison of study results. Taking into consideration the small to very small sample sizes and other methodological flaws with high potential of bias, the validity of the results with regard to effectiveness and cost-effectiveness has to be considered limited. The duration of treatment and follow-up examinations is not long enough to assess the sustainability of the intervention and the surveillance of ulcer recurrences or treatment related adverse events like the development of malignancy. Conclusions There are indications of an advantage for the add-on therapy with growth factors in diabetic foot ulcers concerning complete wound closure and the time to complete wound healing. Further more studies of high methodological quality with adequate sample sizes and sufficient follow-up periods are necessary also investigating patient-relevant parameters like the health-related quality of life, the acceptance and tolerance of the intervention in addition to clinical outcomes. PMID:21289885

  2. Microinjection of Francisella tularensis and Listeria monocytogenes reveals the importance of bacterial and host factors for successful replication.

    PubMed

    Meyer, Lena; Bröms, Jeanette E; Liu, Xijia; Rottenberg, Martin E; Sjöstedt, Anders

    2015-08-01

    Certain intracellular bacteria use the host cell cytosol as the replicative niche. Although it has been hypothesized that the successful exploitation of this compartment requires a unique metabolic adaptation, supportive evidence is lacking. For Francisella tularensis, many genes of the Francisella pathogenicity island (FPI) are essential for intracellular growth, and therefore, FPI mutants are useful tools for understanding the prerequisites of intracytosolic replication. We compared the growth of bacteria taken up by phagocytic or nonphagocytic cells with that of bacteria microinjected directly into the host cytosol, using the live vaccine strain (LVS) of F. tularensis; five selected FPI mutants thereof, i.e., ΔiglA, ΔiglÇ ΔiglG, ΔiglI, and ΔpdpE strains; and Listeria monocytogenes. After uptake in bone marrow-derived macrophages (BMDM), ASC(-/-) BMDM, MyD88(-/-) BMDM, J774 cells, or HeLa cells, LVS, ΔpdpE and ΔiglG mutants, and L. monocytogenes replicated efficiently in all five cell types, whereas the ΔiglA and ΔiglC mutants showed no replication. After microinjection, all 7 strains showed effective replication in J774 macrophages, ASC(-/-) BMDM, and HeLa cells. In contrast to the rapid replication in other cell types, L. monocytogenes showed no replication in MyD88(-/-) BMDM and LVS showed no replication in either BMDM or MyD88(-/-) BMDM after microinjection. Our data suggest that the mechanisms of bacterial uptake as well as the permissiveness of the cytosolic compartment per se are important factors for the intracytosolic replication. Notably, none of the investigated FPI proteins was found to be essential for intracytosolic replication after microinjection. PMID:26034213

  3. Microinjection of Francisella tularensis and Listeria monocytogenes Reveals the Importance of Bacterial and Host Factors for Successful Replication

    PubMed Central

    Meyer, Lena; Bröms, Jeanette E.; Liu, Xijia; Rottenberg, Martin E.

    2015-01-01

    Certain intracellular bacteria use the host cell cytosol as the replicative niche. Although it has been hypothesized that the successful exploitation of this compartment requires a unique metabolic adaptation, supportive evidence is lacking. For Francisella tularensis, many genes of the Francisella pathogenicity island (FPI) are essential for intracellular growth, and therefore, FPI mutants are useful tools for understanding the prerequisites of intracytosolic replication. We compared the growth of bacteria taken up by phagocytic or nonphagocytic cells with that of bacteria microinjected directly into the host cytosol, using the live vaccine strain (LVS) of F. tularensis; five selected FPI mutants thereof, i.e., ΔiglA, ΔiglÇ ΔiglG, ΔiglI, and ΔpdpE strains; and Listeria monocytogenes. After uptake in bone marrow-derived macrophages (BMDM), ASC−/− BMDM, MyD88−/− BMDM, J774 cells, or HeLa cells, LVS, ΔpdpE and ΔiglG mutants, and L. monocytogenes replicated efficiently in all five cell types, whereas the ΔiglA and ΔiglC mutants showed no replication. After microinjection, all 7 strains showed effective replication in J774 macrophages, ASC−/− BMDM, and HeLa cells. In contrast to the rapid replication in other cell types, L. monocytogenes showed no replication in MyD88−/− BMDM and LVS showed no replication in either BMDM or MyD88−/− BMDM after microinjection. Our data suggest that the mechanisms of bacterial uptake as well as the permissiveness of the cytosolic compartment per se are important factors for the intracytosolic replication. Notably, none of the investigated FPI proteins was found to be essential for intracytosolic replication after microinjection. PMID:26034213

  4. Improvement of low bioavailability of a novel factor Xa inhibitor through formulation of cationic additives in its oral dosage form.

    PubMed

    Fujii, Yoshimine; Kanamaru, Taro; Kikuchi, Hiroshi; Nakagami, Hiroaki; Yamashita, Shinji; Akashi, Mitsuru; Sakuma, Shinji

    2011-12-15

    A clinical trial of (2S)-2-[4-[[(3S)-1-acetimidoyl-3-pyrrolidinyl]oxy]phenyl]-3-(7-amidino-2-naphtyl) propanoic acid (DX-9065) revealed that its oral bioavailability was only 3% when it was administered as a conventional capsule formulation. The low bioavailability of DX-9065 was likely caused by both its poor membrane permeability and its electrostatic interaction with anionic bile acids. We hypothesized that DX-9065 absorption would be enhanced when the cationic drug was free from the complex through its replacement with other cationic substances. Polystyrene nanospheres coated with cationic poly(vinylamine) and cholestyramine, which is clinically used as a cholesterol-lowering agent, dramatically prevented DX-9065 from interacting with chenodeoxycholic acid in vitro. Successive animal experiments showed that bioavailability of DX-9065 administered with these cationic substances was 2-3 times that of DX-9065 administered solely. A dry syrup formulation with one-half of a minimal cholesterol-lowering equivalent dose of cholestyramine was designed, and the clinical trial was resumed. A 1.3-fold increase in bioavailability of DX-9065 was observed when the dry syrup was administered. We successfully demonstrated that DX-9065 absorption was enhanced when the drug was administered with cationic additives; however, it appeared that the absorption-enhancing function of cholestyramine largely depended on its dose. The dose escalation is probably prerequisite for the significant improvement of DX-9065 absorption in humans. PMID:22001539

  5. In vitro regeneration and optimization of factors affecting Agrobacterium mediated transformation in Artemisia Pallens, an important medicinal plant.

    PubMed

    Alok, Anshu; Shukla, Vishnu; Pala, Zarna; Kumar, Jitesh; Kudale, Subhash; Desai, Neetin

    2016-04-01

    Artemisia pallens is an important medicinal plant. In-vitro regeneration and multiplication of A. pallens have been established using attached cotyledons. Different growth regulators were considered for regeneration of multiple shoots. An average of 36 shoots per explants were obtained by culturing attached cotyledons on Murashige and Skoog's medium containing 2 mg/L BAP and 0.1 mg/L NAA, after 45 days. The shoots were rooted best on half Murashige and Skoog's medium with respect to media containing 1 mg/L IBA or 1 mg/L NAA. Different parameters such as type of bacterial strains, OD600 of bacterial culture, co-cultivation duration, concentration of acetosyringone and explants type were optimized for transient expression of the reporter gene. Agrobacterium tumefaciens harbouring pCambia1301 plasmid carrying β-glucuronidase as a reporter gene and hygromycin phosphotransferase as plant selectable marker genes were used for genetic transformation of A. pallens. Hygromycin lethality test showed concentration of 15 mg/L were sufficient to inhibit the growth of attached cotyledons and multiple shoot buds of nontransgenics in selection media. Up to 83 % transient transformation was found when attached cotyledons were co-cultivated with Agrobacterium strain AGL1 for 2 days at 22 °C on shoot induction medium. The bacterial growth was eliminated by addition of cefotaxime (200 mg/L) in selection media. T0 transgenic plants were confirmed by GUS histochemical assay and further by polymerase chain reaction (PCR) using uidA and hpt gene specific primers. The study is useful in establishing technological improvement in A. pallens by genetic engineering. PMID:27436917

  6. Corticotropin-releasing factor receptors CRF1 and CRF2 exert both additive and opposing influences on defensive startle behavior.

    PubMed

    Risbrough, Victoria B; Hauger, Richard L; Roberts, Amanda L; Vale, Wylie W; Geyer, Mark A

    2004-07-21

    The corticotropin-releasing factor (CRF) receptors (CRF1 and CRF2) are crucial mediators of physiological and behavioral responses to stress. In animals, CRF1 appears to primarily mediate CRF-induced anxiety-like responses, but the role of CRF2 during stress is still unclear. Here we report the effects of CRF1 and CRF2 on the magnitude and plasticity of defensive startle responses in mice. Startle plasticity is measured by inhibition of startle by sensory stimuli, i.e., prepulse inhibition (PPI), and is disrupted in patients with panic or posttraumatic stress disorders in which CRF neurotransmission may be overactive. Pharmacological blockade of CRF1 reversed both CRF-induced increases in startle and CRF-induced deficits in PPI. CRF2 blockade attenuated high-dose but not low-dose CRF-induced increases in startle and reduced PPI. Conversely, activation of CRF2 enhanced PPI. CRF had no effect on startle and increased PPI in CRF1 knock-out mice. These data indicate that CRF receptors act in concert to increase the magnitude of defensive startle yet in opposition to regulate the flexibility of startle. These data support a new model of respective CRF receptor roles in stress-related behavior such that, although both receptors enhance the magnitude of defensive responses, CRF1 receptors contravene, whereas CRF2 receptors enhance, the impact of sensory information on defensive behavior. We hypothesize that excessive CRF1 activation combined with reduced CRF2 signaling may contribute to information processing deficits seen in panic and posttraumatic stress disorder patients and support CRF1-specific pharmacotherapy. PMID:15269266

  7. The severity of retinal pathology in homozygous Crb1rd8/rd8 mice is dependent on additional genetic factors

    PubMed Central

    Luhmann, Ulrich F.O.; Carvalho, Livia S.; Holthaus, Sophia-Martha kleine; Cowing, Jill A.; Greenaway, Simon; Chu, Colin J.; Herrmann, Philipp; Smith, Alexander J.; Munro, Peter M.G.; Potter, Paul; Bainbridge, James W.B.; Ali, Robin R.

    2015-01-01

    Understanding phenotype–genotype correlations in retinal degeneration is a major challenge. Mutations in CRB1 lead to a spectrum of autosomal recessive retinal dystrophies with variable phenotypes suggesting the influence of modifying factors. To establish the contribution of the genetic background to phenotypic variability associated with the Crb1rd8/rd8 mutation, we compared the retinal pathology of Crb1rd8/rd8/J inbred mice with that of two Crb1rd8/rd8 lines backcrossed with C57BL/6JOlaHsd mice. Topical endoscopic fundal imaging and scanning laser ophthalmoscopy fundus images of all three Crb1rd8/rd8 lines showed a significant increase in the number of inferior retinal lesions that was strikingly variable between the lines. Optical coherence tomography, semithin, ultrastructural morphology and assessment of inflammatory and vascular marker by immunohistochemistry and quantitative reverse transcriptase-polymerase chain reaction revealed that the lesions were associated with photoreceptor death, Müller and microglia activation and telangiectasia-like vascular remodelling—features that were stable in the inbred, variable in the second, but virtually absent in the third Crb1rd8/rd8 line, even at 12 months of age. This suggests that the Crb1rd8/rd8 mutation is necessary, but not sufficient for the development of these degenerative features. By whole-genome SNP analysis of the genotype–phenotype correlation, a candidate region on chromosome 15 was identified. This may carry one or more genetic modifiers for the manifestation of the retinal pathology associated with mutations in Crb1. This study also provides insight into the nature of the retinal vascular lesions that likely represent a clinical correlate for the formation of retinal telangiectasia or Coats-like vasculopathy in patients with CRB1 mutations that are thought to depend on such genetic modifiers. PMID:25147295

  8. The severity of retinal pathology in homozygous Crb1rd8/rd8 mice is dependent on additional genetic factors.

    PubMed

    Luhmann, Ulrich F O; Carvalho, Livia S; Holthaus, Sophia-Martha Kleine; Cowing, Jill A; Greenaway, Simon; Chu, Colin J; Herrmann, Philipp; Smith, Alexander J; Munro, Peter M G; Potter, Paul; Bainbridge, James W B; Ali, Robin R

    2015-01-01

    Understanding phenotype-genotype correlations in retinal degeneration is a major challenge. Mutations in CRB1 lead to a spectrum of autosomal recessive retinal dystrophies with variable phenotypes suggesting the influence of modifying factors. To establish the contribution of the genetic background to phenotypic variability associated with the Crb1(rd8/rd8) mutation, we compared the retinal pathology of Crb1(rd8/rd8)/J inbred mice with that of two Crb1(rd8/rd8) lines backcrossed with C57BL/6JOlaHsd mice. Topical endoscopic fundal imaging and scanning laser ophthalmoscopy fundus images of all three Crb1(rd8/rd8) lines showed a significant increase in the number of inferior retinal lesions that was strikingly variable between the lines. Optical coherence tomography, semithin, ultrastructural morphology and assessment of inflammatory and vascular marker by immunohistochemistry and quantitative reverse transcriptase-polymerase chain reaction revealed that the lesions were associated with photoreceptor death, Müller and microglia activation and telangiectasia-like vascular remodelling-features that were stable in the inbred, variable in the second, but virtually absent in the third Crb1(rd8/rd8) line, even at 12 months of age. This suggests that the Crb1(rd8/rd8) mutation is necessary, but not sufficient for the development of these degenerative features. By whole-genome SNP analysis of the genotype-phenotype correlation, a candidate region on chromosome 15 was identified. This may carry one or more genetic modifiers for the manifestation of the retinal pathology associated with mutations in Crb1. This study also provides insight into the nature of the retinal vascular lesions that likely represent a clinical correlate for the formation of retinal telangiectasia or Coats-like vasculopathy in patients with CRB1 mutations that are thought to depend on such genetic modifiers. PMID:25147295

  9. Physiological basis of tolerance to complete submergence in rice involves genetic factors in addition to the SUB1 gene.

    PubMed

    Singh, Sudhanshu; Mackill, David J; Ismail, Abdelbagi M

    2014-01-01

    1 lines. This suggests the possibility of further improvements in submergence tolerance by incorporating additional traits present in FR13A or other similar landraces. PMID:25281725

  10. Physiological basis of tolerance to complete submergence in rice involves genetic factors in addition to the SUB1 gene

    PubMed Central

    Singh, Sudhanshu; Mackill, David J.; Ismail, Abdelbagi M.

    2014-01-01

    1 lines. This suggests the possibility of further improvements in submergence tolerance by incorporating additional traits present in FR13A or other similar landraces. PMID:25281725

  11. DNA-binding site for two skeletal actin promoter factors is important for expression in muscle cells

    SciTech Connect

    Walsh, K.; Schimmel, P.

    1988-04-01

    Two nuclear factors bind to the same site in the chicken skeletal actin promoter. Mutations in the footprint sequence which eliminate detectable binding decrease expression in transfected skeletal muscle cells by a factor of 25 to 50 and do not elevate the flow expression in nonmuscle cells. These results show that the factor-binding site contributes to the activation of expression in muscle cells and that it alone does not contribute significantly to repress expression in nonmuscle cells.

  12. Impact Factors for the "Journal of Teaching in Physical Education"--What Are They and Are They Important?

    ERIC Educational Resources Information Center

    McBride, Ron

    2006-01-01

    The notion of an impact factor was first posited by Eugene Garfield (1972) to study the use, prestige, and status of scientific journals. The Institute for Scientific Information created the impact factor as a means to measure the number of times an "average article" published in a journal was cited over a particular time period ("The impact…

  13. A Multidimensional Approach to Understanding Under-Eating in Homebound Older Adults: The Importance of Social Factors

    ERIC Educational Resources Information Center

    Locher, Julie L.; Ritchie, Christine S.; Robinson, Caroline O.; Roth, David L.; West, Delia Smith; Burgio, Kathryn L.

    2008-01-01

    Purpose: The purpose of this study was to identify relationships between medical, functional, economic, oral health, social, religious, and psychological factors and under-eating in homebound older adults. The focus of the study was on identifying potentially modifiable factors amenable to social and behavioral interventions. Design and Methods: A…

  14. Assessment of the Electronic Factors Determining the Thermodynamics of "Oxidative Addition" of C-H and N-H Bonds to Ir(I) Complexes.

    PubMed

    Wang, David Y; Choliy, Yuriy; Haibach, Michael C; Hartwig, John F; Krogh-Jespersen, Karsten; Goldman, Alan S

    2016-01-13

    A study of electronic factors governing the thermodynamics of C-H and N-H bond addition to Ir(I) complexes was conducted. DFT calculations were performed on an extensive series of trans-(PH3)2IrXL complexes (L = NH3 and CO; X = various monodentate ligands) to parametrize the relative σ- and π-donating/withdrawing properties of the various ligands, X. Computed energies of oxidative addition of methane to a series of three- and four-coordinate Ir(I) complexes bearing an ancillary ligand, X, were correlated with the resulting (σ(X), π(X)) parameter set. Regression analysis indicates that the thermodynamics of addition of methane to trans-(PH3)2IrX are generally strongly disfavored by increased σ-donation from the ligand X, in contradiction to widely held views on oxidative addition. The trend for oxidative addition of methane to four-coordinate Ir(I) was closely related to that observed for the three-coordinate complexes, albeit slightly more complicated. The computational analysis was found to be consistent with the rates of reductive elimination of benzene from a series of isoelectronic Ir(III) phenyl hydride complexes, measured experimentally in this work and previously reported. Extending the analysis of ancillary ligand energetic effects to the oxidative addition of ammonia to three-coordinate Ir(I) complexes leads to the conclusion that increasing σ-donation by X also disfavors oxidative addition of N-H bonds to trans-(PH3)2IrX. However, coordination of NH3 to the Ir(I) center is disfavored even more strongly by increasing σ-donation by X, which explains why the few documented examples of H-NH2 oxidative addition to transition metals involve complexes with strongly σ-donating ligands situated trans to the site of addition. An orbital-based rationale for the observed results is presented. PMID:26652221

  15. Mercury contamination in fish in midcontinent great rivers of the United States: Importance of species traits and environmental factors

    EPA Science Inventory

    We measured mercury (Hg) concentrations in whole fish from the Upper Mississippi, Missouri and Ohio Rivers to characterize the extent and magnitude of Hg contamination and to identify environmental factors influencing Hg concentrations. Concentrations were generally lower than th...

  16. S. 1082: This Act may be cited as the Hazardous and Additional Waste Export and Import Act of 1991, introduced in the US Senate, One Hundred Second Congress, First Session, May 15, 1991

    SciTech Connect

    Not Available

    1991-01-01

    This bill was introduced into the US Senate on May 15, 1991 to amend the Solid Waste Disposal Act. This legislation prohibits the export from and import into the United States of Hazardous and additional waste except in compliance with the requirements of this bill. The purpose of this act is to implement the Basel Convention on the Control of Transboundary Movements of Hazardous Wastes and Their Disposal, done at Basel, Switzerland, March 22, 1989. Key sections of this bill address the following: international shipments of hazardous and additional waste; objectives and national policy; retention of existing authority; and conforming amendments.

  17. Gladiolus hybridus ABSCISIC ACID INSENSITIVE 5 (GhABI5) is an important transcription factor in ABA signaling that can enhance Gladiolus corm dormancy and Arabidopsis seed dormancy

    PubMed Central

    Wu, Jian; Seng, Shanshan; Sui, Juanjuan; Vonapartis, Eliana; Luo, Xian; Gong, Benhe; Liu, Chen; Wu, Chenyu; Liu, Chao; Zhang, Fengqin; He, Junna; Yi, Mingfang

    2015-01-01

    The phytohormone abscisic acid (ABA) regulates plant development and is crucial for abiotic stress response. In this study, cold storage contributes to reducing endogenous ABA content, resulting in dormancy breaking of Gladiolus. The ABA inhibitor fluridone also promotes germination, suggesting that ABA is an important hormone that regulates corm dormancy. Here, we report the identification and functional characterization of the Gladiolus ABI5 homolog (GhABI5), which is a basic leucine zipper motif transcriptional factor (TF). GhABI5 is expressed in dormant vegetative organs (corm, cormel, and stolon) as well as in reproductive organs (stamen), and it is up-regulated by ABA or drought. Complementation analysis reveals that GhABI5 rescues the ABA insensitivity of abi5-3 during seed germination and induces the expression of downstream ABA response genes in Arabidopsis thaliana (EM1, EM6, and RD29B). Down-regulation of GhABI5 in dormant cormels via virus induced gene silence promotes sprouting and reduces the expression of downstream genes (GhLEA and GhRD29B). The results of this study reveal that GhABI5 regulates bud dormancy (vegetative organ) in Gladiolus in addition to its well-studied function in Arabidopsis seeds (reproductive organ). PMID:26579187

  18. TreeTFDB: An Integrative Database of the Transcription Factors from Six Economically Important Tree Crops for Functional Predictions and Comparative and Functional Genomics

    PubMed Central

    Mochida, Keiichi; Yoshida, Takuhiro; Sakurai, Tetsuya; Yamaguchi-Shinozaki, Kazuko; Shinozaki, Kazuo; Tran, Lam-Son Phan

    2013-01-01

    Crop plants, whose productivity is affected by a wide range of growing and environmental conditions, are grown for economic purposes. Transcription factors (TFs) play central role in regulation of many biological processes, including plant development and responses to environmental stimuli, by activating or repressing spatiotemporal gene expression. Here, we describe the TreeTFDB (http://treetfdb.bmep.riken.jp/index.pl) that houses the TF repertoires of six economically important tree crop species: Jatropha curcas, papaya, cassava, poplar, castor bean and grapevine. Among these, the TF repertoire of J. curcas has not been reported by any other TF databases. In addition to their basic information, such as sequence and domain features, domain alignments, gene ontology assignment and sequence comparison, information on available full-length cDNAs, identity and positions of all types of known cis-motifs found in the promoter regions, gene expression data are provided. With its newly designed and friendly interface and its unique features, TreeTFDB will enable research community to predict the functions and provide access to available genetic resources for performing comparative and functional genomics of the crop TFs, either individually or at whole family level, in a comprehensive and convenient manner. PMID:23284086

  19. Slow rise of Ca2+ and slow release of reactive oxygen species are two cross-talked events important in tumour necrosis factor-alpha-mediated apoptosis.

    PubMed

    Ko, S; Kwok, T T; Fung, K P; Choy, Y M; Lee, C Y; Kong, S K

    2000-09-01

    Tumour necrosis factor-alpha (TNF-alpha) was found to be a cell cycle-independent apoptogenic cytokine in cultured fibroblast L929 cells. This assertion is based on the observations (1) TNF-alpha increased the number of cells with hypo-diploid DNA in a time dependent manner as revealed by flow cytometry, and (2) TNF-alpha induced DNA fragmentation as resolved by agarose gel electrophoresis. When cells were exposed to TNF-alpha (50 ng/ml), a slow rise in intracellular free Ca2+ level and a delayed increase in the production of reactive oxygen species (ROS) (both observed 3 h after the addition of TNF-alpha) were observed in fluo-3 and fura-red or dichlorofluorescein loaded cells, respectively. Interestingly, challenge of cells with TNF-alpha in the presence of BAPTA/AM, an intracellular Ca2+ chelator, decreased the release of ROS. Removal of ROS by 4-hydroxy 2,2,6,6-tetra-methyl-piperidinooxy (4OH-TEMPO) blocked the TNF-alpha-mediated Ca2+ rise. Moreover, when cells were exposed to TNF-alpha with both 4OH-TEMPO and BAPTA/AM, more viable cells were found than from treatment with either BAPTA/AM or 4OH-TEMPO. These results suggest that ROS and cellular Ca2+ are two cross-talk messengers important in TNF-alpha-mediated apoptosis. PMID:10993483

  20. The Importance of Physical Fitness versus Physical Activity for Coronary Artery Disease Risk Factors: A Cross-Sectional Analysis.

    ERIC Educational Resources Information Center

    Young, Deborah Rohm; Steinhardt, Mary A.

    1993-01-01

    This cross-sectional study examined relationships among physical fitness, physical activity, and risk factors for coronary artery disease (CAD) in male police officers. Data from screenings and physical fitness assessments indicated physical activity must be sufficient to influence fitness before obtaining statistically significant risk-reducing…

  1. Differences between Juvenile Offenders with and without Intellectual Disabilities in the Importance of Static and Dynamic Risk Factors for Recidivism

    ERIC Educational Resources Information Center

    van der Put, C. E.; Asscher, J. J.; Stams, G. J. J. M.; Moonen, X. M. H.

    2014-01-01

    Background: Juvenile offenders with intellectual disability (ID) have been largely ignored in the literature of risk assessment, while they are overrepresented in the criminal justice system, and ID is a risk factor for juvenile delinquency and recidivism. The aim of this study was to examine whether there are differences between juvenile…

  2. Diagnostics and Psychotherapy with Minority Groups: The Importance of Sociocultural Factors in the Training of Clinical Psychologists.

    ERIC Educational Resources Information Center

    Sanua, Victor D.

    There are problems in using the traditional approaches of psychotherapy with various ethnic minority and national groups in the United States. Mental health practitioners, besides making errors in diagnosis, may also be handicapped in developing a therapeutic relationship with the patient. Numerous studies indicate that sociocultural factors tend…

  3. Identification of factors most important for ammonia emission from fertilized soils for potato production using principle component analysis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The goal of this study was to identify the primary factors affecting ammonia (NH3) emission from fertilized soils in potato production fields using principal component analysis (PCA). A dataset consisting of 14 different variables and 1800 NH3 emission rates was geometrically classified for analysi...

  4. Mental Health Problems in Norwegian School Children Placed Out-of-Home: The Importance of Family Risk Factors

    ERIC Educational Resources Information Center

    Havnen, Karen Skaale; Jakobsen, Reidar; Stormark, Kjell Morten

    2009-01-01

    The main aim of this article is to explore the association between mental health problems in children placed out-of-home and family risk factors reported as reasons for placement. The sample consisted of 109 Norwegian children aged 6-12 years. Mental health problems were assessed by the Revised Rutter scales reported by the parents and the…

  5. Occupational Injuries in Germany: Population-Wide National Survey Data Emphasize the Importance of Work-Related Factors.

    PubMed

    Rommel, Alexander; Varnaccia, Gianni; Lahmann, Nils; Kottner, Jan; Kroll, Lars Eric

    2016-01-01

    Unintentional injuries cause much of the global mortality burden, with the workplace being a common accident setting. Even in high-income economies, occupational injury figures remain remarkably high. Because risk factors for occupational injuries are prone to confounding, the present research takes a comprehensive approach. To better understand the occurrence of occupational injuries, sociodemographic factors and work- and health-related factors are tested simultaneously. Thus, the present analysis aims to develop a comprehensive epidemiological model that facilitates the explanation of varying injury rates in the workplace. The representative phone survey German Health Update 2010 provides information on medically treated occupational injuries sustained in the year prior to the interview. Data were collected on sociodemographics, occupation, working conditions, health-related behaviors, and chronic diseases. For the economically active population (18-70 years, n = 14,041), the 12-month prevalence of occupational injuries was calculated with a 95% confidence interval (CI). Blockwise multiple logistic regression was applied to successively include different groups of variables. Overall, 2.8% (95% CI 2.4-3.2) of the gainfully employed population report at least one occupational injury (women: 0.9%; 95% CI 0.7-1.2; men: 4.3%; 95% CI 3.7-5.0). In the fully adjusted model, male gender (OR 3.16) and age 18-29 (OR 1.54), as well as agricultural (OR 5.40), technical (OR 3.41), skilled service (OR 4.24) or manual (OR 5.12), and unskilled service (OR 3.13) or manual (OR 4.97) occupations are associated with higher chances of occupational injuries. The same holds for frequent stressors such as heavy carrying (OR 1.78), working in awkward postures (OR 1.46), environmental stress (OR 1.48), and working under pressure (OR 1.41). Among health-related variables, physical inactivity (OR 1.47) and obesity (OR 1.73) present a significantly higher chance of occupational injuries

  6. Occupational Injuries in Germany: Population-Wide National Survey Data Emphasize the Importance of Work-Related Factors

    PubMed Central

    Rommel, Alexander; Varnaccia, Gianni; Lahmann, Nils; Kottner, Jan; Kroll, Lars Eric

    2016-01-01

    Unintentional injuries cause much of the global mortality burden, with the workplace being a common accident setting. Even in high-income economies, occupational injury figures remain remarkably high. Because risk factors for occupational injuries are prone to confounding, the present research takes a comprehensive approach. To better understand the occurrence of occupational injuries, sociodemographic factors and work- and health-related factors are tested simultaneously. Thus, the present analysis aims to develop a comprehensive epidemiological model that facilitates the explanation of varying injury rates in the workplace. The representative phone survey German Health Update 2010 provides information on medically treated occupational injuries sustained in the year prior to the interview. Data were collected on sociodemographics, occupation, working conditions, health-related behaviors, and chronic diseases. For the economically active population (18–70 years, n = 14,041), the 12-month prevalence of occupational injuries was calculated with a 95% confidence interval (CI). Blockwise multiple logistic regression was applied to successively include different groups of variables. Overall, 2.8% (95% CI 2.4–3.2) of the gainfully employed population report at least one occupational injury (women: 0.9%; 95% CI 0.7–1.2; men: 4.3%; 95% CI 3.7–5.0). In the fully adjusted model, male gender (OR 3.16) and age 18–29 (OR 1.54), as well as agricultural (OR 5.40), technical (OR 3.41), skilled service (OR 4.24) or manual (OR 5.12), and unskilled service (OR 3.13) or manual (OR 4.97) occupations are associated with higher chances of occupational injuries. The same holds for frequent stressors such as heavy carrying (OR 1.78), working in awkward postures (OR 1.46), environmental stress (OR 1.48), and working under pressure (OR 1.41). Among health-related variables, physical inactivity (OR 1.47) and obesity (OR 1.73) present a significantly higher chance of occupational

  7. INFORMING INTERVENTIONS: THE IMPORTANCE OF CONTEXTUAL FACTORS IN THE PREDICTION OF SEXUAL RISK BEHAVIORS AMONG TRANSGENDER WOMEN

    PubMed Central

    Sevelius, Jae M.; Reznick, Olga Grinstead; Hart, Stacey L.; Schwarcz, Sandy

    2015-01-01

    This study identifies contextual factors that predict risky sexual behavior among 153 transgender women who participated in a structured survey soliciting information on demographics, substance use, HIV status, risk behaviors, and other health and psychosocial factors. Multivariate logistic regression models were used to determine predictors. Inconsistent condom use was associated with stimulant use, unstable housing, and recruitment site. Substance use during sex was associated with unstable housing and stimulant use. Sex work was associated with hormone use, gender confirming surgeries, and younger age. When developing interventions for transgender women, it may be useful to focus on predictors of risk behavior rather than predictors of current HIV status (i.e., race/ethnicity as “risk factor”), because these behaviors are the target of interventions aimed at sexual risk reduction. Implications include potential benefits of context-specific interventions, structural interventions addressing barriers to housing and health care, and culturally specific substance abuse treatment programs for transgender women. PMID:19397434

  8. Longitudinal changes in functioning and disability in patients with disorders of consciousness: the importance of environmental factors.

    PubMed

    Willems, Michelle; Sattin, Davide; Vingerhoets, Ad J J M; Leonardi, Matilde

    2015-04-01

    Disorders of consciousness are neurological conditions associated with low levels of functioning which pose a serious challenge to public health systems. The current study aimed to examine longitudinal changes in functioning in patients with disorders of consciousness and to identify associated biopsychosocial factors using the International Classification of Functioning, Disability, and Health. An Italian sample of 248 patients was assessed longitudinally. Differences in relative variability (an index of change that controls for baseline levels) between acute and chronic patients and predictors of relative variability in "Activities & Participation" were examined. Results showed that there were subgroups of patients whose functioning improved over time. The number of problems in "Activities & Participation" decreased in acute patients over time, whereas in chronic patients, an increase was found. The significant difference in relative variability for the environmental factor "support and relationships" reflects the increase in facilitators in acute patients, whereas the number of facilitators in chronic patients remained unchanged over time. Age at event, time from event, and relative variability in "Environmental Factors" were significant predictors of relative variability in "Activities & Participation". It is of clinical relevance that patients with disorders of consciousness are kept in a supportive and facilitative environment, in order to prevent a decline in their functioning. Moreover, caregivers should receive tailored support in order to enhance and facilitate appropriate care of patients with disorders of consciousness. PMID:25837348

  9. A Meta-analysis of Factors Impacting Detection of Antidepressant Efficacy in Clinical Trials: The Importance of Academic Sites

    PubMed Central

    Dunlop, Boadie W; Thase, Michael E; Wun, Chuan-Chuan; Fayyad, Rana; Guico-Pabia, Christine J; Musgnung, Jeff; Ninan, Philip T

    2012-01-01

    Variability in placebo response greatly complicates the design, conduct, and interpretation of clinical trials of antidepressant medications. To identify factors that impact detection of antidepressant–placebo differences, we conducted a meta-analysis of all relevant phase II–IV clinical trials for major depressive disorder conducted by the manufacturer of venlafaxine and desvenlafaxine completed by March 2011. We examined 15 factors potentially relevant to trial outcomes, using the standardized mean difference on the Hamilton Rating Scale for Depression (HAM-D17) score as the primary outcome. Thirty trials comprising 8933 patients were included. In univariate analyses, antidepressant efficacy (ie, drug vs placebo difference) was predicted most strongly (β=3.74, p=0.0002) by the proportion of patients in the trial enrolled from academic sites. Other factors predicting larger drug–placebo differences included lower participant completion rate, fewer post-baseline study visits, earlier year of study, and study drug (venlafaxine>desvenlafaxine). In multivariate meta-regression modeling, only the proportion of patients from academic sites maintained statistical significance as a predictor of drug–placebo separation for both HAM-D17 continuous score change (β=2.24, p=0.034) and response rate (β=2.26, p=0.035). Including a higher proportion of academic sites may increase the ability to detect differences between active drug and placebo in clinical trials of major depressive disorder. PMID:22910458

  10. A Multidimensional Approach to Understanding Under-Eating in Homebound Older Adults: The Importance of Social Factors

    PubMed Central

    Locher, Julie L.; Ritchie, Christine S.; Robinson, Caroline O.; Roth, David L.; West, Delia Smith; Burgio, Kathryn L.

    2009-01-01

    Purpose The purpose of this study was to identify relationships between medical, functional, economic, oral health, social, religious, and psychological factors and under-eating in homebound older adults. The focus of the study was on identifying potentially modifiable factors amenable to social and behavioral interventions. Design and Methods A total of 230 homebound older adults who were currently receiving home health services participated in interviews in their homes using a questionnaire to assess eating behaviors and factors that could possibly affect those eating behaviors. Interviewers measured height and weight, and participants completed three 24-hr dietary recalls. Results The mean age of participants was 79.1 years. The sample comprised 78% women and 38% African Americans. We found that 70% of participants were under-eating, defined as not consuming enough calories to maintain their current body weight. Participants who were at higher risk of under-eating included men, those receiving either infrequent care or very frequent care by a caregiver, those who had been hospitalized prior to receipt of home health services, and those with a higher body mass index. Implications Findings from the study have implications for both practice and policy. Experts must develop evidence-based interventions targeted at under-eating in this particularly vulnerable and growing population of homebound older adults. This study provides an initial foundation for the development of targeted evidence-based behavioral nutritional interventions that are noninvasive and cost effective. PMID:18483434

  11. Three important components in the regeneration of the cavernous nerve: brain-derived neurotrophic factor, vascular endothelial growth factor and the JAK/STAT signaling pathway.

    PubMed

    Zhang, Hai-Yang; Jin, Xun-Bo; Lue, Tom F

    2011-03-01

    Retroperitoneal operations, such as radical prostatectomy, often damage the cavernous nerve, resulting in a high incidence of erectile dysfunction. Although improved nerve-sparing techniques have reduced the incidence of nerve injury, and the administration of phosphodiesterase type 5 inhibitors has revolutionized the treatment of erectile dysfunction, this problem remains a considerable challenge. In recent years, scientists have focused on brain-derived neurotrophic factor and vascular endothelial growth factor in the treatment of cavernous nerve injury in rat models. Results showed that both compounds were capable of enhancing the regeneration of the cavernous nerve and that activation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway played a major role in the process. PMID:21170078

  12. Role of Growth Differentiation Factor 9 and Bone Morphogenetic Protein 15 in Ovarian Function and Their Importance in Mammalian Female Fertility — A Review

    PubMed Central

    de Castro, Fernanda Cavallari; Cruz, Maria Helena Coelho; Leal, Claudia Lima Verde

    2016-01-01

    Growth factors play an important role during early ovarian development and folliculogenesis, since they regulate the migration of germ cells to the gonadal ridge. They also act on follicle recruitment, proliferation/atresia of granulosa cells and theca, steroidogenesis, oocyte maturation, ovulation and luteinization. Among the growth factors, the growth differentiation factor 9 (GDF9) and the bone morphogenetic protein 15 (BMP15), belong to the transforming growth factor beta (TGF-β) superfamily, have been implicated as essential for follicular development. The GDF9 and BMP15 participate in the evolution of the primordial follicle to primary follicle and play an important role in the later stages of follicular development and maturation, increasing the steroidogenic acute regulatory protein expression, plasminogen activator and luteinizing hormone receptor (LHR). These factors are also involved in the interconnections between the oocyte and surrounding cumulus cells, where they regulate absorption of amino acids, glycolysis and biosynthesis of cholesterol cumulus cells. Even though the mode of action has not been fully established, in vitro observations indicate that the factors GDF9 and BMP15 stimulate the growth of ovarian follicles and proliferation of cumulus cells through the induction of mitosis in cells and granulosa and theca expression of genes linked to follicular maturation. Thus, seeking greater understanding of the action of these growth factors on the development of oocytes, the role of GDF9 and BMP15 in ovarian function is summarized in this brief review. PMID:26954112

  13. Role of Growth Differentiation Factor 9 and Bone Morphogenetic Protein 15 in Ovarian Function and Their Importance in Mammalian Female Fertility - A Review.

    PubMed

    de Castro, Fernanda Cavallari; Cruz, Maria Helena Coelho; Leal, Claudia Lima Verde

    2016-08-01

    Growth factors play an important role during early ovarian development and folliculogenesis, since they regulate the migration of germ cells to the gonadal ridge. They also act on follicle recruitment, proliferation/atresia of granulosa cells and theca, steroidogenesis, oocyte maturation, ovulation and luteinization. Among the growth factors, the growth differentiation factor 9 (GDF9) and the bone morphogenetic protein 15 (BMP15), belong to the transforming growth factor beta (TGF-β) superfamily, have been implicated as essential for follicular development. The GDF9 and BMP15 participate in the evolution of the primordial follicle to primary follicle and play an important role in the later stages of follicular development and maturation, increasing the steroidogenic acute regulatory protein expression, plasminogen activator and luteinizing hormone receptor (LHR). These factors are also involved in the interconnections between the oocyte and surrounding cumulus cells, where they regulate absorption of amino acids, glycolysis and biosynthesis of cholesterol cumulus cells. Even though the mode of action has not been fully established, in vitro observations indicate that the factors GDF9 and BMP15 stimulate the growth of ovarian follicles and proliferation of cumulus cells through the induction of mitosis in cells and granulosa and theca expression of genes linked to follicular maturation. Thus, seeking greater understanding of the action of these growth factors on the development of oocytes, the role of GDF9 and BMP15 in ovarian function is summarized in this brief review. PMID:26954112

  14. Factors influencing the abundance of pests in production fields and rates of interception of Dracaena marginata imported from Costa Rica.

    PubMed

    Hidalgo, Eduardo; Benjamin, Tamara; Casanoves, Fernando; Sadof, Clifford

    2013-10-01

    Importation of live nursery plants, like Dracaena marginata Lamoureux (Ruscaceae), can provide a significant pathway for the entry of foliar pests from overseas into the United States. We studied the abundance of foliar pests of quarantine importance found on Costa Rican-grown D. marginata. These include five genera of leafhoppers (Heteroptera: Cicadellidae, Oncometopia, Caldweliola, Diestostema, Cypona, and Empoasca), Florida red scale (Heteroptera: Disapididae, Chrysomphalus aoinidum (L.)), katydids (Orthoptera: Tettigoniidae), and a snail (Succinea costarricana von Martens (Gastropoda, Stylommatophora, Succineidae)). In our first study, we examined the rationale behind size restrictions on Dracaena cuttings imported into the United States from Costa Rica. When comparing plant size, no differences were found in the abundance of quarantined pests on small (15-46 cm), medium (46-81 cm), and large (81-152 cm) propagules. In a second study, we estimated monthly abundances of pests in production plots for 1 yr to determine their relationship to rates of interception at U.S. ports. In any given month, < 6% of the marketable shoots standing in the field were infested with at least one quarantine pest. There was no relationship between the average monthly frequencies of pest detection in the field and in U.S. inspection ports. Pest detections increased during the 1 mo when average monthly shipments were abnormally high. Our data suggest that off-shore postprocessing efforts to remove pest-infested material from the market stream need to be adjusted to accommodate sharp increases in the volume of shipped plants. PMID:24224243

  15. Comparison of toxaphene congeners levels in five seal species from eastern Canada: what is the importance of biological factors?

    PubMed

    Gouteux, Bruno; Lebeuf, Michel; Hammill, Mike O; Muir, Derek C G; Gagné, Jean-Pierre

    2005-03-15

    Environmentally relevant chlorobornanes (CHBs) were measured in blubber samples of harbor (Phoca vitulina), gray (Halichoerus grypus), harp (Phoca groenlandica), and hooded seals (Cystophora cristata) sampled in different part of the St. Lawrence marine ecosystem (SLME) and ringed seals (Phoca hispida) sampled in the eastern Canadian Arctic waters. The purpose of this study was to compare the levels of six CHBs (Parlar-26, -40/-41, -44, -50, and -62) among the five seal species. Seal species could be separated into three groups based on their respective sigmaCHB mean concentrations (+/-standard error): gray (49+/-3.9 ng/g lipid weight) and harbor (80+/-20 ng/g lipid weight) seals were more contaminated than ringed seals (18+/-7.6 ng/g lipid weight) but less contaminated than harp (370+/-87 ng/g lipid weight) and hooded (680+/-310 ng/g lipid weight) seals. These differences are not expected to be related to different sources of toxaphene contamination, since both the SLME and the eastern Canadian Arctic environments are thought to be mainly contaminated via atmospheric transportfrom the southeastern part of the United States. Thus, biological factors such as sex, age, nutritive condition, metabolism capacity, and diet of the animals collected were considered. Results reported in this study indicated that the diet is likely the main factor accounting for interspecies variations in toxaphene contamination in seals from eastern Canada. PMID:15819196

  16. Longitudinal Changes in Functioning and Disability in Patients with Disorders of Consciousness: The Importance of Environmental Factors

    PubMed Central

    Willems, Michelle; Sattin, Davide; Vingerhoets, Ad J.J.M.; Leonardi, Matilde

    2015-01-01

    Disorders of consciousness are neurological conditions associated with low levels of functioning which pose a serious challenge to public health systems. The current study aimed to examine longitudinal changes in functioning in patients with disorders of consciousness and to identify associated biopsychosocial factors using the International Classification of Functioning, Disability, and Health. An Italian sample of 248 patients was assessed longitudinally. Differences in relative variability (an index of change that controls for baseline levels) between acute and chronic patients and predictors of relative variability in “Activities & Participation” were examined. Results showed that there were subgroups of patients whose functioning improved over time. The number of problems in “Activities & Participation” decreased in acute patients over time, whereas in chronic patients, an increase was found. The significant difference in relative variability for the environmental factor “support and relationships” reflects the increase in facilitators in acute patients, whereas the number of facilitators in chronic patients remained unchanged over time. Age at event, time from event, and relative variability in “Environmental Factors” were significant predictors of relative variability in “Activities & Participation”. It is of clinical relevance that patients with disorders of consciousness are kept in a supportive and facilitative environment, in order to prevent a decline in their functioning. Moreover, caregivers should receive tailored support in order to enhance and facilitate appropriate care of patients with disorders of consciousness. PMID:25837348

  17. Creating Cycling-Friendly Environments for Children: Which Micro-Scale Factors Are Most Important? An Experimental Study Using Manipulated Photographs

    PubMed Central

    Ghekiere, Ariane; Deforche, Benedicte; Mertens, Lieze; De Bourdeaudhuij, Ilse; Clarys, Peter; de Geus, Bas; Cardon, Greet; Nasar, Jack; Salmon, Jo; Van Cauwenberg, Jelle

    2015-01-01

    Background Increasing participation in transportation cycling represents a useful strategy for increasing children’s physical activity levels. Knowledge on how to design environments to encourage adoption and maintenance of transportation cycling is limited and relies mainly on observational studies. The current study experimentally investigates the relative importance of micro-scale environmental factors for children’s transportation cycling, as these micro-scale factors are easier to change within an existing neighborhood compared to macro-scale environmental factors (i.e. connectivity, land-use mix, …). Methods Researchers recruited children and their parents (n = 1232) via 45 randomly selected schools across Flanders and completed an online questionnaire which consisted of 1) demographic questions; and 2) a choice-based conjoint (CBC) task. During this task, participants chose between two photographs which we had experimentally manipulated in seven micro-scale environmental factors: type of cycle path; evenness of cycle path; traffic speed; traffic density; presence of speed bumps; environmental maintenance; and vegetation. Participants indicated which route they preferred to (let their child) cycle along. To find the relative importance of these micro-scale environmental factors, we conducted Hierarchical Bayes analyses. Results Type of cycle path emerged as the most important factor by far among both children and their parents, followed by traffic density and maintenance, and evenness of the cycle path among children. Among parents, speed limits and maintenance emerged as second most important, followed by evenness of the cycle path, and traffic density. Conclusion Findings indicate that improvements in micro-scale environmental factors might be effective for increasing children’s transportation cycling, since they increase the perceived supportiveness of the physical environment for transportation cycling. Investments in creating a clearly designated

  18. Genotype is an important determinant factor of host susceptibility to periodontitis in the Collaborative Cross and inbred mouse populations

    PubMed Central

    2013-01-01

    Background Periodontal infection (Periodontitis) is a chronic inflammatory disease, which results in the breakdown of the supporting tissues of the teeth. Previous epidemiological studies have suggested that resistance to chronic periodontitis is controlled to some extent by genetic factors of the host. The aim of this study was to determine the phenotypic response of inbred and Collaborative Cross (CC) mouse populations to periodontal bacterial challenge, using an experimental periodontitis model. In this model, mice are co-infected with Porphyromonas gingivalis and Fusobacterium nucleatum, bacterial strains associated with human periodontal disease. Six weeks following the infection, the maxillary jaws were harvested and analyzed for alveolar bone loss relative to uninfected controls, using computerized microtomography (microCT). Initially, four commercial inbred mouse strains were examined to calibrate the procedure and test for gender effects. Subsequently, we applied the same protocol to 23 lines (at inbreeding generations 10–18) from the newly developed mouse genetic reference population, the Collaborative Cross (CC) to determine heritability and genetic variation of control bone volume prior to infection (CBV, naïve bone volume around the teeth of uninfected mice), and residual bone volume (RBV, bone volume after infection) and loss of bone volume (LBV, the difference between CBV and RBV) following infection. Results BALB/CJ mice were highly susceptible (P<0.05) whereas DBA/2J, C57BL/6J and A/J mice were resistant. Six lines of the tested CC population were susceptible, whereas the remaining lines were resistant to alveolar bone loss. Gender effects on bone volume were tested across the four inbred and 23 CC lines, and found not to be significant. Based on ANOVA analyses, broad-sense heritabilities were statistically significant and equal to 0.4 for CBV and 0.2 for LBV. Conclusions The moderate heritability values indicate that the variation in host

  19. Use of a Generalized Additive Model to Investigate Key Abiotic Factors Affecting Microcystin Cellular Quotas in Heavy Bloom Areas of Lake Taihu

    PubMed Central

    Tao, Min; Xie, Ping; Chen, Jun; Qin, Boqiang; Zhang, Dawen; Niu, Yuan; Zhang, Meng; Wang, Qing; Wu, Laiyan

    2012-01-01

    Lake Taihu is the third largest freshwater lake in China and is suffering from serious cyanobacterial blooms with the associated drinking water contamination by microcystin (MC) for millions of citizens. So far, most studies on MCs have been limited to two small bays, while systematic research on the whole lake is lacking. To explain the variations in MC concentrations during cyanobacterial bloom, a large-scale survey at 30 sites across the lake was conducted monthly in 2008. The health risks of MC exposure were high, especially in the northern area. Both Microcystis abundance and MC cellular quotas presented positive correlations with MC concentration in the bloom seasons, suggesting that the toxic risks during Microcystis proliferations were affected by variations in both Microcystis density and MC production per Microcystis cell. Use of a powerful predictive modeling tool named generalized additive model (GAM) helped visualize significant effects of abiotic factors related to carbon fixation and proliferation of Microcystis (conductivity, dissolved inorganic carbon (DIC), water temperature and pH) on MC cellular quotas from recruitment period of Microcystis to the bloom seasons, suggesting the possible use of these factors, in addition to Microcystis abundance, as warning signs to predict toxic events in the future. The interesting relationship between macrophytes and MC cellular quotas of Microcystis (i.e., high MC cellular quotas in the presence of macrophytes) needs further investigation. PMID:22384128

  20. Use of a generalized additive model to investigate key abiotic factors affecting microcystin cellular quotas in heavy bloom areas of Lake Taihu.

    PubMed

    Tao, Min; Xie, Ping; Chen, Jun; Qin, Boqiang; Zhang, Dawen; Niu, Yuan; Zhang, Meng; Wang, Qing; Wu, Laiyan

    2012-01-01

    Lake Taihu is the third largest freshwater lake in China and is suffering from serious cyanobacterial blooms with the associated drinking water contamination by microcystin (MC) for millions of citizens. So far, most studies on MCs have been limited to two small bays, while systematic research on the whole lake is lacking. To explain the variations in MC concentrations during cyanobacterial bloom, a large-scale survey at 30 sites across the lake was conducted monthly in 2008. The health risks of MC exposure were high, especially in the northern area. Both Microcystis abundance and MC cellular quotas presented positive correlations with MC concentration in the bloom seasons, suggesting that the toxic risks during Microcystis proliferations were affected by variations in both Microcystis density and MC production per Microcystis cell. Use of a powerful predictive modeling tool named generalized additive model (GAM) helped visualize significant effects of abiotic factors related to carbon fixation and proliferation of Microcystis (conductivity, dissolved inorganic carbon (DIC), water temperature and pH) on MC cellular quotas from recruitment period of Microcystis to the bloom seasons, suggesting the possible use of these factors, in addition to Microcystis abundance, as warning signs to predict toxic events in the future. The interesting relationship between macrophytes and MC cellular quotas of Microcystis (i.e., high MC cellular quotas in the presence of macrophytes) needs further investigation. PMID:22384128

  1. Outpatient management of postbiopsy pneumothorax with small-caliber chest tubes: factors affecting the need for prolonged drainage and additional interventions.

    PubMed

    Gupta, Sanjay; Hicks, Marshall E; Wallace, Michael J; Ahrar, Kamran; Madoff, David C; Murthy, Ravi

    2008-01-01

    The aim of this study was to evaluate the efficacy of outpatient management of postbiopsy pneumothoraces with small-caliber chest tubes and to assess the factors that influence the need for prolonged drainage or additional interventions. We evaluated the medical records of patients who were treated with small-caliber chest tubes attached to Heimlich valves for pneumothoraces resulting from image-guided transthoracic needle biopsy to determine the hospital admission rates, the number of days the catheters were left in place, and the need for further interventions. We also evaluated the patient, lesion, and biopsy technique characteristics to determine their influence on the need for prolonged catheter drainage or additional interventions. Of the 191 patients included in our study, 178 (93.2%) were treated as outpatients. Ten patients (5.2%) were admitted for chest tube-related problems, either for underwater suction (n = 8) or for pain control (n = 2). No further interventions were required in 146 patients (76.4%), with successful removal of the chest tubes the day after the biopsy procedure. Prolonged catheter drainage (mean, 4.3 days) was required in 44 patients (23%). Nineteen patients (9.9%) underwent additional interventions for management of pneumothorax. Presence of emphysema was noted more frequently in patients who required additional interventions or prolonged chest tube drainage than in those who did not (51.1% vs. 24.7%; p = 0.001). We conclude that use of the Heimlich valve allows safe and successful outpatient treatment of most patients requiring chest tube placement for postbiopsy pneumothorax. Additional interventions or prolonged chest tube drainage are needed more frequently in patients with emphysema in the needle path. PMID:18074173

  2. Outpatient Management of Postbiopsy Pneumothorax with Small-Caliber Chest Tubes: Factors Affecting the Need for Prolonged Drainage and Additional Interventions

    SciTech Connect

    Gupta, Sanjay Hicks, Marshall E.; Wallace, Michael J.; Ahrar, Kamran; Madoff, David C.; Murthy, Ravi

    2008-03-15

    The aim of this study was to evaluate the efficacy of outpatient management of postbiopsy pneumothoraces with small-caliber chest tubes and to assess the factors that influence the need for prolonged drainage or additional interventions.We evaluated the medical records of patients who were treated with small-caliber chest tubes attached to Heimlich valves for pneumothoraces resulting from image-guided transthoracic needle biopsy to determine the hospital admission rates, the number of days the catheters were left in place, and the need for further interventions. We also evaluated the patient, lesion, and biopsy technique characteristics to determine their influence on the need for prolonged catheter drainage or additional interventions. Of the 191 patients included in our study, 178 (93.2%) were treated as outpatients. Ten patients (5.2%) were admitted for chest tube-related problems, either for underwater suction (n = 8) or for pain control (n = 2). No further interventions were required in 146 patients (76.4%), with successful removal of the chest tubes the day after the biopsy procedure. Prolonged catheter drainage (mean, 4.3 days) was required in 44 patients (23%). Nineteen patients (9.9%) underwent additional interventions for management of pneumothorax. Presence of emphysema was noted more frequently in patients who required additional interventions or prolonged chest tube drainage than in those who did not (51.1% vs. 24.7%; p = 0.001).We conclude that use of the Heimlich valve allows safe and successful outpatient treatment of most patients requiring chest tube placement for postbiopsy pneumothorax. Additional interventions or prolonged chest tube drainage are needed more frequently in patients with emphysema in the needle path.

  3. Additive Manufacturing/Diagnostics via the High Frequency Induction Heating of Metal Powders: The Determination of the Power Transfer Factor for Fine Metallic Spheres

    SciTech Connect

    Rios, Orlando; Radhakrishnan, Balasubramaniam; Caravias, George; Holcomb, Matthew

    2015-03-11

    Grid Logic Inc. is developing a method for sintering and melting fine metallic powders for additive manufacturing using spatially-compact, high-frequency magnetic fields called Micro-Induction Sintering (MIS). One of the challenges in advancing MIS technology for additive manufacturing is in understanding the power transfer to the particles in a powder bed. This knowledge is important to achieving efficient power transfer, control, and selective particle heating during the MIS process needed for commercialization of the technology. The project s work provided a rigorous physics-based model for induction heating of fine spherical particles as a function of frequency and particle size. This simulation improved upon Grid Logic s earlier models and provides guidance that will make the MIS technology more effective. The project model will be incorporated into Grid Logic s power control circuit of the MIS 3D printer product and its diagnostics technology to optimize the sintering process for part quality and energy efficiency.

  4. Additivity of factor effects in reading tasks is still a challenge for computational models: Reply to Ziegler, Perry, and Zorzi (2009).

    PubMed

    Besner, Derek; O'Malley, Shannon

    2009-01-01

    J. C. Ziegler, C. Perry, and M. Zorzi (2009) have claimed that their connectionist dual process model (CDP+) can simulate the data reported by S. O'Malley and D. Besner. Most centrally, they have claimed that the model simulates additive effects of stimulus quality and word frequency on the time to read aloud when words and nonwords are randomly intermixed. This work represents an important attempt given that computational models of reading processes have to date largely ignored the issue of whether it is possible to simulate additive effects. Despite CDP+'s success at capturing many other phenomena, it is clear that CDP+ fails to capture the full pattern seen with skilled readers in these experiments. PMID:19210105

  5. Importance of interaction between nerve growth factor and α9β1 integrin in glial tumor angiogenesis

    PubMed Central

    Walsh, Erin M.; Kim, Richard; Del Valle, Luis; Weaver, Michael; Sheffield, Joel; Lazarovici, Philip; Marcinkiewicz, Cezary

    2012-01-01

    NGF is a growth factor for which the role in the promotion of angiogenesis is still not completely understood. We found that NGF promotes the pathological neovascularization process in glioma through a direct interaction with α9β1 integrin, which is up-regulated on microvascular endothelial cells in cancer tissue. We propagated gHMVEC primary cells using a new method of immune-selection, and these cells demonstrated α9β1 integrin-dependent binding of NGF in a cell adhesion assay. Moreover, NGF induced gHMVEC proliferation and chemotaxis inhibited by specific blockers of α9β1 integrin, such as MLD-disintegrins and monoclonal antibody Y9A2. A Matrigel tube formation assay revealed that NGF significantly increased capillary-like growth from gHMVEC to a level comparable to treatment with VEGF. The snake venom disintegrin, VLO5, inhibited the agonistic effect of both growth factors, whereas the effect of Y9A2 was not statistically significant. Angiogenesis exogenously induced by NGF  was also α9β1-integrin dependent in an embryonic quail CAM system. However, angiogenesis pathologically induced by developing glioma in this system was only sensitive for inhibition with MLD-disintegrin, suggesting a more complex effect of cancer cells on the neovascularization process. The anti-angiogenic effect of MLD-disintegrins is probably related to their pro-apoptotic ability induced in activated tumoral endothelial cells. Therefore, the molecular basis of these disintegrins may be useful for developing new angiostatic pharmaceuticals for application in cancer therapy. PMID:22611032

  6. Incidence and Risk Factors of Acute Kidney Injury after Radical Cystectomy: Importance of Preoperative Serum Uric Acid Level

    PubMed Central

    Joung, Kyoung-Woon; Choi, Seong-Soo; Kong, Yu-Gyeong; Yu, Jihion; Lim, Jinwook; Hwang, Jai-Hyun; Kim, Young-Kug

    2015-01-01

    Background: Acute kidney injury (AKI) is a common complication after surgery and increases costs, morbidity, and mortality of hospitalized patients. While radical cystectomy associates significantly with an increased risk of serious complications, including AKI, risk factors of AKI after radical cystectomy has not been reported. This study was performed to determine the incidence and independent predictors of AKI after radical cystectomy. Methods: All consecutive patients who underwent radical cystectomy in 2001-2013 in a single tertiary-care center were identified. Their demographics, laboratory values, and intraoperative data were recorded. Postoperative AKI was defined and staged according to the Acute Kidney Injury Network criteria on the basis of postoperative changes in creatinine levels. Independent predictors of AKI were identified by univariate and multivariate logistic regression analyses. Results: Of the 238 patients who met the eligibility criteria, 91 (38.2%) developed AKI. Univariate logistic regression analyses showed that male gender, high serum uric acid level, and long operation time associated with the development of AKI. On multivariate logistic regression analysis, preoperative serum uric acid concentration (odds ratio [OR] = 1.251; 95% confidence interval [CI] = 1.048-1.493; P = 0.013) and operation time (OR = 1.005; 95% CI = 1.002-1.008; P = 0.003) remained as independent predictors of AKI after radical cystectomy. Conclusions: AKI after radical cystectomy was a relatively common complication. Its independent risk factors were high preoperative serum uric acid concentration and long operation time. These observations can help to prevent AKI after radical cystectomy. PMID:26283877

  7. Minimal promoter systems reveal the importance of conserved residues in the B-finger of human transcription factor IIB.

    PubMed

    Thompson, Nancy E; Glaser, Bryan T; Foley, Katherine M; Burton, Zachary F; Burgess, Richard R

    2009-09-11

    The "B-finger" of transcription factor IIB (TFIIB) is highly conserved and believed to play a role in the initiation process. We performed alanine substitutions across the B-finger of human TFIIB, made change-of-charge mutations in selected residues, and substituted the B-finger sequence from other organisms. Mutant proteins were examined in two minimal promoter systems (containing only RNA polymerase II, TATA-binding protein, and TFIIB) and in a complex system, using TFIIB-immunodepleted HeLa cell nuclear extract (NE). Mutations in conserved residues located on the sides of the B-finger had the greatest effect on activity in both minimal promoter systems, with mutations in residues Glu-51 and Arg-66 eliminating activity. The double change-of-charge mutant (E51R:R66E) did not show activity in either minimal promoter system. Mutations in the nonconserved residues at the tip of the B-finger did not significantly affect activity. However, all of the mutations in the B-finger showed at least 25% activity in the HeLa cell NE. Chimeric proteins, containing B-finger sequences from species with conserved residues on the side of the B-finger, showed wild-type activity in a minimal promoter system and in the HeLa cell NE. However, chimeric proteins whose sequence showed divergence on the sides of the B-finger had reduced activity. Transcription factor IIF (TFIIF) partially restored activity of the inactive mutants in the minimal promoter system, suggesting that TFIIF in HeLa cell NE helps to rescue the inactive mutations by interacting with either the B-finger or another component of the initiation complex that is influenced by the B-finger. PMID:19590095

  8. Female gender and Helicobacter pylori infection, the most important predisposition factors in a cohort of gastric cancer: A longitudinal study

    PubMed Central

    Agah, Shahram; Khedmat, Hossein; Ghamar-Chehred, Mohammad Ebrahim; Hadi, Reza; Aghaei, Aghdas

    2016-01-01

    Background: Gastric cancer (GC) is one of the most common Cancers in the world and Helicobacter pylori (HP) infection is considered a causative factor. The aim of this study was to determine the characteristics and the associated factors of (GC) in a small cohort. Methods: Overall, 54 patients with diagnosed gastric cancer were followed-up at the Department of Gastroenterology & Hepatology at Baqiyatallah University of Medical Sciences. 37 (68.5%) of them were positive for H pylori infection in histopathological evaluations. Univariate and multivariate regression analyses were used to determine the associations of demographic features and HP infection status with GC characteristics and prognosis. Results: Univariate analysis showed female gender (odds ratio (OR): 6.53; 95% confidence interval (95%CI): 1.59-26.8; P=0.008), and illiteracy (compared to intermediate education; OR: 5.9, 95%CI: 1.37-25.43; p=0.05) were associated significantly with higher rate of HP infection. After a mean±SD follow-up duration of 254±329 months, only female gender was significantly associated with HP infection in GC (OR:4.56; 95% CI: 1.0-21.76; P=0.05). H pylori positive patients had significantly higher grade of GC (OR: 3.97; 95% CI: 1.0-16.16; P=0.05), and a trend toward greater GC stage (OR: 4.46, 95% CI: 9.39-21.23; p=0.06). There was no association between survival rate and H pylori infection. Conclusion: In the current study, we found a significant association of female gender with GN and an association of higher grade of GC with female gender. These findings may indicate a sex disparity in susceptibility to HP infection regarding GC future studies of larger populations are recommended.

  9. "It's Too Crowded": A Qualitative Study of the Physical Environment Factors That Adolescent Girls Perceive to Be Important and Influential on Their PE Experience

    ERIC Educational Resources Information Center

    Niven, Ailsa; Henretty, Joan; Fawkner, Samantha

    2014-01-01

    Many adolescent girls do not achieve a health-enhancing level of physical activity. This study aimed to identify the school physical environment factors that adolescent girls perceive to be important and influential regarding their physical education (PE) behaviour. Adolescent girls (n = 38; aged 13-16) participated in eight moderated focus…

  10. Factors affecting adventitious regeneration from in vitro leaf explants of 'Improved French' plum, the most important dried plum cultivar in the USA

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An adventitious shoot regeneration protocol from leaves of the most important dried plum cultivar in the U.S., 'Improved French', has been established. Factors affecting regeneration were studied, and relatively high percentages have been obtained. The proliferation medium were shoots, used as the...

  11. Statistical Analyses of Scatterplots to Identify Important Factors in Large-Scale Simulations, 1: Review and Comparison of Techniques

    SciTech Connect

    Kleijnen, J.P.C.; Helton, J.C.

    1999-03-24

    The robustness of procedures for identifying patterns in scatterplots generated in Monte Carlo sensitivity analyses is investigated. These procedures are based on attempts to detect increasingly complex patterns in the scatterplots under consideration and involve the identification of (i) linear relationships with correlation coefficients, (ii) monotonic relationships with rank correlation coefficients, (iii) trends in central tendency as defined by means, medians and the Kruskal-Wallis statistic, (iv) trends in variability as defined by variances and interquartile ranges, and (v) deviations from randomness as defined by the chi-square statistic. The following two topics related to the robustness of these procedures are considered for a sequence of example analyses with a large model for two-phase fluid flow: the presence of Type I and Type II errors, and the stability of results obtained with independent Latin hypercube samples. Observations from analysis include: (i) Type I errors are unavoidable, (ii) Type 11errors can occur when inappropriate analysis procedures are used, (iii) physical explanations should always be sought for why statistical procedures identify variables as being important, and (iv) the identification of important variables tends to be stable for independent Latin hypercube samples.

  12. Silencing of the transforming growth factor-beta (TGFbeta) receptor II by Kruppel-like factor 14 underscores the importance of a negative feedback mechanism in TGFbeta signaling.

    PubMed

    Truty, Mark J; Lomberk, Gwen; Fernandez-Zapico, Martin E; Urrutia, Raul

    2009-03-01

    The role of non-Smad proteins in the regulation of transforming growth factor-beta (TGFbeta) signaling is an emerging line of active investigation. Here, we characterize the role of KLF14, as a TGFbeta-inducible, non-Smad protein that silences the TGFbeta receptor II (TGFbetaRII) promoter. Together with endocytosis, transcriptional silencing is a critical mechanism for down-regulating TGFbeta receptors at the cell surface. However, the mechanisms underlying transcriptional repression of these receptors remain poorly understood. KLF14 has been chosen from a comprehensive screen of 24 members of the Sp/KLF family due to its TGFbeta inducibility, its ability to regulate the TGFbetaRII promoter, and the fact that this protein had yet to be functionally characterized. We find that KLF14 represses the TGFbetaRII, a function that is augmented by TGFbeta treatment. Mapping of the TGFbetaRII promoter, in combination with site-directed mutagenesis, electromobility shift, and chromatin immunoprecipitation assays, have identified distinct GC-rich sequences used by KLF14 to regulate this promoter. Mechanistically, KLF14 represses the TGFbetaRII promoter via a co-repressor complex containing mSin3A and HDAC2. Furthermore, the TGFbeta pathway activation leads to recruitment of a KLF14-mSin3A-HDAC2 repressor complex to the TGFbetaRII promoter, as well as the remodeling of chromatin to increase histone marks that associate with transcriptional silencing. Thus, these results describe a novel negative-feedback mechanism by which TGFbetaRII activation at the cell surface induces the expression of KLF14 to ultimately silence the TGFbetaRII and further expand the network of non-Smad transcription factors that participate in the TGFbeta pathway. PMID:19088080

  13. Increased Circulating ANG II and TNF-α Represents Important Risk Factors in Obese Saudi Adults with Hypertension Irrespective of Diabetic Status and BMI

    PubMed Central

    Al-Daghri, Nasser M.; Bindahman, Lotfi S.; Al-Attas, Omar S.; Saleem, Tahia H.; Alokail, Majed S.; Alkharfy, Khalid M.; Draz, Hossam M.; Yakout, Sobhy; Mohamed, Amany O.; Harte, Alison L.; McTernan, Philip G.

    2012-01-01

    Central adiposity is a significant determinant of obesity-related hypertension risk, which may arise due to the pathogenic inflammatory nature of the abdominal fat depot. However, the influence of pro-inflammatory adipokines on blood pressure in the obese hypertensive phenotype has not been well established in Saudi subjects. As such, our study investigated whether inflammatory factors may represent useful biomarkers to delineate hypertension risk in a Saudi cohort with and without hypertension and/or diabetes mellitus type 2 (DMT2). Subjects were subdivided into four groups: healthy lean controls (age: 47.9±5.1 yr; BMI: 22.9±2.1 Kg/m2), non-hypertensive obese (age: 46.1±5.0 yr; BMI: 33.7±4.2 Kg/m2), hypertensive obese (age: 48.6±6.1 yr; BMI: 36.5±7.7 Kg/m2) and hypertensive obese with DMT2 (age: 50.8±6.0 yr; BMI: 35.3±6.7 Kg/m2). Anthropometric data were collected from all subjects and fasting blood samples were utilized for biochemical analysis. Serum angiotensin II (ANG II) levels were elevated in hypertensive obese (p<0.05) and hypertensive obese with DMT2 (p<0.001) compared with normotensive controls. Systolic blood pressure was positively associated with BMI (p<0.001), glucose (p<0.001), insulin (p<0.05), HOMA-IR (p<0.001), leptin (p<0.01), TNF-α (p<0.001) and ANG II (p<0.05). Associations between ANG II and TNF-α with systolic blood pressure remained significant after controlling for BMI. Additionally CRP (p<0.05), leptin (p<0.001) and leptin/adiponectin ratio (p<0.001) were also significantly associated with the hypertension phenotype. In conclusion our data suggests that circulating pro-inflammatory adipokines, particularly ANG II and, TNF-α, represent important factors associated with a hypertension phenotype and may directly contribute to predicting and exacerbating hypertension risk. PMID:23251471

  14. Statistical Analyses of Scatterplots to Identify Important Factors in Large-Scale Simulations, 2. Robustness of Techniques

    SciTech Connect

    Helton, J.C.; Kleijnen, J.P.C.

    1999-03-24

    Procedures for identifying patterns in scatterplots generated in Monte Carlo sensitivity analyses are described and illustrated. These procedures attempt to detect increasingly complex patterns in scatterplots and involve the identification of (i) linear relationships with correlation coefficients, (ii) monotonic relationships with rank correlation coefficients, (iii) trends in central tendency as defined by means, medians and the Kruskal-Wallis statistic, (iv) trends in variability as defined by variances and interquartile ranges, and (v) deviations from randomness as defined by the chi-square statistic. A sequence of example analyses with a large model for two-phase fluid flow illustrates how the individual procedures can differ in the variables that they identify as having effects on particular model outcomes. The example analyses indicate that the use of a sequence of procedures is a good analysis strategy and provides some assurance that an important effect is not overlooked.

  15. Crystallization and preliminary X-ray crystallographic analysis of YfcM: an important factor for EF-P hydroxylation.

    PubMed

    Kobayashi, Kan; Suzuki, Takehiro; Dohmae, Naoshi; Ishitani, Ryuichiro; Nureki, Osamu

    2014-09-01

    Elongation factor P (EF-P) plays an essential role in the translation of polyproline-containing proteins in bacteria. It becomes functional by the post-translational modification of its highly conserved lysine residue. It is first β-lysylated by PoxA and then hydroxylated by YfcM. In this work, the YfcM protein from Escherichia coli was overexpressed, purified and crystallized. The crystal of YfcM was obtained by the in situ proteolysis crystallization method and diffracted X-rays to 1.45 Å resolution. It belonged to space group C2, with unit-cell parameters a = 124.4, b = 37.0, c = 37.6 Å, β = 101.2°. The calculated Matthews coefficient (VM) of the crystal was 1.91 Å(3) Da(-1), indicating that one YfcM molecule is present in the asymmetric unit with a solvent content of 35.7%. PMID:25195899

  16. Mercury contamination in fish in midcontinent great rivers of the united states: Importance of species traits and environmental factors

    USGS Publications Warehouse

    Walters, D.M.; Blocksom, K.A.; Lazorchak, J.M.; Jicha, T.; Angradi, T.R.; Bolgrien, D.W.

    2010-01-01

    We measured mercury (Hg) concentrations in whole fish from the Upper Mississippi, Missouri, and Ohio Rivers to characterize the extent and magnitude of Hg contamination and to identify environmental factors influencing Hg accumulation. Concentrations were generally lower (80% of values between 20?200 ng g1 wet weight) than those reported for other regions (e.g., upper Midwest and Northeast U.S.). Mercury exceeded the risk threshold for belted kingfisher (Ceryle alcyon, the most sensitive species considered) in 33?75% of river length and 1?7% of river length for humans. Concentrations were lower in the Missouri than in the Mississippi and Ohio Rivers, consistent with continental-scale patterns in atmospheric Hg deposition. Body size and trophic guild were the best predictors of Hg concentrations, which were highest in large-bodied top predators. Site geochemical and landscape properties were weakly related with fish Hg. Moreover, relationships often ran contrary to conventional wisdom, and the slopes of the relationships (positive or negative) were inconsistent among fish guilds and rivers. For example, sulfate is positively associated with fish Hg concentrations but was negatively correlated with Hg in five of six regression models of tissue concentrations. Variables such as pH, acid neutralizing capacity, and total phosphorus did not occur at levels associated with high fish Hg concentrations, partially explaining the relatively low Hg values we observed. ?? 2010 American Chemical Society.

  17. The importance of low serum levels of high-density lipoprotein cholesterol (HDL-C) as a cardiovascular risk factor.

    PubMed

    Espinosa-Larrañaga, Francisco; Vejar-Jalaf, Margarita; Medina-Santillán, Roberto

    2005-10-01

    In order to discuss and establish a joint position on the treatment of low serum levels of high-density lipoprotein cholesterol (HDL-C), a group of experts involved in the care of people with dyslipidaemia and at risk of cardiovascular disease met in Miami, Florida, U.S., on 5th and 6th March 2005. The experts came from the Latin American countries Argentina, Brazil, Chile, Colombia, Ecuador, Guatemala, Mexico and Venezuela and had at least five years of experience in the care of patients with dyslipidaemia and low HDL-C. The main objective of the meeting was to discuss and propose a treatment for low serum HDL-C levels as a cardiovascular risk factor in patients and to create a group of useful recommendations in this regard, applicable to the daily clinical practice of physicians dealing with patients with dyslipidaemia and cardiovascular disease. This document describes the methodology developed to obtain these recommendations and presents the results of this academic meeting. PMID:16342610

  18. [Severe neuropsychiatric disorders in an asthmatic infant who received repeated glucocorticoid treatment: the importance of associated factors].

    PubMed

    Cathala, J-M; Petitpain, N; Roy, B; Ferrand, M; Tréchot, P

    2009-08-01

    Children and adults may experience neuropsychiatric disorders during glucocorticoid treatment, most of which are reversible upon drug withdrawal. Whereas the occurrence of these disorders is well documented in teenagers, only a few cases have been reported in children under 3 years of age. We report on severe neuropsychiatric disorders that occurred in a 27-month-old child during glucocorticoid treatment for asthma that did not regress when treatment was stopped. The psychiatric symptoms suggested autism and were associated with deterioration of the child-mother relationship. This led the medical staff to initiate a dual therapy (conducted by a psychiatrist and a speech therapist) focused on the restoration of the maternal bond. A dramatic improvement in both the child's and the mother's behavior was observed within a few months. Severe psychiatric disorders induced by glucocorticoids can occur in young children and be worsened by environmental factors. The quality of the child-parent relationship should be kept in mind during the management of drug-induced psychiatric disorders. PMID:19577441

  19. Development of an Aerosol Model of Cryptococcus Reveals Humidity as an Important Factor Affecting the Viability of Cryptococcus during Aerosolization

    PubMed Central

    Springer, Deborah J.; Saini, Divey; Byrnes, Edmond J.; Heitman, Joseph; Frothingham, Richard

    2013-01-01

    Cryptococcus is an emerging global health threat that is annually responsible for over 1,000,000 infections and one third of all AIDS patient deaths. There is an ongoing outbreak of cryptococcosis in the western United States and Canada. Cryptococcosis is a disease resulting from the inhalation of the infectious propagules from the environment. The current and most frequently used animal infection models initiate infection via liquid suspension through intranasal instillation or intravenous injection. These models do not replicate the typically dry nature of aerosol exposure and may hinder our ability to decipher the initial events that lead to clearance or the establishment of infection. We have established a standardized aerosol model of murine infection for the human fungal pathogen Cryptococcus. Aerosolized cells were generated utilizing a Collison nebulizer in a whole-body Madison Chamber at different humidity conditions. The aerosols inside the chamber were sampled using a BioSampler to determine viable aerosol concentration and spray factor (ratio of viable aerosol concentration to total inoculum concentration). We have effectively delivered yeast and yeast-spore mixtures to the lungs of mice and observed the establishment of disease. We observed that growth conditions prior to exposure and humidity within the Madison Chamber during exposure can alter Cryptococcus survival and dose retained in mice. PMID:23894542

  20. Mercury contamination in fish in midcontinent great rivers of the United States: importance of species traits and environmental factors.

    PubMed

    Walters, David M; Blocksom, Karen A; Lazorchak, James M; Jicha, Terri; Angradi, Theodore R; Bolgrien, David W

    2010-04-15

    We measured mercury (Hg) concentrations in whole fish from the Upper Mississippi, Missouri, and Ohio Rivers to characterize the extent and magnitude of Hg contamination and to identify environmental factors influencing Hg accumulation. Concentrations were generally lower (80% of values between 20-200 ng g(-1) wet weight) than those reported for other regions (e.g., upper Midwest and Northeast U.S.). Mercury exceeded the risk threshold for belted kingfisher (Ceryle alcyon, the most sensitive species considered) in 33-75% of river length and 1-7% of river length for humans. Concentrations were lower in the Missouri than in the Mississippi and Ohio Rivers, consistent with continental-scale patterns in atmospheric Hg deposition. Body size and trophic guild were the best predictors of Hg concentrations, which were highest in large-bodied top predators. Site geochemical and landscape properties were weakly related with fish Hg. Moreover, relationships often ran contrary to conventional wisdom, and the slopes of the relationships (positive or negative) were inconsistent among fish guilds and rivers. For example, sulfate is positively associated with fish Hg concentrations but was negatively correlated with Hg in five of six regression models of tissue concentrations. Variables such as pH, acid neutralizing capacity, and total phosphorus did not occur at levels associated with high fish Hg concentrations, partially explaining the relatively low Hg values we observed. PMID:20297812

  1. Pseudomonas fluorescens Filamentous Hemagglutinin, an Iron-Regulated Protein, Is an Important Virulence Factor that Modulates Bacterial Pathogenicity.

    PubMed

    Sun, Yuan-Yuan; Chi, Heng; Sun, Li

    2016-01-01

    Pseudomonas fluorescens is a common bacterial pathogen to a wide range of aquaculture animals including various species of fish. In this study, we employed proteomic analysis and identified filamentous hemagglutinin (FHA) as an iron-responsive protein secreted by TSS, a pathogenic P. fluorescens isolate. In vitro study showed that compared to the wild type, the fha mutant TSSfha (i) exhibited a largely similar vegetative growth profile but significantly retarded in the ability of biofilm growth and producing extracellular matrix, (ii) displayed no apparent flagella and motility, (iii) was defective in the attachment to host cells and unable to form self-aggregation, (iv) displayed markedly reduced capacity of hemagglutination and surviving in host serum. In vivo infection analysis revealed that TSSfha was significantly attenuated in the ability of dissemination in fish tissues and inducing host mortality, and that antibody blocking of the natural FHA produced by the wild type TSS impaired the infectivity of the pathogen. Furthermore, when introduced into turbot as a subunit vaccine, recombinant FHA elicited a significant protection against lethal TSS challenge. Taken together, these results indicate for the first time that P. fluorescens FHA is a key virulence factor essential to multiple biological processes associated with pathogenicity. PMID:27602029

  2. Phosphorylation-Coupled Proteolysis of the Transcription Factor MYC2 Is Important for Jasmonate-Signaled Plant Immunity

    PubMed Central

    Zhai, Qingzhe; Yan, Liuhua; Tan, Dan; Chen, Rong; Sun, Jiaqiang; Gao, Liyan; Dong, Meng-Qiu; Wang, Yingchun; Li, Chuanyou

    2013-01-01

    As a master regulator of jasmonic acid (JA)–signaled plant immune responses, the basic helix-loop-helix (bHLH) Leu zipper transcription factor MYC2 differentially regulates different subsets of JA–responsive genes through distinct mechanisms. However, how MYC2 itself is regulated at the protein level remains unknown. Here, we show that proteolysis of MYC2 plays a positive role in regulating the transcription of its target genes. We discovered a 12-amino-acid element in the transcription activation domain (TAD) of MYC2 that is required for both the proteolysis and the transcriptional activity of MYC2. Interestingly, MYC2 phosphorylation at residue Thr328, which facilitates its turnover, is also required for the MYC2 function to regulate gene transcription. Together, these results reveal that phosphorylation-coupled turnover of MYC2 stimulates its transcription activity. Our results exemplify that, as with animals, plants employ an “activation by destruction” mechanism to fine-tune their transcriptome to adapt to their ever-changing environment. PMID:23593022

  3. Pseudomonas fluorescens Filamentous Hemagglutinin, an Iron-Regulated Protein, Is an Important Virulence Factor that Modulates Bacterial Pathogenicity

    PubMed Central

    Sun, Yuan-Yuan; Chi, Heng; Sun, Li

    2016-01-01

    Pseudomonas fluorescens is a common bacterial pathogen to a wide range of aquaculture animals including various species of fish. In this study, we employed proteomic analysis and identified filamentous hemagglutinin (FHA) as an iron-responsive protein secreted by TSS, a pathogenic P. fluorescens isolate. In vitro study showed that compared to the wild type, the fha mutant TSSfha (i) exhibited a largely similar vegetative growth profile but significantly retarded in the ability of biofilm growth and producing extracellular matrix, (ii) displayed no apparent flagella and motility, (iii) was defective in the attachment to host cells and unable to form self-aggregation, (iv) displayed markedly reduced capacity of hemagglutination and surviving in host serum. In vivo infection analysis revealed that TSSfha was significantly attenuated in the ability of dissemination in fish tissues and inducing host mortality, and that antibody blocking of the natural FHA produced by the wild type TSS impaired the infectivity of the pathogen. Furthermore, when introduced into turbot as a subunit vaccine, recombinant FHA elicited a significant protection against lethal TSS challenge. Taken together, these results indicate for the first time that P. fluorescens FHA is a key virulence factor essential to multiple biological processes associated with pathogenicity. PMID:27602029

  4. Crystallization and preliminary X-ray crystallographic analysis of YfcM: an important factor for EF-P hydroxylation

    SciTech Connect

    Kobayashi, Kan; Suzuki, Takehiro; Dohmae, Naoshi; Ishitani, Ryuichiro; Nureki, Osamu

    2014-08-27

    E. coli YfcM was expressed, purified and crystallized. Crystals of YfcM were obtained by the in situ proteolysis crystallization method. Using these crystals, an X-ray diffraction data set was collected at 1.45 Å resolution. Elongation factor P (EF-P) plays an essential role in the translation of polyproline-containing proteins in bacteria. It becomes functional by the post-translational modification of its highly conserved lysine residue. It is first β-lysylated by PoxA and then hydroxylated by YfcM. In this work, the YfcM protein from Escherichia coli was overexpressed, purified and crystallized. The crystal of YfcM was obtained by the in situ proteolysis crystallization method and diffracted X-rays to 1.45 Å resolution. It belonged to space group C2, with unit-cell parameters a = 124.4, b = 37.0, c = 37.6 Å, β = 101.2°. The calculated Matthews coefficient (V{sub M}) of the crystal was 1.91 Å{sup 3} Da{sup −1}, indicating that one YfcM molecule is present in the asymmetric unit with a solvent content of 35.7%.

  5. A novel nuclear localization signal in the auxiliary domain of apobec-1 complementation factor regulates nucleocytoplasmic import and shuttling.

    PubMed

    Blanc, Valerie; Kennedy, Susan; Davidson, Nicholas O

    2003-10-17

    C to U editing of the nuclear apolipoprotein B (apoB) transcript is mediated by a core enzyme containing a catalytic deaminase, apobec-1, and an RNA binding subunit, apobec-1 complementation factor (ACF). ACF expression is predominantly nuclear, including mutant proteins with deletions of a putative nuclear localization signal. We have now identified a novel 41-residue motif (ANS) in the auxiliary domain of ACF that functions as an authentic nuclear localization signal. ANS-green fluorescence protein and ANS-beta-galactosidase chimeras were both expressed exclusively in the nucleus, whereas wild-type chimeras or an ACF deletion mutant lacking the ANS were cytoplasmic. Nuclear accumulation of ACF is transcription-dependent, temperature-sensitive, and reversible, features reminiscent of a shuttling protein. ACF relocates to the cytoplasm after actinomycin D treatment, an effect blocked by the CRM1 inhibitor leptomycin B. Heterokaryon assays confirmed directly that ACF shuttles in vivo. ACF binds to the protein carrier, transportin 2 in vivo, and colocalizes to the nucleus as determined by confocal microscopy. Co-immunoprecipitation experiments revealed that transportin 2 binds directly to the ANS motif. These data suggest that directed nuclear localization and compartmentalization of the core complex of the apoB RNA editing enzyme is regulated through a dominant targeting sequence (ANS) contained within ACF. PMID:12896982

  6. Cows' milk protein-sensitive enteropathy. An important factor in prolonging diarrhoea of acute infective enteritis in early infancy.

    PubMed Central

    Iyngkaran, N; Robinson, M J; Sumithran, E; Lam, S K; Puthucheary, S D; Yadav, M

    1978-01-01

    The possible role of cows' milk protein in prolonging diarrhoea in very young infants with acute infective enteritis was studied in 14 infants, 9 under the age of 2 months and 5 older than 6 months. Bacterial pathogens were isolated from the stools of 4 infants from the younger age group. After appropriate initial treatment the infants were maintained on a cows' milk protein-free formula. 6 weeks later jejunal biopsies were performed before and 24 hours after challenge with a low lactose cows' milk protein formula. The immunoglobulin and complement levels in the serum and duodenal juice were also estimated at these times. Attempts to isolate bacterial and viral pathogens in stools were again made in all patients. The 5 older infants clinically tolerated cows' milk protein and their pre- and postchallenge jejunal biopsies were within normal limits. However, significant histological changes were observed in the postchallenge jejunal biopsies of all 9 infants under 2 months of age. In addition, 5 of these infants developed diarrhoea. This suggests that the jejunal mucosa of very young infants previously fed a cows' milk protein-based formula and who contract infective enteritis suffers damage when rechallenged with cows' milk protein. PMID:646417

  7. A petunia ethylene-responsive element binding factor, PhERF2, plays an important role in antiviral RNA silencing.

    PubMed

    Sun, Daoyang; Nandety, Raja Sekhar; Zhang, Yanlong; Reid, Michael S; Niu, Lixin; Jiang, Cai-Zhong

    2016-05-01

    Virus-induced RNA silencing is involved in plant antiviral defense and requires key enzyme components, including RNA-dependent RNA polymerases (RDRs), Dicer-like RNase III enzymes (DCLs), and Argonaute proteins (AGOs). However, the transcriptional regulation of these critical components is largely unknown. In petunia (Petunia hybrida), an ethylene-responsive element binding factor, PhERF2, is induced by Tobacco rattle virus (TRV) infection. Inclusion of a PhERF2 fragment in a TRV silencing construct containing reporter fragments of phytoene desaturase (PDS) or chalcone synthase (CHS) substantially impaired silencing efficiency of both the PDS and CHS reporters. Silencing was also impaired in PhERF2- RNAi lines, where TRV-PhPDS infection did not show the expected silencing phenotype (photobleaching). In contrast, photobleaching in response to infiltration with the TRV-PhPDS construct was enhanced in plants overexpressing PhERF2 Transcript abundance of the RNA silencing-related genes RDR2, RDR6, DCL2, and AGO2 was lower in PhERF2-silenced plants but higher in PhERF2-overexpressing plants. Moreover, PhERF2-silenced lines showed higher susceptibility to Cucumber mosaic virus (CMV) than wild-type (WT) plants, while plants overexpressing PhERF2 exhibited increased resistance. Interestingly, growth and development of PhERF2-RNAi lines were substantially slower, whereas the overexpressing lines were more vigorous than the controls. Taken together, our results indicate that PhERF2 functions as a positive regulator in antiviral RNA silencing. PMID:27099376

  8. A petunia ethylene-responsive element binding factor, PhERF2, plays an important role in antiviral RNA silencing

    PubMed Central

    Sun, Daoyang; Nandety, Raja Sekhar; Zhang, Yanlong; Reid, Michael S.; Niu, Lixin; Jiang, Cai-Zhong

    2016-01-01

    Virus-induced RNA silencing is involved in plant antiviral defense and requires key enzyme components, including RNA-dependent RNA polymerases (RDRs), Dicer-like RNase III enzymes (DCLs), and Argonaute proteins (AGOs). However, the transcriptional regulation of these critical components is largely unknown. In petunia (Petunia hybrida), an ethylene-responsive element binding factor, PhERF2, is induced by Tobacco rattle virus (TRV) infection. Inclusion of a PhERF2 fragment in a TRV silencing construct containing reporter fragments of phytoene desaturase (PDS) or chalcone synthase (CHS) substantially impaired silencing efficiency of both the PDS and CHS reporters. Silencing was also impaired in PhERF2- RNAi lines, where TRV-PhPDS infection did not show the expected silencing phenotype (photobleaching). In contrast, photobleaching in response to infiltration with the TRV-PhPDS construct was enhanced in plants overexpressing PhERF2. Transcript abundance of the RNA silencing-related genes RDR2, RDR6, DCL2, and AGO2 was lower in PhERF2-silenced plants but higher in PhERF2-overexpressing plants. Moreover, PhERF2-silenced lines showed higher susceptibility to Cucumber mosaic virus (CMV) than wild-type (WT) plants, while plants overexpressing PhERF2 exhibited increased resistance. Interestingly, growth and development of PhERF2-RNAi lines were substantially slower, whereas the overexpressing lines were more vigorous than the controls. Taken together, our results indicate that PhERF2 functions as a positive regulator in antiviral RNA silencing. PMID:27099376

  9. The Importance of Family Factors to Protect Against Substance Use Related Problems among Mexican Heritage and White Youth*

    PubMed Central

    Kopak, Albert M.; Chen, Angela Chia-Chen; Haas, Steven A.; Gillmore, Mary Rogers

    2012-01-01

    INTRODUCTION This study examined the ability of family cohesion, parental control, and parent-child attachment to prevent adolescents with a history of drug or alcohol use from experiencing subsequent problems related to their use. METHODS Data came from Wave I and Wave II of the National Longitudinal Study of Adolescent Health and included Mexican heritage and White adolescents who reported alcohol use (n = 4,894, 25% prevalence) or any other drug use (n = 2,875, 14% prevalence) in their lifetime. RESULTS Logistic regression results indicate greater parent-child attachment predicted lower risk of experiencing drug use problems (OR = 0.87, 95% CI = 0.77 – 0.98) while stronger family cohesion predicted lower odds of experiencing drug- (OR = 0.82, 95% CI = 0.70 – 0.97) or alcohol-related (OR = 0.74, 95% CI = 0.65 – 0.84) problems. Parental control was also negatively associated with odds of problems related to drug use (OR = 0.93, 95% CI = 0.86 – 0.99) or alcohol use (OR = 0.94, 95% CI = 0.90 – 0.99). Results also indicated family cohesion was the only protective factor for Mexican heritage youth while family cohesion and parent-child attachment were protective among White youth. Parental control protected White female adolescents from drug use problems more than males. Mexican heritage male adolescents experienced more protection from drug problems compared to females. CONCLUSION Findings highlight the need for prevention interventions to emphasize parent-child attachment for White youth and family cohesion for both Mexican-heritage and White youth to decrease adolescent substance users’ drug- and alcohol-related problems. PMID:22222253

  10. Food additives

    MedlinePlus

    Food additives are substances that become part of a food product when they are added during the processing or making of that food. "Direct" food additives are often added during processing to: Add nutrients ...

  11. Additive influence of genetic predisposition and conventional risk factors in the incidence of coronary heart disease: a population-based study in Greece

    PubMed Central

    Yiannakouris, Nikos; Katsoulis, Michail; Trichopoulou, Antonia; Ordovas, Jose M; Trichopoulos, Dimitrios

    2014-01-01

    Objectives An additive genetic risk score (GRS) for coronary heart disease (CHD) has previously been associated with incident CHD in the population-based Greek European Prospective Investigation into Cancer and nutrition (EPIC) cohort. In this study, we explore GRS-‘environment’ joint actions on CHD for several conventional cardiovascular risk factors (ConvRFs), including smoking, hypertension, type-2 diabetes mellitus (T2DM), body mass index (BMI), physical activity and adherence to the Mediterranean diet. Design A case–control study. Setting The general Greek population of the EPIC study. Participants and outcome measures 477 patients with medically confirmed incident CHD and 1271 controls participated in this study. We estimated the ORs for CHD by dividing participants at higher or lower GRS and, alternatively, at higher or lower ConvRF, and calculated the relative excess risk due to interaction (RERI) as a measure of deviation from additivity. Results The joint presence of higher GRS and higher risk ConvRF was in all instances associated with an increased risk of CHD, compared with the joint presence of lower GRS and lower risk ConvRF. The OR (95% CI) was 1.7 (1.2 to 2.4) for smoking, 2.7 (1.9 to 3.8) for hypertension, 4.1 (2.8 to 6.1) for T2DM, 1.9 (1.4 to 2.5) for lower physical activity, 2.0 (1.3 to 3.2) for high BMI and 1.5 (1.1 to 2.1) for poor adherence to the Mediterranean diet. In all instances, RERI values were fairly small and not statistically significant, suggesting that the GRS and the ConvRFs do not have effects beyond additivity. Conclusions Genetic predisposition to CHD, operationalised through a multilocus GRS, and ConvRFs have essentially additive effects on CHD risk. PMID:24500614

  12. Importance of Inhibition of Binding of Complement Factor H for Serum Bactericidal Antibody Responses to Meningococcal Factor H-binding Protein Vaccines

    PubMed Central

    Konar, Monica; Granoff, Dan M.; Beernink, Peter T.

    2013-01-01

    Background. Factor H (fH) binding protein (fHbp) is part of vaccines developed for prevention of meningococcal serogroup B disease. More than 610 fHbp amino acid sequence variants have been identified, which can be classified into 2 subfamilies. The extent of cross-protection within a subfamily has been difficult to assess because of strain variation in fHbp expression. Methods. Using isogenic mutant strains, we compared cross-protective serum antibody responses of mice immunized with 7 divergent fHbp variants in subfamily B, including identification numbers (ID) 1 and 55, which were chosen for vaccine development. Results and Conclusions. In the presence of the human complement downregulator fH, the ability of the anti-fHbp antibodies to deposit sufficient complement C3b on the bacterial surface to elicit bactericidal activity required inhibition of binding of fH by the anti-fHbp antibodies. With less bound fH, the bacteria became more susceptible to complement-mediated bactericidal activity. Among the different fHbp sequence variants, those more central in a phylogenic network than ID 1 or 55 elicited anti-fHbp antibodies with broader inhibition of fH binding and broader bactericidal activity. Thus, the more central variants show promise of extending protection to strains with divergent fHbp sequences that are covered poorly by fHbp variants in clinical development. PMID:23715659

  13. Case Series of Imported Enteric Fever at a Referral Center in Tokyo, Japan: Antibiotic Susceptibility and Risk Factors for Relapse.

    PubMed

    Matono, Takashi; Kato, Yasuyuki; Morita, Masatomo; Izumiya, Hidemasa; Yamamoto, Kei; Kutsuna, Satoshi; Takeshita, Nozomi; Hayakawa, Kayoko; Mezaki, Kazuhisa; Kawamura, Maho; Konishi, Noriko; Mizuno, Yasutaka; Kanagawa, Shuzo; Ohmagari, Norio

    2016-07-01

    Owing to the increase in Salmonella strains with decreased fluoroquinolone susceptibility in the endemic areas, we have been treating enteric fever with intravenous ceftriaxone empirically since 2007. In this study, we reevaluated our treatment protocol. This retrospective cohort study was conducted at a single institute in Tokyo, Japan, between January 2006 and December 2013. Enteric fever was defined as isolation of Salmonella Typhi or Salmonella Paratyphi A, B, and C from the blood and/or stool of patients with fever. Of the 35 patients with imported enteric fever, 28 (80%) had returned from south Asia. Ciprofloxacin-susceptible strains were detected in only 12% of the cases. The isolates showed excellent susceptibility to ampicillin (91%), chloramphenicol (94%), ceftriaxone (97%), and azithromycin (97%). One case of Salmonella Paratyphi B was excluded, and of the remaining 34 patients, 56% were treated with ceftriaxone alone, 26% with ceftriaxone then fluoroquinolone, and 9% with levofloxacin alone. The overall relapse rate was 6.1%; however, among those receiving ceftriaxone monotherapy, the relapse rate was 11% (N = 2). The relapse group was characterized by longer times to treatment initiation (P = 0.035) and defervescence (> 7 days) after treatment initiation (P = 0.022). In such cases, we recommend that ceftriaxone treatment be continued for > 4 days after defervescence or be changed to fluoroquinolone if the strains are found to be susceptible to prevent relapse. Furthermore, ampicillin and chloramphenicol, which are no longer prescribed, may be reconsidered as treatment options in Asia. PMID:27162265

  14. Factors contributing to the perpetration of workplace incivility: the importance of organizational aspects and experiencing incivility from others

    PubMed Central

    Torkelson, Eva; Holm, Kristoffer; Bäckström, Martin; Schad, Elinor

    2016-01-01

    ABSTRACT In recent years a growing amount of research has been conducted in the area of workplace incivility. Whereas many studies have focused on the victims and the consequences of incivility, little attention has been paid to the perpetrators and antecedents of workplace incivility. This study aims to identify possible antecedents of workplace incivility, by investigating organizational aspects as well as the possibility that being the target of incivility from co-workers and supervisors could induce incivility. A total of 512 employees (378 women and 133 men) in the school sector in a Swedish municipality completed an online questionnaire. Overall, the results of structural equation modelling analyses showed that organizational variables were related to the perpetration of incivility. A direct relationship was found between being uncivil and organizational change, job insecurity, low social support from co-workers and high job demands. However, the strongest relationship was found between experienced incivility from co-workers and instigated incivility. This could be reflecting a climate or culture of incivility in the organization, and carry implications for future practice in interventions against workplace incivility. The results indicate the importance of focusing on the perspective of the instigator to gain knowledge about the process of workplace incivility. PMID:27226677

  15. The Perceived Socioeconomic Status Is an Important Factor of Health Recovery for Victims of Occupational Accidents in Korea

    PubMed Central

    Roh, Jaehoon

    2016-01-01

    We aimed to examine whether there is a correlation between the health recovery of industrial accident victims and their perceived socioeconomic status. Data were obtained from the first Panel Study of Worker's Compensation Insurance, which included 2,000 participants. We performed multivariate regression analysis and determined the odds ratios for participants with a subjectively lower socioeconomic status and for those with a subjectively lower middle socioeconomic status using 95% confidence intervals. An additional multivariate regression analysis yielded the odds ratios for participants with a subjectively lower socioeconomic status and those with a subjectively upper middle socioeconomic class using 95% confidence intervals. Of all participants, 299 reported a full recovery, whereas 1,701 did not. We examined the odds ratio (95% confidence intervals) for participants' health recovery according to their subjective socioeconomic status while controlling for sex, age, education, tobacco use, alcohol use, subjective state of health prior to the accident, chronic disease, employment duration, recovery period, accident type, disability status, disability rating, and economic participation. The odds of recovery in participants with a subjectively lower middle socioeconomic status were 1.707 times greater (1.264-2.305) than that of those with a subjectively lower socioeconomic status. Similarly, the odds of recovery in participants with a subjectively upper middle socioeconomic status were 3.124 times greater (1.795-5.438) than that of those with a subjectively lower socioeconomic status. Our findings indicate that participants' perceived socioeconomic disparities extend to disparities in their health status. The reinforcement of welfare measures is greatly needed to temper these disparities. PMID:26839467

  16. The Perceived Socioeconomic Status Is an Important Factor of Health Recovery for Victims of Occupational Accidents in Korea.

    PubMed

    Seok, Hongdeok; Yoon, Jin-Ha; Lee, Wanhyung; Lee, June-Hee; Jung, Pil Kyun; Roh, Jaehoon; Won, Jong-Uk

    2016-02-01

    We aimed to examine whether there is a correlation between the health recovery of industrial accident victims and their perceived socioeconomic status. Data were obtained from the first Panel Study of Worker's Compensation Insurance, which included 2,000 participants. We performed multivariate regression analysis and determined the odds ratios for participants with a subjectively lower socioeconomic status and for those with a subjectively lower middle socioeconomic status using 95% confidence intervals. An additional multivariate regression analysis yielded the odds ratios for participants with a subjectively lower socioeconomic status and those with a subjectively upper middle socioeconomic class using 95% confidence intervals. Of all participants, 299 reported a full recovery, whereas 1,701 did not. We examined the odds ratio (95% confidence intervals) for participants' health recovery according to their subjective socioeconomic status while controlling for sex, age, education, tobacco use, alcohol use, subjective state of health prior to the accident, chronic disease, employment duration, recovery period, accident type, disability status, disability rating, and economic participation. The odds of recovery in participants with a subjectively lower middle socioeconomic status were 1.707 times greater (1.264-2.305) than that of those with a subjectively lower socioeconomic status. Similarly, the odds of recovery in participants with a subjectively upper middle socioeconomic status were 3.124 times greater (1.795-5.438) than that of those with a subjectively lower socioeconomic status. Our findings indicate that participants' perceived socioeconomic disparities extend to disparities in their health status. The reinforcement of welfare measures is greatly needed to temper these disparities. PMID:26839467

  17. The ubiquitin-conjugating enzyme UBE2E3 and its import receptor importin-11 regulate the localization and activity of the antioxidant transcription factor NRF2

    PubMed Central

    Plafker, Kendra S.; Plafker, Scott M.

    2015-01-01

    The transcription factor NF-E2 p45–related factor (Nrf2) induces the expression of cytoprotective proteins that maintain and restore redox homeostasis. Nrf2 levels and activity are tightly regulated, and three subcellular populations of the transcription factor have been identified. During homeostasis, the majority of Nrf2 is degraded in the cytoplasm by ubiquitin (Ub)-mediated degradation. A second population is transcriptionally active in the nucleus, and a third population localizes to the outer mitochondrial membrane. Still unresolved are the mechanisms and factors that govern Nrf2 distribution between its subcellular locales. We show here that the Ub-conjugating enzyme UBE2E3 and its nuclear import receptor importin 11 (Imp-11) regulate Nrf2 distribution and activity. Knockdown of UBE2E3 reduces nuclear Nrf2, decreases Nrf2 target gene expression, and relocalizes the transcription factor to a perinuclear cluster of mitochondria. In a complementary manner, Imp-11 functions to restrict KEAP1, the major suppressor of Nrf2, from prematurely extracting the transcription factor off of a subset of target gene promoters. These findings identify a novel pathway of Nrf2 modulation during homeostasis and support a model in which UBE2E3 and Imp-11 promote Nrf2 transcriptional activity by restricting the transcription factor from partitioning to the mitochondria and limiting the repressive activity of nuclear KEAP1. PMID:25378586

  18. Disentangling the relative importance of host tree community, abiotic environment and spatial factors on ectomycorrhizal fungal assemblages along an elevation gradient.

    PubMed

    Matsuoka, Shunsuke; Mori, Akira S; Kawaguchi, Eri; Hobara, Satoru; Osono, Takashi

    2016-05-01

    Recent studies have shown that changes in community compositions of ectomycorrhizal (ECM) fungi along elevation gradients are mainly affected by changes in host tree communities and/or in abiotic environments. However, few studies have taken the effects of processes related to fungal dispersal (i.e. spatial processes) into account and distinguished the effects of host community, abiotic environment and spatial processes on community composition along elevation gradients. This has left unclear the relative importance of these factors in structuring the ECM community assemblages. To address this, we investigated the community composition of ECM fungi along an elevation gradient in northern Japan with 454 meta-barcoding. We found that the community composition of ECM fungi changed along the elevation and that all three factors jointly affected the compositional changes. We separated the magnitude of importance of the three factors in structuring ECM fungal communities and found that most of the spatial variation in ECM fungal community was explained by host communities and abiotic environments. Our results suggest that while biotic and/or abiotic environments can be important factors in determining the ECM fungal community composition along an elevation gradient, spatial processes may also be a primary determinant. PMID:26917782

  19. Food additives

    PubMed Central

    Spencer, Michael

    1974-01-01

    Food additives are discussed from the food technology point of view. The reasons for their use are summarized: (1) to protect food from chemical and microbiological attack; (2) to even out seasonal supplies; (3) to improve their eating quality; (4) to improve their nutritional value. The various types of food additives are considered, e.g. colours, flavours, emulsifiers, bread and flour additives, preservatives, and nutritional additives. The paper concludes with consideration of those circumstances in which the use of additives is (a) justified and (b) unjustified. PMID:4467857

  20. A mutation in the yeast heat-shock factor gene causes temperature-sensitive defects in both mitochondrial protein import and the cell cycle.

    PubMed Central

    Smith, B J; Yaffe, M P

    1991-01-01

    Yeast cells containing the recessive mas3 mutation display temperature-sensitive defects in both mitochondrial protein import and the cell division cycle. The import defect is characterized by two pools of mitochondrial precursors and a dramatically slower rate of posttranslational import. The effect of mas3 on cell cycle progression occurs within one cell cycle at the nonpermissive temperature and retards progression through the G2 stage. The mas3 mutation maps to the gene encoding yeast heat-shock transcription factor (HSF), and expression of wild-type HSF complements the temperature-sensitive defects. The mas3 lesion has no apparent effect on protein secretion. In mas3 cells, induction of a major heat-shock gene, SSA1, is defective at 37 degrees C. The properties of the mas3 mutant cells indicate that HSF mediates the response to stress of two basic cellular processes: mitochondrial protein import and cell cycle progression. Images PMID:2017170

  1. Important factors for achieving survival of five years or more in non-small cell lung cancer patients with distant metastasis.

    PubMed

    Hirashima, Tomonori; Suzuki, Hidekazu; Okamoto, Norio; Morishita, Naoko; Yamadori, Tadahiro; Tamiya, Motohiro; Shiroyama, Takayuki; Kurata, Kanako; Kawase, Ichiro

    2014-07-01

    In order to examine which factors were important for achieving a ≥5 year survival time in non-small cell lung cancer (NSCLC) patients with distant metastasis, 268 NSCLC patients who received first-line chemotherapy between January 2004 and December 2007 were retrospectively examined. The median survival time of the patients was 14 months, with 22 surviving for ≥5 years, 48 for ≥2 years, but <5 years, and 198 surviving <2 years. Multivariate analysis determined that never having smoked, a good performance status, relapse following thoracic surgery and intra-thoracic metastasis were significantly favorable prognostic factors, while abdominal metastasis was a significantly poor prognostic factor. The ≥5 years and ≥2-5 years groups had significantly more favorable prognostic factors than the <2 years group. The never-smoked status was a particularly important factor for ≥5 years of survival. The ≥5 years and ≥2-5 years groups achieved a significantly more favorable response to first-line chemotherapy, and a greater number of regimens, total months of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) treatment and cytotoxic agent treatment cycles compared with the <2 years group. In total, ~50% of the patients received palliative radiotherapy. In the ≥5 years group, patients with EGFR drug-sensitive mutations achieved ≥5 years of survival mainly by EGFR-TKI therapy, while those without EGFR mutations achieved ≥5 years of survival by continuing effective cytotoxic agents. Achievement of >5 years of survival was found to correlate with the presence of favorable prognostic factors, response to first-line chemotherapy, provision of appropriate EGFR-TKI therapy according to genetic testing results, continuing effective cytotoxic regimens and the use of radiotherapy as local therapy. PMID:24959271

  2. Important factors for achieving survival of five years or more in non-small cell lung cancer patients with distant metastasis

    PubMed Central

    HIRASHIMA, TOMONORI; SUZUKI, HIDEKAZU; OKAMOTO, NORIO; MORISHITA, NAOKO; YAMADORI, TADAHIRO; TAMIYA, MOTOHIRO; SHIROYAMA, TAKAYUKI; KURATA, KANAKO; KAWASE, ICHIRO

    2014-01-01

    In order to examine which factors were important for achieving a ≥5 year survival time in non-small cell lung cancer (NSCLC) patients with distant metastasis, 268 NSCLC patients who received first-line chemotherapy between January 2004 and December 2007 were retrospectively examined. The median survival time of the patients was 14 months, with 22 surviving for ≥5 years, 48 for ≥2 years, but <5 years, and 198 surviving <2 years. Multivariate analysis determined that never having smoked, a good performance status, relapse following thoracic surgery and intra-thoracic metastasis were significantly favorable prognostic factors, while abdominal metastasis was a significantly poor prognostic factor. The ≥5 years and ≥2–5 years groups had significantly more favorable prognostic factors than the <2 years group. The never-smoked status was a particularly important factor for ≥5 years of survival. The ≥5 years and ≥2–5 years groups achieved a significantly more favorable response to first-line chemotherapy, and a greater number of regimens, total months of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) treatment and cytotoxic agent treatment cycles compared with the <2 years group. In total, ~50% of the patients received palliative radiotherapy. In the ≥5 years group, patients with EGFR drug-sensitive mutations achieved ≥5 years of survival mainly by EGFR-TKI therapy, while those without EGFR mutations achieved ≥5 years of survival by continuing effective cytotoxic agents. Achievement of >5 years of survival was found to correlate with the presence of favorable prognostic factors, response to first-line chemotherapy, provision of appropriate EGFR-TKI therapy according to genetic testing results, continuing effective cytotoxic regimens and the use of radiotherapy as local therapy. PMID:24959271

  3. 5-Aminosalicylic Acid Azo-Linked to Procainamide Acts as an Anticolitic Mutual Prodrug via Additive Inhibition of Nuclear Factor kappaB.

    PubMed

    Kim, Wooseong; Nam, Joon; Lee, Sunyoung; Jeong, Seongkeun; Jung, Yunjin

    2016-06-01

    To improve the anticolitic efficacy of 5-aminosalicylic acid (5-ASA), a colon-specific mutual prodrug of 5-ASA was designed. 5-ASA was coupled to procainamide (PA), a local anesthetic, via an azo bond to prepare 5-(4-{[2-(diethylamino)ethyl]carbamoyl}phenylazo)salicylic acid (5-ASA-azo-PA). 5-ASA-azo-PA was cleaved to 5-ASA and PA up to about 76% at 10 h in the cecal contents while remaining stable in the small intestinal contents. Oral gavage of 5-ASA-azo-PA and sulfasalazine, a colon-specific prodrug currently used in clinic, to rats showed similar efficiency in delivery of 5-ASA to the large intestine, and PA was not detectable in the blood after 5-ASA-azo-PA administration. Oral gavage of 5-ASA-azo-PA alleviated 2,4,6-trinitrobenzenesulfonic acid-induced rat colitis. Moreover, combined intracolonic treatment with 5-ASA and PA elicited an additive ameliorative effect. Furthermore, combined treatment with 5-ASA and PA additively inhibited nuclear factor-kappaB (NFκB) activity in human colon carcinoma cells and inflamed colonic tissues. Finally, 5-ASA-azo-PA administered orally was able to reduce inflammatory mediators, NFκB target gene products, in the inflamed colon. 5-ASA-azo-PA may be a colon-specific mutual prodrug acting against colitis, and the mutual anticolitic effects occurred at least partly through the cooperative inhibition of NFκB activity. PMID:27112518

  4. A Risk Score with Additional Four Independent Factors to Predict the Incidence and Recovery from Metabolic Syndrome: Development and Validation in Large Japanese Cohorts

    PubMed Central

    Obokata, Masaru; Negishi, Kazuaki; Ohyama, Yoshiaki; Okada, Haruka; Imai, Kunihiko; Kurabayashi, Masahiko

    2015-01-01

    Background Although many risk factors for Metabolic syndrome (MetS) have been reported, there is no clinical score that predicts its incidence. The purposes of this study were to create and validate a risk score for predicting both incidence and recovery from MetS in a large cohort. Methods Subjects without MetS at enrollment (n = 13,634) were randomly divided into 2 groups and followed to record incidence of MetS. We also examined recovery from it in rest 2,743 individuals with prevalent MetS. Results During median follow-up of 3.0 years, 878 subjects in the derivation and 757 in validation cohorts developed MetS. Multiple logistic regression analysis identified 12 independent variables from the derivation cohort and initial score for subsequent MetS was created, which showed good discrimination both in the derivation (c-statistics 0.82) and validation cohorts (0.83). The predictability of the initial score for recovery from MetS was tested in the 2,743 MetS population (906 subjects recovered from MetS), where nine variables (including age, sex, γ-glutamyl transpeptidase, uric acid and five MetS diagnostic criteria constituents.) remained significant. Then, the final score was created using the nine variables. This score significantly predicted both the recovery from MetS (c-statistics 0.70, p<0.001, 78% sensitivity and 54% specificity) and incident MetS (c-statistics 0.80) with an incremental discriminative ability over the model derived from five factors used in the diagnosis of MetS (continuous net reclassification improvement: 0.35, p < 0.001 and integrated discrimination improvement: 0.01, p<0.001). Conclusions We identified four additional independent risk factors associated with subsequent MetS, developed and validated a risk score to predict both incident and recovery from MetS. PMID:26230621

  5. A Zinc-Finger-Family Transcription Factor, AbVf19, Is Required for the Induction of a Gene Subset Important for Virulence in Alternaria brassicicola

    SciTech Connect

    Srivastava, Akhil; Ohm, Robin A.; Oxiles, Lindsay; Brooks, Fred; Lawrence, Christopher B.; Grigoriev, Igor V.; Cho, Yangrae

    2011-10-26

    Alternaria brassicicola is a successful saprophyte and necrotrophic plant pathogen with a broad host range within the family Brassicaceae. It produces secondary metabolites that marginally affect virulence. Cell wall degrading enzymes (CDWE) have been considered important for pathogenesis but none of them individually have been identified as significant virulence factors in A. brassicicola. In this study, knockout mutants of a gene, AbVf19, were created and produced considerably smaller lesions than the wild type on inoculated host plants. The presence of tandem zinc-finger domains in the predicted amino acid sequence and nuclear localization of AbVf19- reporter protein suggested that it was a transcription factor. Gene expression comparisons using RNA-seq identified 74 genes being downregulated in the mutant during a late stage of infection. Among the 74 downregulated genes, 28 were putative CWDE genes. These were hydrolytic enzyme genes that composed a small fraction of genes within each family of cellulases, pectinases, cutinases, and proteinases. The mutants grew slower than the wild type on an axenic medium with pectin as a major carbon source. This study demonstrated the existence and the importance of a transcription factor that regulates a suite of genes that are important for decomposing and utilizing plant material during the late stage of plant infection.

  6. Genetic Factors of Ophthalmic Importance.

    ERIC Educational Resources Information Center

    Pollard, Zane F.

    Reviewed are chromosomal anomalies affecting one's eyes. Brief descriptions are given of the genetic etiology of bilateral retinoblastoma (malignant tumors), aniridia (absence of the iris), cataracts, congenital glaucoma, Reginitis Pigmentosa (progressive deterioration of the visual cells), Choroidermia (degeneration of the vascular coat of the…

  7. SU-E-T-491: Importance of Energy Dependent Protons Per MU Calibration Factors in IMPT Dose Calculations Using Monte Carlo Technique

    SciTech Connect

    Randeniya, S; Mirkovic, D; Titt, U; Guan, F; Mohan, R

    2014-06-01

    Purpose: In intensity modulated proton therapy (IMPT), energy dependent, protons per monitor unit (MU) calibration factors are important parameters that determine absolute dose values from energy deposition data obtained from Monte Carlo (MC) simulations. Purpose of this study was to assess the sensitivity of MC-computed absolute dose distributions to the protons/MU calibration factors in IMPT. Methods: A “verification plan” (i.e., treatment beams applied individually to water phantom) of a head and neck patient plan was calculated using MC technique. The patient plan had three beams; one posterior-anterior (PA); two anterior oblique. Dose prescription was 66 Gy in 30 fractions. Of the total MUs, 58% was delivered in PA beam, 25% and 17% in other two. Energy deposition data obtained from the MC simulation were converted to Gy using energy dependent protons/MU calibrations factors obtained from two methods. First method is based on experimental measurements and MC simulations. Second is based on hand calculations, based on how many ion pairs were produced per proton in the dose monitor and how many ion pairs is equal to 1 MU (vendor recommended method). Dose distributions obtained from method one was compared with those from method two. Results: Average difference of 8% in protons/MU calibration factors between method one and two converted into 27 % difference in absolute dose values for PA beam; although dose distributions preserved the shape of 3D dose distribution qualitatively, they were different quantitatively. For two oblique beams, significant difference in absolute dose was not observed. Conclusion: Results demonstrate that protons/MU calibration factors can have a significant impact on absolute dose values in IMPT depending on the fraction of MUs delivered. When number of MUs increases the effect due to the calibration factors amplify. In determining protons/MU calibration factors, experimental method should be preferred in MC dose calculations

  8. Phosphorylation and Dephosphorylation of the Presequence of Precursor MULTIPLE ORGANELLAR RNA EDITING FACTOR3 during Import into Mitochondria from Arabidopsis1[OPEN

    PubMed Central

    Law, Yee-Song; Zhang, Renshan; Guan, Xiaoqian; Cheng, Shifeng; Sun, Feng; Duncan, Owen; Murcha, Monika W.; Whelan, James; Lim, Boon Leong

    2015-01-01

    The nucleus-encoded mitochondria-targeted proteins, multiple organellar RNA editing factors (MORF3, MORF5, and MORF6), interact with Arabidopsis (Arabidopsis thaliana) PURPLE ACID PHOSPHATASE2 (AtPAP2) located on the chloroplast and mitochondrial outer membranes in a presequence-dependent manner. Phosphorylation of the presequence of the precursor MORF3 (pMORF3) by endogenous kinases in wheat germ translation lysate, leaf extracts, or STY kinases, but not in rabbit reticulocyte translation lysate, resulted in the inhibition of protein import into mitochondria. This inhibition of import could be overcome by altering threonine/serine residues to alanine on the presequence, thus preventing phosphorylation. Phosphorylated pMORF3, but not the phosphorylation-deficient pMORF3, can form a complex with 14-3-3 proteins and HEAT SHOCK PROTEIN70. The phosphorylation-deficient mutant of pMORF3 also displayed faster rates of import when translated in wheat germ lysates. Mitochondria isolated from plants with altered amounts of AtPAP2 displayed altered protein import kinetics. The import rate of pMORF3 synthesized in wheat germ translation lysate into pap2 mitochondria was slower than that into wild-type mitochondria, and this rate disparity was not seen for pMORF3 synthesized in rabbit reticulocyte translation lysate, the latter translation lysate largely deficient in kinase activity. Taken together, these results support a role for the phosphorylation and dephosphorylation of pMORF3 during the import into plant mitochondria. These results suggest that kinases, possibly STY kinases, and AtPAP2 are involved in the import of protein into both mitochondria and chloroplasts and provide a mechanism by which the import of proteins into both organelles may be coordinated. PMID:26304849

  9. Additive effect of calreticulin and translation initiation factor eIF4E on secreted protein production in the baculovirus expression system.

    PubMed

    Teng, Chao-Yi; van Oers, Monique M; Wu, Tzong-Yuan

    2013-10-01

    The baculovirus expression vector system is widely used for the production of recombinant proteins. However, the yield of membrane-bound or secreted proteins is relatively low when compared with intracellular or nuclear proteins. In a previous study, we had demonstrated that the co-expression of the human chaperones calreticulin (CALR) or β-synuclein (β-syn) increased the production of a secreted protein considerably. A similar effect was also seen when co-expressing insect translation initiation factor eIF4E. In this study, different combinations of the three genes were tested (CALR alone, β-syn + CALR, or β-syn + CALR + eIF4E) to further improve secretory protein production by assessing the expression level of a recombinant secreted alkaline phosphatase (SEFP). An additional 1.8-fold increment of SEFP production was obtained when cells co-expressed all the three "helper" genes, compared to cells, in which only CALR was co-produced with SEFP. Moreover, the duration of the SEFP production lasted much longer in cells that co-expressed these three "helper" genes, up to 10 dpi was observed. Utilization of this "triple-supporters" containing vector offers significant advantages when producing secreted proteins and is likely to have benefits for the production of viral vaccines and other pharmaceutical products. PMID:23900798

  10. Thermoregulation of Meningococcal fHbp, an Important Virulence Factor and Vaccine Antigen, Is Mediated by Anti-ribosomal Binding Site Sequences in the Open Reading Frame.

    PubMed

    Loh, Edmund; Lavender, Hayley; Tan, Felicia; Tracy, Alexander; Tang, Christoph M

    2016-08-01

    During colonisation of the upper respiratory tract, bacteria are exposed to gradients of temperatures. Neisseria meningitidis is often present in the nasopharynx of healthy individuals, yet can occasionally cause severe disseminated disease. The meningococcus can evade the human complement system using a range of strategies that include recruitment of the negative complement regulator, factor H (CFH) via factor H binding protein (fHbp). We have shown previously that fHbp levels are influenced by the ambient temperature, with more fHbp produced at higher temperatures (i.e. at 37°C compared with 30°C). Here we further characterise the mechanisms underlying thermoregulation of fHbp, which occurs gradually over a physiologically relevant range of temperatures. We show that fHbp thermoregulation is not dependent on the promoters governing transcription of the bi- or mono-cistronic fHbp mRNA, or on meningococcal specific transcription factors. Instead, fHbp thermoregulation requires sequences located in the translated region of the mono-cistronic fHbp mRNA. Site-directed mutagenesis demonstrated that two anti-ribosomal binding sequences within the coding region of the fHbp transcript are involved in fHbp thermoregulation. Our results shed further light on mechanisms underlying the control of the production of this important virulence factor and vaccine antigen. PMID:27560142

  11. Thermoregulation of Meningococcal fHbp, an Important Virulence Factor and Vaccine Antigen, Is Mediated by Anti-ribosomal Binding Site Sequences in the Open Reading Frame

    PubMed Central

    Loh, Edmund; Lavender, Hayley; Tan, Felicia; Tracy, Alexander; Tang, Christoph M.

    2016-01-01

    During colonisation of the upper respiratory tract, bacteria are exposed to gradients of temperatures. Neisseria meningitidis is often present in the nasopharynx of healthy individuals, yet can occasionally cause severe disseminated disease. The meningococcus can evade the human complement system using a range of strategies that include recruitment of the negative complement regulator, factor H (CFH) via factor H binding protein (fHbp). We have shown previously that fHbp levels are influenced by the ambient temperature, with more fHbp produced at higher temperatures (i.e. at 37°C compared with 30°C). Here we further characterise the mechanisms underlying thermoregulation of fHbp, which occurs gradually over a physiologically relevant range of temperatures. We show that fHbp thermoregulation is not dependent on the promoters governing transcription of the bi- or mono-cistronic fHbp mRNA, or on meningococcal specific transcription factors. Instead, fHbp thermoregulation requires sequences located in the translated region of the mono-cistronic fHbp mRNA. Site-directed mutagenesis demonstrated that two anti-ribosomal binding sequences within the coding region of the fHbp transcript are involved in fHbp thermoregulation. Our results shed further light on mechanisms underlying the control of the production of this important virulence factor and vaccine antigen. PMID:27560142

  12. Proteomics Profiling of Chikungunya-Infected Aedes albopictus C6/36 Cells Reveal Important Mosquito Cell Factors in Virus Replication

    PubMed Central

    Lee, Regina Ching Hua; Chu, Justin Jang Hann

    2015-01-01

    Chikungunya virus (CHIKV) is the only causative agent of CHIKV fever with persistent arthralgia, and in some cases may lead to neurological complications which can be highly fatal, therefore it poses severe health issues in many parts of the world. CHIKV transmission can be mediated via the Aedes albopictus mosquito; however, very little is currently known about the involvement of mosquito cellular factors during CHIKV-infection within the mosquito cells. Unravelling the neglected aspects of mosquito proteome changes in CHIKV-infected mosquito cells may increase our understanding on the differences in the host factors between arthropod and mammalian cells for successful replication of CHIKV. In this study, the CHIKV-infected C6/36 cells with differential cellular proteins expression were profiled using two-dimensional gel electrophoresis (2DE) coupled with the use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). 2DE analysis on CHIKV-infected C6/36 cells has shown 23 mosquito cellular proteins that are differentially regulated, and which are involved diverse biological pathways, such as protein folding and metabolic processes. Among those identified mosquito proteins, spermatogenesis-associated factor, enolase phosphatase e-1 and chaperonin-60kD have been found to regulate CHIKV infection. Furthermore, siRNA-mediated gene knockdown of these proteins has demonstrated the biological importance of these host proteins that mediate CHIKV infection. These findings have provided an insight to the importance of mosquito host factors in the replication of CHIKV, thus providing a potential channel for developing novel antiviral strategies against CHIKV transmission. PMID:25738640

  13. Solving the Big Data (BD) Problem in Advanced Manufacturing (Subcategory for work done at Georgia Tech. Study Process and Design Factors for Additive Manufacturing Improvement)

    SciTech Connect

    Clark, Brett W.; Diaz, Kimberly A.; Ochiobi, Chinaza Darlene; Paynabar, Kamran

    2015-09-01

    3D printing originally known as additive manufacturing is a process of making 3 dimensional solid objects from a CAD file. This ground breaking technology is widely used for industrial and biomedical purposes such as building objects, tools, body parts and cosmetics. An important benefit of 3D printing is the cost reduction and manufacturing flexibility; complex parts are built at the fraction of the price. However, layer by layer printing of complex shapes adds error due to the surface roughness. Any such error results in poor quality products with inaccurate dimensions. The main purpose of this research is to measure the amount of printing errors for parts with different geometric shapes and to analyze them for finding optimal printing settings to minimize the error. We use a Design of Experiments framework, and focus on studying parts with cone and ellipsoid shapes. We found that the orientation and the shape of geometric shapes have significant effect on the printing error. From our analysis, we also determined the optimal orientation that gives the least printing error.

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

    PubMed Central

    2011-01-01

    Background Salt stress hinders the growth of plants and reduces crop production worldwide. However, different plant species might possess different adaptive mechanisms to mitigate salt stress. We conducted a detailed pathway analysis of transcriptional dynamics in the roots of Medicago truncatula seedlings under salt stress and selected a transcription factor gene, MtCBF4, for experimental validation. Results A microarray experiment was conducted using root samples collected 6, 24, and 48 h after application of 180 mM NaCl. Analysis of 11 statistically significant expression profiles revealed different behaviors between primary and secondary metabolism pathways in response to external stress. Secondary metabolism that helps to maintain osmotic balance was induced. One of the highly induced transcription factor genes was successfully cloned, and was named MtCBF4. Phylogenetic analysis revealed that MtCBF4, which belongs to the AP2-EREBP transcription factor family, is a novel member of the CBF transcription factor in M. truncatula. MtCBF4 is shown to be a nuclear-localized protein. Expression of MtCBF4 in M. truncatula was induced by most of the abiotic stresses, including salt, drought, cold, and abscisic acid, suggesting crosstalk between these abiotic stresses. Transgenic Arabidopsis over-expressing MtCBF4 enhanced tolerance to drought and salt stress, and activated expression of downstream genes that contain DRE elements. Over-expression of MtCBF4 in M. truncatula also enhanced salt tolerance and induced expression level of corresponding downstream genes. Conclusion Comprehensive transcriptomic analysis revealed complex mechanisms exist in plants in response to salt stress. The novel transcription factor gene MtCBF4 identified here played an important role in response to abiotic stresses, indicating that it might be a good candidate gene for genetic improvement to produce stress-tolerant plants. PMID:21718548

  15. Social and Demographic Factors Associated with Morbidities in Young Children in Egypt: A Bayesian Geo-Additive Semi-Parametric Multinomial Model

    PubMed Central

    Khatab, Khaled; Adegboye, Oyelola; Mohammed, Taofeeq Ibn

    2016-01-01

    Background Globally, the burden of mortality in children, especially in poor developing countries, is alarming and has precipitated concern and calls for concerted efforts in combating such health problems. Examples of diseases that contribute to this burden of mortality include diarrhoea, cough, fever, and the overlap between these illnesses, causing childhood morbidity and mortality. Methods To gain insight into these health issues, we employed the 2008 Demographic and Health Survey Data of Egypt, which recorded details from 10,872 children under five. This data focused on the demographic and socio-economic characteristics of household members. We applied a Bayesian multinomial model to assess the area-specific spatial effects and risk factors of co-morbidity of fever, diarrhoea and cough for children under the age of five. Results The results showed that children under 20 months of age were more likely to have the three diseases (OR: 6.8; 95% CI: 4.6–10.2) than children between 20 and 40 months (OR: 2.14; 95% CI: 1.38–3.3). In multivariate Bayesian geo-additive models, the children of mothers who were over 20 years of age were more likely to have only cough (OR: 1.2; 95% CI: 0.9–1.5) and only fever (OR: 1.2; 95% CI: 0.91–1.51) compared with their counterparts. Spatial results showed that the North-eastern region of Egypt has a higher incidence than most of other regions. Conclusions This study showed geographic patterns of Egyptian governorates in the combined prevalence of morbidity among Egyptian children. It is obvious that the Nile Delta, Upper Egypt, and south-eastern Egypt have high rates of diseases and are more affected. Therefore, more attention is needed in these areas. PMID:27442018

  16. The effectiveness of power-generating complexes constructed on the basis of nuclear power plants combined with additional sources of energy determined taking risk factors into account

    NASA Astrophysics Data System (ADS)

    Aminov, R. Z.; Khrustalev, V. A.; Portyankin, A. V.

    2015-02-01

    The effectiveness of combining nuclear power plants equipped with water-cooled water-moderated power-generating reactors (VVER) with other sources of energy within unified power-generating complexes is analyzed. The use of such power-generating complexes makes it possible to achieve the necessary load pickup capability and flexibility in performing the mandatory selective primary and emergency control of load, as well as participation in passing the night minimums of electric load curves while retaining high values of the capacity utilization factor of the entire power-generating complex at higher levels of the steam-turbine part efficiency. Versions involving combined use of nuclear power plants with hydrogen toppings and gas turbine units for generating electricity are considered. In view of the fact that hydrogen is an unsafe energy carrier, the use of which introduces additional elements of risk, a procedure for evaluating these risks under different conditions of implementing the fuel-and-hydrogen cycle at nuclear power plants is proposed. Risk accounting technique with the use of statistical data is considered, including the characteristics of hydrogen and gas pipelines, and the process pipelines equipment tightness loss occurrence rate. The expected intensities of fires and explosions at nuclear power plants fitted with hydrogen toppings and gas turbine units are calculated. In estimating the damage inflicted by events (fires and explosions) occurred in nuclear power plant turbine buildings, the US statistical data were used. Conservative scenarios of fires and explosions of hydrogen-air mixtures in nuclear power plant turbine buildings are presented. Results from calculations of the introduced annual risk to the attained net annual profit ratio in commensurable versions are given. This ratio can be used in selecting projects characterized by the most technically attainable and socially acceptable safety.

  17. Potlining Additives

    SciTech Connect

    Rudolf Keller

    2004-08-10

    In this project, a concept to improve the performance of aluminum production cells by introducing potlining additives was examined and tested. Boron oxide was added to cathode blocks, and titanium was dissolved in the metal pool; this resulted in the formation of titanium diboride and caused the molten aluminum to wet the carbonaceous cathode surface. Such wetting reportedly leads to operational improvements and extended cell life. In addition, boron oxide suppresses cyanide formation. This final report presents and discusses the results of this project. Substantial economic benefits for the practical implementation of the technology are projected, especially for modern cells with graphitized blocks. For example, with an energy savings of about 5% and an increase in pot life from 1500 to 2500 days, a cost savings of $ 0.023 per pound of aluminum produced is projected for a 200 kA pot.

  18. Phosphazene additives

    SciTech Connect

    Harrup, Mason K; Rollins, Harry W

    2013-11-26

    An additive comprising a phosphazene compound that has at least two reactive functional groups and at least one capping functional group bonded to phosphorus atoms of the phosphazene compound. One of the at least two reactive functional groups is configured to react with cellulose and the other of the at least two reactive functional groups is configured to react with a resin, such as an amine resin of a polycarboxylic acid resin. The at least one capping functional group is selected from the group consisting of a short chain ether group, an alkoxy group, or an aryloxy group. Also disclosed are an additive-resin admixture, a method of treating a wood product, and a wood product.

  19. Relative importance of fluorescent siderophores and other factors in biological control of Gaeumannomyces graminis var. tritici by Pseudomonas fluorescens 2-79 and M4-80R.

    PubMed Central

    Hamdan, H; Weller, D M; Thomashow, L S

    1991-01-01

    Pseudomonas fluorescens 2-79 suppresses take-all, a major root disease of wheat caused by Gaeumannomyces graminis var. tritici. The bacteria produce an antibiotic, phenazine-1-carboxylic acid (PCA), and a fluorescent pyoverdin siderophore. Previous studies have established that PCA has an important role in the biological control of take-all but that antibiotic production does not account fully for the suppressiveness of the strain. To define the role of the pyoverdin siderophore more precisely, mutants deficient in production of the antibiotic, the siderophore, or both factors were constructed and compared with the parental strain for control of take-all on wheat roots. In all cases, strains that produced PCA were more suppressive than those that did not, and pyoverdin-deficient mutant derivatives controlled take-all as effectively as their respective fluorescent parental strains. Thus, the phenazine antibiotic was the dominant factor in disease suppression and the fluorescent siderophore had little or no role. The siderophore also was of minor importance in a second strain, P. fluorescens M4-80R, that does not produce PCA. Strains 2-79 and M4-80R both produced substances distinct from the pyoverdin siderophore that were responsible for fungal inhibition in vitro under iron limitation, but these substances also had, at most, a minor role in disease suppression in situ. PMID:1838240

  20. The constitutive level of vascular endothelial growth factor (VEGF) is more important than hypoxia-induced VEGF up-regulation in the angiogenesis of human melanoma xenografts

    PubMed Central

    Danielsen, T; Rofstad, E K

    2000-01-01

    Angiogenesis of tumours might develop as a result of environmental conditions, such as hypoxia, and/or as a result of genetic alterations specific for tumour cells. The relative contributions of these mechanisms were investigated by comparing the in vivo expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) to the hypoxic fraction, the angiogenic potential and the vascular density of four human melanoma lines (A-07, D-12, R-18, U-25) grown intradermally in Balb/c nu/nu mice. VEGF expression, bFGF expression and expression of pimonidazole, a marker of hypoxic cells, were investigated by immunohistochemistry. An association between high VEGF and bFGF expression and high angiogenic potential was detected, suggesting an important role for VEGF/bFGF in the angiogenesis of melanomas. High VEGF/bFGF expression was also related to low hypoxic fraction and high vascular density. Thus, the constitutive, genetically determined level of VEGF was probably more important than hypoxia-induced upregulation in the angiogenesis of the melanoma xenografts. © 2000 Cancer Research Campaign PMID:10789719

  1. Environmental factors associated with the distribution of Anopheles gambiae s.s in Ghana; an important vector of lymphatic filariasis and malaria.

    PubMed

    de Souza, Dziedzom; Kelly-Hope, Louise; Lawson, Bernard; Wilson, Michael; Boakye, Daniel

    2010-01-01

    Anopheles gambiae s.s mosquitoes are important vectors of lymphatic filariasis (LF) and malaria in Ghana. To better understand their ecological aspects and influence on disease transmission, we examined the spatial distribution of the An. gambiae (M and S) molecular forms and associated environmental factors, and determined their relationship with disease prevalence. Published and current data available on the An. gambiae species in Ghana were collected in a database for analysis, and the study sites were georeferenced and mapped. Using the An. gambiae s.s sites, environmental data were derived from climate, vegetation and remote-sensed satellite sources, and disease prevalence data from existing LF and malaria maps in the literature. The data showed that An. gambiae M and S forms were sympatric in most locations. However, the S form predominated in the central region, while the M form predominated in the northern and coastal savanna regions. Bivariate and multiple regression analyses identified temperature as a key factor distinguishing their distributions. An. gambiae M was significantly correlated with LF, and 2.5 to 3 times more prevalent in the high LF zone than low to medium zones. There were no significant associations between high prevalence An. gambiae s.s locations and malaria. The distribution of the An. gambiae M and S forms and the diseases they transmit in Ghana appear to be distinct, driven by different environmental factors. This study provides useful baseline information for disease control, and future work on the An. gambiae s.s in Ghana. PMID:20360950

  2. Mental health is the most important factor influencing quality of life in elderly left behind when families migrate out of rural China1

    PubMed Central

    Xie, Jian-fei; Ding, Si-qing; Zhong, Zhu-qing; Yi, Qi-feng; Zeng, Sai-nan; Hu, Jun-hua; Zhou, Jian-da

    2014-01-01

    Objectives to investigate the quality of life and the associated factors on left behind elderly in rural China. Method the research was conducted cluster sampling to select 456 elderly left behind when family members migrated out of rural China to participate in a cross-sectional study by completing a general data questionnaire and Quality of Life questionnaire. Results 91.5% of the elderly requested psychological counseling and education. For the elderly, scores for mental health (39.56±13.73) were significantly lower compared with Chinese standard data (61.6±13.7) (P<0.001). Age, chronic disease type, gender, residence pattern and economic support from children were the main psychological factors influencing this population. Conclusion mental health is the most important factor influencing quality of life of elderly left behind when family members migrated out of rural China. Our study suggested a need to widely establish a general practitioner team for psychological intervention for improving rural elderly people's Quality of Life level, especially in the psychological domain. PMID:25029045

  3. Importin 8 mediates m7G cap-sensitive nuclear import of the eukaryotic translation initiation factor eIF4E.

    PubMed

    Volpon, Laurent; Culjkovic-Kraljacic, Biljana; Osborne, Michael J; Ramteke, Anup; Sun, Qingxiang; Niesman, Ashley; Chook, Yuh Min; Borden, Katherine L B

    2016-05-10

    Regulation of nuclear-cytoplasmic trafficking of oncoproteins is critical for growth homeostasis. Dysregulated trafficking contributes to malignancy, whereas understanding the process can reveal unique therapeutic opportunities. Here, we focus on eukaryotic translation initiation factor 4E (eIF4E), a prooncogenic protein highly elevated in many cancers, including acute myeloid leukemia (AML). Typically, eIF4E is localized to both the nucleus and cytoplasm, where it acts in export and translation of specific methyl 7-guanosine (m(7)G)-capped mRNAs, respectively. Nuclear accumulation of eIF4E in patients who have AML is correlated with increased eIF4E-dependent export of transcripts encoding oncoproteins. The subcellular localization of eIF4E closely correlates with patients' responses. During clinical responses to the m(7)G-cap competitor ribavirin, eIF4E is mainly cytoplasmic. At relapse, eIF4E reaccumulates in the nucleus, leading to elevated eIF4E-dependent mRNA export. We have identified importin 8 as a factor that directly imports eIF4E into the nucleus. We found that importin 8 is highly elevated in untreated patients with AML, leading to eIF4E nuclear accumulation. Importin 8 only imports cap-free eIF4E. Cap-dependent changes to the structure of eIF4E underpin this selectivity. Indeed, m(7)G cap analogs or ribavirin prevents nuclear entry of eIF4E, which mirrors the trafficking phenotypes observed in patients with AML. Our studies also suggest that nuclear entry is important for the prooncogenic activity of eIF4E, at least in this context. These findings position nuclear trafficking of eIF4E as a critical step in its regulation and position the importin 8-eIF4E complex as a novel therapeutic target. PMID:27114554

  4. mRNA biogenesis-related helicase eIF4AIII from Arabidopsis thaliana is an important factor for abiotic stress adaptation.

    PubMed

    Pascuan, Cecilia; Frare, Romina; Alleva, Karina; Ayub, Nicolás Daniel; Soto, Gabriela

    2016-05-01

    Similar to other plant species, Arabidopsis has a huge repertoire of predicted helicases, including the eIF4AIII factor, a putative component of the exon junction complex related to mRNA biogenesis. In this article, we integrated evolutionary and functional approaches to have a better understanding of eIF4AIII function in plants. Phylogenetic analysis showed that the mRNA biogenesis-related helicase eIF4AIII is the ortholog of the stress-related helicases PDH45 from Pisum sativum and MH1 from Medicago sativa, suggesting evolutionary and probably functional equivalences between mRNA biogenesis and stress-related plant helicases. Molecular and genetic analyses confirmed the relevance of eIF4AIII during abiotic stress adaptation in Arabidopsis. Therefore, in addition to its function in mRNA biogenesis, eIF4AIII can play a role in abiotic stress adaptation. PMID:26883227

  5. The Arabidopsis bHLH Transcription Factors MYC3 and MYC4 Are Targets of JAZ Repressors and Act Additively with MYC2 in the Activation of Jasmonate Responses[C][W

    PubMed Central

    Fernández-Calvo, Patricia; Chini, Andrea; Fernández-Barbero, Gemma; Chico, José-Manuel; Gimenez-Ibanez, Selena; Geerinck, Jan; Eeckhout, Dominique; Schweizer, Fabian; Godoy, Marta; Franco-Zorrilla, José Manuel; Pauwels, Laurens; Witters, Erwin; Puga, María Isabel; Paz-Ares, Javier; Goossens, Alain; Reymond, Philippe; De Jaeger, Geert; Solano, Roberto

    2011-01-01

    Jasmonates (JAs) trigger an important transcriptional reprogramming of plant cells to modulate both basal development and stress responses. In spite of the importance of transcriptional regulation, only one transcription factor (TF), the Arabidopsis thaliana basic helix-loop-helix MYC2, has been described so far as a direct target of JAZ repressors. By means of yeast two-hybrid screening and tandem affinity purification strategies, we identified two previously unknown targets of JAZ repressors, the TFs MYC3 and MYC4, phylogenetically closely related to MYC2. We show that MYC3 and MYC4 interact in vitro and in vivo with JAZ repressors and also form homo- and heterodimers with MYC2 and among themselves. They both are nuclear proteins that bind DNA with sequence specificity similar to that of MYC2. Loss-of-function mutations in any of these two TFs impair full responsiveness to JA and enhance the JA insensitivity of myc2 mutants. Moreover, the triple mutant myc2 myc3 myc4 is as impaired as coi1-1 in the activation of several, but not all, JA-mediated responses such as the defense against bacterial pathogens and insect herbivory. Our results show that MYC3 and MYC4 are activators of JA-regulated programs that act additively with MYC2 to regulate specifically different subsets of the JA-dependent transcriptional response. PMID:21335373

  6. Dual-energy precursor and nuclear erythroid-related factor 2 activator treatment additively improve redox glutathione levels and neuron survival in aging and Alzheimer mouse neurons upstream of reactive oxygen species.

    PubMed

    Ghosh, Debolina; LeVault, Kelsey R; Brewer, Gregory J

    2014-01-01

    To determine whether glutathione (GSH) loss or increased reactive oxygen species (ROS) are more important to neuron loss, aging, and Alzheimer's disease (AD), we stressed or boosted GSH levels in neurons isolated from aging 3xTg-AD neurons compared with those from age-matched nontransgenic (non-Tg) neurons. Here, using titrating with buthionine sulfoximine, an inhibitor of γ-glutamyl cysteine synthetase (GCL), we observed that GSH depletion increased neuronal death of 3xTg-AD cultured neurons at increasing rates across the age span, whereas non-Tg neurons were resistant to GSH depletion until old age. Remarkably, the rate of neuron loss with ROS did not increase in old age and was the same for both genotypes, which indicates that cognitive deficits in the AD model were not caused by ROS. Therefore, we targeted for neuroprotection activation of the redox sensitive transcription factor, nuclear erythroid-related factor 2 (Nrf2) by 18 alpha glycyrrhetinic acid to stimulate GSH synthesis through GCL. This balanced stimulation of a number of redox enzymes restored the lower levels of Nrf2 and GCL seen in 3xTg-AD neurons compared with those of non-Tg neurons and promoted translocation of Nrf2 to the nucleus. By combining the Nrf2 activator together with the NADH precursor, nicotinamide, we increased neuron survival against amyloid beta stress in an additive manner. These stress tests and neuroprotective treatments suggest that the redox environment is more important for neuron survival than ROS. The dual neuroprotective treatment with nicotinamide and an Nrf2 inducer indicates that these age-related and AD-related changes are reversible. PMID:23954169

  7. Lnk is an important modulator of insulin-like growth factor-1/Akt/peroxisome proliferator-activated receptor-gamma axis during adipogenesis of mesenchymal stem cells.

    PubMed

    Lee, Jun Hee; Lee, Sang Hun; Lee, Hyang Seon; Ji, Seung Taek; Jung, Seok Yun; Kim, Jae Ho; Bae, Sun Sik; Kwon, Sang-Mo

    2016-09-01

    Adipogenic differentiation of mesenchymal stem cells (MSCs) is critical for metabolic homeostasis and nutrient signaling during development. However, limited information is available on the pivotal modulators of adipogenic differentiation of MSCs. Adaptor protein Lnk (Src homology 2B3 [SH2B3]), which belongs to a family of SH2-containing proteins, modulates the bioactivities of different stem cells, including hematopoietic stem cells and endothelial progenitor cells. In this study, we investigated whether an interaction between insulin-like growth factor-1 receptor (IGF-1R) and Lnk regulated IGF-1-induced adipogenic differentiation of MSCs. We found that wild-type MSCs showed greater adipogenic differentiation potential than Lnk (-/-) MSCs. An ex vivo adipogenic differentiation assay showed that Lnk (-/-) MSCs had decreased adipogenic differentiation potential compared with wild-type MSCs. Interestingly, we found that Lnk formed a complex with IGF-1R and that IGF-1 induced the dissociation of this complex. In addition, we observed that IGF-1-induced increase in the phosphorylation of Akt and mammalian target of rapamycin was triggered by the dissociation of the IGF-1R-Lnk complex. Expression levels of a pivotal transcription factor peroxisome proliferator-activated receptor gamma (PPAR-γ) and its adipogenic target genes (LPL and FABP4) significantly decreased in Lnk (-/-) MSCs. These results suggested that Lnk adaptor protein regulated the adipogenesis of MSCs through the IGF-1/Akt/PPAR-γ pathway. PMID:27610032

  8. Lnk is an important modulator of insulin-like growth factor-1/Akt/peroxisome proliferator-activated receptor-gamma axis during adipogenesis of mesenchymal stem cells

    PubMed Central

    Lee, Jun Hee; Lee, Sang Hun; Lee, Hyang Seon; Ji, Seung Taek; Jung, Seok Yun; Kim, Jae Ho; Bae, Sun Sik

    2016-01-01

    Adipogenic differentiation of mesenchymal stem cells (MSCs) is critical for metabolic homeostasis and nutrient signaling during development. However, limited information is available on the pivotal modulators of adipogenic differentiation of MSCs. Adaptor protein Lnk (Src homology 2B3 [SH2B3]), which belongs to a family of SH2-containing proteins, modulates the bioactivities of different stem cells, including hematopoietic stem cells and endothelial progenitor cells. In this study, we investigated whether an interaction between insulin-like growth factor-1 receptor (IGF-1R) and Lnk regulated IGF-1-induced adipogenic differentiation of MSCs. We found that wild-type MSCs showed greater adipogenic differentiation potential than Lnk–/– MSCs. An ex vivo adipogenic differentiation assay showed that Lnk–/– MSCs had decreased adipogenic differentiation potential compared with wild-type MSCs. Interestingly, we found that Lnk formed a complex with IGF-1R and that IGF-1 induced the dissociation of this complex. In addition, we observed that IGF-1-induced increase in the phosphorylation of Akt and mammalian target of rapamycin was triggered by the dissociation of the IGF-1R–Lnk complex. Expression levels of a pivotal transcription factor peroxisome proliferator-activated receptor gamma (PPAR-γ) and its adipogenic target genes (LPL and FABP4) significantly decreased in Lnk–/– MSCs. These results suggested that Lnk adaptor protein regulated the adipogenesis of MSCs through the IGF-1/Akt/PPAR-γ pathway. PMID:27610032

  9. Store-operated Ca2+ Entry-associated Regulatory factor (SARAF) Plays an Important Role in the Regulation of Arachidonate-regulated Ca2+ (ARC) Channels.

    PubMed

    Albarran, Letizia; Lopez, Jose J; Woodard, Geoffrey E; Salido, Gines M; Rosado, Juan A

    2016-03-25

    The store-operated Ca(2+)entry-associated regulatory factor (SARAF) has recently been identified as a STIM1 regulatory protein that facilitates slow Ca(2+)-dependent inactivation of store-operated Ca(2+)entry (SOCE). Both the store-operated channels and the store-independent arachidonate-regulated Ca(2+)(ARC) channels are regulated by STIM1. In the present study, we show that, in addition to its location in the endoplasmic reticulum, SARAF is constitutively expressed in the plasma membrane, where it can interact with plasma membrane (PM)-resident ARC forming subunits in the neuroblastoma cell line SH-SY5Y. Using siRNA-based and overexpression approaches we report that SARAF negatively regulates store-independent Ca(2+)entry via the ARC channels. Arachidonic acid (AA) increases the association of PM-resident SARAF with Orai1. Finally, our results indicate that SARAF modulates the ability of AA to promote cell survival in neuroblastoma cells. In addition to revealing new insight into the biology of ARC channels in neuroblastoma cells, these findings provide evidence for an unprecedented location of SARAF in the plasma membrane. PMID:26817842

  10. Early activation of splenic macrophages by tumor necrosis factor alpha is important in determining the outcome of experimental histoplasmosis in mice.

    PubMed Central

    Wu-Hsieh, B A; Lee, G S; Franco, M; Hofman, F M

    1992-01-01

    Experimental infection of animals with Histoplasma capsulatum caused a massive macrophage infiltration into the spleen and induced the production of tumor necrosis factor alpha (TNF-alpha) locally. The cytokine was also produced in vitro by peritoneal exudate macrophages exposed to a large inoculum of yeast cells. Depletion of the cytokine by injection of polyclonal sheep anti-TNF-alpha antibody was detrimental to sublethally infected mice. Fungous burdens in the spleens of TNF-alpha-depleted mice were higher than they were in the infected control mice at days 2, 7, and 9 after infection, and the antibody-treated animals succumbed to the infection. Histopathological study of spleen sections revealed that splenic macrophages were not able to control proliferation of intracellular yeasts as a result of TNF-alpha depletion. It seems that TNF-alpha plays a role in early activation of splenic macrophages which is important in controlling the outcome of an infection. Images PMID:1398934

  11. Non-extractable procyanidins and lignin are important factors in the bile acid binding and radical scavenging properties of cell wall material in some fruits.

    PubMed

    Hamauzu, Yasunori; Mizuno, Yukari

    2011-03-01

    The cell wall components and the food functions of alcohol-insoluble solids (AIS) of Chinese quince, quince, hawthorn, apple, pear and blueberry fruits were analyzed. Chinese quince contained characteristically high contents of cellulose, lignin, and non-extractable procyanidins (NEPCs). On the other hand, the quince AIS contained the highest proportion of NEPCs, the highest mean degree of polymerization (mDP), the strongest radical scavenging activity, and strong bile acid binding activity. In fruit AIS, the lignin and NEPC contents both showed positive correlations with the bile acid binding and radical scavenging activities. The value for mDP × NEPC content was a good index for the radical scavenging activity. The results suggest that highly polymerized NEPCs and lignin are important factors of cell wall components of fruits to having a high functionality, and Chinese quince and quince are interesting fruits from this view point. PMID:21243435

  12. Analytic Hierarchy Process to Define the Most Important Factors and Related Technologies for Empowering Elderly People in Taking an Active Role in their Health.

    PubMed

    Fico, G; Gaeta, E; Arredondo, M T; Pecchia, L

    2015-09-01

    Successful management of health conditions in older population is determined by strategic involvement of a professional team of careers and by empowering patients and their caregivers to take over a central role and responsibility in the daily management of condition. Identifying, structuring and ranking the most important needs related to these aspects could pave the way for improved strategies in designing systems and technological solutions supporting user empowerment. This paper presents the preliminary results of a study aiming to elicit these needs. Healthcare professionals, working together in the European and Innovation Partnership on Active and Healthy Ageing (EIP-AHA) initiative, have defined a set of needs and factors that have been organized in two hierarchies around the concepts of patient activation and proactive and prepared care team, defined in the Chronic Care Model. The two hierarchies have been mapped, by a team of experts in computer science, with technologies and solutions that could facilitate the achievement of the identified needs. PMID:26254254

  13. National Dairy Council Award for Excellence in Medical/Dental Nutrition Education Lecture, 1995: medical-nutrition education--factors important for developing a successful program.

    PubMed

    Weinsier, R L

    1995-10-01

    Currently, there are no established guidelines which define the goals, the course content, or the approach to developing a successful medical-nutrition education program. The result has been great variability in the approach to teaching nutrition to medical students. A common concern among medical educators is how to teach all of the material currently known. The obvious outcome of trying to teach the constantly expanding body of facts is an increasing demand and competition for instructional time. In turn, nutrition educators have fallen into the trap of vying for more time and claiming success for their program on the basis of their acquired number of hours of instruction rather than on the demonstrated quality or effectiveness of their program. The purpose of this report is to recommend a set of goals for nutrition training of medical students and to highlight those factors which appear to be most (and least) important to achieving those goals. It is my belief that the primary goal of educating medical students should be to sensitize students to the relevance of nutrition in the prevention and treatment of disease. A secondary goal should be to impart important information about nutrition. Relative to these goals, and based on previous studies and on my experience at the University of Alabama at Birmingham School of Medicine, I believe that two factors are critical to the success of any medical-nutrition education program: 1) demonstrated relevance of the course material to the practice of medicine, and 2) positive role modeling.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7572717

  14. Kinome Screen Identifies PFKFB3 and Glucose Metabolism as Important Regulators of the Insulin/Insulin-like Growth Factor (IGF)-1 Signaling Pathway.

    PubMed

    Trefely, Sophie; Khoo, Poh-Sim; Krycer, James R; Chaudhuri, Rima; Fazakerley, Daniel J; Parker, Benjamin L; Sultani, Ghazal; Lee, James; Stephan, Jean-Philippe; Torres, Eric; Jung, Kenneth; Kuijl, Coenraad; James, David E; Junutula, Jagath R; Stöckli, Jacqueline

    2015-10-23

    The insulin/insulin-like growth factor (IGF)-1 signaling pathway (ISP) plays a fundamental role in long term health in a range of organisms. Protein kinases including Akt and ERK are intimately involved in the ISP. To identify other kinases that may participate in this pathway or intersect with it in a regulatory manner, we performed a whole kinome (779 kinases) siRNA screen for positive or negative regulators of the ISP, using GLUT4 translocation to the cell surface as an output for pathway activity. We identified PFKFB3, a positive regulator of glycolysis that is highly expressed in cancer cells and adipocytes, as a positive ISP regulator. Pharmacological inhibition of PFKFB3 suppressed insulin-stimulated glucose uptake, GLUT4 translocation, and Akt signaling in 3T3-L1 adipocytes. In contrast, overexpression of PFKFB3 in HEK293 cells potentiated insulin-dependent phosphorylation of Akt and Akt substrates. Furthermore, pharmacological modulation of glycolysis in 3T3-L1 adipocytes affected Akt phosphorylation. These data add to an emerging body of evidence that metabolism plays a central role in regulating numerous biological processes including the ISP. Our findings have important implications for diseases such as type 2 diabetes and cancer that are characterized by marked disruption of both metabolism and growth factor signaling. PMID:26342081

  15. The checkpoint-dependent nuclear accumulation of Rho1p exchange factor Rgf1p is important for tolerance to chronic replication stress

    PubMed Central

    Muñoz, Sofía; Manjón, Elvira; García, Patricia; Sunnerhagen, Per; Sánchez, Yolanda

    2014-01-01

    Guanine nucleotide exchange factors control many aspects of cell morphogenesis by turning on Rho-GTPases. The fission yeast exchange factor Rgf1p (Rho gef1) specifically regulates Rho1p during polarized growth and localizes to cortical sites. Here we report that Rgf1p is relocalized to the cell nucleus during the stalled replication caused by hydroxyurea (HU). Import to the nucleus is mediated by a nuclear localization sequence at the N-terminus of Rgf1p, whereas release into the cytoplasm requires two leucine-rich nuclear export sequences at the C-terminus. Moreover, Rgf1p nuclear accumulation during replication arrest depends on the 14-3-3 chaperone Rad24p and the DNA replication checkpoint kinase Cds1p. Both proteins control the nuclear accumulation of Rgf1p by inhibition of its nuclear export. A mutant, Rgf1p-9A, that substitutes nine serine potential phosphorylation Cds1p sites for alanine fails to accumulate in the nucleus in response to replication stress, and this correlates with a severe defect in survival in the presence of HU. In conclusion, we propose that the regulation of Rgf1p could be part of the mechanism by which Cds1p and Rad24p promote survival in the presence of chronic replication stress. It will be of general interest to understand whether the same is true for homologues of Rgf1p in budding yeast and higher eukaryotes. PMID:24478458

  16. Pip, a lymphoid-restricted IRF, contains a regulatory domain that is important for autoinhibition and ternary complex formation with the Ets factor PU.1.

    PubMed

    Brass, A L; Kehrli, E; Eisenbeis, C F; Storb, U; Singh, H

    1996-09-15

    Pip is a lymphoid-restricted IRF transcription factor that is recruited to composite elements within immunoglobulin light-chain gene enhancers through a specific interaction with the Ets factor PU.1. We have examined the transcriptional regulatory properties of Pip as well as the requirements for its interaction with PU.1 and DNA to form a ternary complex. We demonstrate that Pip is a dichotomous regulator; it specifically stimulates transcription in conjunction with PU.1, but represses alpha/beta-interferon-inducible transcription in the absence of PU.1. Thus, during B-cell activation and differentiation, Pip may function both as an activator to promote B cell-specific gene expression and as a repressor to inhibit the antiproliferative effects of alpha/beta-interferons. Mutational analysis of Pip reveals a carboxy-terminal segment that is important for autoinhibition of DNA binding and ternary complex formation. A domain of Pip containing this segment confers autoinhibition and PU.1-dependent binding activity to the DNA-binding domain of the related IRF family member, p48. On the basis of these and other data we propose a model for PU.1/Pip ternary complex formation. PMID:8824592

  17. A Meta-Analytic Test of Redundancy and Relative Importance of the Dark Triad and Five-Factor Model of Personality.

    PubMed

    O'Boyle, Ernest H; Forsyth, Donelson R; Banks, George C; Story, Paul A; White, Charles D

    2015-12-01

    We examined the relationships between Machiavellianism, narcissism, and psychopathy-the three traits of the Dark Triad (DT)-and the Five-Factor Model (FFM) of personality. The review identified 310 independent samples drawn from 215 sources and yielded information pertaining to global trait relationships and facet-level relationships. We used meta-analysis to examine (a) the bivariate relations between the DT and the five global traits and 30 facets of the FFM, (b) the relative importance of each of the FFM global traits in predicting DT, and (c) the relationship between the DT and FFM facets identified in translational models of narcissism and psychopathy. These analyses identified consistent and theoretically meaningful associations between the DT traits and the facets of the FFM. The five traits of the FFM, in a relative importance analysis, accounted for much of the variance in Machiavellianism, narcissism, and psychopathy, respectively, and facet-level analyses identified specific facets of each FFM trait that were consistently associated with narcissism (e.g., angry/hostility, modesty) and psychopathy (e.g., straightforwardness, deliberation). The FFM explained nearly all of the variance in psychopathy (R(2) c  = .88) and a substantial portion of the variance in narcissism (R(2) c  = .42). PMID:25168647

  18. Rac1 augments Wnt signaling by stimulating β-catenin-lymphoid enhancer factor-1 complex assembly independent of β-catenin nuclear import.

    PubMed

    Jamieson, Cara; Lui, Christina; Brocardo, Mariana G; Martino-Echarri, Estefania; Henderson, Beric R

    2015-11-01

    β-Catenin transduces the Wnt signaling pathway and its nuclear accumulation leads to gene transactivation and cancer. Rac1 GTPase is known to stimulate β-catenin-dependent transcription of Wnt target genes and we confirmed this activity. Here we tested the recent hypothesis that Rac1 augments Wnt signaling by enhancing β-catenin nuclear import; however, we found that silencing/inhibition or up-regulation of Rac1 had no influence on nuclear accumulation of β-catenin. To better define the role of Rac1, we employed proximity ligation assays (PLA) and discovered that a significant pool of Rac1-β-catenin protein complexes redistribute from the plasma membrane to the nucleus upon Wnt or Rac1 activation. More importantly, active Rac1 was shown to stimulate the formation of nuclear β-catenin-lymphoid enhancer factor 1 (LEF-1) complexes. This regulation required Rac1-dependent phosphorylation of β-catenin at specific serines, which when mutated (S191A and S605A) reduced β-catenin binding to LEF-1 by up to 50%, as revealed by PLA and immunoprecipitation experiments. We propose that Rac1-mediated phosphorylation of β-catenin stimulates Wnt-dependent gene transactivation by enhancing β-catenin-LEF-1 complex assembly, providing new insight into the mechanism of cross-talk between Rac1 and canonical Wnt/β-catenin signaling. PMID:26403202

  19. Rac1 augments Wnt signaling by stimulating β-catenin–lymphoid enhancer factor-1 complex assembly independent of β-catenin nuclear import

    PubMed Central

    Jamieson, Cara; Lui, Christina; Brocardo, Mariana G.; Martino-Echarri, Estefania; Henderson, Beric R.

    2015-01-01

    ABSTRACT β-Catenin transduces the Wnt signaling pathway and its nuclear accumulation leads to gene transactivation and cancer. Rac1 GTPase is known to stimulate β-catenin-dependent transcription of Wnt target genes and we confirmed this activity. Here we tested the recent hypothesis that Rac1 augments Wnt signaling by enhancing β-catenin nuclear import; however, we found that silencing/inhibition or up-regulation of Rac1 had no influence on nuclear accumulation of β-catenin. To better define the role of Rac1, we employed proximity ligation assays (PLA) and discovered that a significant pool of Rac1–β-catenin protein complexes redistribute from the plasma membrane to the nucleus upon Wnt or Rac1 activation. More importantly, active Rac1 was shown to stimulate the formation of nuclear β-catenin–lymphoid enhancer factor 1 (LEF-1) complexes. This regulation required Rac1-dependent phosphorylation of β-catenin at specific serines, which when mutated (S191A and S605A) reduced β-catenin binding to LEF-1 by up to 50%, as revealed by PLA and immunoprecipitation experiments. We propose that Rac1-mediated phosphorylation of β-catenin stimulates Wnt-dependent gene transactivation by enhancing β-catenin–LEF-1 complex assembly, providing new insight into the mechanism of cross-talk between Rac1 and canonical Wnt/β-catenin signaling. PMID:26403202

  20. Physics of Intrinsic and Extrinsic Factors that Cause the Onset of the Deadliest Illness of Mankind and are Important for Diagnostics and Treatment

    NASA Astrophysics Data System (ADS)

    Saxena, Arjun

    One of the most important topic of research in the field of Physics of Behavior is the deadliest illness of mankind which is the group of illnesses called mental illnesses. They are getting attention increasingly worldwide by the medical communities and their respective governments, because of the following fact. It is now well established that these illnesses cause more loss of human lives, destruction of families, businesses and overall economy than all the other illnesses combined. The purpose of this paper is to identify and provide solutions to two fundamental issues of such illnesses which still remain as problems. One is the stigma associated with them because of their name ``mental''. The patients are regarded as less than normal because their illness is only ``mental'' in origin. The second is that it is still not widely recognized that they are caused by medical problems in their ``brain'' which afflict their ``mind''. This paper explains this and gives an improved 3-D model using the physics of intrinsic and extrinsic factors of both ``brain'' and ``mind''. It leads to an important new name, ``BAMI'' (Brain and Mind Illness), which eliminates the stigma and gives quantitative parameters to diagnose the illness and monitor medicines to treat such illnesses.

  1. An Epstein-Barr Virus Encoded Inhibitor of Colony Stimulating Factor-1 Signaling Is an Important Determinant for Acute and Persistent EBV Infection

    PubMed Central

    Ohashi, Makoto; Fogg, Mark H.; Orlova, Nina; Quink, Carol; Wang, Fred

    2012-01-01

    Acute Epstein-Barr virus (EBV) infection is the most common cause of Infectious Mononucleosis. Nearly all adult humans harbor life-long, persistent EBV infection which can lead to development of cancers including Hodgkin Lymphoma, Burkitt Lymphoma, nasopharyngeal carcinoma, gastric carcinoma, and lymphomas in immunosuppressed patients. BARF1 is an EBV replication-associated, secreted protein that blocks Colony Stimulating Factor 1 (CSF-1) signaling, an innate immunity pathway not targeted by any other virus species. To evaluate effects of BARF1 in acute and persistent infection, we mutated the BARF1 homologue in the EBV-related herpesvirus, or lymphocryptovirus (LCV), naturally infecting rhesus macaques to create a recombinant rhLCV incapable of blocking CSF-1 (ΔrhBARF1). Rhesus macaques orally challenged with ΔrhBARF1 had decreased viral load indicating that CSF-1 is important for acute virus infection. Surprisingly, ΔrhBARF1 was also associated with dramatically lower virus setpoints during persistent infection. Normal acute viral load and normal viral setpoints during persistent rhLCV infection could be restored by Simian/Human Immunodeficiency Virus-induced immunosuppression prior to oral inoculation with ΔrhBARF1 or infection of immunocompetent animals with a recombinant rhLCV where the rhBARF1 was repaired. These results indicate that BARF1 blockade of CSF-1 signaling is an important immune evasion strategy for efficient acute EBV infection and a significant determinant for virus setpoint during persistent EBV infection. PMID:23300447

  2. Importin 8 mediates m7G cap-sensitive nuclear import of the eukaryotic translation initiation factor eIF4E

    PubMed Central

    Volpon, Laurent; Culjkovic-Kraljacic, Biljana; Osborne, Michael J.; Ramteke, Anup; Sun, Qingxiang; Niesman, Ashley; Chook, Yuh Min; Borden, Katherine L. B.

    2016-01-01

    Regulation of nuclear-cytoplasmic trafficking of oncoproteins is critical for growth homeostasis. Dysregulated trafficking contributes to malignancy, whereas understanding the process can reveal unique therapeutic opportunities. Here, we focus on eukaryotic translation initiation factor 4E (eIF4E), a prooncogenic protein highly elevated in many cancers, including acute myeloid leukemia (AML). Typically, eIF4E is localized to both the nucleus and cytoplasm, where it acts in export and translation of specific methyl 7-guanosine (m7G)–capped mRNAs, respectively. Nuclear accumulation of eIF4E in patients who have AML is correlated with increased eIF4E-dependent export of transcripts encoding oncoproteins. The subcellular localization of eIF4E closely correlates with patients’ responses. During clinical responses to the m7G-cap competitor ribavirin, eIF4E is mainly cytoplasmic. At relapse, eIF4E reaccumulates in the nucleus, leading to elevated eIF4E-dependent mRNA export. We have identified importin 8 as a factor that directly imports eIF4E into the nucleus. We found that importin 8 is highly elevated in untreated patients with AML, leading to eIF4E nuclear accumulation. Importin 8 only imports cap-free eIF4E. Cap-dependent changes to the structure of eIF4E underpin this selectivity. Indeed, m7G cap analogs or ribavirin prevents nuclear entry of eIF4E, which mirrors the trafficking phenotypes observed in patients with AML. Our studies also suggest that nuclear entry is important for the prooncogenic activity of eIF4E, at least in this context. These findings position nuclear trafficking of eIF4E as a critical step in its regulation and position the importin 8–eIF4E complex as a novel therapeutic target. PMID:27114554

  3. Nuclear Import of the Retrotransposon Tf1 Is Governed by a Nuclear Localization Signal That Possesses a Unique Requirement for the FXFG Nuclear Pore Factor Nup124p

    PubMed Central

    Dang, Van-Dinh; Levin, Henry L.

    2000-01-01

    Retroviruses, such as human immunodeficiency virus, that infect nondividing cells generate integration precursors that must cross the nuclear envelope to reach the host genome. As a model for retroviruses, we investigated the nuclear entry of Tf1, a long-terminal-repeat-containing retrotransposon of the fission yeast Schizosaccharomyces pombe. Because the nuclear envelope of yeasts remains intact throughout the cell cycle, components of Tf1 must be transported through the envelope before integration can occur. The nuclear localization of the Gag protein of Tf1 is different from that of other proteins tested in that it has a specific requirement for the FXFG nuclear pore factor, Nup124p. Using extensive mutagenesis, we found that Gag contained three nuclear localization signals (NLSs) which, when included individually in a heterologous protein, were sufficient to direct nuclear import. In the context of the intact transposon, mutations in the NLS that mapped to the first 10 amino acid residues of Gag significantly impaired Tf1 retrotransposition and abolished nuclear localization of Gag. Interestingly, this NLS activity in the heterologous protein was specifically dependent upon the presence of Nup124p. Deletion analysis of heterologous proteins revealed the surprising result that the residues in Gag with the NLS activity were independent from the residues that conveyed the requirement for Nup124p. In fact, a fragment of Gag that lacked NLS activity, residues 10 to 30, when fused to a heterologous protein, was sufficient to cause the classical NLS of simian virus 40 to require Nup124p for nuclear import. Within the context of the current understanding of nuclear import, these results represent the novel case of a short amino acid sequence that specifies the need for a particular nuclear pore complex protein. PMID:11003674

  4. The importance of interactions among nutrition, seasonality and socio-sexual factors in the development of hormone-free methods for controlling fertility.

    PubMed

    Scaramuzzi, R J; Martin, G B

    2008-07-01

    Around the world, consumers are demanding animal products that are produced to agreed standards for human health, environmental management and animal welfare. This has led to the development in Australia of the concept of 'clean, green and ethical' (CGE) animal production based on the manipulation of nutrition ('focus feeding') and the application of phenomena, such as the 'male effect', to provide 'natural' methods for managing small ruminant production systems. With respect to the management of fertility, CGE involves utilization of the inherited responses of animals to environmental factors to manipulate their reproductive processes. The successful development and implementation of this new generation of management tools depends on a thorough yet holistic understanding of the interactions among environmental factors and the ways these interactions affect reproductive physiology and behaviour of the animal. For sheep and goats, a central aspect of CGE management is the way in which ovarian function is affected by three major factors (nutrition, photoperiod and socio-sexual signals) and by interactions among them. Nutrition can exert two profound yet contrasting types of effect on ovarian activity: (i) the complete inhibition of reproduction by undernutrition through the hypothalamic mechanism that controls ovulation and (ii) the enhancement of fecundity by nutritional supplementation, through a direct ovarian mechanism, in females that are already ovulating. A similarly profound control over ovarian function in female sheep and goats is exerted by the well-known endocrine responses to photoperiod (seasonality) and to male socio-sexual signals. The 'male effect' already has a long history as a valuable technique for inducing a synchronized fertile ovulation during seasonal and post-partum anoestrus in sheep and goats. Importantly, experimentation has shown that these three major environmental factors interact, synergistically and antagonistically, but the precise

  5. Clinical spectrum and survival analysis of 145 cases of HIV-negative Castleman’s disease: renal function is an important prognostic factor

    PubMed Central

    Zhang, Lu; Li, Zhiyuan; Cao, Xinxin; Feng, Jun; Zhong, Dingrong; Wang, Shujie; Zhou, Daobin; Li, Jian

    2016-01-01

    Castleman’s disease (CD) is a rare lymphoproliferative disorder with clinical features and prognostic factors that are incompletely characterized. This retrospective single-center study reviewed the largest HIV-negative CD patient cohort (n = 145) to date. By clinical classification, we identified 69 patients (47.6%) as unicentric CD (UCD) and 76 patients (52.4%) as multicentric CD (MCD). Pathological classification identified 74 patients (51.0%) with the hyaline-vascular variant, 51 patients (35.2%) with the plasma-cell variant, and 20 patients (13.8%) with a mixed variant. After a median follow-up duration of 58 months (range, 1–180 months), the 1-year and 5-year survival rates were 95.1% and 91.0%, respectively. UCD patients exhibited significantly better survival (1-year and 5-year survival rates of 98.5% and 97.1%, respectively) compared with MCD patients (1-year and 5-year survival rates of 92.1% and 85.5%, respectively; p = 0.005). By univariate and multivariate Cox regression analyses, the estimated glomerular filtration rate < 60 ml/min (with the MDRD equation; hazard ratio = 4.60; 95% confidence interval, 1.50–14.12; p = 0.008) was clinically significant and represented an independent predictor for death in MCD patients. In summary, this large-scale study suggests that UCD patients enjoy better survival than MCD patients and that renal function is an important prognostic factor for MCD patients. PMID:27029894

  6. DExD-box RNA-helicases in Listeria monocytogenes are important for growth, ribosomal maturation, rRNA processing and virulence factor expression

    PubMed Central

    Bäreclev, Caroline; Vaitkevicius, Karolis; Netterling, Sakura; Johansson, Jörgen

    2014-01-01

    RNA-helicases are proteins required for the unwinding of occluding secondary RNA structures, especially at low temperatures. In this work, we have deleted all 4 DExD-box RNA helicases in various combinations in the Gram-positive pathogen Listeria monocytogenes. Our results show that 3 out of 4 RNA-helicases were important for growth at low temperatures, whereas the effect was less prominent at 37°C. Over-expression of one RNA-helicase, Lmo1450, was able to overcome the reduced growth of the quadruple mutant strain at temperatures above 26°C, but not at lower temperatures. The maturation of ribosomes was affected in different degrees in the various strains at 20°C, whereas the effect was marginal at 37°C. This was accompanied by an increased level of immature 23S rRNA precursors in some of the RNA-helicase mutants at low temperatures. Although the expression of the PrfA regulated virulence factors ActA and LLO decreased in the quadruple mutant strain, this strain showed a slightly increased infection ability. Interestingly, even though the level of the virulence factor LLO was decreased in the quadruple mutant strain as compared with the wild-type strain, the hly-transcript (encoding LLO) was increased. Hence, our results could suggest a role for the RNA-helicases during translation. In this work, we show that DExD-box RNA-helicases are involved in bacterial virulence gene-expression and infection of eukaryotic cells. PMID:25590644

  7. Complement factor B is the downstream effector of TLRs and plays an important role in a mouse model of severe sepsis.

    PubMed

    Zou, Lin; Feng, Yan; Li, Yan; Zhang, Ming; Chen, Chan; Cai, Jiayan; Gong, Yu; Wang, Larry; Thurman, Joshua M; Wu, Xiaobo; Atkinson, John P; Chao, Wei

    2013-12-01

    Severe sepsis involves massive activation of the innate immune system and leads to high mortality. Previous studies have demonstrated that various types of TLRs mediate a systemic inflammatory response and contribute to organ injury and mortality in animal models of severe sepsis. However, the downstream mechanisms responsible for TLR-mediated septic injury are poorly understood. In this article, we show that activation of TLR2, TLR3, and TLR4 markedly enhanced complement factor B (cfB) synthesis and release by macrophages and cardiac cells. Polymicrobial sepsis, created by cecal ligation and puncture in a mouse model, augmented cfB levels in the serum, peritoneal cavity, and major organs including the kidney and heart. Cecal ligation and puncture also led to the alternative pathway activation, C3 fragment deposition in the kidney and heart, and cfB-dependent C3dg elevation. Bacteria isolated from septic mice activated the serum alternative pathway via a factor D-dependent manner. MyD88 deletion attenuated cfB/C3 upregulation as well as cleavage induced by polymicrobial infection. Importantly, during sepsis, absence of cfB conferred a protective effect with improved survival and cardiac function and markedly attenuated acute kidney injury. cfB deletion also led to increased neutrophil migratory function during the early phase of sepsis, decreased local and systemic bacterial load, attenuated cytokine production, and reduced neutrophil reactive oxygen species production. Together, our data indicate that cfB acts as a downstream effector of TLR signaling and plays a critical role in the pathogenesis of severe bacterial sepsis. PMID:24154627

  8. Prevalence, risk factors, and antimicrobial resistance profiles of Salmonella from commercial broiler farms in two important poultry-producing regions of Colombia.

    PubMed

    Donado-Godoy, P; Gardner, I; Byrne, B A; Leon, M; Perez-Gutierrez, E; Ovalle, M V; Tafur, M A; Miller, W

    2012-05-01

    Salmonella is one of the most common foodborne pathogens associated with diarrheal disease in humans. Food animals, especially poultry, are important direct and indirect sources of human salmonellosis, and antimicrobial resistance is an emerging problem of public health concern. The use of antimicrobials benefits producers but contributes to the emergence of antimicrobial resistant bacteria. As a step toward implementing the Colombian Integrated Program for Antimicrobial Resistance Surveillance, this study was conducted to establish the prevalence, distribution of serovars, antimicrobial resistance profiles, and risk factors for Salmonella on poultry farms in the two largest states of poultry production in Colombia. Salmonella was isolated from 41% of farms and 65% of the 315 chicken houses sampled. Salmonella Paratyphi B variant Java was the most prevalent serovar (76%), followed by Salmonella Heidelberg (23%). All Salmonella isolates were resistant to 2 to 15 of the antimicrobial drugs tested in this study. For Salmonella Paratyphi B variant Java, 34 drug resistance patterns were present. The predominant resistance pattern was ciprofloxacin, nitrofurantoin, tetracycline, trimethoprim-sulfamethoxazole, ceftiofur, streptomycin, enrofloxacin, and nalidixic acid; this pattern was detected in 15% of isolates. The resistance pattern of tetracycline, ceftiofur, and nalidixic acid was found in over 40% of the isolates of Salmonella Heidelberg. Of the biosecurity practices considered, two factors were significantly associated with reduction in Salmonella: cleaning of fixed equipment and composting of dead birds on the farm. Findings from the present study provide scientific evidence to inform implementation of official policies that support new biosecurity legislation in an effort to decrease the prevalence of Salmonella on Colombian poultry farms. PMID:22564936

  9. Complement Factor B is the Downstream Effector of Toll-Like Receptors and Plays an Important Role in a Mouse Model of Severe Sepsis¶

    PubMed Central

    Zou, Lin; Feng, Yan; Li, Yan; Zhang, Ming; Chen, Chan; Cai, Jiayan; Gong, Yu; Wang, Larry; Thurman, Joshua M.; Wu, Xiaobo; Atkinson, John P.; Chao, Wei

    2013-01-01

    Severe sepsis involves massive activation of the innate immune system and leads to high mortality. Previous studies have demonstrated that various types of Toll-like receptors (TLRs) mediate a systemic inflammatory response and contribute to organ injury and mortality in animal models of severe sepsis. However, the downstream mechanisms responsible for TLR-mediated septic injury are poorly understood. Here, we show that activation of TLR2, TLR3 and TLR4 markedly enhanced complement factor B (cfB) synthesis and release by macrophages and cardiac cells. Polymicrobial sepsis, created by cecal ligation and puncture (CLP) in a mouse model, augmented cfB levels in the serum, peritoneal cavity and major organs including the kidney and heart. CLP also led to the alternative pathway (AP) activation, C3 fragment deposition in the kidney and heart, and cfB-dependent C3dg elevation. Bacteria isolated from septic mice activated the serum AP via a factor D-dependent manner. MyD88 deletion attenuated cfB/C3 up-regulation as well as cleavage induced by polymicrobial infection. Importantly, during sepsis, absence of cfB conferred a protective effect with improved survival and cardiac function, and markedly attenuated acute kidney injury. cfB deletion also led to increased neutrophil migratory function during the early phase of sepsis, decreased local and systemic bacterial load, attenuated cytokine production and reduced neutrophil reactive oxygen species production. Together, our data indicate that cfB acts as a downstream effector of TLR signaling and plays a critical role in the pathogenesis of severe bacterial sepsis. PMID:24154627

  10. Important factors governing exposure of the population and countermeasure application in rural settlements of the Russian Federation in the long-term after the Chernobyl accident.

    PubMed

    Fesenko, S; Jacob, P; Alexakhin, R; Sanzharova, N I; Panov, A; Fesenko, G; Cecille, L

    2001-01-01

    Rural settlements located in areas of the Russian Federation contaminated after the Chernobyl accident and exceeding an annual dose of 1 mSv a-1 have been classified according to 137Cs contamination density, internal dose and the neighbourhood of forests. It has been shown that, with the exception of the most contaminated areas, the internal doses decreased in accordance with a decline in 137Cs availability for plant root uptake. An inverse tendency was observed in areas with 137Cs contamination above 555 kBq m-2 which can be explained by a reduction or even termination of countermeasure application and by an increasing consumption of forest products in areas where restrictive countermeasures are still implemented. Twenty-seven settlements have been studied to estimate the effectiveness of countermeasures applied previously and to identify the most important factors governing the radiation exposure to the population and its change with time. It has been shown that the effectiveness of countermeasures which resulted in a decrease of up to 40% of doses has a tendency to decline in the long term. The need for continuation of remediation in rural settlements was evaluated both for selected settlements and extrapolated to the whole contaminated area and it has been shown that the application of countermeasures will be of importance at least up to the year 2045. Rather high effectiveness in terms of internal dose reduction (factor of 2-2.5) of radical improvement (disking, ploughing and reseeding) and administration of Cs binders to animals (Ferrocyn) was demonstrated for the selected settlements. It could be demonstrated that for forest-remote settlements there is a linear dependence between internal dose normalised to the density of contamination and the proportion of peat soils around settlements. For near-forest settlements, this dependence was less pronounced which can be explained by the high contribution of forest food products to the internal dose. Milk is still

  11. Antecedents of Charter School Success in New York State: Charter School Management Agencies and Additional Factors That Affect English/Language Arts Test Scores in Elementary Charter Schools

    ERIC Educational Resources Information Center

    Schwarz, Jennifer

    2013-01-01

    Charter schools frequently receive public as well as federal attention, and there is a growing body of research becoming available examining charter schools. With all this research there is still a need for further studies which deal specifically with antecedents of charter school success. This study examined factors contributing toward the…

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

    PubMed Central

    Zhang, Zijin; Chen, Jieming; Su, Yongying; Liu, Hanmei; Chen, Yanger; Luo, Peigao; Du, Xiaogang; Wang, Dan; Zhang, Huaiyu

    2015-01-01

    LHY (late elongated hypocotyl) is an important gene that regulates and controls biological rhythms in plants. Additionally, LHY is highly expressed in the SSH (suppression subtractive hybridization) cDNA library-induced stripe rust pathogen (CYR32) in our previous research. To identify the function of the LHY gene in disease resistance against stripe rust, we used RACE-PCR technology to clone TaLHY in the wheat variety Chuannong19. The cDNA of TaLHY is 3085 bp long with an open reading frame of 1947 bp. TaLHY is speculated to encode a 70.3 kDa protein of 648 amino acids , which has one typical plant MYB-DNA binding domain; additionally, phylogenetic tree shows that TaLHY has the highest homology with LHY of Brachypodium distachyon(BdLHY-like). Quantitative fluorescence PCR indicates that TaLHY has higher expression in the leaf, ear and stem of wheat but lower expression in the root. Infestation of CYR32 can result in up-regulated expression of TaLHY, peaking at 72 h. Using VIGS (virus-induced gene silencing) technology to disease-resistant wheat in the fourth leaf stage, plants with silenced TaLHY cannot complete their heading stage. Through the compatible interaction with the stripe rust physiological race CYR32, Chuannong 19 loses its immune capability toward the stripe rust pathogen, indicating that TaLHY may regulate and participate in the heading of wheat, as well as the defense responses against stripe rust infection. PMID:26010918

  13. On the importance of shrub encroachment by sprouters, climate, species richness and anthropic factors for ecosystem multifunctionality in semi-arid Mediterranean ecosystems

    PubMed Central

    Quero, José L.; Maestre, Fernando T.; Ochoa, Victoria; García-Gómez, Miguel; Delgado-Baquerizo, Manuel

    2016-01-01

    One of the most important changes taking place in drylands worldwide is the increase of the cover and dominance of shrubs in areas formerly devoid of them (shrub encroachment). A large body of research has evaluated the causes and consequences of shrub encroachment for both ecosystem structure and functioning. However, there are virtually no studies evaluating how shrub encroachment affects the ability of ecosystems to maintain multiple functions and services simultaneously (multifunctionality). We aimed to do so by gathering data from ten ecosystem functions linked to the maintenance of primary production and nutrient cycling and storage (organic C, activity of β-glucosidase, pentoses, hexoses, total N, total available N, amino acids, proteins, available inorganic P and phosphatase activity), and summarizing them in a multifunctionality index (M). We assessed how climate, species richness, anthropic factors (distance to the nearest town, sandy and asphalted road, and human population in the nearest town at several historical periods) and encroachment by sprouting shrubs impacted both the functions in isolation and M along a regional (ca. 350 km) gradient in Mediterranean grasslands and shrublands dominated by a non-sprouting shrub. Values of M were higher in those grasslands and shrublands containing sprouting shrubs (43% and 62%, respectively). A similar response was found when analyzing the different functions in isolation, as encroachment by sprouting shrubs increased functions by 2%–80% compared to unencroached areas. Encroachment was the main driver of changes in M along the regional gradient evaluated, followed by anthropic factors and species richness. Climate had little effects on M in comparison to the other factors studied. Similar responses were observed when evaluating the functions in isolation. Overall, our results showed that M was higher at sites with higher sprouting shrub cover, longer distance to roads and higher perennial plant species

  14. Additivity of Factor Effects in Reading Tasks Is Still a Challenge for Computational Models: Reply to Ziegler, Perry, and Zorzi (2009)

    ERIC Educational Resources Information Center

    Besner, Derek; O'Malley, Shannon

    2009-01-01

    J. C. Ziegler, C. Perry, and M. Zorzi (2009) have claimed that their connectionist dual process model (CDP+) can simulate the data reported by S. O'Malley and D. Besner. Most centrally, they have claimed that the model simulates additive effects of stimulus quality and word frequency on the time to read aloud when words and nonwords are randomly…

  15. Additive influence of genetic predisposition and conventional risk factors in the incidence of coronary heart disease: a population-based study in Greece

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An additive genetic risk score (GRS) for coronary heart disease (CHD) has previously been associated with incident CHD in the population-based Greek European Prospective Investigation into Cancer and nutrition (EPIC) cohort. In this study, we explore GRS-‘environment’ joint actions on CHD for severa...

  16. The Importance of Permafrost Thaw, Fire and Logging Disturbances as Driving Factors of Historical and Projected Carbon Dynamics in Alaskan Ecosystems

    NASA Astrophysics Data System (ADS)

    Genet, H.; Zhang, Y.; McGuire, A. D.; He, Y.; Johnson, K. D.; D'Amore, D. V.; Zhou, X.; Bennett, A.; Breen, A. L.; Biles, F. E.; Bliss, N. B.; Euskirchen, E. S.; Kurkowski, T. A.; Pastick, N.; Rupp, S. T.; Wylie, B. K.; Zhu, Z.; Zhuang, Q.

    2014-12-01

    Carbon dynamics of natural ecosystems are influenced by disturbance regimes of various frequencies and magnitudes. With global change, these disturbances are projected to increase in frequency and/or magnitude and may have significant effects on future net carbon balance, especially in high latitude ecosystems where carbon stocks are among the largest on Earth and climate change is substantial. In Alaska, permafrost degradation and fire in the boreal and arctic regions and logging in the southern coastal region are the main disturbances that affect ecosystems. Large uncertainties related to the effects of these disturbances on the capacity of these regions to store carbon still exist mainly due to difficulty in representing permafrost degradation in current ecosystem models. We ran the Terrestrial Ecosystem Model (TEM), which explicitly simulates the carbon cycle and permafrost dynamics, coupled with a disturbance model (the Alaska Frame Based Ecosystem Code, ALFRESCO) to assess the relative importance of permafrost thaw, wildfire, and forest management on historical and projected carbon balance and carbon stocks in Alaska, from 1950 to 2100, at a 1-km resolution. Our simulations showed that the increase in plant productivity in response to warming in boreal and arctic regions is offset by soil carbon loss due to permafrost degradation and wildfire combustion during both historical and future simulations. Fire disturbances act as a catalyst accelerating permafrost degradation and associated soil carbon loss. In addition, our preliminary results for south coastal regions of Alaska indicate that logging of second growth forests could influence carbon dynamics in that region. Overall, these results have implications for land management strategies and illustrate the importance of taking into account multiple types of disturbance regimes in ecosystem models for Alaska.

  17. FgMon1, a guanine nucleotide exchange factor of FgRab7, is important for vacuole fusion, autophagy and plant infection in Fusarium graminearum.

    PubMed

    Li, Ying; Li, Bing; Liu, Luping; Chen, Huaigu; Zhang, Haifeng; Zheng, Xiaobo; Zhang, Zhengguang

    2015-01-01

    The Ccz1-Mon1 protein complex, the guanine nucleotide exchange factor (GEF) of the late endosomal Rab7 homolog Ypt7, is required for the late step of multiple vacuole delivery pathways, such as cytoplasm-to-vacuole targeting (Cvt) pathway and autophagy processes. Here, we identified and characterized the yeast Mon1 homolog in Fusarium graminearum, named FgMon1. FgMON1 encodes a trafficking protein and is well conserved in filamentous fungi. Targeted gene deletion showed that the ∆Fgmon1 mutant was defective in vegetative growth, asexual/sexual development, conidial germination and morphology, plant infection and deoxynivalenol production. Cytological examination revealed that the ∆Fgmon1 mutant was also defective in vacuole fusion and autophagy, and delayed in endocytosis. Yeast two hybrid and in vitro GST-pull down assays approved that FgMon1 physically interacts with a Rab GTPase FgRab7 which is also important for the development, infection, membrane fusion and autophagy in F. graminearum. FgMon1 likely acts as a GEF of FgRab7 and constitutively activated FgRab7 was able to rescue the defects of the ∆Fgmon1 mutant. In summary, our study provides evidences that FgMon1 and FgRab7 are critical components that modulate vesicle trafficking, endocytosis and autophagy, and thereby affect the development, plant infection and DON production of F. graminearum. PMID:26657788

  18. Importance of the NCp7-like domain in the recognition of pre-let-7g by the pluripotency factor Lin28.

    PubMed

    Desjardins, Alexandre; Yang, Ao; Bouvette, Jonathan; Omichinski, James G; Legault, Pascale

    2012-02-01

    The pluripotency factor Lin28 is a highly conserved protein comprising a unique combination of RNA-binding motifs, an N-terminal cold-shock domain and a C-terminal region containing two retroviral-type CCHC zinc-binding domains. An important function of Lin28 is to inhibit the biogenesis of the let-7 family of microRNAs through a direct interaction with let-7 precursors. Here, we systematically characterize the determinants of the interaction between Lin28 and pre-let-7 g by investigating the effect of protein and RNA mutations on in vitro binding. We determine that Lin28 binds with high affinity to the extended loop of pre-let-7 g and that its C-terminal domain contributes predominantly to the affinity of this interaction. We uncover remarkable similarities between this C-terminal domain and the NCp7 protein of HIV-1, not only in terms of primary structure but also in their modes of RNA binding. This NCp7-like domain of Lin28 recognizes a G-rich bulge within pre-let-7 g, which is adjacent to one of the Dicer cleavage sites. We hypothesize that the NCp7-like domain initiates RNA binding and partially unfolds the RNA. This partial unfolding would then enable multiple copies of Lin28 to bind the extended loop of pre-let-7 g and protect the RNA from cleavage by the pre-microRNA processing enzyme Dicer. PMID:22013165

  19. Importance of the NCp7-like domain in the recognition of pre-let-7g by the pluripotency factor Lin28

    PubMed Central

    Desjardins, Alexandre; Yang, Ao; Bouvette, Jonathan; Omichinski, James G.; Legault, Pascale

    2012-01-01

    The pluripotency factor Lin28 is a highly conserved protein comprising a unique combination of RNA-binding motifs, an N-terminal cold-shock domain and a C-terminal region containing two retroviral-type CCHC zinc-binding domains. An important function of Lin28 is to inhibit the biogenesis of the let-7 family of microRNAs through a direct interaction with let-7 precursors. Here, we systematically characterize the determinants of the interaction between Lin28 and pre-let-7g by investigating the effect of protein and RNA mutations on in vitro binding. We determine that Lin28 binds with high affinity to the extended loop of pre-let-7g and that its C-terminal domain contributes predominantly to the affinity of this interaction. We uncover remarkable similarities between this C-terminal domain and the NCp7 protein of HIV-1, not only in terms of primary structure but also in their modes of RNA binding. This NCp7-like domain of Lin28 recognizes a G-rich bulge within pre-let-7g, which is adjacent to one of the Dicer cleavage sites. We hypothesize that the NCp7-like domain initiates RNA binding and partially unfolds the RNA. This partial unfolding would then enable multiple copies of Lin28 to bind the extended loop of pre-let-7g and protect the RNA from cleavage by the pre-microRNA processing enzyme Dicer. PMID:22013165

  20. FgMon1, a guanine nucleotide exchange factor of FgRab7, is important for vacuole fusion, autophagy and plant infection in Fusarium graminearum

    PubMed Central

    Li, Ying; Li, Bing; Liu, Luping; Chen, Huaigu; Zhang, Haifeng; Zheng, Xiaobo; Zhang, Zhengguang

    2015-01-01

    The Ccz1-Mon1 protein complex, the guanine nucleotide exchange factor (GEF) of the late endosomal Rab7 homolog Ypt7, is required for the late step of multiple vacuole delivery pathways, such as cytoplasm-to-vacuole targeting (Cvt) pathway and autophagy processes. Here, we identified and characterized the yeast Mon1 homolog in Fusarium graminearum, named FgMon1. FgMON1 encodes a trafficking protein and is well conserved in filamentous fungi. Targeted gene deletion showed that the ∆Fgmon1 mutant was defective in vegetative growth, asexual/sexual development, conidial germination and morphology, plant infection and deoxynivalenol production. Cytological examination revealed that the ∆Fgmon1 mutant was also defective in vacuole fusion and autophagy, and delayed in endocytosis. Yeast two hybrid and in vitro GST-pull down assays approved that FgMon1 physically interacts with a Rab GTPase FgRab7 which is also important for the development, infection, membrane fusion and autophagy in F. graminearum. FgMon1 likely acts as a GEF of FgRab7 and constitutively activated FgRab7 was able to rescue the defects of the ∆Fgmon1 mutant. In summary, our study provides evidences that FgMon1 and FgRab7 are critical components that modulate vesicle trafficking, endocytosis and autophagy, and thereby affect the development, plant infection and DON production of F. graminearum. PMID:26657788

  1. The Importance of Efficacy: Using the Extended Parallel Process Model to Examine Factors Related to Preschool-Age Children Enrolled in Medicaid Receiving Preventive Dental Visits.

    PubMed

    Askelson, Natoshia M; Chi, Donald L; Momany, Elizabeth T; Kuthy, Raymond A; Carter, Knute D; Field, Kathryn; Damiano, Peter C

    2015-12-01

    Early preventive dental visits are vital to the oral health of children. Yet many children, especially preschool-age children enrolled in Medicaid, do not receive early visits. This study attempts to uncover factors that can be used to encourage parents to seek preventive dental care for preschool-age children enrolled in Medicaid. The extended parallel process model was used as a theoretical framework for this research. This model suggests that people will act if the perceived threat (severity and susceptibility) is high enough and if efficacy levels (self-efficacy and response efficacy) are likewise high. Following Witte's method of categorizing people's perceptions and emotions into one of four categories based on levels of threat and efficacy, this article describes four groups (high threat/high efficacy, high threat/low efficacy, low threat/high efficacy, and low threat/low efficacy) of parents and how they compare to each other. Using logistic regression to model if a child had a preventive visit, results indicate that parents with low threat/high efficacy and parents with high threat/high efficacy had approximately 2.5 times the odds of having a child with a preventive oral health visit compared to parents with low threat/low efficacy, when controlling for perceived oral health status, health literacy, and child's age. The importance of efficacy needs to be incorporated in interventions aimed at increasing preventive dental visits for young children. PMID:25862302

  2. Environmental and biological factors controlling the spring phytoplankton bloom at the Patagonian shelf-break front - Degraded fucoxanthin pigments and the importance of microzooplankton grazing

    NASA Astrophysics Data System (ADS)

    Carreto, José I.; Montoya, Nora G.; Carignan, Mario O.; Akselman, Rut; Acha, E. Marcelo; Derisio, Carla

    2016-08-01

    The aim of this study was to investigate the biotic and abiotic factors controlling the spring phytoplankton blooms at the Patagonian shelf-break front (PSBF). Using a CHEMTAX analysis of HPLC pigment data and other methods, the biomass and spatial variability of plankton communities were studied in four sections (39-48°S) across the PSBF during October 2005. Environmental factors and the biomass and composition of plankton communities exhibited a marked spatial heterogeneity. The latitudinal and cross-shelf progression in the timing of the spring bloom initiation and the nutritive properties of the water masses (Subantarctic Shelf Waters and Malvinas Current Waters) seemed to be the key factors. Three plankton regions were distinguished: (a) Outer shelf (OS), (b) Shelf-break front (SBF) and (c) Malvinas Current (MC). At the highly stratified OS region, the post-bloom community showed low-biomasshigh-phytoplankton diversity formed mainly by small cells (haptophytes 30-62%, diatoms 17-49%, chlorophytes 0-34%, and prasinophytes 0-21% of total Chl a). High amounts of degraded fucoxanthin were found associated with the heterotrophic dinoflagellate, Protoperidinium capurroi. Grazing by this microheterotroph on the diatom population seemed to be the most important factor for the spring bloom decay at the OS. A remarkable quasi monospecific bloom (∼90%) of a nanodiatom (Thalassiosira bioculata var. raripora) associated with high Chl a (up to 20 mg m-3) occurred along (∼1000 km) the SBF and in the most northern extension of the MC. In the southern region, the bloom was developed under absent or incipient density stratification, increasing solar irradiance, high nitrate and phosphate availability, and low numbers of phytoplankton grazers. The average mixedlayer PAR irradiance (<2.0 mol quanta PAR m-2 d-1) and Si:N ratios (<0.2) were low, suggesting a diatom population limited by light and under progressive silicate limitation. The more stratified northern region of the

  3. Vascular Endothelial Cell Injury Is an Important Factor in the Development of Encapsulating Peritoneal Sclerosis in Long-Term Peritoneal Dialysis Patients

    PubMed Central

    Tawada, Mitsuhiro; Ito, Yasuhiko; Hamada, Chieko; Honda, Kazuho; Mizuno, Masashi; Suzuki, Yasuhiro; Sakata, Fumiko; Terabayashi, Takeshi; Matsukawa, Yoshihisa; Maruyama, Shoichi; Imai, Enyu; Matsuo, Seiichi; Takei, Yoshifumi

    2016-01-01

    Background and Objectives Encapsulating peritoneal sclerosis (EPS) is a rare but serious and life-threatening complication of peritoneal dialysis (PD). However, the precise pathogenesis remains unclear; in addition, predictors and early diagnostic biomarkers for EPS have not yet to be established. Methods Eighty-three peritoneal membrane samples taken at catheter removal were examined to identify pathological characteristics of chronic peritoneal deterioration, which promotes EPS in patients undergoing long-term PD treatment with low occurrence of peritonitis. Results According to univariable logistic regression analysis of the pathological findings, thickness of the peritoneal membrane (P = 0.045), new membrane formation score (P = 0.006), ratio of luminal diameter to vessel diameter (L/V ratio, P<0.001), presence of CD31-negative vessels (P = 0.021), fibrin deposition (P<0.001), and collagen volume fraction (P = 0.018) were associated with EPS development. In analyses of samples with and without EPS matched for PD treatment period, non-diabetes, and PD solution, univariable analysis identified L/V ratio (per 0.1 increase: odds ratio (OR) 0.44, P = 0.003) and fibrin deposition (OR 6.35, P = 0.027) as the factors associated with EPS. L/V ratio was lower in patients with fibrin exudation than in patients without fibrin exudation. Conclusions These findings suggest that damage to vascular endothelial cells, as represented by low L/V ratio, could be a predictive finding for the development of EPS, particularly in long-term PD patients unaffected by peritonitis. PMID:27119341

  4. Patient-centred care, health behaviours and cardiovascular risk factor levels in people with recently diagnosed type 2 diabetes: 5-year follow-up of the ADDITION-Plus trial cohort

    PubMed Central

    Dambha-Miller, Hajira; Cooper, Andrew J M; Simmons, Rebecca K; Kinmonth, Ann Louise; Griffin, Simon J

    2016-01-01

    Objective To examine the association between the experience of patient-centred care (PCC), health behaviours and cardiovascular disease (CVD) risk factor levels among people with type 2 diabetes. Design Population-based prospective cohort study. Setting 34 general practices in East Anglia, UK, delivering organised diabetes care. Participants 478 patients recently diagnosed with type 2 diabetes aged between 40 and 69 years enrolled in the ADDITION-Plus trial. Main outcome measures Self-reported and objectively measured health behaviours (diet, physical activity, smoking status), CVD risk factor levels (blood pressure, lipid levels, glycated haemoglobin, body mass index, waist circumference) and modelled 10-year CVD risk. Results Better experiences of PCC early in the course of living with diabetes were not associated with meaningful differences in self-reported physical activity levels including total activity energy expenditure (β-coefficient: 0.080 MET h/day (95% CI 0.017 to 0.143; p=0.01)), moderate-to-vigorous physical activity (β-coefficient: 5.328 min/day (95% CI 0.796 to 9.859; p=0.01)) and reduced sedentary time (β-coefficient: −1.633 min/day (95% CI −2.897 to −0.368; p=0.01)). PCC was not associated with clinically meaningful differences in levels of high-density lipoprotein cholesterol (β-coefficient: 0.002 mmol/L (95% CI 0.001 to 0.004; p=0.03)), systolic blood pressure (β-coefficient: −0.561 mm Hg (95% CI −0.653 to −0.468; p=0.01)) or diastolic blood pressure (β-coefficient: −0.565 mm Hg (95% CI −0.654 to −0.476; p=0.01)). Over an extended follow-up of 5 years, we observed no clear evidence that PCC was associated with self-reported, clinical or biochemical outcomes, except for waist circumference (β-coefficient: 0.085 cm (95% CI 0.015 to 0.155; p=0.02)). Conclusions We found little evidence that experience of PCC early in the course of diabetes was associated with clinically important changes in health

  5. Clinical, geographical, and temporal risk factors associated with presentation and outcome of vivax malaria imported into the United Kingdom over 27 years: observational study

    PubMed Central

    Broderick, Claire; Nadjm, Behzad; Smith, Valerie; Blaze, Marie; Checkley, Anna; Chiodini, Peter L

    2015-01-01

    Objective To examine temporal and geographical trends, risk factors, and seasonality of imported vivax malaria in the United Kingdom to inform clinical advice and policy. Design Observational study. Setting National surveillance data from the UK Public Health England Malaria Reference Laboratory, data from the International Passenger Survey, and international climactic data. Participants All confirmed and notified cases of malaria in the UK (n=50 187) from 1987 to 2013, focusing on 12 769 cases of vivax malaria. Main outcome measures Mortality, sociodemographic details (age, UK region, country of birth and residence, and purpose of travel), destination, and latency (time between arrival in the UK and onset of symptoms). Results Of the malaria cases notified, 25.4% (n=12 769) were due to Plasmodium vivax, of which 78.6% were imported from India and Pakistan. Most affected patients (53.5%) had travelled to visit friends and relatives, and 11.1% occurred in tourists. Imported P vivax is concentrated in areas with large communities of south Asian heritage. Overall mortality was 7/12 725 (0.05%), but with no deaths in 9927 patients aged under 50 years. Restricting the analysis to those aged more than 50 years, mortality was 7/2798 (0.25%), increasing to 4/526 (0.76%) (adjusted odds ratio 32.0, 95% confidence interval 7.1 to 144.0, P<0.001) in those aged 70 years or older. Annual notifications decreased sharply over the period, while traveller numbers between the UK and South Asia increased. The risk of acquiring P vivax from South Asia was year round but was twice as high from June to September (40 per 100 000 trips) compared with the rest of the year. There was strong seasonality in the latency from arrival in the UK to presentation, significantly longer in those arriving in the UK from South Asia from October to March (median 143 days) versus those arriving from April to September (37 days, P<0.001). Conclusions Travellers visiting friends and family in

  6. LMO7 Mediates Cell-Specific Activation of the Rho-Myocardin-Related Transcription Factor-Serum Response Factor Pathway and Plays an Important Role in Breast Cancer Cell Migration ▿

    PubMed Central

    Hu, Qiande; Guo, Chun; Li, Yali; Aronow, Bruce J.; Zhang, Jinsong

    2011-01-01

    Serum response factor (SRF) is a ubiquitously expressed transcription factor that regulates cell-specific functions such as muscle development and breast cancer metastasis. The myocardin-related transcription factors (MRTFs), which are transcriptional coactivators mediating cell-specific functions of SRF, are also ubiquitously expressed. How MRTFs and SRF drive cell-specific transcription is still not fully understood. Here we show that LIM domain only 7 (LMO7) is a cell-specific regulator of MRTFs and plays an important role in breast cancer cell migration. LMO7 activates MRTFs by relieving actin-mediated inhibition in a manner that requires, and is synergistic with, Rho GTPase. Whereas Rho is required for LMO7 to activate full-length MRTFs that have three RPEL actin-binding motifs, the disruption of individual actin-RPEL interactions is sufficient to eliminate the Rho dependency and to allow the strong Rho-independent function of LMO7. Mechanistically, we show that LMO7 colocalizes with F-actin and reduces the G-actin/F-actin ratio via a Rho-independent mechanism. The knockdown of LMO7 in HeLa and MDA-MB-231 cells compromises both basal and Rho-stimulated MRTF activities and impairs the migration of MDA-MB-231 breast cancer cells. We also show that LMO7 is upregulated in the stroma of invasive breast carcinoma in a manner that correlates with the increased expression of SRF target genes that regulate muscle and actin cytoskeleton functions. Together, this study reveals a novel cell-specific mechanism regulating Rho-MRTF-SRF signaling and breast cancer cell migration and identifies a role for actin-RPEL interactions in integrating Rho and cell-specific signals to achieve both the synergistic and Rho-dependent activation of MRTFs. PMID:21670154

  7. siRNA Screening Identifies the Host Hexokinase 2 (HK2) Gene as an Important Hypoxia-Inducible Transcription Factor 1 (HIF-1) Target Gene in Toxoplasma gondii-Infected Cells

    PubMed Central

    Menendez, Matthew T.; Teygong, Crystal; Wade, Kristin; Florimond, Celia

    2015-01-01

    ABSTRACT Although it is established that oxygen availability regulates cellular metabolism and growth, little is known regarding how intracellular pathogens use host factors to grow at physiological oxygen levels. Therefore, large-scale human small interfering RNA screening was performed to identify host genes important for growth of the intracellular protozoan parasite Toxoplasma gondii at tissue oxygen tensions. Among the genes identified by this screen, we focused on the hexokinase 2 (HK2) gene because its expression is regulated by hypoxia-inducible transcription factor 1 (HIF-1), which is important for Toxoplasma growth. Toxoplasma increases host HK2 transcript and protein levels in a HIF-1-dependent manner. In addition, parasite growth at 3% oxygen is restored in HIF-1-deficient cells transfected with HK2 expression plasmids. Both HIF-1 activation and HK2 expression were accompanied by increases in host glycolytic flux, suggesting that enhanced HK2 expression in parasite-infected cells is functionally significant. Parasite dependence on host HK2 and HIF-1 expression is not restricted to transformed cell lines, as both are required for parasite growth in nontransformed C2C12 myoblasts and HK2 is upregulated in vivo following infection. While HK2 is normally associated with the cytoplasmic face of the outer mitochondrial membrane at physiological O2 levels, HK2 relocalizes to the host cytoplasm following infection, a process that is required for parasite growth at 3% oxygen. Taken together, our findings show that HIF-1-dependent expression and relocalization of HK2 represent a novel mechanism by which Toxoplasma establishes its replicative niche at tissue oxygen tensions. PMID:26106078

  8. Human NR5A1/SF-1 Mutations Show Decreased Activity on BDNF (Brain-Derived Neurotrophic Factor), an Important Regulator of Energy Balance: Testing Impact of Novel SF-1 Mutations Beyond Steroidogenesis

    PubMed Central

    Malikova, Jana; Camats, Núria; Fernández-Cancio, Mónica; Heath, Karen; González, Isabel; Caimarí, María; del Campo, Miguel; Albisu, Marian; Kolouskova, Stanislava; Audí, Laura; Flück, Christa E.

    2014-01-01

    Context Human NR5A1/SF-1 mutations cause 46,XY disorder of sex development (DSD) with broad phenotypic variability, and rarely cause adrenal insufficiency although SF-1 is an important transcription factor for many genes involved in steroidogenesis. In addition, the Sf-1 knockout mouse develops obesity with age. Obesity might be mediated through Sf-1 regulating activity of brain-derived neurotrophic factor (BDNF), an important regulator of energy balance in the ventromedial hypothalamus. Objective To characterize novel SF-1 gene variants in 4 families, clinical, genetic and functional studies were performed with respect to steroidogenesis and energy balance. Patients 5 patients with 46,XY DSD were found to harbor NR5A1/SF-1 mutations including 2 novel variations. One patient harboring a novel mutation also suffered from adrenal insufficiency. Methods SF-1 mutations were studied in cell systems (HEK293, JEG3) for impact on transcription of genes involved in steroidogenesis (CYP11A1, CYP17A1, HSD3B2) and in energy balance (BDNF). BDNF regulation by SF-1 was studied by promoter assays (JEG3). Results Two novel NR5A1/SF-1 mutations (Glu7Stop, His408Profs*159) were confirmed. Glu7Stop is the 4th reported SF-1 mutation causing DSD and adrenal insufficiency. In vitro studies revealed that transcription of the BDNF gene is regulated by SF-1, and that mutant SF-1 decreased BDNF promoter activation (similar to steroid enzyme promoters). However, clinical data from 16 subjects carrying SF-1 mutations showed normal birth weight and BMI. Conclusions Glu7Stop and His408Profs*159 are novel SF-1 mutations identified in patients with 46,XY DSD and adrenal insufficiency (Glu7Stop). In vitro, SF-1 mutations affect not only steroidogenesis but also transcription of BDNF which is involved in energy balance. However, in contrast to mice, consequences on weight were not found in humans with SF-1 mutations. PMID:25122490

  9. The RNA-Binding Chaperone Hfq Is an Important Global Regulator of Gene Expression in Pasteurella multocida and Plays a Crucial Role in Production of a Number of Virulence Factors, Including Hyaluronic Acid Capsule.

    PubMed

    Mégroz, Marianne; Kleifeld, Oded; Wright, Amy; Powell, David; Harrison, Paul; Adler, Ben; Harper, Marina; Boyce, John D

    2016-05-01

    The Gram-negative bacterium Pasteurella multocida is the causative agent of a number of economically important animal diseases, including avian fowl cholera. Numerous P. multocida virulence factors have been identified, including capsule, lipopolysaccharide (LPS), and filamentous hemagglutinin, but little is known about how the expression of these virulence factors is regulated. Hfq is an RNA-binding protein that facilitates riboregulation via interaction with small noncoding RNA (sRNA) molecules and their mRNA targets. Here, we show that a P. multocida hfq mutant produces significantly less hyaluronic acid capsule during all growth phases and displays reduced in vivo fitness. Transcriptional and proteomic analyses of the hfq mutant during mid-exponential-phase growth revealed altered transcript levels for 128 genes and altered protein levels for 78 proteins. Further proteomic analyses of the hfq mutant during the early exponential growth phase identified 106 proteins that were produced at altered levels. Both the transcript and protein levels for genes/proteins involved in capsule biosynthesis were reduced in the hfq mutant, as were the levels of the filamentous hemagglutinin protein PfhB2 and its secretion partner LspB2. In contrast, there were increased expression levels of three LPS biosynthesis genes, encoding proteins involved in phosphocholine and phosphoethanolamine addition to LPS, suggesting that these genes are negatively regulated by Hfq-dependent mechanisms. Taken together, these data provide the first evidence that Hfq plays a crucial role in regulating the global expression of P. multocida genes, including the regulation of key P. multocida virulence factors, capsule, LPS, and filamentous hemagglutinin. PMID:26883595

  10. Müller glia as an important source of cytokines and inflammatory factors present in the gliotic retina during proliferative vitreoretinopathy.

    PubMed

    Eastlake, K; Banerjee, P J; Angbohang, A; Charteris, D G; Khaw, P T; Limb, G A

    2016-04-01

    Retinal gliosis is characterized by biochemical and physiological changes that often lead to Müller glia proliferation and hypertrophy and is a feature of many neuro-degenerative and inflammatory diseases such as proliferative vitreoretinopathy (PVR). Although Müller glia are known to release inflammatory factors and cytokines, it is not clear whether cytokine production by these cells mirrors the pattern of factors present in the gliotic retina. Lysates from normal cadaveric retina and gliotic retinal specimens from patients undergoing retinectomy for treatment of PVR, the Müller cell line MIO-M1 and four human Müller glial cell preparations isolated from normal retina were examined for their expression of cytokines and inflammatory factors using semi-quantitative dot blot antibody arrays and quantitative arrays. Comparative analysis of the expression of inflammatory factors showed that in comparison with normal retina, gliotic retina exhibited greater than twofold increase in 24/102 factors examined by semiquantitative arrays, and a significant increase in 19 out of 27 factors assessed by quantitative methods (P < 0.05 to P < 0.001). It was observed that with the exception of some chemotactic factors, the majority of cytokines and inflammatory factors were produced by Müller glia in vitro and included G-CSF, MCP-1, PDGF-bb, RANTES, VEGF, and TGFβ2. These results showed that a large number of inflammatory factors expressed by Müller glia in vitro are upregulated in the gliotic retina, suggesting that targeting the production of inflammatory factors by Müller glia may constitute a valid approach to prevent neural damage during retinal gliosis and this merits further investigations. PMID:26556395

  11. Higher TSH can be used as an additional risk factor in prediction of malignancy in euthyroid thyroid nodules evaluated by cytology based on Bethesda system.

    PubMed

    Baser, Husniye; Topaloglu, Oya; Tam, Abbas Ali; Evranos, Berna; Alkan, Afra; Sungu, Nuran; Dumlu, Ersin Gurkan; Ersoy, Reyhan; Cakir, Bekir

    2016-08-01

    Recently, it has been suggested that thyrotropin (TSH) concentration can be used as a marker for prediction of thyroid malignancy. In this study, we aimed to investigate the association between TSH levels and prediction of malignancy in euthyroid patients with different Bethesda categories. The data of 1433 euthyroid patients with 3206 thyroid nodules who underwent thyroidectomy were screened retrospectively. The preoperative cytology results, thyroid function tests, thyroid autoantibodies, and presence of histopathological Hashimoto's thyroiditis (HT) were recorded. Of the 1433 patients, 585 (40.8 %) had malignant and 848 (59.2 %) had benign histopathology. Malignant group had smaller nodule size, elevated TSH levels, and higher rate of presence of HT compared to benign group (p < 0.001, all). Cytology results of 3206 nodules were as follows: 832 nondiagnostic (ND), 1666 benign, 392 atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), 68 follicular neoplasm/suspicious for follicular neoplasm (FN/SFN), 133 suspicious for malignancy (SM), and 115 malignant. Both SM and malignant cytology groups had higher TSH levels than other 4 Bethesda categories (p < 0.05, all). Benign cytology group had significantly lower TSH levels compared to other cytology groups (p < 0.05, all). Patients with malignant final histopathology in ND and AUS/FLUS cytology groups had significantly higher TSH levels compared to patients with benign final histopathology (p < 0.05, all). Moreover, TSH levels showed to increase from Bethesda categories II to VI. In addition to cytology, higher TSH levels can be used as a supplementary marker in prediction of malignancy in certain Bethesda categories. PMID:26972701

  12. Electrophilic addition of astatine

    SciTech Connect

    Norseev, Yu.V.; Vasaros, L.; Nhan, D.D.; Huan, N.K.

    1988-03-01

    It has been shown for the first time that astatine is capable of undergoing addition reactions to unsaturated hydrocarbons. A new compound of astatine, viz., ethylene astatohydrin, has been obtained, and its retention numbers of squalane, Apiezon, and tricresyl phosphate have been found. The influence of various factors on the formation of ethylene astatohydrin has been studied. It has been concluded on the basis of the results obtained that the univalent cations of astatine in an acidic medium is protonated hypoastatous acid.

  13. Multi-Faceted Proteomic Characterization of Host Protein Complement of Rift Valley Fever Virus Virions and Identification of Specific Heat Shock Proteins, Including HSP90, as Important Viral Host Factors

    PubMed Central

    Nuss, Jonathan E.; Kehn-Hall, Kylene; Benedict, Ashwini; Costantino, Julie; Ward, Michael; Peyser, Brian D.; Retterer, Cary J.; Tressler, Lyal E.; Wanner, Laura M.; McGovern, Hugh F.; Zaidi, Anum; Anthony, Scott M.; Kota, Krishna P.; Bavari, Sina; Hakami, Ramin M.

    2014-01-01

    Rift Valley fever is a potentially fatal disease of humans and domestic animals caused by Rift Valley fever virus (RVFV). Infection with RVFV in ruminants can cause near 100% abortion rates and recent outbreaks in naïve human populations have suggested case fatality rates of greater than thirty percent. To elucidate the roles that host proteins play during RVFV infection, proteomic analysis of RVFV virions was conducted using complementary analytical approaches, followed by functional validation studies of select identified host factors. Coupling the more traditional Gel LC/MS/MS approach (SDS PAGE followed by liquid chromatography tandem mass spectrometry) with an alternative technique that preserves protein complexes allowed the protein complement of these viral particles to be thoroughly examined. In addition to viral proteins present within the virions and virion-associated host proteins, multiple macromolecular complexes were identified. Bioinformatic analysis showed that host chaperones were among over-represented protein families associated with virions, and functional experiments using siRNA gene silencing and small molecule inhibitors identified several of these heat shock proteins, including heat shock protein 90 (HSP90), as important viral host factors. Further analysis indicated that HSP inhibition effects occur during the replication/transcription phase of the virus life cycle, leading to significant lowering of viral titers without compromising the functional capacity of released virions. Overall, these studies provide much needed further insight into interactions between RVFV and host cells, increasing our understanding of the infection process and suggesting novel strategies for anti-viral development. In particular, considering that several HSP90 inhibitors have been advancing through clinical trials for cancer treatment, these results also highlight the exciting potential of repurposing HSP90 inhibitors to treat RVF. PMID:24809507

  14. Additively Manufactured 3D Porous Ti-6Al-4V Constructs Mimic Trabecular Bone Structure and Regulate Osteoblast Proliferation, Differentiation and Local Factor Production in a Porosity and Surface Roughness Dependent Manner

    PubMed Central

    Cheng, Alice; Humayun, Aiza; Cohen, David J.; Boyan, Barbara D.; Schwartz, Zvi

    2014-01-01

    Additive manufacturing by laser sintering is able to produce high resolution metal constructs for orthopaedic and dental implants. In this study, we used a human trabecular bone template to design and manufacture Ti-6Al-4V constructs with varying porosity via laser sintering. Characterization of constructs revealed interconnected porosities ranging from 15–70% with compressive moduli of 2063–2954 MPa. These constructs with macro porosity were further surface-treated to create a desirable multi-scale micro-/nano-roughness, which has been shown to enhance the osseointegration process. Osteoblasts (MG63 cells) exhibited high viability when grown on the constructs. Proliferation (DNA) and alkaline phosphatase specific activity (ALP), an early differentiation marker, decreased as porosity increased, while osteocalcin (OCN), a late differentiation marker, as well as osteoprotegerin (OPG), vascular endothelial growth factor (VEGF) and bone morphogenetic proteins 2 and 4 (BMP2, BMP4) increased with increasing porosity. 3D constructs with the highest porosity and surface modification supported the greatest osteoblast differentiation and local factor production. These results indicate that additively manufactured 3D porous constructs mimicking human trabecular bone and produced with additional surface treatment can be customized for increased osteoblast response. Increased factors for osteoblast maturation and differentiation on high porosity constructs suggest the enhanced performance of these surfaces for increasing osseointegration in vivo. PMID:25287305

  15. The Pill vs. the Sword: Additional Considerations

    PubMed Central

    Lottes, Ilsa L.

    2015-01-01

    In this paper, I present additional information for policy-makers and researchers to consider in response to the view proposed by Potts et al that "the pill is mightier than the sword." I identify states with both high rates of terrorism and a youth bulge and discuss correlates of both these societal characteristics. The research examined supports the view that factors other than access to family planning are more important in facilitating terrorism. PMID:26673473

  16. The Importance of Efficacy: Using the Extended Parallel Process Model to Examine Factors Related to Preschool-Age Children Enrolled in Medicaid Receiving Preventive Dental Visits

    ERIC Educational Resources Information Center

    Askelson, Natoshia M.; Chi, Donald L.; Momany, Elizabeth T.; Kuthy, Raymond A.; Carter, Knute D.; Field, Kathryn; Damiano, Peter C.

    2015-01-01

    Early preventive dental visits are vital to the oral health of children. Yet many children, especially preschool-age children enrolled in Medicaid, do not receive early visits. This study attempts to uncover factors that can be used to encourage parents to seek preventive dental care for preschool-age children enrolled in Medicaid. The extended…

  17. Conserved Ser residues in the basic region of the bZIP-type transcription factor HBP-1a(17): importance in DNA binding and possible targets for phosphorylation.

    PubMed

    Meshi, T; Moda, I; Minami, M; Okanami, M; Iwabuchi, M

    1998-01-01

    HBP-1a(17) is representative of a group of plant bZIP-type transcription factors which includes HBP-1a proteins and G-box-binding factors. We found kinase activity in wheat nuclear extract that phosphorylated HBP-1a(17). Experiments using recombinant HBP-1a(17) derivatives as substrates revealed that all three of the Ser residues in the basic region, Ser-261, Ser-265, and Ser-269, were phosphorylated in a Ca(2+)-stimulated manner. DNA-binding analysis of mutants with a Ser-to-Glu change, prepared to mimic the phosphorylated proteins, indicated that introduction of a negative charge at position 265 or 269 prevents HBP-1a(17) from binding DNA not only in the homodimer of mutants but also in heterodimers with a wild-type protein. It is therefore suggested that the phosphorylation regulates the function of HBP-1a(17) at least at the level of DNA binding. Since Ser-265 and Ser-269 are highly conserved among the plant bZIP-type factors known to date, a common Ca(2+)-mediated regulatory mechanism may exert an effect on the bZIP-type factors through phosphorylation of these conserved Ser residues. PMID:9484468

  18. Peroxisome protein import: a complex journey

    PubMed Central

    Baker, Alison; Hogg, Thomas Lanyon; Warriner, Stuart L.

    2016-01-01

    The import of proteins into peroxisomes possesses many unusual features such as the ability to import folded proteins, and a surprising diversity of targeting signals with differing affinities that can be recognized by the same receptor. As understanding of the structure and function of many components of the protein import machinery has grown, an increasingly complex network of factors affecting each step of the import pathway has emerged. Structural studies have revealed the presence of additional interactions between cargo proteins and the PEX5 receptor that affect import potential, with a subtle network of cargo-induced conformational changes in PEX5 being involved in the import process. Biochemical studies have also indicated an interdependence of receptor–cargo import with release of unloaded receptor from the peroxisome. Here, we provide an update on recent literature concerning mechanisms of protein import into peroxisomes. PMID:27284042

  19. Importance of Simultaneous Evaluation of Multiple Risk Factors for Hemodialysis Patients’ Mortality and Development of a Novel Index: Dialysis Outcomes and Practice Patterns Study

    PubMed Central

    2015-01-01

    Background For hemodialysis (HD) patients, many risk factors for death are associated with each other intricately. However, they are often considered separately in clinical settings. We evaluated the maintenance HD patients’ risk of death within one year from multiple risk factors simultaneously considering their interrelationships using a novel index (survival index, SI) for HD patients in the United States developed using data from the Dialysis Outcomes and Practice Patterns Study (DOPPS). Methods We analyzed data from 3899 and 3765 patients to develop and validate SI, respectively. To predict death within one year, candidate models were developed using logistic regression models. The final model was determined by comparing the accuracy among the models for the prediction of deaths. Results The model included age; body mass index; serum creatinine, albumin, total cholesterol and phosphorus levels; history of cardiovascular diseases; and arteriovenous fistula use. SI showed a higher accuracy in predicting death (c-statistic, 0.739) than geriatric nutritional risk index (0.647) and serum albumin level (0.637). The probability of death predicted on the basis of SI matched the observed number of deaths. Cox proportional hazard models for time-dependent SI showed that patients with low SI had a higher risk of death than patients with high SI [reference, Group 4 (26.1≤SI)]; Group 1 (SI<12.7), adjusted hazard ratio, 7.97 (95% CI, 5.02, 12.65); Group 2 (12.7≤SI<19.0), 3.18 (95% CI, 1.96, 5.16); Group 3 (19.0≤SI<26.1), 2.20 (95% CI, 1.33, 3.66). Conclusion Results of this study suggest that the simultaneous evaluation of multiple risk factors can more accurately assess patients’ prognosis and identify patients at an increased risk of death than single factors. PMID:26030526

  20. Math achievement is important, but task values are critical, too: examining the intellectual and motivational factors leading to gender disparities in STEM careers.

    PubMed

    Wang, Ming-Te; Degol, Jessica; Ye, Feifei

    2015-01-01

    Although young women now obtain higher course grades in math than boys and are just as likely to be enrolled in advanced math courses in high school, females continue to be underrepresented in some Science, Technology, Engineering, and Mathematics (STEM) occupations. This study drew on expectancy-value theory to assess (1) which intellectual and motivational factors in high school predict gender differences in career choices and (2) whether students' motivational beliefs mediated the pathway of gender on STEM career via math achievement by using a national longitudinal sample in the United States. We found that math achievement in 12th grade mediated the association between gender and attainment of a STEM career by the early to mid-thirties. However, math achievement was not the only factor distinguishing gender differences in STEM occupations. Even though math achievement explained career differences between men and women, math task value partially explained the gender differences in STEM career attainment that were attributed to math achievement. The identification of potential factors of women's underrepresentation in STEM will enhance our ability to design intervention programs that are optimally tailored to female needs to impact STEM achievement and occupational choices. PMID:25741292

  1. Math achievement is important, but task values are critical, too: examining the intellectual and motivational factors leading to gender disparities in STEM careers

    PubMed Central

    Wang, Ming-Te; Degol, Jessica; Ye, Feifei

    2015-01-01

    Although young women now obtain higher course grades in math than boys and are just as likely to be enrolled in advanced math courses in high school, females continue to be underrepresented in some Science, Technology, Engineering, and Mathematics (STEM) occupations. This study drew on expectancy-value theory to assess (1) which intellectual and motivational factors in high school predict gender differences in career choices and (2) whether students’ motivational beliefs mediated the pathway of gender on STEM career via math achievement by using a national longitudinal sample in the United States. We found that math achievement in 12th grade mediated the association between gender and attainment of a STEM career by the early to mid-thirties. However, math achievement was not the only factor distinguishing gender differences in STEM occupations. Even though math achievement explained career differences between men and women, math task value partially explained the gender differences in STEM career attainment that were attributed to math achievement. The identification of potential factors of women’s underrepresentation in STEM will enhance our ability to design intervention programs that are optimally tailored to female needs to impact STEM achievement and occupational choices. PMID:25741292

  2. [Additional administration of dutasteride in patients with benign prostatic hyperplasia who did not respond sufficiently to α1-adrenoceptor antagonist : investigation of clinical factors affecting the therapeutic effect of dutasteride].

    PubMed

    Masuda, Mitsunobu; Murai, Tetsuo; Osada, Yutaka; Kawai, Masaki; Kasuga, Jun; Yokomizo, Yumiko; Kuroda, Shinnosuke; Nakamura, Mami; Noguchi, Go

    2014-02-01

    We performed additional administration of dutasteride in patients who did not respond sufficiently to α1-adrenoceptor antagonist treatment for lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) (LUTS/BPH). Among 76 registered patients, efficacy was analyzed in 58 patients. International Prostate Symptom Score (IPSS), subscores for voiding and storage symptoms and quality of life (QOL) on the IPSS, and Overactive Bladder Symptom Score (OABSS) were all significantly improved from the third month of administration compared to the time of initiating additional administration of dutasteride. Additional administration of dutasteride also significantly reduced prostate volume, and residual urine with the exception of the sixth month after administration. Age at initiation of administration and voiding symptom subscore on the IPSS were clinical factors affecting the therapeutic effects of dutasteride. The rate of improvement with treatment decreased with increasing age at initiation of dutasteride administration, and increased as voiding symptom subscore on the IPSS increased. Therefore, additional administration of dutasteride appears useful for cases of LUTS/BPH in which a sufficient response is not achieved with α1-adrenoceptor antagonist treatment. Because patients who have severe voiding symptoms or begin dutasteride at an early age may be expected to respond particularly well to dutasteride in terms of clinical efficacy, they were considered to be suitable targets for additional administration. PMID:24755815

  3. The Importance of Microbes in Nutrition and Health of Honey Bee Colonies Part-2: Factors Affecting the Microbial Community in Honey Bee Colonies

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Honey bee colonies have innumerable symbiotic bacteria and fungi that are essential to the health of the colony. In the first part of this series, we discussed the importance of microbes in maintaining the health of honey bee colonies. The bacteria, yeasts and molds that live in a healthy colony a...

  4. The nucleotide exchange factor MGE exerts a key function in the ATP-dependent cycle of mt-Hsp70-Tim44 interaction driving mitochondrial protein import.

    PubMed Central

    Schneider, H C; Westermann, B; Neupert, W; Brunner, M

    1996-01-01

    Import of preproteins into the mitochondrial matrix is driven by the ATP-dependent interaction of mt-Hsp70 with the peripheral inner membrane import protein Tim44 and the preprotein in transit. We show that Mge1p, a co-chaperone of mt-Hsp70, plays a key role in the ATP-dependent import reaction cycle in yeast. Our data suggest a cycle in which the mt-Hsp70-Tim44 complex forms with ATP: Mge1p promotes assembly of the complex in the presence of ATP. Hydrolysis of ATP by mt-Hsp70 occurs in complex with Tim44. Mge1p is then required for the dissociation of the ADP form of mt-Hsp70 from Tim44 after release of inorganic phosphate but before release of ADP. ATP hydrolysis and complex dissociation are accompanied by tight binding of mt-Hsp70 to the preprotein in transit. Subsequently, the release of mt-Hsp70 from the polypeptide chain is triggered by Mge1p which promotes release of ADP from mt-Hsp70. Rebinding of ATP to mt-Hsp70 completes the reaction cycle. Images PMID:8918457

  5. AIRTRAQ8 OPTICAL LARYNGOSCOPE FOR TRACHEAL INTUBATION IN A PATIENT WITH AN UNCOMMON GIANT LIPOMA ON THE POSTERIOR ASPECT OF NECK AND ADDITIONAL RISK FACTORS OF ANTICIPATED DIFFICULT AIRWAY: A CASE REPORT.

    PubMed

    Dimitriou, Vassilios; El Kouny, Amr; Al Harbi, Mohammed; Wambi, Freddie; Tawfeeq, Nasser; Tanweer, Aziz; Al Atassi, Abdulallem; Geldhof, Georges

    2015-10-01

    Patients with restricted neck movement present a difficult airway situation because of improper positioning and inadequate extension of the atlanto-occipital joint. The Airtraq optical laryngoscope is a new single use device that permits an indirect view of the glottis without the need to achieve a direct line of sight by conventional use of the 'sniffing position'. We present and discuss a case of uncommon giant lipoma (16 x 12 x 10 cm) in the posterior aspect of the neck in addition with other independent factors of anticipated difficult airway, intubated successfully in the semi-lateral position with the use of Airtraq. PMID:26860029

  6. The risk factors and prevention of cardiovascular disease: the importance of electrocardiogram in the diagnosis and treatment of acute coronary syndrome

    PubMed Central

    Rosiek, Anna; Leksowski, Krzysztof

    2016-01-01

    Acute coronary syndrome is a leading cause of emergency medical treatment and hospitalization in Poland. High-speed electrocardiogram (ECG) has shown good accuracy of the initial diagnosis and of the final diagnosis in treated cardiac patients. Initial diagnosis and definitive diagnosis were analyzed statistically (P<0.0001). Although much is said about the prevention of sudden death in heart failure, the elimination of risk factors health care in Poland does not pay due attention to the need for early diagnosis and ECG analysis (at the stage of prevention). This article presents the inclusion of ECG in the prevention process and shows that it allows for early detection of cardiovascular diseases. In Poland, ST-segment elevation myocardial infarction patients are identified in the ambulance that reduces time to door-to-balloon. PMID:27540297

  7. The risk factors and prevention of cardiovascular disease: the importance of electrocardiogram in the diagnosis and treatment of acute coronary syndrome.

    PubMed

    Rosiek, Anna; Leksowski, Krzysztof

    2016-01-01

    Acute coronary syndrome is a leading cause of emergency medical treatment and hospitalization in Poland. High-speed electrocardiogram (ECG) has shown good accuracy of the initial diagnosis and of the final diagnosis in treated cardiac patients. Initial diagnosis and definitive diagnosis were analyzed statistically (P<0.0001). Although much is said about the prevention of sudden death in heart failure, the elimination of risk factors health care in Poland does not pay due attention to the need for early diagnosis and ECG analysis (at the stage of prevention). This article presents the inclusion of ECG in the prevention process and shows that it allows for early detection of cardiovascular diseases. In Poland, ST-segment elevation myocardial infarction patients are identified in the ambulance that reduces time to door-to-balloon. PMID:27540297

  8. [Inadequate burials as an important factor in plague epidemic amongst Serbs in the Habsburg monarchy by the end of the 18th century: a historical analysis].

    PubMed

    Vasin, Goran; Božanić, Snežana; Božić, Milica Kisić

    2014-01-01

    Analysis of the archaic customs of burying the deceased in Srem, primarily amongst Serbs, in the second half of the 18th century is the essential part of the paper that aims at clarifying the consequences of this negative habit onto the spreading of plague epidemic. The Austrian Empire tried to stop and prevent the epidemic with an array of legal norms, but in practice, these orders were often not upheld. Serbian Metropolitans Pavle Nenadović and Stefan Stratimirović insisted on eradicating superstition and retrograde, often uncivilized actions in burial rituals, and they partially succeeded. The example of plague in Irig and the surroundings in 1795-1796 explicitly shows the hazardous effects of the inadequate attitude towards the deceased as one of the factors in spreading the epidemic. Using primary archives, and published sources, with adequate literature, authors depict this complex historical process. PMID:25731012

  9. Involvement of PKC{alpha} in insulin-induced PKC{delta} expression: Importance of SP-1 and NF{kappa}B transcription factors

    SciTech Connect

    Horovitz-Fried, Miriam; Sampson, Sanford R. . E-mail: sampsos@mail.biu.ac.il

    2007-01-05

    Protein kinase C delta (PKC{delta}) is a key molecule in insulin signaling essential for insulin-induced glucose transport in skeletal muscle. Recent studies in our laboratory have shown that insulin rapidly stimulates PKC{delta} activity and increases PKC{delta} protein and RNA levels, and that the SP-1 transcription factor is involved in insulin-induced transcription of the PKC{delta} gene. Activation of SP-1 involves serine phosphorylation and translocation to the nucleus. In this study we examined the possibility that PKC{alpha} might be involved in serine phosphorylation and activation of SP-1. We found that insulin rapidly phosphorylates and translocates SP-1. In the cytoplasm, SP-1 was constitutively associated with PKC{alpha}, and insulin stimulation caused these proteins to dissociate. In contrast, in the nucleus insulin induced an increase in association between PKC{alpha} and SP-1. PKC{alpha} inhibition blocked insulin-induced serine phosphorylation of SP-1 and its association with PKC{alpha} in the nucleus. Inhibition of PKC{alpha} also reduced the insulin-induced increase in PKC{delta} RNA and protein in the cytoplasmic and nuclear fractions. We also attempted to determine if another transcription factor might be involved in regulation of PKC{delta} expression. We earlier showed that insulin did not affect nuclear NF{kappa}B levels. Inhibition of NF{kappa}B, however, increased insulin-induced increase in PKC{delta} RNA and protein in the cytoplasmic and nuclear fractions. Surprisingly, this inhibition reduced the insulin-induced increase in cytoplasmic and nuclear PKC{alpha} RNA and protein. Inhibition of PKC{delta} reduced I{kappa}B{alpha} phosphorylation as well as NF{kappa}B activation. Thus, PKC{alpha} regulates insulin-induced PKC{delta} expression levels and this regulation involves activation of SP-1 and NF{kappa}B.

  10. The Interplay Between Peroxiredoxin-2 and Nuclear Factor-Erythroid 2 Is Important in Limiting Oxidative Mediated Dysfunction in β-Thalassemic Erythropoiesis

    PubMed Central

    Matte, Alessandro; De Falco, Luigia; Iolascon, Achille; Mohandas, Narla; An, Xiuli; Siciliano, Angela; Leboeuf, Christophe; Janin, Anne; Bruno, Mariasole; Choi, Soo Young; Kim, Dae Won

    2015-01-01

    Abstract Aims: β-Thalassemia is a common inherited red cell disorder characterized by ineffective erythropoiesis and severe oxidative stress. Peroxiredoxin-2 (Prx2), a typical 2-cysteine peroxiredoxin, is upregulated during β-thalassemic erythropoiesis, but its contribution to stress erythropoiesis, a common feature of thalassemia, is yet to be fully defined. Results: Here, we showed that Prx2−/− mice displayed reactive oxygen species related abnormalities in erythropoiesis similar to that of Hbbth3/+ mice associated with activation of redox response transcriptional factor nuclear factor-erythroid 2 (Nrf2). We generated β-thalassemic mice genetically lacking Prx2 (Prx2−/−Hbbth3/+) and documented a worsened β-thalassemic hematological phenotype with severe ineffective erythropoiesis. To further validate a key role of Prx2 in stress erythropoiesis, we administrated fused recombinant PEP1Prx2 to Hbbth3/+ mice and documented a decrease in ineffective erythropoiesis. We further show that Prx2 effects are mediated by activation of Nrf2 and upregulation of genes that protect against oxidative damage such as gluthatione S-transferase, heme-oxygenase-1, and NADPH dehydrogenase quinone-1. Innovation: We propose Prx2 as a key antioxidant system and Nrf2 activation is a cellular adaptive process in response to oxidative stress, resulting in upregulation of antioxidant (antioxidant responsive element) genes required to ensure cell survival. Conclusion: Our data shed new light on adaptive mechanisms against oxidative damage through the interplay of Prx2 and Nrf2 during stress erythropoiesis and suggest new therapeutic options to decrease ineffective erythropoiesis by modulation of endogenous antioxidant systems. Antioxid. Redox Signal. 23, 1284–1297. PMID:26058667

  11. Mechanisms Underlying the Delayed Activation of the Cap1 Transcription Factor in Candida albicans following Combinatorial Oxidative and Cationic Stress Important for Phagocytic Potency

    PubMed Central

    Kos, Iaroslava; Patterson, Miranda J.; Znaidi, Sadri; Kaloriti, Despoina; da Silva Dantas, Alessandra; Herrero-de-Dios, Carmen M.; d’Enfert, Christophe; Brown, Alistair J. P.

    2016-01-01

    ABSTRACT Following phagocytosis, microbes are exposed to an array of antimicrobial weapons that include reactive oxygen species (ROS) and cationic fluxes. This is significant as combinations of oxidative and cationic stresses are much more potent than the corresponding single stresses, triggering the synergistic killing of the fungal pathogen Candida albicans by “stress pathway interference.” Previously we demonstrated that combinatorial oxidative plus cationic stress triggers a dramatic increase in intracellular ROS levels compared to oxidative stress alone. Here we show that activation of Cap1, the major regulator of antioxidant gene expression in C. albicans, is significantly delayed in response to combinatorial stress treatments and to high levels of H2O2. Cap1 is normally oxidized in response to H2O2; this masks the nuclear export sequence, resulting in the rapid nuclear accumulation of Cap1 and the induction of Cap1-dependent genes. Here we demonstrate that following exposure of cells to combinatorial stress or to high levels of H2O2, Cap1 becomes trapped in a partially oxidized form, Cap1OX-1. Notably, Cap1-dependent gene expression is not induced when Cap1 is in this partially oxidized form. However, while Cap1OX-1 readily accumulates in the nucleus and binds to target genes following high-H2O2 stress, the nuclear accumulation of Cap1OX-1 following combinatorial H2O2 and NaCl stress is delayed due to a cationic stress-enhanced interaction with the Crm1 nuclear export factor. These findings define novel mechanisms that delay activation of the Cap1 transcription factor, thus preventing the rapid activation of the stress responses vital for the survival of C. albicans within the host. PMID:27025253

  12. A Study of the Relationship of Three Factors--Perceived Need Deficiency, Importance of Need Fulfillment, Perception of Education as a Mobility Facilitator--to Participation in Educational Activities.

    ERIC Educational Resources Information Center

    LeClair, Lowell Vincent

    This study assessed three factors in adult education participation by industrial employees: (1) perceived need deficiency on the job; (2) importance of need fulfillment; (3) perception of education as a means of advancement. A measure of perceived need deficiency was applied to 177 participants and 149 nonparticipants in classes at Purdue…

  13. New Host Factors Important for Respiratory Syncytial Virus (RSV) Replication Revealed by a Novel Microfluidics Screen for Interactors of Matrix (M) Protein*

    PubMed Central

    Kipper, Sarit; Hamad, Samar; Caly, Leon; Avrahami, Dorit; Bacharach, Eran; Jans, David A.; Gerber, Doron; Bajorek, Monika

    2015-01-01

    Although human respiratory syncytial virus (RSV) is the most common cause of bronchiolitis and pneumonia in infants and elderly worldwide, there is no licensed RSV vaccine or effective drug treatment available. The RSV Matrix protein plays key roles in virus life cycle, being found in the nucleus early in infection in a transcriptional inhibitory role, and later localizing in viral inclusion bodies before coordinating viral assembly and budding at the plasma membrane. In this study, we used a novel, high throughput microfluidics platform and custom human open reading frame library to identify novel host cell binding partners of RSV matrix. Novel interactors identified included proteins involved in host transcription regulation, the innate immunity response, cytoskeletal regulation, membrane remodeling, and cellular trafficking. A number of these interactions were confirmed by immunoprecipitation and cellular colocalization approaches. Importantly, the physiological significance of matrix interaction with the actin-binding protein cofilin 1, caveolae protein Caveolin 2, and the zinc finger protein ZNF502 was confirmed. siRNA knockdown of the host protein levels resulted in reduced RSV virus production in infected cells. These results have important implications for future antiviral strategies aimed at targets of RSV matrix in the host cell. PMID:25556234

  14. Molecular Characterization, Antibiotic Resistance, and Virulence Factors of Methicillin-Resistant Staphylococcus aureus Strains Isolated from Imported and Domestic Meat in Korea.

    PubMed

    Kim, Young Jo; Oh, Deog Hwan; Song, Bo Ra; Heo, Eun Jeong; Lim, Jong Su; Moon, Jin San; Park, Hyun Jung; Wee, Sung Hwan; Sung, Kidon

    2015-05-01

    During a nationwide surveillance in Korea, 13 methicillin-resistant Staphylococcus aureus (MRSA) strains were isolated from imported and domestic meat between 2009 and 2011. The predominant MRSA genotype was SCCmec type V, and only two agr types (I and II) were found. Unexpectedly, sequence type ST72 comprised more than 50% of the isolates; this is the first instance of type ST72 in food from Canada. Two Spanish pork isolates were ST398, which caused human disease in Europe, and they carried leukotoxin genes, lukS, lukF, and lukE-lukD. Furthermore, P71 and P6 harbored all of the known leukocidin genes, lukS-lukF-lukE-lukD-lukM. Our collected MRSA strains were multidrug resistant with various antimicrobial and heavy-metal resistance genes. Toxin genes that are commonly found in clinical MRSA also were detected in our meat strains. One MRSA strain exhibited an uncommon type of enterotoxin, sec-see-seg-sei-sel-sem-sen-seo-sep. Plasmids (1.5-15.0 kb) were found in 12 of the 13 MRSA isolates. Repetitive sequence-based polymerase chain reaction of the genomic DNA showed 3 clusters with 95% similarity. The presence of multidrug-resistant and toxigenic MRSA in meat products suggests that comprehensive surveillance should be continued for imported meats in Korea. PMID:25789540

  15. Markedly Elevated Antibody Responses in Wild versus Captive Spotted Hyenas Show that Environmental and Ecological Factors Are Important Modulators of Immunity.

    PubMed

    Flies, Andrew S; Mansfield, Linda S; Grant, Chris K; Weldele, Mary L; Holekamp, Kay E

    2015-01-01

    Evolutionary processes have shaped the vertebrate immune system over time, but proximal mechanisms control the onset, duration, and intensity of immune responses. Based on testing of the hygiene hypothesis, it is now well known that microbial exposure is important for proper development and regulation of the immune system. However, few studies have examined the differences between wild animals in their natural environments, in which they are typically exposed to a wide array of potential pathogens, and their conspecifics living in captivity. Wild spotted hyenas (Crocuta crocuta) are regularly exposed to myriad pathogens, but there is little evidence of disease-induced mortality in wild hyena populations, suggesting that immune defenses are robust in this species. Here we assessed differences in immune defenses between wild spotted hyenas that inhabit their natural savanna environment and captive hyenas that inhabit a captive environment where pathogen control programs are implemented. Importantly, the captive population of spotted hyenas was derived directly from the wild population and has been in captivity for less than four generations. Our results show that wild hyenas have significantly higher serum antibody concentrations, including total IgG and IgM, natural antibodies, and autoantibodies than do captive hyenas; there was no difference in the bacterial killing capacity of sera collected from captive and wild hyenas. The striking differences in serum antibody concentrations observed here suggest that complementing traditional immunology studies, with comparative studies of wild animals in their natural environment may help to uncover links between environment and immune function, and facilitate progress towards answering immunological questions associated with the hygiene hypothesis. PMID:26444876

  16. Markedly Elevated Antibody Responses in Wild versus Captive Spotted Hyenas Show that Environmental and Ecological Factors Are Important Modulators of Immunity

    PubMed Central

    Flies, Andrew S.; Mansfield, Linda S.; Grant, Chris K.; Weldele, Mary L.; Holekamp, Kay E.

    2015-01-01

    Evolutionary processes have shaped the vertebrate immune system over time, but proximal mechanisms control the onset, duration, and intensity of immune responses. Based on testing of the hygiene hypothesis, it is now well known that microbial exposure is important for proper development and regulation of the immune system. However, few studies have examined the differences between wild animals in their natural environments, in which they are typically exposed to a wide array of potential pathogens, and their conspecifics living in captivity. Wild spotted hyenas (Crocuta crocuta) are regularly exposed to myriad pathogens, but there is little evidence of disease-induced mortality in wild hyena populations, suggesting that immune defenses are robust in this species. Here we assessed differences in immune defenses between wild spotted hyenas that inhabit their natural savanna environment and captive hyenas that inhabit a captive environment where pathogen control programs are implemented. Importantly, the captive population of spotted hyenas was derived directly from the wild population and has been in captivity for less than four generations. Our results show that wild hyenas have significantly higher serum antibody concentrations, including total IgG and IgM, natural antibodies, and autoantibodies than do captive hyenas; there was no difference in the bacterial killing capacity of sera collected from captive and wild hyenas. The striking differences in serum antibody concentrations observed here suggest that complementing traditional immunology studies, with comparative studies of wild animals in their natural environment may help to uncover links between environment and immune function, and facilitate progress towards answering immunological questions associated with the hygiene hypothesis. PMID:26444876

  17. Analyzing the Transcriptomes of Two Quorum-Sensing Controlled Transcription Factors, RcsA and LrhA, Important for Pantoea stewartii Virulence.

    PubMed

    Kernell Burke, Alison; Duong, Duy An; Jensen, Roderick V; Stevens, Ann M

    2015-01-01

    The Gram-negative proteobacterium Pantoea stewartii subsp. stewartii causes wilt disease in corn plants. Wilting is primarily due to bacterial exopolysaccharide (EPS) production that blocks water transport in the xylem during the late stages of infection. EsaR, the master quorum-sensing (QS) regulator in P. stewartii, modulates EPS levels. At low cell densities EsaR represses or activates expression of a number of genes in the absence of its acyl homoserine lactone (AHL) ligand. At high cell densities, binding of AHL inactivates EsaR leading to derepression or deactivation of its direct targets. Two of these direct targets are the key transcription regulators RcsA and LrhA, which in turn control EPS production and surface motility/adhesion, respectively. In this study, RNA-Seq was used to further examine the physiological impact of deleting the genes encoding these two second-tier regulators. Quantitative reverse transcription PCR (qRT-PCR) was used to validate the regulation observed in the RNA-Seq data. A GFP transcriptional fusion reporter confirmed the existence of a regulatory feedback loop in the system between LrhA and RcsA. Plant virulence assays carried out with rcsA and lrhA deletion and complementation strains demonstrated that both transcription factors play roles during establishment of wilt disease in corn. These efforts further define the hierarchy of the QS-regulated network controlling plant virulence in P. stewartii. PMID:26699719

  18. Development of a surgical site infection (SSI) surveillance system, calculation of SSI rates and specification of important factors affecting SSI in a digestive organ surgical department.

    PubMed

    Kimura, Koji; Sawa, Akihiro; Akagi, Shinji; Kihira, Kenji

    2007-06-01

    We have developed an original system to conduct surgical site infection (SSI) surveillance. This system accumulates SSI surveillance information based on the National Nosocomial Infections Surveillance (NNIS) System and the Japanese Nosocomial Infections Surveillance (JNIS) System. The features of this system are as follows: easy input of data, high generality, data accuracy, SSI rate by operative procedure and risk index category (RIC) can be promptly calculated and compared with the current NNIS SSI rate, and the SSI rates and accumulated data can be exported electronically. Using this system, we monitored 798 patients in 24 operative procedure categories in the Digestive Organs Surgery Department of Mazda Hospital, Mazda Motor Corporation, from January 2004 through December 2005. The total number and rate of SSI were 47 and 5.89%, respectively. The SSI rates of 777 patients were calculated based on 15 operative procedure categories and Risk Index Categories (RIC). The highest SSI rate was observed in the rectum surgery of RIC 1 (30%), followed by the colon surgery of RIC3 (28.57%). About 30% of the isolated infecting bacteria were Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli. Using quantification theory type 2, the American Society of Anesthesiology score (4.531), volume of hemorrhage under operation (3.075), wound classification (1.76), operation time (1.352), and history of diabetes (0.989) increased to higher ranks as factors for SSI. Therefore, we evaluated this system as a useful tool in safety control for operative procedures. PMID:17760267

  19. Multiple phosphorylation sites at the C-terminus regulate nuclear import of HCMV DNA polymerase processivity factor ppUL44

    SciTech Connect

    Alvisi, Gualtiero; Marin, Oriano; Pari, Gregory; Mancini, Manuela; Avanzi, Simone; Loregian, Arianna; Jans, David A.; Ripalti, Alessandro

    2011-09-01

    The processivity factor of human cytomegalovirus DNA polymerase, phosphoprotein ppUL44, is essential for viral replication. During viral infection ppUL44 is phosphorylated by the viral kinase pUL97, but neither the target residues on ppUL44 nor the effect of phosphorylation on ppUL44's activity are known. We report here that ppUL44 is phosphorylated when transiently expressed in mammalian cells and coimmunoprecipitates with cellular kinases. Of three potential phosphorylation sites (S413, S415, S418) located upstream of ppUL44's nuclear localization signal (NLS) and one (T427) within the NLS itself, protein kinase CK2 (CK2) specifically phosphorylates S413, to trigger a cascade of phosphorylation of S418 and S415 by CK1 and CK2, respectively. Negative charge at the CK2/CK1 target serine residues facilitates optimal nuclear accumulation of ppUL44, whereas negative charge on T427, a potential cyclin-dependent 1 phosphorylation site, strongly decreases nuclear accumulation. Thus, nuclear transport of ppUL44 is finely tuned during viral infection through complex phosphorylation events.

  20. Sorting nexin 9 differentiates ligand-activated Smad3 from Smad2 for nuclear import and transforming growth factor β signaling

    PubMed Central

    Wilkes, Mark C.; Repellin, Claire E.; Kang, Jeong-Han; Andrianifahanana, Mahefatiana; Yin, Xueqian; Leof, Edward B.

    2015-01-01

    Transforming growth factor β (TGFβ) is a pleiotropic protein secreted from essentially all cell types and primary tissues. While TGFβ’s actions reflect the activity of a number of signaling networks, the primary mediator of TGFβ responses are the Smad proteins. Following receptor activation, these cytoplasmic proteins form hetero-oligomeric complexes that translocate to the nucleus and affect gene transcription. Here, through biological, biochemical, and immunofluorescence approaches, sorting nexin 9 (SNX9) is identified as being required for Smad3-dependent responses. SNX9 interacts with phosphorylated (p) Smad3 independent of Smad2 or Smad4 and promotes more rapid nuclear delivery than that observed independent of ligand. Although SNX9 does not bind nucleoporins Nup153 or Nup214 or some β importins (Imp7 or Impβ), it mediates the association of pSmad3 with Imp8 and the nuclear membrane. This facilitates nuclear translocation of pSmad3 but not SNX9. PMID:26337383

  1. Analyzing the Transcriptomes of Two Quorum-Sensing Controlled Transcription Factors, RcsA and LrhA, Important for Pantoea stewartii Virulence

    PubMed Central

    Jensen, Roderick V.; Stevens, Ann M.

    2015-01-01

    The Gram-negative proteobacterium Pantoea stewartii subsp. stewartii causes wilt disease in corn plants. Wilting is primarily due to bacterial exopolysaccharide (EPS) production that blocks water transport in the xylem during the late stages of infection. EsaR, the master quorum-sensing (QS) regulator in P. stewartii, modulates EPS levels. At low cell densities EsaR represses or activates expression of a number of genes in the absence of its acyl homoserine lactone (AHL) ligand. At high cell densities, binding of AHL inactivates EsaR leading to derepression or deactivation of its direct targets. Two of these direct targets are the key transcription regulators RcsA and LrhA, which in turn control EPS production and surface motility/adhesion, respectively. In this study, RNA-Seq was used to further examine the physiological impact of deleting the genes encoding these two second-tier regulators. Quantitative reverse transcription PCR (qRT-PCR) was used to validate the regulation observed in the RNA-Seq data. A GFP transcriptional fusion reporter confirmed the existence of a regulatory feedback loop in the system between LrhA and RcsA. Plant virulence assays carried out with rcsA and lrhA deletion and complementation strains demonstrated that both transcription factors play roles during establishment of wilt disease in corn. These efforts further define the hierarchy of the QS-regulated network controlling plant virulence in P. stewartii. PMID:26699719

  2. Transition from Consultation to Monitoring-NRC's Increasingly Focused Review of Factors Important to F-Area Tank Farm Facility Performance - 13153

    SciTech Connect

    Barr, Cynthia; Grossman, Christopher; Alexander, George; Parks, Leah; Fuhrmann, Mark; Shaffner, James; McKenney, Christepher; Pabalan, Roberto; Pickett, David; Dinwiddie, Cynthia

    2013-07-01

    In consultation with the NRC, DOE issued a waste determination for the F-Area Tank Farm (FTF) facility in March 2012. The FTF consists of 22 underground tanks, each 2.8 to 4.9 million liters in capacity, used to store liquid high-level waste generated as a result of spent fuel reprocessing. The waste determination concluded stabilized waste residuals and associated tanks and auxiliary components at the time of closure are not high-level and can be disposed of as LLW. Prior to issuance of the final waste determination, during the consultation phase, NRC staff reviewed and provided comments on DOE's revision 0 and revision 1 FTF PAs that supported the waste determination and produced a technical evaluation report documenting the results of its multi-year review in October 2011. Following issuance of the waste determination, NRC began to monitor DOE disposal actions to assess compliance with the performance objectives in 10 CFR Part 61, Subpart C. To facilitate its monitoring responsibilities, NRC developed a plan to monitor DOE disposal actions. NRC staff was challenged in developing a focused monitoring plan to ensure limited resources are spent in the most cost-effective manner practical. To address this challenge, NRC prioritized monitoring areas and factors in terms of risk significance and timing. This prioritization was informed by NRC staff's review of DOE's PA documentation, independent probabilistic modeling conducted by NRC staff, and NRC-sponsored research conducted by the Center for Nuclear Waste Regulatory Analyses in San Antonio, TX. (authors)

  3. A Clinicopathologic Study of Lennert Lymphoma and Possible Prognostic Factors: The Importance of Follicular Helper T-cell Markers and the Association With Angioimmunoblastic T-cell Lymphoma.

    PubMed

    Kurita, Daisuke; Miyoshi, Hiroaki; Yoshida, Noriaki; Sasaki, Yuya; Kato, Seiichi; Niino, Daisuke; Sugita, Yasuo; Hatta, Yoshihiro; Takei, Masami; Makishima, Makoto; Ohshima, Koichi

    2016-09-01

    Lennert lymphoma (LeL) is a variant of peripheral T-cell lymphoma, not otherwise specified. Few clinicopathologic studies have investigated LeL, which is a rare disease. Here, we analyzed the clinicopathologic features of 26 patients with LeL to identify potential prognostic factors. Neoplastic cells positive for CD4, CD8, CD4/CD8, TIA-1, and granzyme B were observed in 21 (80.8%), 4 (15.4%), 1 (3.8%), 4 (15.3%), and 0 (0.0%) patients, respectively. Regarding follicular helper T-cell (TFH) markers, neoplastic cells positive for programmed cell death-1 (PD-1), CXCL13, CD10, and BCL6 were observed in 14 (53.8%), 13 (50.0%), 1 (3.8%), and 0 (0.0%) patients, respectively. Patients with positivity for at least 1 TFH cell marker (PD-1, CXCL13, CD10, and/or BCL6) were defined as being TFH cell marker-positive (n=15) and had a worse prognosis than TFH cell marker-negative patients (n=11) (P=0.011). Clinicopathologic characteristics did not differ significantly between TFH cell marker-positive and marker-negative LeL patients. Moreover, prognosis did not differ significantly between TFH cell marker-positive LeL patients and patients with angioimmunoblastic T-cell lymphoma (AITL) (n=42). Nevertheless, as compared with AITL, TFH cell marker-positive LeL was associated with significantly lower frequencies of B symptoms, skin rash, high-intermediate-risk or high-risk international prognostic index values, expanded follicular dendritic cell meshworks, polymorphic infiltrate, clear cells, and positivity for CD10 and BCL6. Although it may be difficult to definitively distinguish between TFH cell marker-positive LeL and AITL, our results suggest that TFH cell markers are useful for identifying LeL patients who will experience unfavorable outcomes. PMID:27428734

  4. Influence of substrate and pH on the diversity of the aeroterrestrial alga Klebsormidium (Klebsormidiales, Streptophyta): a potentially important factor for sympatric speciation

    PubMed Central

    Ryšánek, David; Holzinger, Andreas; Škaloud, Pavel

    2016-01-01

    Our knowledge of the processes involved in speciation of microalgae remains highly limited. In the present study, we investigated a potential role of ecological speciation processes in diversification of the filamentous green alga Klebsormidium. We examined 12 strains representing four different genotypes. The strains were collected from sandstone and limestone rocks and were cultivated at five different pH levels ranging from pH 4 to pH 8. We determined the responses of the 12 strains to the experimental pH conditions by (1) measuring the effective quantum yield of photosystem II, and (2) determining the growth rates after cultivation at different pH levels. Strong differences were found between the results obtained by these two methods. Direct counting of cells revealed a strong ecological differentiation of strains of Klebsormidium isolated from different substrate types. Strains isolated from limestone showed the highest growth rates at higher pH levels; whereas, the strains isolated from sandstone exhibited two distinct growth responses with optima at pH 5 and 6, respectively. In contrast, the effective quantum yield of photosystem II was always down-regulated at lower pH values, probably due to dissolved inorganic carbon limitation. In general, we determined distinct ecophysiological differentiation among distantly and closely related lineages, thereby corroborating our hypothesis that the sympatric speciation of terrestrial algae is driven by ecological divergence. We clearly showed that pH is a critical ecological factor that influences the diversity of autotrophic protists in terrestrial habitats. PMID:27293301

  5. Resuscitation-Promoting Factors Are Cell Wall-Lytic Enzymes with Important Roles in the Germination and Growth of Streptomyces coelicolor

    PubMed Central

    Sexton, Danielle L.; St-Onge, Renée J.; Haiser, Henry J.; Yousef, Mary R.; Brady, Lauren; Gao, Chan; Leonard, Jacqueline

    2014-01-01

    Dormancy is a common strategy adopted by bacterial cells as a means of surviving adverse environmental conditions. For Streptomyces bacteria, this involves developing chains of dormant exospores that extend away from the colony surface. Both spore formation and subsequent spore germination are tightly controlled processes, and while significant progress has been made in understanding the underlying regulatory and enzymatic bases for these, there are still significant gaps in our understanding. One class of proteins with a potential role in spore-associated processes are the so-called resuscitation-promoting factors, or Rpfs, which in other actinobacteria are needed to restore active growth to dormant cell populations. The model species Streptomyces coelicolor encodes five Rpf proteins (RpfA to RfpE), and here we show that these proteins have overlapping functions during growth. Collectively, the S. coelicolor Rpfs promote spore germination and are critical for growth under nutrient-limiting conditions. Previous studies have revealed structural similarities between the Rpf domain and lysozyme, and our in vitro biochemical assays revealed various levels of peptidoglycan cleavage capabilities for each of these five Streptomyces enzymes. Peptidoglycan remodeling by enzymes such as these must be stringently governed so as to retain the structural integrity of the cell wall. Our results suggest that one of the Rpfs, RpfB, is subject to a unique mode of enzymatic autoregulation, mediated by a domain of previously unknown function (DUF348) located within the N terminus of the protein; removal of this domain led to significantly enhanced peptidoglycan cleavage. PMID:25512314

  6. Estimating changes in heat energy stored within a column of wetland surface water and factors controlling their importance in the surface energy budget

    USGS Publications Warehouse

    Shoemaker, W.B.; Sumner, D.M.; Castillo, A.

    2005-01-01

    [1] Changes in heat energy stored within a column of wetland surface water can be a considerable component of the surface energy budget, an attribute that is demonstrated by comparing changes in stored heat energy to net radiation at seven sites in the wetland areas of southern Florida, including the Everglades. The magnitude of changes in stored heat energy approached the magnitude of net radiation more often during the winter dry season than during the summer wet season. Furthermore, the magnitude of changes in stored heat energy in wetland surface water generally decreased as surface energy budgets were upscaled temporally. A new method was developed to estimate changes in stored heat energy that overcomes an important data limitation, namely, the limited spatial and temporal availability of water temperature measurements. The new method is instead based on readily available air temperature measurements and relies on the convolution of air temperature changes with a regression-defined transfer function to estimate changes in water temperature. The convolution-computed water temperature changes are used with water depths and heat capacity to estimate changes in stored heat energy within the Everglades wetland areas. These results likely can be adapted to other humid subtropical wetlands characterized by open water, saw grass, and rush vegetation type communities. Copyright 2005 by the American Geophysical Union.

  7. Novel small RNA expression libraries uncover hsa-miR-30b and hsa-miR-30c as important factors in anoikis resistance

    PubMed Central

    Moreno-Mateos, Miguel A.; Barragán, Verónica; Torres, Belén; Rodríguez-Mateo, Cristina; Méndez-Vidal, Cristina; Berezikov, Eugene; Mudduluru, Giridhar; Allgayer, Heike; Pintor-Toro, José A.

    2013-01-01

    MicroRNAs (miRNAs) have been widely studied in order to elucidate their biological functions. MicroRNA microarrays or miRNA overexpression libraries generated by synthesis and cloning of individual miRNAs have been used to study their different roles. In this work, we have developed a novel methodology to express mature miRNAs and other small RNAs from a double convergent RNA polymerase III promoter. We show that the generated miRNAs function similarly to those processed from primary transcripts or pri-miRNAs. This system allowed us to produce a lentiviral library expressing the whole population of small RNAs present in a metastatic cell line. A functional screening using this library led to the identification of hsa-miR-30b and hsa-miR-30c as negative regulators of cell death induced by loss of attachment (anoikis). Importantly, we demonstrated that the acquisition of anoikis resistance via these miRNAs is achieved through down-regulation of caspase 3 expression. Moreover, overexpression of these miRNAs resulted in a decrease of other types of caspase 3-dependent cell death and enhanced the survival of MCF10A acinar cells in morphogenesis assays, suggesting a putative role as oncomirs. In summary, this novel methodology provides a powerful and effective way for identifying novel small RNAs involved in a particular biological process. PMID:24129493

  8. Proteome Analysis Identifies the Dpr Protein of Streptococcus mutans as an Important Factor in the Presence of Early Streptococcal Colonizers of Tooth Surfaces

    PubMed Central

    Yoshida, Akihiro; Niki, Mamiko; Yamamoto, Yuji; Yasunaga, Ai; Ansai, Toshihiro

    2015-01-01

    Oral streptococci are primary colonizers of tooth surfaces and Streptococcus mutans is the principal causative agent of dental caries in humans. A number of proteins are involved in the formation of monospecies biofilms by S. mutans. This study analyzed the protein expression profiles of S. mutans biofilms formed in the presence or absence of S. gordonii, a pioneer colonizer of the tooth surface, by two-dimensional gel electrophoresis (2-DE). After identifying S. mutans proteins by Mass spectrometric analysis, their expression in the presence of S. gordonii was analyzed. S. mutans was inoculated with or without S. gordonii DL1. The two species were compartmentalized using 0.2-μl Anopore membranes. The biofilms on polystyrene plates were harvested, and the solubilized proteins were separated by 2-DE. When S. mutans biofilms were formed in the presence of S. gordonii, the peroxide resistance protein Dpr of the former showed 4.3-fold increased expression compared to biofilms that developed in the absence of the pioneer colonizer. In addition, we performed a competition assay using S. mutans antioxidant protein mutants together with S. gordonii and other initial colonizers. Growth of the dpr-knockout S. mutans mutant was significantly inhibited by S. gordonii, as well as by S. sanguinis. Furthermore, a cell viability assay revealed that the viability of the dpr-defective mutant was significantly attenuated compared to the wild-type strain when co-cultured with S. gordonii. Therefore, these results suggest that Dpr might be one of the essential proteins for S. mutans survival on teeth in the presence of early colonizing oral streptococci. PMID:25816242

  9. Clinically important improvement in the WOMAC and predictor factors for response to non-specific non-steroidal anti-inflammatory drugs in osteoarthritic patients: a prospective study

    PubMed Central

    2012-01-01

    Background The aims of the present study were first to detect MCID for WOMAC in a Moroccan population, and second, to identify the best pre-treatment predictors on the change of health after treatment by non-specific, non-steroidal anti-inflammatory drugs (NSAIDs), and to evaluate whether the predictors were dependent on the choice of the response criterion. Methods The study involved 173 patients with osteoarthritis in whom primary care physicians decided to start treatment with non-selective NSAIDs. Assessments at admission and after 6 weeks were conducted. In order to determine the threshold levels associated with a definition of clinically important improvement, the receiver operating characteristic method was used. Three different measures of response to a 6-week NSAIDs treatment were used: one indirect measure (MCID in the total WOMAC score), one direct measure (transition question) and a combination of both criteria. Results Eighty patients (46.3%) reported "a slightly better" general health status compared to that of 6 weeks before NSAIDs treatment. The MCID proportion is a 16.0% reduction in WOMAC. The most stable pre-treatment predictors on the improvement of health after treatment by NSAIDs were the absence of previous knee injury and a high level of education. Conclusions In our data, a 16.0% reduction of the total WOMAC score from baseline was associated with the highest degree of improvement on the transition scale category. This cut-off point had good accuracy, and should be appropriate for use in the interpretation of clinical studies results, as well as in clinical care. PMID:22269793

  10. [Host factors and viral factors in hepatitis C treatment].

    PubMed

    Sakamoto, Minoru; Enomoto, Nobuyuki

    2015-02-01

    In the interferon-based therapy for hepatitis C, host factors such as age, gender, liver fibrosis and steatosis are important as a therapeutic effect predictor, and viral factors such as HCV genotype, HCV viral load, HCV gene (IL28B, ITPA) are also important. In addition in genotype 1b, ISDR/IRRDR and core amino acid substitution are important. Also in the DAA treatment, viral factors are also important at the view of therapeutic effect and difficulty of acquisition of drug resistance mutation. In addition, the goal of treatment of hepatitis C are suppression of liver fibrosis progression and liver cancer and improvement of quality of life due to this (quality of life: QOL) and life prognosis, it is important to understand the host factors and HCV viral factors. PMID:25764672

  11. Irrigated agriculture is an important risk factor for West Nile virus disease in the hyperendemic Larimer-Boulder-Weld area of north central Colorado.

    PubMed

    Eisen, Lars; Barker, Christopher M; Moore, Chester G; Pape, W John; Winters, Anna M; Cheronis, Nicholas

    2010-09-01

    This study focused on two West Nile virus (WNV) disease outbreak years, 2003 and 2007, and included a three-county area (Larimer, Boulder, and Weld) in North Central Colorado that is hyperendemic for WNV disease. We used epidemiological data for reported WNV disease cases at the census tract scale to: (1) elucidate whether WNV disease incidence differs between census tracts classified as having high versus lower human population density (based on a threshold value of 580 persons/km2) and (2) determine associations between WNV disease incidence and habitat types suitable as development sites for the larval stage of Culex mosquito vectors. WNV disease incidence was significantly elevated in census tracts with lower human population density, compared with those with high density of human population, in both 2003 (median per census tract of 223 and 143 cases per 100,000 population, respectively) and 2007 (median per census tract of 46 and 19 cases per 100,000 population). This is most likely related, in large part, to greater percentages of coverage in less densely populated census tracts by habitats suitable as development sites for Culex larvae (open water, developed open space, pasture/hay, cultivated crops, woody wetlands, and emergent herbaceous wetlands) and, especially, for the subset of these habitats made up by irrigated agricultural land (pasture/hay and cultivated crops) that presumably serve as major producers of the locally most important vector of WNV to humans: Culex tarsalis. A series of analyses produced significant positive associations between greater coverage of or shorter distance to irrigated agricultural land and elevated WNV disease incidence. As an exercise to produce data with potential to inform spatial implementation schemes for prevention and control measures within the study area, we mapped the spatial patterns, by census tract, of WNV disease incidence in 2003 and 2007 as well as the locations of census tracts that had either low (<25th

  12. Enantioselective Michael Addition of Water

    PubMed Central

    Chen, Bi-Shuang; Resch, Verena; Otten, Linda G; Hanefeld, Ulf

    2015-01-01

    The enantioselective Michael addition using water as both nucleophile and solvent has to date proved beyond the ability of synthetic chemists. Herein, the direct, enantioselective Michael addition of water in water to prepare important β-hydroxy carbonyl compounds using whole cells of Rhodococcus strains is described. Good yields and excellent enantioselectivities were achieved with this method. Deuterium labeling studies demonstrate that a Michael hydratase catalyzes the water addition exclusively with anti-stereochemistry. PMID:25529526

  13. S. 2375: a bill to disapprove of certain deferrals of Strategic Petroleum Reserve budget authority, to authorize additional appropriations with respect to the Strategic Petroleum Reserve, and to increase oil import fees. Introduced in the Senate of the United States, Ninety-Ninth Congress, Second Session, April 28, 1986

    SciTech Connect

    Not Available

    1986-01-01

    The purpose of this bill is to disapprove of certain deferrals of the Strategic Petroleum Reserve (SPR) budget authority, to authorize additional appropriations to the SPR, and to increase oil import fees. The bill authorizes $1 billion for fiscal years 1987, 88, and 89 for crude oil acquisitions for the SPR and $163 million for storage and related facility construction during 1987. It also instructs the Energy Secretary to cease production from the Naval Petroleum Reserve at Elk Hills for six months to allow the reservoir depletion to stabilize.

  14. Pretreatment carcinoembryonic antigen level is a risk factor for para-aortic lymph node recurrence in addition to squamous cell carcinoma antigen following definitive concurrent chemoradiotherapy for squamous cell carcinoma of the uterine cervix

    PubMed Central

    2012-01-01

    Background To identify pretreatment carcinoembryonic antigen (CEA) levels as a risk factor for para-aortic lymph node (PALN) recurrence following concurrent chemoradiotherapy (CCRT) for cervical cancer. Methods From March 1995 to January 2008, 188 patients with squamous cell carcinoma (SCC) of the uterine cervix were analyzed retrospectively. No patient received PALN irradiation as the initial treatment. CEA and squamous cell carcinoma antigen (SCC-Ag) were measured before and after radiotherapy. PALN recurrence was detected by computer tomography (CT) scans. We analyzed the actuarial rates of PALN recurrence by using Kaplan-Meier curves. Multivariate analyses were carried out with Cox regression models. We stratified the risk groups based on the hazard ratios (HR). Results Both pretreatment CEA levels ≥ 10 ng/mL and SCC-Ag levels < 10 ng/mL (p < 0.001, HR = 8.838), SCC-Ag levels ≥ 40 ng/mL (p < 0.001, HR = 12.551), and SCC-Ag levels of 10-40 ng/mL (p < 0.001, HR = 4.2464) were significant factors for PALN recurrence. The corresponding 5-year PALN recurrence rates were 51.5%, 84.8%, and 27.5%, respectively. The 5-year PALN recurrence rate for patients with both low (< 10 ng/mL) SCC and CEA was only 9.6%. CEA levels ≥ 10 ng/mL or SCC-Ag levels ≥ 10 ng/mL at PALN recurrence were associated with overall survival after an isolated PALN recurrence. Pretreatment CEA levels ≥ 10 ng/mL were also associated with survival after an isolated PALN recurrence. Conclusions Pretreatment CEA ≥ 10 ng/mL is an additional risk factor of PALN relapse following definitive CCRT for SCC of the uterine cervix in patients with pretreatment SCC-Ag levels < 10 ng/mL. More comprehensive examinations before CCRT and intensive follow-up schedules are suggested for early detection and salvage in patients with SCC-Ag or CEA levels ≥ 10 ng/mL. PMID:22289572

  15. The Ugandan Youth Quality of Life index: assessing the relevance of incorporating perceived importance into the quality of life measure and factors associated with the quality of life among youth in slum areas of Kampala, Uganda

    PubMed Central

    Renzaho, Andre M. N.; Kamara, Joseph Kihika; Kamanga, Gilbert

    2016-01-01

    Background While quality of life (QoL) has long been an explicit policy goal for international development programmes, no instruments have specifically been developed for measuring health-related QoL in resource-limited settings. The aim of this study was to develop and validate a QoL instrument for use in international aid and development programmes and to assess factors associated with QoL among youth participating in a civic engagement project in Kampala. Design Using systematic random sampling, data were collected on 663 participants aged between 13 and 24 years in Kampala. The QoL questionnaire included 36 questions divided into a two-part scale: 18 questions rated for satisfaction (Part 1) and 18 other questions rated on importance (Part 2). The total sample was randomly divided into two split-half samples: one for the exploratory factor analysis (EFA; N=310) and the other for the confirmatorty factor analysis (CFA; N=353). The effect of demographic, socio-economic, and lifestyle factors on QoL was assessed using linear regressions. Results The EFA yielded three factors: living conditions and lifestyle (seven items, α=0.84), social relationships (five items, α=0.86), and personal independence (five items, α=0.76). In the CFA, the initial model demonstrated a poor to marginal fit model. Its re-specification by examining modification indices resulted in a good model fit: Comparative Fit Index=0.95, Root Mean Square Error of Approximation=0.06, and p of Close Fit >0.05. The model incorporating perceived importance had lower Akaike Information Criteria and Bayesian Information Criteria values than the unweighted model, thereby providing very strong support to weight satisfaction scores with importance ratings when measuring QoL in Uganda. Poor QoL was associated with poor educational attainment, drug and substance misuse, and family disruption. Conclusions The findings suggest that there is a relationship between QoL and lifestyle and structural issues among

  16. Expression, purification, and biochemical characterization of recombinant DNA polymerase beta of the Trypanosoma cruzi TcI lineage: requirement of additional factors and detection of phosphorylation of the native form.

    PubMed

    Maldonado, Edio; Rojas, Diego A; Moreira-Ramos, Sandra; Urbina, Fabiola; Miralles, Vicente J; Solari, Aldo; Venegas, Juan

    2015-04-01

    Chagas disease, caused by the protozoan Trypanosoma cruzi, is a major parasitic disease that affects millions of people in America. However, despite the high impact of this disease on human health, no effective and safe treatment has been found that eliminates the infecting parasite from human patients. Among the possible chemotherapeutic targets that could be considered for study in T. cruzi are the DNA polymerases, in particular DNA polymerase beta (polß), which previous studies have shown to be involved in kinetoplast DNA replication and repair. In this paper, we describe the expression, purification, and biochemical characterization of the Miranda clone polß, corresponding to lineage T. cruzi I (TcI). The recombinant enzyme purified to homogeneity displayed specific activity in the range described for a highly purified mammalian polß. However, the trypanosome enzyme exhibited important differences in biochemical properties compared to the mammalian enzymes, specifically an almost absolute dependency on KCl, high sensitivity to N-ethylmaleimide (NEM), and low sensitivity to ddTTP. Immuno-affinity purification of T. cruzi polymerase beta (Tcpolß) from epimastigote extracts showed that the native enzyme was phosphorylated. In addition, it was demonstrated that Tcpolß interacts with some proteins in a group of about 15 proteins which are required to repair 1-6 bases of gaps of a double strand damaged DNA. It is possible that these proteins form part of a DNA repair complex, analogous to that described in mammals and some trypanosomatids. PMID:25566774

  17. The importance of intersectoral factors in promoting equity-oriented universal health coverage: a multilevel analysis of social determinants affecting neonatal infant and under-five mortality in Bangladesh

    PubMed Central

    Huda, Tanvir M.; Tahsina, Tazeen; El Arifeen, Shams; Dibley, Michael J.

    2016-01-01

    Introduction Health is multidimensional and affected by a wide range of factors, many of which are outside the health sector. To improve population health and reduce health inequality, it is important that we take into account the complex interactions among social, environmental, behavioural, and biological factors and design our health interventions accordingly. Objectives This study examines mortality differentials in children of different age groups by key social determinants of health (SDH) including parental education and employment, mother's level of autonomy, age, asset index, living arrangements (utilities), and other geographical contextual factors (area of residence, road conditions). Design We used data from the two rounds of Bangladesh Health and Demographic Survey, a nationally representative sample survey of the population residing in Bangladesh. Multilevel logistic models were used to study the impact of SDH on child mortality. Results The study found that the mother's age, the education of both parents, the mother's autonomy to take decisions about matters linked to the health of her child, the household socio-economic conditions, the geographical region of residence, and the condition of the roads were significantly associated with higher risks of neonatal, infant, and under-five mortality in Bangladesh. Conclusion The study findings suggest there are complex relationships among different SDH. Thus larger intersectoral actions will be needed to reduce disparities in child health and mortality and achieve meaningful progress towards equity-oriented universal health coverage. PMID:26880153

  18. The development of decision limits for the GH-2000 detection methodology using additional insulin-like growth factor-I and amino-terminal pro-peptide of type III collagen assays.

    PubMed

    Holt, Richard I G; Böhning, Walailuck; Guha, Nishan; Bartlett, Christiaan; Cowan, David A; Giraud, Sylvain; Bassett, E Eryl; Sönksen, Peter H; Böhning, Dankmar

    2015-09-01

    The GH-2000 and GH-2004 projects have developed a method for detecting GH misuse based on measuring insulin-like growth factor-I (IGF-I) and the amino-terminal pro-peptide of type III collagen (P-III-NP). The objectives were to analyze more samples from elite athletes to improve the reliability of the decision limit estimates, to evaluate whether the existing decision limits needed revision, and to validate further non-radioisotopic assays for these markers. The study included 998 male and 931 female elite athletes. Blood samples were collected according to World Anti-Doping Agency (WADA) guidelines at various sporting events including the 2011 International Association of Athletics Federations (IAAF) World Athletics Championships in Daegu, South Korea. IGF-I was measured by the Immunotech A15729 IGF-I IRMA, the Immunodiagnostic Systems iSYS IGF-I assay and a recently developed mass spectrometry (LC-MS/MS) method. P-III-NP was measured by the Cisbio RIA-gnost P-III-P, Orion UniQ™ PIIINP RIA and Siemens ADVIA Centaur P-III-NP assays. The GH-2000 score decision limits were developed using existing statistical techniques. Decision limits were determined using a specificity of 99.99% and an allowance for uncertainty because of the finite sample size. The revised Immunotech IGF-I - Orion P-III-NP assay combination decision limit did not change significantly following the addition of the new samples. The new decision limits are applied to currently available non-radioisotopic assays to measure IGF-I and P-III-NP in elite athletes, which should allow wider flexibility to implement the GH-2000 marker test for GH misuse while providing some resilience against manufacturer withdrawal or change of assays. PMID:25645199

  19. [Food additives and healthiness].

    PubMed

    Heinonen, Marina

    2014-01-01

    Additives are used for improving food structure or preventing its spoilage, for example. Many substances used as additives are also naturally present in food. The safety of additives is evaluated according to commonly agreed principles. If high concentrations of an additive cause adverse health effects for humans, a limit of acceptable daily intake (ADI) is set for it. An additive is a risk only when ADI is exceeded. The healthiness of food is measured on the basis of nutrient density and scientifically proven effects. PMID:24772784

  20. Polyimide processing additives

    NASA Technical Reports Server (NTRS)

    Pratt, J. R.; St. Clair, T. L.; Burks, H. D.; Stoakley, D. M.

    1987-01-01

    A method has been found for enhancing the melt flow of thermoplastic polyimides during processing. A high molecular weight 422 copoly(amic acid) or copolyimide was fused with approximately 0.05 to 5 pct by weight of a low molecular weight amic acid or imide additive, and this melt was studied by capillary rheometry. Excellent flow and improved composite properties on graphite resulted from the addition of a PMDA-aniline additive to LARC-TPI. Solution viscosity studies imply that amic acid additives temporarily lower molecular weight and, hence, enlarge the processing window. Thus, compositions containing the additive have a lower melt viscosity for a longer time than those unmodified.

  1. Statistical controversies in clinical research: the importance of importance.

    PubMed

    Gleiss, A; Zeillinger, R; Braicu, E I; Trillsch, F; Vergote, I; Schemper, M

    2016-07-01

    We define the notion of 'importance' of prognostic factors in studies of survival and suggest quantifying it by the Schemper-Henderson measure of explained variation. Conceptual differences to the standard approach for the statistical analysis of oncologic studies of survival are discussed and exemplified by means of a study of ovarian cancer. Explained variation permits to establish a ranking of the importance of factors, also if measured on different scales, or of different types (dichotomous, qualitative or continuous), and permits to compare groups of related factors. In practice, the importance of prognostic factors often is disappointingly low. From this, it follows that even strong and highly significant prognostic factors often do not translate into close determination of individual survival of patients. PMID:27052655

  2. Transcriptional up-regulation of the mouse cytosolic glutathione peroxidase gene in erythroid cells is due to a tissue-specific 3' enhancer containing functionally important CACC/GT motifs and binding sites for GATA and Ets transcription factors.

    PubMed Central

    O'Prey, J; Ramsay, S; Chambers, I; Harrison, P R

    1993-01-01

    Nuclear run-on experiments have shown that the high level of expression of the mouse cytosolic glutathione peroxidase mRNA in erythroid cells is due to up-regulation of the gene at the transcriptional level. Studies of the chromatin structure around the cytosolic glutathione peroxidase gene have revealed a series of DNase I hypersensitive sites (DHSS) in the 3' flanking region of the gene in erythroid and other high-expression tissues that are lacking in low-expression cells, in addition to a DHSS over the promoter region in both high- and low-expression tissues. Functional transfection experiments have demonstrated that one of the 3' DHSS regions functions as an enhancer in erythroid cells but not in a low-expression epithelial cell line; and site-directed mutagenesis and footprinting experiments reveal that the activity of the erythroid cell-specific enhancer requires a cluster of binding sites for the CACC/GT box factors and the GATA and Ets families of transcription factors. Images PMID:8413228

  3. Porphyromonas gingivalis-derived lysine gingipain enhances osteoclast differentiation induced by tumor necrosis factor-α and interleukin-1β but suppresses that by interleukin-17A: importance of proteolytic degradation of osteoprotegerin by lysine gingipain.

    PubMed

    Akiyama, Tomohito; Miyamoto, Yoichi; Yoshimura, Kentaro; Yamada, Atsushi; Takami, Masamichi; Suzawa, Tetsuo; Hoshino, Marie; Imamura, Takahisa; Akiyama, Chie; Yasuhara, Rika; Mishima, Kenji; Maruyama, Toshifumi; Kohda, Chikara; Tanaka, Kazuo; Potempa, Jan; Yasuda, Hisataka; Baba, Kazuyoshi; Kamijo, Ryutaro

    2014-05-30

    Periodontitis is a chronic inflammatory disease accompanied by alveolar bone resorption by osteoclasts. Porphyromonas gingivalis, an etiological agent for periodontitis, produces cysteine proteases called gingipains, which are classified based on their cleavage site specificity (i.e. arginine (Rgps) and lysine (Kgps) gingipains). We previously reported that Kgp degraded osteoprotegerin (OPG), an osteoclastogenesis inhibitory factor secreted by osteoblasts, and enhanced osteoclastogenesis induced by various Toll-like receptor (TLR) ligands (Yasuhara, R., Miyamoto, Y., Takami, M., Imamura, T., Potempa, J., Yoshimura, K., and Kamijo, R. (2009) Lysine-specific gingipain promotes lipopolysaccharide- and active-vitamin D3-induced osteoclast differentiation by degrading osteoprotegerin. Biochem. J. 419, 159-166). Osteoclastogenesis is induced not only by TLR ligands but also by proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-17A, in inflammatory conditions, such as periodontitis. Although Kgp augmented osteoclastogenesis induced by TNF-α and IL-1β in co-cultures of mouse osteoblasts and bone marrow cells, it suppressed that induced by IL-17A. In a comparison of proteolytic degradation of these cytokines by Kgp in a cell-free system with that of OPG, TNF-α and IL-1β were less susceptible, whereas IL-17A and OPG were equally susceptible to degradation by Kgp. These results indicate that the enhancing effect of Kgp on cytokine-induced osteoclastogenesis is dependent on the difference in degradation efficiency between each cytokine and OPG. In addition, elucidation of the N-terminal amino acid sequences of OPG fragments revealed that Kgp primarily cleaved OPG in its death domain homologous region, which might prevent dimer formation of OPG required for inhibition of receptor activator of nuclear factor κB ligand. Collectively, our results suggest that degradation of OPG by Kgp is a crucial event in the development of

  4. Additive usage levels.

    PubMed

    Langlais, R

    1996-01-01

    With the adoption of the European Parliament and Council Directives on sweeteners, colours and miscellaneous additives the Commission is now embarking on the project of coordinating the activities of the European Union Member States in the collection of the data that are to make up the report on food additive intake requested by the European Parliament. This presentation looks at the inventory of available sources on additive use levels and concludes that for the time being national legislation is still the best source of information considering that the directives have yet to be transposed into national legislation. Furthermore, this presentation covers the correlation of the food categories as found in the additives directives with those used by national consumption surveys and finds that in a number of instances this correlation still leaves a lot to be desired. The intake of additives via food ingestion and the intake of substances which are chemically identical to additives but which occur naturally in fruits and vegetables is found in a number of cases to be higher than the intake of additives added during the manufacture of foodstuffs. While the difficulties are recognized in contributing to the compilation of food additive intake data, industry as a whole, i.e. the food manufacturing and food additive manufacturing industries, are confident that in a concerted effort, use data on food additives by industry can be made available. Lastly, the paper points out that with the transportation of the additives directives into national legislation and the time by which the food industry will be able to make use of the new food legislative environment several years will still go by; food additives use data by the food industry will thus have to be reviewed at the beginning of the next century. PMID:8792135

  5. An additional middle cuneiform?

    PubMed Central

    Brookes-Fazakerley, S.D.; Jackson, G.E.; Platt, S.R.

    2015-01-01

    Additional cuneiform bones of the foot have been described in reference to the medial bipartite cuneiform or as small accessory ossicles. An additional middle cuneiform has not been previously documented. We present the case of a patient with an additional ossicle that has the appearance and location of an additional middle cuneiform. Recognizing such an anatomical anomaly is essential for ruling out second metatarsal base or middle cuneiform fractures and for the preoperative planning of arthrodesis or open reduction and internal fixation procedures in this anatomical location. PMID:26224890

  6. The +37 kb Cebpa Enhancer Is Critical for Cebpa Myeloid Gene Expression and Contains Functional Sites that Bind SCL, GATA2, C/EBPα, PU.1, and Additional Ets Factors

    PubMed Central

    Cooper, Stacy; Guo, Hong; Friedman, Alan D.

    2015-01-01

    The murine Cebpa gene contains an evolutionarily conserved 453 bp enhancer located at +37 kb that, together with its promoter, directs expression to myeloid progenitors and to long-term hematopoietic stem cells in transgenic mice. In human acute myeloid leukemia cases, the enhancer lacks point mutations but binds the RUNX1-ETO oncoprotein. The enhancer contains the H3K4me1 and H3K27Ac histone modifications, denoting an active enhancer, at progressively increasing levels as long-term hematopoietic stem cells transition to granulocyte-monocyte progenitors. We previously identified four enhancer sites that bind RUNX1 and demonstrated that their integrity is required for maximal enhancer activity in 32Dcl3 myeloid cells. The +37 kb Cebpa enhancer also contains C/EBP, Ets factor, Myb, GATA, and E-box consensus sites conserved in the human +42 kb CEBPA enhancer. Mutation of the two C/EBP, seven Ets, one Myb, two GATA, or two E-box sites reduces activity of an enhancer-promoter reporter in 32Dcl3 cells. In 293T gel shift assays, exogenous C/EBPα binds both C/EBP sites, c-Myb binds the Myb site, PU.1 binds the second Ets site, PU.1, Fli-1, ERG, and Ets1 bind the sixth Ets site, GATA2 binds both GATA sites, and SCL binds the second E-box. Endogenous hematopoietic RUNX1, PU.1, Fli-1, ERG, C/EBPα, GATA2, and SCL were previously shown to bind the enhancer, and we find that endogenous PU.1 binds the second Ets site in 32Dcl3 cells. Using CRISPR/Cas9, we developed 32Dcl3 lines in which the wild-type enhancer alleles are replaced with a variant mutant in the seven Ets sites. These lines have 20-fold reduced Cebpa mRNA when cultured in IL-3 or G-CSF, demonstrating a critical requirement for enhancer integrity for optimal Cebpa expression. In addition, these results indicate that the +37 kb Cebpa enhancer is the focus of multiple regulatory transcriptional pathways that impact its expression during normal hematopoiesis and potentially during myeloid transformation. PMID:25938608

  7. Identification of two factors which bind to the upstream sequences of a number of nuclear genes coding for mitochondrial proteins and to genetic elements important for cell division in yeast.

    PubMed Central

    Dorsman, J C; van Heeswijk, W C; Grivell, L A

    1988-01-01

    Two abundant factors, GFI and GFII which interact with the 5' flanking regions of nuclear genes coding for proteins of the mitochondrial respiratory chain have been identified. In one case (subunit VIII of QH2: cytochrome c oxidoreductase) the binding sites for both factors overlap completely and their binding is mutually exclusive. For the other 5' regions tested the GFI and GFII binding sites do not coincide. Interestingly, binding sites for GFI and GFII are also present in or at the 3' ends of the coding regions of two genes of the PHO gene family and in DNA elements important for optimal ARS and CEN function respectively. The sites recognized by GFI conform to the consensus RTCRNNNNNNACGNR, while those recognized by GFII contain the element RTCACGTG. We speculate that GFI and GFII may play a role in different cellular processes, dependent on the context of their binding sites and that one of these processes may be the coordination of the expression of genes involved in mitochondrial biogenesis with the progress of the cell cycle. Images PMID:3045755

  8. Carbamate deposit control additives

    SciTech Connect

    Honnen, L.R.; Lewis, R.A.

    1980-11-25

    Deposit control additives for internal combustion engines are provided which maintain cleanliness of intake systems without contributing to combustion chamber deposits. The additives are poly(oxyalkylene) carbamates comprising a hydrocarbyloxyterminated poly(Oxyalkylene) chain of 2-5 carbon oxyalkylene units bonded through an oxycarbonyl group to a nitrogen atom of ethylenediamine.

  9. MicroRNAs regulate T-cell production of interleukin-9 and identify hypoxia-inducible factor-2α as an important regulator of T helper 9 and regulatory T-cell differentiation.

    PubMed

    Singh, Yogesh; Garden, Oliver A; Lang, Florian; Cobb, Bradley S

    2016-09-01

    MicroRNAs (miRNAs) regulate many aspects of helper T cell (Th) development and function. Here we found that they are required for the suppression of interleukin-9 (IL-9) expression in Th9 cells and other Th subsets. Two highly related miRNAs (miR-15b and miR-16) that we previously found to play an important role in regulatory T (Treg) cell differentiation were capable of suppressing IL-9 expression when they were over-expressed in Th9 cells. We used these miRNAs as tools to identify novel regulators of IL-9 expression and found that they could regulate the expression of Epas1, which encodes hypoxia-inducible factor (HIF)-2α. HIF proteins regulate metabolic pathway usage that is important in determining appropriate Th differentiation. The related protein, HIF-1α enhances Th17 differentiation and inhibits Treg cell differentiation. Here we found that HIF-2α was required for IL-9 expression in Th9 cells, but its expression was not sufficient in other Th subsets. Furthermore, HIF-2α suppressed Treg cell differentiation like HIF-1α, demonstrating both similar and distinct roles of the HIF proteins in Th differentiation and adding a further dimension to their function. Ironically, even though miR-15b and miR-16 suppressed HIF-2α expression in Treg cells, inhibiting their function in Treg cells did not lead to an increase in IL-9 expression. Therefore, the physiologically relevant miRNAs that regulate IL-9 expression in Treg cells and other subsets remain unknown. Nevertheless, the analysis of miR-15b and miR-16 function led to the discovery of the importance of HIF-2α so this work demonstrated the utility of studying miRNA function to identify novel regulatory pathways in helper T-cell development. PMID:27278750

  10. Polyimide processing additives

    NASA Technical Reports Server (NTRS)

    Fletcher, James C. (Inventor); Pratt, J. Richard (Inventor); St.clair, Terry L. (Inventor); Stoakley, Diane M. (Inventor); Burks, Harold D. (Inventor)

    1992-01-01

    A process for preparing polyimides having enhanced melt flow properties is described. The process consists of heating a mixture of a high molecular weight poly-(amic acid) or polyimide with a low molecular weight amic acid or imide additive in the range of 0.05 to 15 percent by weight of additive. The polyimide powders so obtained show improved processability, as evidenced by lower melt viscosity by capillary rheometry. Likewise, films prepared from mixtures of polymers with additives show improved processability with earlier onset of stretching by TMA.

  11. Polyimide processing additives

    NASA Technical Reports Server (NTRS)

    Pratt, J. Richard (Inventor); St.clair, Terry L. (Inventor); Stoakley, Diane M. (Inventor); Burks, Harold D. (Inventor)

    1993-01-01

    A process for preparing polyimides having enhanced melt flow properties is described. The process consists of heating a mixture of a high molecular weight poly-(amic acid) or polyimide with a low molecular weight amic acid or imide additive in the range of 0.05 to 15 percent by weight of the additive. The polyimide powders so obtained show improved processability, as evidenced by lower melt viscosity by capillary rheometry. Likewise, films prepared from mixtures of polymers with additives show improved processability with earlier onset of stretching by TMA.

  12. Interaction: Additivity plus Nonlinearity?

    ERIC Educational Resources Information Center

    Hutchinson, T. P.

    2004-01-01

    Whether or not there is an interaction between two factors in their effects on a dependent variable is often a central question. This paper proposes a general mechanism by which an interaction may arise: (a) the two factors are the same thing--or, at least, have a dimension in common--in the sense that it is meaningful to add (or subtract) them;…

  13. How important is importance for prospective memory? A review

    PubMed Central

    Walter, Stefan; Meier, Beat

    2014-01-01

    Forgetting to carry out an intention as planned can have serious consequences in everyday life. People sometimes even forget intentions that they consider as very important. Here, we review the literature on the impact of importance on prospective memory performance. We highlight different methods used to manipulate the importance of a prospective memory task such as providing rewards, importance relative to other ongoing activities, absolute importance, and providing social motives. Moreover, we address the relationship between importance and other factors known to affect prospective memory and ongoing task performance such as type of prospective memory task (time-, event-, or activity-based), cognitive loads, and processing overlaps. Finally, we provide a connection to motivation, we summarize the effects of task importance and we identify important venues for future research. PMID:25018743

  14. Smog control fuel additives

    SciTech Connect

    Lundby, W.

    1993-06-29

    A method is described of controlling, reducing or eliminating, ozone and related smog resulting from photochemical reactions between ozone and automotive or industrial gases comprising the addition of iodine or compounds of iodine to hydrocarbon-base fuels prior to or during combustion in an amount of about 1 part iodine per 240 to 10,000,000 parts fuel, by weight, to be accomplished by: (a) the addition of these inhibitors during or after the refining or manufacturing process of liquid fuels; (b) the production of these inhibitors for addition into fuel tanks, such as automotive or industrial tanks; or (c) the addition of these inhibitors into combustion chambers of equipment utilizing solid fuels for the purpose of reducing ozone.

  15. Food Additives and Hyperkinesis

    ERIC Educational Resources Information Center

    Wender, Ester H.

    1977-01-01

    The hypothesis that food additives are causally associated with hyperkinesis and learning disabilities in children is reviewed, and available data are summarized. Available from: American Medical Association 535 North Dearborn Street Chicago, Illinois 60610. (JG)

  16. Additional Types of Neuropathy

    MedlinePlus

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